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  1. Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?

    Directory of Open Access Journals (Sweden)

    Bell Jimmy D

    2009-04-01

    Full Text Available Abstract The metabolic syndrome may have its origins in thriftiness, insulin resistance and one of the most ancient of all signalling systems, redox. Thriftiness results from an evolutionarily-driven propensity to minimise energy expenditure. This has to be balanced with the need to resist the oxidative stress from cellular signalling and pathogen resistance, giving rise to something we call 'redox-thriftiness'. This is based on the notion that mitochondria may be able to both amplify membrane-derived redox growth signals as well as negatively regulate them, resulting in an increased ATP/ROS ratio. We suggest that 'redox-thriftiness' leads to insulin resistance, which has the effect of both protecting the individual cell from excessive growth/inflammatory stress, while ensuring energy is channelled to the brain, the immune system, and for storage. We also suggest that fine tuning of redox-thriftiness is achieved by hormetic (mild stress signals that stimulate mitochondrial biogenesis and resistance to oxidative stress, which improves metabolic flexibility. However, in a non-hormetic environment with excessive calories, the protective nature of this system may lead to escalating insulin resistance and rising oxidative stress due to metabolic inflexibility and mitochondrial overload. Thus, the mitochondrially-associated resistance to oxidative stress (and metabolic flexibility may determine insulin resistance. Genetically and environmentally determined mitochondrial function may define a 'tipping point' where protective insulin resistance tips over to inflammatory insulin resistance. Many hormetic factors may induce mild mitochondrial stress and biogenesis, including exercise, fasting, temperature extremes, unsaturated fats, polyphenols, alcohol, and even metformin and statins. Without hormesis, a proposed redox-thriftiness tipping point might lead to a feed forward insulin resistance cycle in the presence of excess calories. We therefore suggest

  2. Insulin resistance in pregnant women with and without polycystic ovary syndrome, and measures of body composition in offspring at birth and three years of age.

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    Finnbogadóttir, Sara K; Glintborg, Dorte; Jensen, Tina K; Kyhl, Henriette B; Nohr, Ellen A; Andersen, Marianne

    2017-11-01

    Polycystic ovary syndrome is associated with obesity and insulin resistance in the non-pregnant state, but little is known about insulin sensitivity in the pregnant state. Our objective was to compare insulin resistance in pregnant women with and without polycystic ovary syndrome and explore the impact of polycystic ovary syndrome on body composition in offspring at birth and at three years of age. A prospective cohort study including 2548 live-born singleton mother-child pairs residing in Odense municipality, Denmark, during 2010-2013. Of the 2548 women, 241 (9.4%) had polycystic ovary syndrome. Homeostatic model assessment for insulin resistance assessments were comparable in women with and without polycystic ovary syndrome. However, the subgroup of overweight women with polycystic ovary syndrome had significantly higher levels of homeostatic model assessment for insulin resistance than overweight women without polycystic ovary syndrome (mean ± 2 SD): 4.4 (3.1) vs. 3.6 (3.4), p = 0.004. Maternal polycystic ovary syndrome did not affect offspring birthweight after accounting for age. However, polycystic ovary syndrome, adjusted for maternal body mass index, was associated with increased body mass index at three years of age (mean ± 2 SD): 16.0 (2.2) vs. 15.7 (2.1) kg/m 2 , p = 0.04. In our cohort, maternal polycystic ovary syndrome was not associated with insulin resistance after correcting for body mass index and was not an independent predictor of offspring birthweight. However, both polycystic ovary syndrome and high maternal body mass index may increase risk of childhood obesity at three years of age. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  3. Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome

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    Dhindsa G

    2004-04-01

    Full Text Available It is estimated that 5-10% of women of reproductive age have polycystic ovarian syndrome (PCOS. While insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS cannot be denied. PCOS is associated with insulin resistance independent of total or fat-free body mass. Post-receptor defects in the action of insulin have been described in PCOS which are similar to those found in obesity and type 2 diabetes. Treatment with insulin sensitizers, metformin and thiazolidinediones, improve both metabolic and hormonal patterns and also improve ovulation in PCOS. Recent studies have shown that PCOS women have higher circulating levels of inflammatory mediators like C-reactive protein, tumour necrosis factor- , tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1 . It is possible that the beneficial effect of insulin sensitizers in PCOS may be partly due to a decrease in inflammation.

  4. Diverse impacts of aging on insulin resistance in lean and obese women with polycystic ovary syndrome: evidence from 1345 women with the syndrome.

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    Livadas, Sarantis; Kollias, Anastasios; Panidis, Dimitrios; Diamanti-Kandarakis, Evanthia

    2014-09-01

    Polycystic ovary syndrome (PCOS) represents a moving spectrum of hormonal to metabolic abnormalities, as women with the syndrome are aging. Hormonal abnormalities, anovulation, and hyperandrogenic signs were predominant during the early years of PCOS and fade away with the years. Metabolic abnormalities and insulin resistance (IR) remain throughout the PCOS life cycle; however, it is unclear as to how they change, as women with the syndrome are aging. To evaluate the changes in IR and its associations with clinical, biochemical, hormonal, and ultrasound findings in a large cohort of women with PCOS and controls, as they are aging. A cross-sectional study was carried out to evaluate the diverse impacts of aging on IR. An outpatient clinic was chosen for the study. A total of 1345 women with PCOS (Rotterdam criteria) and 302 controls of Caucasian origin and Greek ethnicity comprised the study group. The impact of age on IR, as calculated using homeostasis model assessment of IR (HOMA-IR) index, and several PCOS characteristics were evaluated. In PCOS, age (-0.045±0.008) was negatively, and BMI positively (0.18±0.007) associated with HOMA-IR (R(2)=0.36). When data were stratified with regard to the BMI status, a negative association of age with HOMA-IR was found in lean, normal, and overweight patients (r: -0.266, -0.233, -0.192, Pwomen (P: 0.202) across age quartiles. Aging increases IR in obese but not in lean and overweight women with PCOS. As BMI and androgens are positively associated with HOMA-IR and androgens decline through time, it appears that if women with PCOS do not become obese they may exhibit a better metabolic profile during their reproductive years. © 2014 European Society of Endocrinology.

  5. Insulin autoimmune syndrome: case report

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    Rodrigo Oliveira Moreira

    Full Text Available CONTEXT: Insulin autoimmune syndrome (IAS, Hirata disease is a rare cause of hypoglycemia in Western countries. It is characterized by hypoglycemic episodes, elevated insulin levels, and positive insulin antibodies. Our objective is to report a case of IAS identified in South America. CASE REPORT: A 56-year-old Caucasian male patient started presenting neuroglycopenic symptoms during hospitalization due to severe trauma. Biochemical evaluation confirmed hypoglycemia and abnormally high levels of insulin. Conventional imaging examinations were negative for pancreatic tumor. Insulin antibodies were above the normal range. Clinical remission of the episodes was not achieved with verapamil and steroids. Thus, a subtotal pancreatectomy was performed due to the lack of response to conservative treatment and because immunosuppressants were contraindicated due to bacteremia. Histopathological examination revealed diffuse hypertrophy of beta cells. The patient continues to have high insulin levels but is almost free of hypoglycemic episodes.

  6. Insulin resistance and polycystic ovary syndrome.

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    Galluzzo, Aldo; Amato, Marco Calogero; Giordano, Carla

    2008-09-01

    Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in humans, affecting approximately 7-8% of women of reproductive age. Despite the criteria adopted, PCOS is considered to be a predominantly hyperandrogenetic syndrome and the evaluation of metabolic parameters and insulin sensitivity is not mandatory. Most women with PCOS also exhibit features of the metabolic syndrome, including insulin resistance, obesity and dyslipidaemia. While the association with type 2 diabetes is well established, whether the incidence of cardiovascular disease is increased in women with PCOS remains unclear. Acknowledging the strong impact of insulin-resistance in the genesis of PCOS could be helpful not only to make the diagnosis more robust, but also for conferring better cardiovascular risk prevention. Several current studies support a strong recommendation that women with PCOS should undergo comprehensive evaluation for the metabolic syndrome and recognized cardiovascular risk factors, and receive appropriate treatment as needed. Lifestyle modifications remain the first-line therapy for all obese women with PCOS. However, many of these women do not lose weight easily. Insulin-sensitizing drugs are discussed as a promising and unique therapeutic option for the chronic treatment of PCOS.

  7. Genetics Home Reference: type A insulin resistance syndrome

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    ... Conditions Type A insulin resistance syndrome Type A insulin resistance syndrome Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Type A insulin resistance syndrome is a rare disorder characterized by severe ...

  8. Correlation Between Insulin, Leptin and Polycystic Ovary Syndrome ...

    African Journals Online (AJOL)

    Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of fertile age. Insulin can stimulate ovarian androgen production in normal women and in women with PCOS. Leptin levels were reduced among women with PCOS treated with insulin sensitizers. Aim: This study aims to ...

  9. Metabolic syndrome and insulin resistance in obese adolescents

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    Amanda Oliva Gobato

    2014-03-01

    Full Text Available Objective: To verify the prevalence of metabolic syndrome and insulin resistance in obese adolescents and its relationship with different body composition indicators. Methods: A cross-sectional study comprising 79 adolescents aged ten to 18 years old. The assessed body composition indicators were: body mass index (BMI, body fat percentage, abdominal circumference, and subcutaneous fat. The metabolic syndrome was diagnosed according to the criteria proposed by Cook et al. The insulin resistance was determined by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR index for values above 3.16. The analysis of ROC curves was used to assess the BMI and the abdominal circumference, aiming to identify the subjects with metabolic syndrome and insulin resistance. The cutoff point corresponded to the percentage above the reference value used to diagnose obesity. Results: The metabolic syndrome was diagnosed in 45.5% of the patients and insulin resistance, in 29.1%. Insulin resistance showed association with HDL-cholesterol (p=0.032 and with metabolic syndrome (p=0.006. All body composition indicators were correlated with insulin resistance (p<0.01. In relation to the cutoff point evaluation, the values of 23.5 and 36.3% above the BMI reference point allowed the identification of insulin resistance and metabolic syndrome. The best cutoff point for abdominal circumference to identify insulin resistance was 40%. Conclusions: All body composition indicators, HDL-cholesterol and metabolic syndrome showed correlation with insulin resistance. The BMI was the most effective anthropometric indicator to identify insulin resistance.

  10. Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a general adult population: effect of gender and age: EPIRCE cross-sectional study.

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    Gayoso-Diz, Pilar; Otero-González, Alfonso; Rodriguez-Alvarez, María Xosé; Gude, Francisco; García, Fernando; De Francisco, Angel; Quintela, Arturo González

    2013-10-16

    Insulin resistance has been associated with metabolic and hemodynamic alterations and higher cardio metabolic risk. There is great variability in the threshold homeostasis model assessment of insulin resistance (HOMA-IR) levels to define insulin resistance. The purpose of this study was to describe the influence of age and gender in the estimation of HOMA-IR optimal cut-off values to identify subjects with higher cardio metabolic risk in a general adult population. It included 2459 adults (range 20-92 years, 58.4% women) in a random Spanish population sample. As an accurate indicator of cardio metabolic risk, Metabolic Syndrome (MetS), both by International Diabetes Federation criteria and by Adult Treatment Panel III criteria, were used. The effect of age was analyzed in individuals with and without diabetes mellitus separately. ROC regression methodology was used to evaluate the effect of age on HOMA-IR performance in classifying cardio metabolic risk. In Spanish population the threshold value of HOMA-IR drops from 3.46 using 90th percentile criteria to 2.05 taking into account of MetS components. In non-diabetic women, but no in men, we found a significant non-linear effect of age on the accuracy of HOMA-IR. In non-diabetic men, the cut-off values were 1.85. All values are between 70th-75th percentiles of HOMA-IR levels in adult Spanish population. The consideration of the cardio metabolic risk to establish the cut-off points of HOMA-IR, to define insulin resistance instead of using a percentile of the population distribution, would increase its clinical utility in identifying those patients in whom the presence of multiple metabolic risk factors imparts an increased metabolic and cardiovascular risk. The threshold levels must be modified by age in non-diabetic women.

  11. Insulin and the polycystic ovary syndrome.

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    Macut, Djuro; Bjekić-Macut, Jelica; Rahelić, Dario; Doknić, Mirjana

    2017-08-01

    Polycystic ovary syndrome (PCOS) is the most prevalent endocrinopathy among women during reproductive age. PCOS is characterised by hyperandrogenaemia, hyperinsulinaemia, and deranged adipokines secretion from the adipose tissue. In addition to the reduced insulin sensitivity, PCOS women exhibit β-cell dysfunction as well. Low birth weight and foetal exposure to androgens may contribute to the development of the PCOS phenotype during life. Further metabolic complications lead to dyslipidaemia, worsening obesity and glucose tolerance, high prevalence of metabolic syndrome, and greater susceptibility to diabetes. PCOS women show age-related existence of hypertension, and subtle endothelial and vascular changes. Adverse reproductive outcomes include anovulatory infertility, and unrecognised potentiation of the hormone-dependent endometrial cancer. The main therapeutic approach is lifestyle modification. Metformin is the primary insulin-sensitising drug to be used as an adjuvant therapy to lifestyle modification in patients with insulin resistance and impaired glucose tolerance, as well as in those referred to infertility treatment. Thiazolidinediones should be reserved for women intolerant of or refractory to metformin, while glucagon-like peptide 1 analogues has a potential therapeutic use in obese PCOS women. Randomised clinical trials and repetitive studies on different PCOS phenotypes for the preventive actions and therapeutic options are still lacking, though. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Hyperinsulinism and polycystic ovary syndrome (PCOS): role of insulin clearance.

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    Amato, M C; Vesco, R; Vigneri, E; Ciresi, A; Giordano, C

    2015-12-01

    Insulin resistance and compensatory hyperinsulinism are the predominant metabolic defects in polycystic ovary syndrome (PCOS). However, hyperinsulinism, as well as being compensatory, can also express a condition of reduced insulin clearance. Our aim was to evaluate the differences in insulin action and metabolism between women with PCOS (with normal glucose tolerance) and age- and BMI-matched women with prediabetes (without hyperandrogenism and ovulatory disorders). 22 women with PCOS and 21 age/BMI-matched women with prediabetes were subjected to a Hyperinsulinemic-euglycemic clamp and an Oral Glucose tolerance Test (OGTT). Insulin sensitivity was assessed by the glucose infusion rate during clamp (M value); insulin secretion by Insulinogenic index, Oral Disposition Index (DIo) and AUC(2h-insulin) during OGTT; and insulin clearance by the metabolic clearance rate of insulin (MCRI) during clamp. Women with PCOS showed significantly higher levels of AUC(2h-insulin) (p PCOS [420 (IQR 227-588) vs. 743 (IQR 597-888) ml m(-2) min(-1): p PCOS group, a strong independent inverse correlation was only observed between MCRI and AUC(2h-insulin) (PCOS: β:-0.878; p PCOS there is peripheral insulin sensitivity similar to that of women with prediabetes. What sets PCOS apart is the hyperinsulinism, today still simplistically defined "compensatory"; actually this is mainly related to decreased insulin clearance whose specific causes and dynamics have yet to be clarified.

  13. Insulin and brain aging

    OpenAIRE

    Baranowska-Bik, Agnieszka; Bik, Wojciech

    2017-01-01

    The world’s population is living much longer than in the past. It is crucial to find as many pathological factors that deteriorate the health condition and well-being of elderly people as possible. Loss of activity and functions over time is typical for elderly people. Aging affects brain function, metabolism and structure in different ways, and these effects have multiple etiologies. Cognitive impairment, impaired neurotransmitter activity and reduction of brain volume are observed in th...

  14. Nonalcoholic Fatty Liver Disease: Prevalence, Influence on Age and Sex, and Relationship with Metabolic Syndrome and Insulin Resistance

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    Hui-Yun Cheng

    2013-12-01

    Conclusion: Fatty liver can be considered as the hepatic consequence of metabolic syndrome, specifically IR. There is a high prevalence of metabolic syndrome and fatty liver among the elderly population. Metabolic disorders are closely related to fatty liver; moreover, fatty liver appears to be a good predictor for the clustering of risk factors for metabolic syndrome.

  15. Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls.

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    Legro, Richard S; Castracane, V Daniel; Kauffman, Robert P

    2004-02-01

    Approximately 50% to 70% of all women with polycystic ovary syndrome (PCOS) have some degree of insulin resistance, and this hormone insensitivity probably contributes to the hyperandrogenism that is responsible for the signs and symptoms of PCOS. Although uncertainty exists, early detection and treatment of insulin resistance in this population could ultimately reduce the incidence or severity of diabetes mellitus, dyslipidemia, hypertension, and cardiovascular disease. Even if that proves to be the case, there are still several problems with our current approach to insulin sensitivity assessment in PCOS, including the apparent lack of consensus on what defines PCOS and "normal" insulin sensitivity, ethnic and genetic variability, the presence of other factors contributing to insulin resistance such as obesity, stress, and aging, and concern about whether simplified models of insulin sensitivity have the precision to predict treatment needs, responses, and future morbidity. Although the hyperinsulinemic-euglycemic clamp technique is the gold standard for measuring insulin sensitivity, it is too expensive, time-consuming, and labor-intensive to be of practical use in an office setting. Homeostatic measurements (fasting glucose/insulin ratio or homeostatic model assessment [HOMA] value) and minimal model tests (particularly the oral glucose tolerance test [OGTT]) represent the easiest office-based assessments of insulin resistance in the PCOS patient. The OGTT is probably the best simple, office-based method to assess women with PCOS because it provides information about both insulin resistance and glucose intolerance. The diagnosis of glucose intolerance holds greater prognostic and treatment implications. All obese women with PCOS should be screened for the presence of insulin resistance by looking for other stigmata of the insulin resistance syndrome such as hypertension, dyslipidemia, central obesity, and glucose intolerance.

  16. Associations of sarcopenic obesity with the metabolic syndrome and insulin resistance over five years in older men: The Concord Health and Ageing in Men Project.

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    Scott, David; Cumming, Robert; Naganathan, Vasi; Blyth, Fiona; Le Couteur, David G; Handelsman, David J; Seibel, Markus; Waite, Louise M; Hirani, Vasant

    2018-04-09

    Previous cross-sectional studies investigating associations of sarcopenic obesity with metabolic syndrome (MetS) and insulin resistance have not utilised consensus definitions of sarcopenia. We aimed to determine associations of sarcopenic obesity with MetS and insulin resistance over five years in community-dwelling older men. 1231 men aged ≥70 years had appendicular lean mass (ALM) and body fat percentage assessed by dual-energy X-ray absorptiometry and hand grip strength and gait speed tests. Sarcopenia was defined as low ALM/height (m 2 ) and low hand grip strength or gait speed (European Working Group definition); obesity was defined as body fat percentage ≥30%. MetS was assessed at baseline and 5-years later. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was assessed at 5-years only. Men with sarcopenic obesity (odds ratio, 95% CI: 2.07, 1.21-3.55) and non-sarcopenic obesity (4.19, 3.16-5.57) had higher MetS likelihood than those with non-sarcopenic non-obesity at baseline. Higher gait speed predicted lower odds for prevalent MetS (0.45, 0.21-0.96 per m/s). Higher body fat predicted increased odds for prevalent and incident MetS (1.14, 1.11-1.17 and 1.11, 1.02-1.20 per kg, respectively) and deleterious 5-year changes in MetS fasting glucose, high-density lipoprotein cholesterol and triglycerides (all P < 0.05). Compared with non-sarcopenic non-obesity, estimated marginal means for HOMA-IR at 5-years were higher in non-sarcopenic obesity only (1.0, 0.8-1.1 vs 1.3, 1.2-1.5; P < 0.001). Similar results were observed when sarcopenic obesity was defined by waist circumference. Sarcopenic obesity does not appear to confer greater risk for incident MetS or insulin resistance than obesity alone in community-dwelling older men. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients.

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    Hu, Xiaolei; Chen, Fengling

    2018-01-01

    Insulin has been used for diabetes therapy and has achieved significant therapeutic effect. In recent years, the use of purified and recombinant human insulin preparations has markedly reduced, but not completely suppressed, the incidence of insulin antibodies (IAs). IAs induced by exogenous insulin in diabetic patients is associated with clinical events, which is named exogenous insulin antibody syndrome (EIAS). The present review is based on our research and summarizes the characterization of IAs, the factors affecting IA development, the clinical significance of IAs and the treatments for EIAS. © 2018 The authors.

  18. An uncommon cause of hypoglycemia: insulin autoimmune syndrome.

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    Savas-Erdeve, Senay; Yılmaz Agladioglu, Sebahat; Onder, Asan; Peltek Kendirci, Havva Nur; Bas, Veysel Nijat; Sagsak, Elif; Cetinkaya, Semra; Aycan, Zehra

    2014-01-01

    Insulin autoimmune syndrome (IAS) is a condition characterized by hypoglycemia associated with the presence of autoantibodies to insulin in patients who have not been injected with insulin. A female patient (aged 16 years and 3 months) presented with the complaint of being overweight. Physical examination revealed a body weight of 78.2 kg (+2.6 SD) and a height of 167 cm (+0.73 SD). While the patient's fasting blood glucose level was found to be 40 mg/dl, blood ketone was negative and the serum insulin level was determined as 379 mIU/ml. The patient was diagnosed with hyperinsulinemic hypoglycemia. Abdominal ultrasound, pancreas MRI and endoscopic ultrasound were normal. The daily blood glucose profile revealed postprandial hyperglycemia and reactive hypoglycemia in addition to fasting hypoglycemia. The results of anti-insulin antibody measurements were as high as 41.8% (normal range 0-7%). A 1,600-calorie diet containing 40% carbohydrate and divided into 6 meals a day was given to the patient. Simple sugars were excluded from the diet. Hypoglycemic episodes were not observed, but during 2 years of observation, serum levels of insulin and anti-insulin antibodies remained elevated. In all hyperinsulinemic hypoglycemia cases, IAS should be considered in the differential diagnosis and insulin antibody measurements should be carried out. © 2014 S. Karger AG, Basel.

  19. Is Insulin Resistance an Intrinsic Defect in Asian Polycystic Ovary Syndrome?

    OpenAIRE

    Lee, Hyejin; Oh, Jee-Young; Sung, Yeon-Ah; Chung, Hyewon

    2013-01-01

    Purpose Approximately 50% to 70% of women with polycystic ovary syndrome (PCOS) have some degree of insulin resistance, and obesity is known to worsen insulin resistance. Many metabolic consequences of PCOS are similar to those of obesity; therefore, defining the cause of insulin resistance in women can be difficult. Our objective was to clarify the factors contributing to insulin resistance in PCOS. Materials and Methods We consecutively recruited 144 women with PCOS [age: 26?5 yr, body mass...

  20. Insulin resistance in polycystic ovary syndrome

    OpenAIRE

    Hutchison, Samantha Kate

    2017-01-01

    Polycystic ovary syndrome (PCOS) affects 8-18% of women, presenting a major public health and economic burden. Women with PCOS have insulin resistance (IR) independent of obesity. IR has an integral aetiological role in the reproductive and metabolic consequences of PCOS including obesity, type 2 diabetes (diabetes) and cardiovascular risk factors. Excess weight exacerbates IR and increases PCOS severity. PCOS combined with obesity presents a useful model to study IR before confounding hyperg...

  1. Insulin, Aging, and the Brain: Mechanisms and Implications

    OpenAIRE

    Akintola, Abimbola A.; van Heemst, Diana

    2015-01-01

    There is now an impressive body of literature implicating insulin and insulin signaling in successful aging and longevity. New information from in vivo and in vitro studies concerning insulin and insulin receptors has extended our understanding of the physiological role of insulin in the brain. However, the relevance of these to aging and longevity remains to be elucidated. Here, we review advances in our understanding of the physiological role of insulin in the brain, how insulin gets into t...

  2. Insulin sensitizers in adolescents with polycystic ovary syndrome.

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    LE, Trang N; Wickham, Edmond P; Nestler, John E

    2017-10-01

    Polycystic ovary syndrome (PCOS) is the most common disorder of androgen excess in women of reproductive age. The diagnosis of PCOS can be more challenging in adolescents than in adult women given significant overlap between normal puberty and the signs of PCOS, including acne, menstrual irregularity, and polycystic ovarian morphology. Optimal treatments for adult women with PCOS vary depending on patient risk factors and reproductive goals, but mainly include hormonal contraception and insulin sensitizers. There is continued interest in targeting the intrinsic insulin resistance that contributes to metabolic and hormonal derangements associated with PCOS. The vast majority of published data on insulin sensitizing PCOS treatments are reported in adult women; these have included weight loss, metformin, thiazolidinediones, and the inositols. Furthermore, there is also a small but growing body of evidence in support of the use of insulin sensitizers in adolescents, with or without oral contraceptives. Discussion of the available treatments, including benefits, potential side effects, and incorporation of patient and family preferences is critical in developing a plan of care aimed at achieving patient-important improvements in PCOS signs and symptoms while addressing the longer-term cardiometabolic risks associated with the syndrome.

  3. Intranasal Insulin Restores Metabolic Parameters and Insulin Sensitivity in Rats with Metabolic Syndrome.

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    Derkach, K V; Ivantsov, A O; Chistyakova, O V; Sukhov, I B; Buzanakov, D M; Kulikova, A A; Shpakov, A O

    2017-06-01

    We studied the effect of 10-week treatment with intranasal insulin (0.5 IU/day) on glucose tolerance, glucose utilization, lipid metabolism, functions of pancreatic β cells, and insulin system in the liver of rats with cafeteria diet-induced metabolic syndrome. The therapy reduced body weight and blood levels of insulin, triglycerides, and atherogenic cholesterol that are typically increased in metabolic syndrome, normalized glucose tolerance and its utilization, and increased activity of insulin signaling system in the liver, thus reducing insulin resistance. The therapy did not affect the number of pancreatic islets and β cells. The study demonstrates prospects of using intranasal insulin for correction of metabolic parameters and reduction of insulin resistance in metabolic syndrome.

  4. The insulin-resistant phenotype of polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Svendsen, Pernille Fog; Madsbad, Sten; Nilas, Lisbeth

    2009-01-01

    OBJECTIVE: To investigate the individual parameters included in the diagnosis of polycystic ovary syndrome (PCOS), and their impact on insulin sensitivity. DESIGN: Cross-sectional study. SETTING: Department of Obstetrics and Gynaecology, Copenhagen University Hospital, Hvidovre, Denmark. PATIENT...... assessment IR index. We found no significant association between ovarian morphology and insulin sensitivity or between menstrual frequency and insulin sensitivity. CONCLUSION(S): The PCOS is associated with IR. Body mass index, hyperandrogenemia, and hyperandrogenism are independent predictors of low insulin...

  5. Insulin resistance, obesity, hypofibrinolysis, hyperandrogenism, and coronary heart disease risk factors in 25 pre-perimenarchal girls age < or =14 years, 13 with precocious puberty, 23 with a first-degree relative with polycystic ovary syndrome.

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    Glueck, Charles J; Morrison, John A; Wang, Ping

    2008-10-01

    Pre-peri-menarchal diagnosis of polycystic ovary syndrome (PCOS) is important, because intervention with metformin-diet may prevent progression to full blown PCOS. In 25 girls age PCOS, 10 pre-, 15 post-menarchal, 13 with precocious puberty, 23 with a first-degree relative with PCOS, we hypothesized that reversible coronary heart disease (CHD) risk factors, insulin resistance, clinical and biochemical hyperandrogenism, and hypofibrinolysis were already established. Fasting measures: insulin, glucose, total, LDL- (LDL-C), and HDL-cholesterol (HDL-C), triglycerides (TG), systolic and diastolic blood pressure (SBP, DBP), plasminogen activator inhibitor activity (PAI-Fx), total (T) and free testosterone (FT), androstenedione, and DHEAS. Clinical and/or biochemical hyperandrogenism was present in all 25 girls, with elevations of T or FT, or androstenedione in seven of ten pre-menarchal girls and in all 15 post-menarche. PAI-Fx was high in 28% of the 25 girls vs 6.5% in age-gender-race matched controls (p = 0.013). Categorized by race-age-specific distributions in 870 schoolgirls, the 25 girls with probable familial PCOS were more likely to have top decile body mass index (BMI), insulin, HOMA-insulin resistance (HOMA-IR), SBP, DBP, and TG, and bottom decile HDL-C. By analysis of variance, adjusting for race, age and BMI, PCOS girls had higher FT and waist circumference than controls, but did not differ for SBP, DBP, HDL-C, or TG (p>0.05). Pre-peri-menarchal acquisition of centripetal obesity amplifies CHD risk factors and hypofibrinolysis in hyperandrogenemic girls with probable familial PCOS and precocious puberty. When schoolgirls become as obese as girls with probable familial PCOS, they acquire the same CHD risk factors, and differ only by lower free T and less centripetal obesity.

  6. Obesity, insulin resistance and Polycystic Ovary Syndrome

    OpenAIRE

    Joham, Anju Elizabeth

    2017-01-01

    Polycystic Ovary Syndrome (PCOS) affects 12 to 21% of Australian reproductive-aged women and is a major public health concern (1-5). Whilst reproductive features (anovulation, infertility) are prominent, PCOS also has major metabolic [obesity, metabolic syndrome, type 2 diabetes (T2DM), cardiovascular disease risk factors] and psychological features (6-8). Obesity is a major chronic disease, with rising prevalence and diverse health impacts. The interplay between PCOS and weight contributes t...

  7. Association of Serum Ferritin Levels with Metabolic Syndrome and Insulin Resistance.

    Science.gov (United States)

    Padwal, Meghana K; Murshid, Mohsin; Nirmale, Prachee; Melinkeri, R R

    2015-09-01

    The impact of CVDs and Type II DM is increasing over the last decade. It has been estimated that by 2025 their incidence will double. Ferritin is one of the key proteins regulating iron homeostasis and is a widely available clinical biomarker of iron status. Some studies suggest that prevalence of atherosclerosis and insulin resistance increases significantly with increasing serum ferritin. Metabolic syndrome is known to be associated with increased risk of atherosclerosis as well as insulin resistance. The present study was designed to explore the association of serum ferritin levels with metabolic syndrome and insulin resistance. The present study was prospective, cross sectional. The study protocol was approved by IEC. The study group consisted of 90 participants (50 cases of metabolic syndrome and 40 age and sex matched controls). Diagnosis of metabolic syndrome was done as per NCEP ATP III criteria. Estimation of serum Ferritin and Insulin was done by Chemiluminescence Immunoassay (CLIA) while Glucose by Glucose Oxidase and Peroxidase (GOD-POD) method. Insulin Resistance was calculated by HOMA IR score. Data obtained was statistically analysed by using student t-test. We found statistically significant rise in the levels of serum ferritin (p=syndrome as compared with controls. High serum ferritin levels though within normal range are significantly associated with both metabolic syndrome and insulin resistance.

  8. The Usefulness of Homeostatic Measurement Assessment-Insulin Resistance (HOMA-IR) for Detection of Glucose Intolerance in Thai Women of Reproductive Age with Polycystic Ovary Syndrome.

    Science.gov (United States)

    Wongwananuruk, Thanyarat; Rattanachaiyanont, Manee; Leerasiri, Pichai; Indhavivadhana, Suchada; Techatraisak, Kitirat; Angsuwathana, Surasak; Tanmahasamut, Prasong; Dangrat, Chongdee

    2012-01-01

    Objectives. To study the cut-off point of Homeostatic Measurement Assessment-Insulin Resistance (HOMA-IR) as a screening test for detection of glucose intolerance in Thai women with polycystic ovary syndrome (PCOS). Study Design. Cross-sectional study. Setting. Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital. Subject. Two hundred and fifty Thai PCOS women who attended the Gynecologic Endocrinology Unit, during May 2007 to January 2009. Materials and Methods. The paitents were interviewed and examined for weight, height, waist circumference, and blood pressure. Venous blood samples were drawn twice, one at 12-hour fasting and the other at 2 hours after glucose loading. Results. The prevalence of glucose intolerance in Thai PCOS women was 20.0%. The mean of HOMA-IR was 3.53  ±  7.7. Area under an ROC curve for HOMA-IR for detecting glucose intolerance was 0.82. Using the cut-off value of HOMA-IR >2.0, there was sensitivity at 84.0%, specificity at 61.0%, positive predictive value at 35.0%, negative predictive value at 93.8%, and accuracy at 65.6%. Conclusion. HOMA-IR >2.0 was used for screening test for glucose intolerance in Thai PCOS women. If the result was positive, a specific test should be done to prove the diagnosis.

  9. The Usefulness of Homeostatic Measurement Assessment-Insulin Resistance (HOMA-IR for Detection of Glucose Intolerance in Thai Women of Reproductive Age with Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Thanyarat Wongwananuruk

    2012-01-01

    Full Text Available Objectives. To study the cut-off point of Homeostatic Measurement Assessment-Insulin Resistance (HOMA-IR as a screening test for detection of glucose intolerance in Thai women with polycystic ovary syndrome (PCOS. Study Design. Cross-sectional study. Setting. Department of Obstetrics and Gynecology, Faculty of Medicine Siriraj Hospital. Subject. Two hundred and fifty Thai PCOS women who attended the Gynecologic Endocrinology Unit, during May 2007 to January 2009. Materials and Methods. The paitents were interviewed and examined for weight, height, waist circumference, and blood pressure. Venous blood samples were drawn twice, one at 12-hour fasting and the other at 2 hours after glucose loading. Results. The prevalence of glucose intolerance in Thai PCOS women was 20.0%. The mean of HOMA-IR was 3.53  ±  7.7. Area under an ROC curve for HOMA-IR for detecting glucose intolerance was 0.82. Using the cut-off value of HOMA-IR >2.0, there was sensitivity at 84.0%, specificity at 61.0%, positive predictive value at 35.0%, negative predictive value at 93.8%, and accuracy at 65.6%. Conclusion. HOMA-IR >2.0 was used for screening test for glucose intolerance in Thai PCOS women. If the result was positive, a specific test should be done to prove the diagnosis.

  10. [Severe type A insulin resistance syndrome due to a mutation in the insulin receptor gene].

    Science.gov (United States)

    Ros, P; Colino-Alcol, E; Grasso, V; Barbetti, F; Argente, J

    2015-01-01

    Insulin resistance syndromes without lipodystrophy are an infrequent and heterogeneous group of disorders with variable clinical phenotypes, associated with hyperglycemia and hyperinsulinemia. The three conditions related to mutations in the insulin receptor gene are leprechaunism or Donohue syndrome, Rabson-Mendenhall syndrome, and Type A syndrome. A case is presented on a patient diagnosed with type A insulin resistance, defined by the triad of extreme insulin resistance, acanthosis nigricans, and hyperandrogenism, carrying a heterozygous mutation in exon 19 of the insulin receptor gene coding for its tyrosine kinase domain that is crucial for the catalytic activity of the receptor. The molecular basis of the syndrome is reviewed, focusing on the structure-function relationships of the insulin receptor, knowing that the criteria for survival are linked to residual insulin receptor function. It is also pointed out that, although type A insulin resistance appears to represent a somewhat less severe condition, these patients have a high morbidity and their treatment is still unsatisfactory. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  11. Prevalence of the insulin resistance syndrome in obesity

    OpenAIRE

    Viner, R; Segal, T; Lichtarowicz-Kryn..., E; Hindmarsh, P

    2005-01-01

    Aims: To assess prevalence of the insulin resistance syndrome (IRS: obesity, abnormal glucose homoeostasis, dyslipidaemia, and hypertension) in obese UK children and adolescents of different ethnicities and to assess whether fasting data is sufficient to identify IRS in childhood obesity.

  12. Homeostatic model assessment for insulin resistance (homa-ir): a better marker for evaluating insulin resistance than fasting insulin in women with polycystic ovarian syndrome

    International Nuclear Information System (INIS)

    Majid, H.; Khan, A.H.; Masood, Q.

    2017-01-01

    To assess the utility of HOMA-IR in assessing insulin resistance in patients with polycystic ovary syndrome (PCOS) and compare it with fasting insulin for assessing insulin resistance (IR). Study Design: Observational study. Place and Duration of Study: Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2009 to September 2012. Methodology: Medical chart review of all women diagnosed with PCOS was performed. Of the 400 PCOS women reviewed, 91 met the inclusion criteria. Insulin resistance was assessed by calculating HOMA-IR using the formula (fasting glucose x fasting insulin)/405, taking normal value =12 micro IU/ml. Results: A total of 91 premenopausal women diagnosed with PCOS were included. Mean age was 30 +-5.5 years. Mean HOMA-IR of women was 3.1 +-1.7, respectively with IR in 69% (n=63) women, while hyperinsulinemia was present in 60% (n=55) women (fasting Insulin 18.5 +-5.8 micro IU/ml). Hyperandrogenism was present in 53.8% (n=49), whereas 38.5% (n=35) women had primary infertility or subfertility, while 65.9% (n=60) had menstrual irregularities; and higher frequencies were observed in women with IR. Eight subjects with IR and endocrine abnormalities were missed by fasting insulin. Conclusion: Insulin resistance is common in PCOS and it is likely a pathogenic factor for development of PCOS. HOMA-IR model performed better than hyperinsulinemia alone for diagnosing IR. (author)

  13. Insulin resistance and its association with the components of the metabolic syndrome among obese children and adolescents.

    Science.gov (United States)

    Juárez-López, Carlos; Klünder-Klünder, Miguel; Medina-Bravo, Patricia; Madrigal-Azcárate, Adrián; Mass-Díaz, Eliezer; Flores-Huerta, Samuel

    2010-06-07

    Insulin resistance is the primary metabolic disorder associated with obesity; yet little is known about its role as a determinant of the metabolic syndrome in obese children. The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among obese children and adolescents. An analytical, cross-sectional and population-based study was performed in forty-four public primary schools in Campeche City, Mexico. A total of 466 obese children and adolescents between 11-13 years of age were recruited. Fasting glucose and insulin concentrations, high density lipoprotein cholesterol, triglycerides, waist circumference, systolic and diastolic blood pressures were measured; insulin resistance and metabolic syndrome were also evaluated. Out of the total population studied, 69% presented low values of high density lipoprotein cholesterol, 49% suffered from abdominal obesity, 29% had hypertriglyceridemia, 8% presented high systolic and 13% high diastolic blood pressure, 4% showed impaired fasting glucose, 51% presented insulin resistance and 20% metabolic syndrome. In spite of being obese, 13% of the investigated population did not present any metabolic disorder. For each one of the components of the metabolic syndrome, when insulin resistance increased so did odds ratios as cardiometabolic risk factors. Regardless of age and gender an increased degree of insulin resistance is associated with a higher prevalence of disorders in each of the components of the metabolic syndrome and with a heightened risk of suffering metabolic syndrome among obese children and adolescents.

  14. Exogenous insulin antibody syndrome (EIAS: a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients

    Directory of Open Access Journals (Sweden)

    Xiaolei Hu

    2018-01-01

    Full Text Available Insulin has been used for diabetes therapy and has achieved significant therapeutic effect. In recent years, the use of purified and recombinant human insulin preparations has markedly reduced, but not completely suppressed, the incidence of insulin antibodies (IAs. IAs induced by exogenous insulin in diabetic patients is associated with clinical events, which is named exogenous insulin antibody syndrome (EIAS. The present review is based on our research and summarizes the characterization of IAs, the factors affecting IA development, the clinical significance of IAs and the treatments for EIAS.

  15. Severe hypoglycaemia in a person with insulin autoimmune syndrome accompanied by insulin receptor anomaly type B.

    Science.gov (United States)

    Kato, T; Itoh, M; Hanashita, J; Itoi, T; Matsumoto, T; Ono, Y; Imamura, S; Hayakawa, N; Suzuki, A; Mizutani, Y; Uchigata, Y; Oda, N

    2007-11-01

    A rare case of the insulin autoimmune syndrome (IAS) accompanied by insulin receptor anomaly is reported. Antibodies to insulin and insulin receptor were determined in the patient with severe hypoglycaemia before and after the treatment with prednisolone. Titers of antibody to insulin and insulin receptors were 73.0% and 41.5%, respectively. Drug-induced lymphocyte stimulation tests were all negative for the suspicious drugs. Her HLA-DR was DRB1*0403/04051. Following steroid therapy, the formation of antibodies was suppressed and alleviated her symptoms. Scatchard analysis yielded findings specific to polyclonal antibodies. The changes in autoantibodies resulted in alleviation of the hypoglycemic symptoms as a result of steroid therapy.

  16. Evaluation of insulin resistance in idiopathic hirsutism compared with polycystic ovary syndrome patients and healthy individuals.

    Science.gov (United States)

    Bonakdaran, Shokoufeh; Kiafar, Bita; Barazandeh Ahmadabadi, Fatemeh

    2016-02-01

    Hirsutism is defined as the excessive male-pattern growth of hair in women. Hirsutism is often idiopathic or the consequence of polycystic ovary syndrome (PCOS). Insulin resistance is common in PCOS (especially in obese patients) but the association between insulin resistance and idiopathic hirsutism (IH) is not clear. The aim of this study was to investigate the rate of insulin resistance in IH, compared with healthy individuals and patients with PCOS. The study included three groups, patients with idiopathic hirsutism, PCOS and healthy women. Each group included 30 non-obese women. Fasting blood sugar (FBS), insulin level and insulin resistance (estimated by the homeostasis model assessment [HOMA-IRIR]) were compared in the three groups. There was a significant difference between the age of the women with IH compared with two other groups. There were no significant difference in levels of serum insulin (P = 0.49, HOMA-IR (P = 0.47) and prevalence of insulin resistance (P = 0.07) in the three groups. The age-adjusted prevalence of insulin resistance was similar in the three groups. Insulin resistance was no more frequent in IH patients than in healthy control groups. © 2014 The Australasian College of Dermatologists.

  17. Berardinelli Seip syndrome with insulin-resistant diabetes mellitus and stroke in an infant.

    Science.gov (United States)

    Indumathi, C K; Lewin, S; Ayyar, Vageesh

    2011-07-01

    Berardinelli Seip congenital lipodystrophy (BSCL) is a rare metabolic disorder characterized by severe generalized lipodystrophy, insulin resistance, and dyslipedemia since infancy, and onset of overt diabetes mellitus in adolescence. Here we report a 5-month-old infant with clinical and metabolic manifestations of Berardinelli Seip syndrome including overt diabetes mellitus and stroke, which are very rare at this age.

  18. Berardinelli Seip syndrome with insulin-resistant diabetes mellitus and stroke in an infant

    OpenAIRE

    C K Indumathi; S Lewin; Vageesh Ayyar

    2011-01-01

    Berardinelli Seip congenital lipodystrophy (BSCL) is a rare metabolic disorder characterized by severe generalized lipodystrophy, insulin resistance, and dyslipedemia since infancy, and onset of overt diabetes mellitus in adolescence. Here we report a 5-month-old infant with clinical and metabolic manifestations of Berardinelli Seip syndrome including overt diabetes mellitus and stroke, which are very rare at this age.

  19. Berardinelli Seip syndrome with insulin-resistant diabetes mellitus and stroke in an infant

    Directory of Open Access Journals (Sweden)

    C K Indumathi

    2011-01-01

    Full Text Available Berardinelli Seip congenital lipodystrophy (BSCL is a rare metabolic disorder characterized by severe generalized lipodystrophy, insulin resistance, and dyslipedemia since infancy, and onset of overt diabetes mellitus in adolescence. Here we report a 5-month-old infant with clinical and metabolic manifestations of Berardinelli Seip syndrome including overt diabetes mellitus and stroke, which are very rare at this age.

  20. Insulin resistance in pregnant women with and without polycystic ovary syndrome, and measures of body composition in offspring at birth and 3 years of age

    DEFF Research Database (Denmark)

    Finnbogadóttir, Sara Kristín; Glintborg, Dorte; Jensen, Tina Kold

    2017-01-01

    model assessment for insulin resistance (HOMA-IR) assessments were comparable in women with and without PCOS. However, the subgroup of overweight women with PCOS had significantly higher levels of HOMA-IR than overweight women without PCOS (mean ±2SD): 4.4 (3.1) vs. 3.6 (3.4), p = 0.004. Maternal PCOS...

  1. Persistent Organic Pollutant Exposure Leads to Insulin Resistance Syndrome

    DEFF Research Database (Denmark)

    Ruzzin, Jérôme; Petersen, Rasmus; Meugnier, Emmanuelle

    2010-01-01

    BACKGROUND: The incidence of the insulin resistance syndrome has increased at an alarming rate worldwide creating a serious challenge to public health care in the 21st century. Recently, epidemiological studies have associated the prevalence of type 2 diabetes with elevated body burdens...... of persistent organic pollutants (POPs). However, experimental evidence demonstrating a causal link between POPs and the development of insulin resistance is lacking. OBJECTIVE: We investigated whether exposure to POPs contributes to insulin resistance and metabolic disorders. METHODS: Wistar rats were exposed...... salmon oil. We measured body weight, whole-body insulin sensitivity, POP accumulation, lipid and glucose homeostasis, gene expression and performed microarray analysis. RESULTS: Adult male rats exposed to crude, but not refined, salmon oil developed insulin resistance, abdominal obesity...

  2. Whole-blood viscosity and the insulin-resistance syndrome.

    Science.gov (United States)

    Høieggen, A; Fossum, E; Moan, A; Enger, E; Kjeldsen, S E

    1998-02-01

    In a previous study we found that elevated blood viscosity was linked to the insulin resistance syndrome, and we proposed that high blood viscosity may increase insulin resistance. That study was based on calculated viscosity. To determine whether directly measured whole-blood viscosity was related to the insulin-resistance syndrome in the same way as calculated viscosity had been found to be. Healthy young men were examined with the hyperinsulinemic isoglycemic glucose clamp technique, and we related insulin sensitivity (glucose disposal rate) to other metabolic parameters and to blood viscosity. We established a technique for direct measurement of whole-blood viscosity. There were statistically significant negative correlations between glucose disposal rate and whole-blood viscosity at low and high shear rates (r = -0.41, P = 0.007 for both, n = 42). Whole-blood viscosity was correlated positively (n = 15) to serum triglyceride (r = 0.54, P = 0.04) and total cholesterol (r = 0.52, P = 0.05), and negatively with high-density lipoprotein cholesterol (r = -0.53, P = 0.04) concentrations. Insulin sensitivity index was correlated positively to high-density lipoprotein cholesterol (r = 0.54, P = 0.04) and negatively to serum triglyceride (r = -0.69, P = 0.005) and to total cholesterol (r = -0.81, P = 0.0003) concentrations. The present results demonstrate for the first time that there is a negative relationship between directly measured whole-blood viscosity and insulin sensitivity as a part of the insulin-resistance syndrome. Whole-blood viscosity contributes to the total peripheral resistance, and these results support the hypothesis that insulin resistance has a hemodynamic basis.

  3. Aging and Down Syndrome

    Science.gov (United States)

    ... to be aw are of the connec tion bet ween Down syndrome and Alzheimer ’s disea se so ... albeing cared for. Make aneffor tto be proactive, thinking ahead to anticipate needs and concerns. x x ...

  4. Endothelial function and insulin resistance in polycystic ovary syndrome: the effects of medical therapy.

    Science.gov (United States)

    Teede, Helena J; Meyer, Caroline; Hutchison, Samantha K; Zoungas, Sophia; McGrath, Barry P; Moran, Lisa J

    2010-01-01

    To assess the interaction between insulin resistance and endothelial function and the optimal treatment strategy addressing cardiovascular risk in polycystic ovary syndrome. Randomized controlled trial. Controlled clinical study. Overweight age- and body mass index-matched women with polycystic ovary syndrome. Six months metformin (1 g two times per day, n = 36) or oral contraceptive pill (OCP) (35 microg ethinyl E(2)-2 mg cytoproterone acetate, n = 30). Fasting and oral glucose tolerance test glucose and insulin levels, endothelial function (flow-mediated dilation, asymmetric dimethylarginine, plasminogen activator inhibitor-1, von Willebrand factor), inflammatory markers (high-sensitivity C-reactive protein), lipids, and hyperandrogenism. The OCP increased levels of glucose and insulin on oral glucose tolerance test, high-sensitivity C-reactive protein, triglycerides, and sex-hormone binding globulin and decreased levels of low-density lipoprotein cholesterol and T. Metformin decreased levels of fasting insulin, oral glucose tolerance test insulin, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. Flow-mediated dilation increased only with metformin (+2.2% +/- 4.8%), whereas asymmetric dimethylarginine decreased equivalently for OCP and metformin (-0.3 +/- 0.1 vs. -0.1 +/- 0.1 mmol/L). Greater decreases in plasminogen activator inhibitor-1 occurred for the OCP than for metformin (-1.8 +/- 1.6 vs. -0.7 +/- 1.7 U/mL). In polycystic ovary syndrome, metformin improves insulin resistance, inflammatory markers, and endothelial function. The OCP worsens insulin resistance and glucose homeostasis, inflammatory markers, and triglycerides and has neutral or positive endothelial effects. The effect of the OCP on cardiovascular risk in polycystic ovary syndrome is unclear. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. Insulin resistance, metabolic syndrome, and lipids in African women

    African Journals Online (AJOL)

    2016-01-27

    Jan 27, 2016 ... high‑density lipoprotein (TG/HDL), total cholesterol (TC)/HDL, and atherogenic index of ... Key words: Insulin resistance, metabolic syndrome, triglycerides, women ... been reported that a TG/HDL ratio of >3.0 is predictive of.

  6. Physical Training Improves Insulin Resistance Syndrome Markers in Obese Adolescents.

    Science.gov (United States)

    Kang, Hyun-Sik; Gutin, Bernard; Barbeau, Paule; Owens, Scott; Lemmon, Christian R.; Allison, Jerry; Litaker, Mark S.; Le, Ngoc-Anh

    2002-01-01

    Tested the hypothesis that physical training (PT), especially high-intensity PT, would favorably affect components of the insulin resistance syndrome (IRS) in obese adolescents. Data on teens randomized into lifestyle education (LSE) alone, LSE plus moderate -intensity PT, and LSE plus high-intensity PT indicated that PT, especially high-intensity…

  7. Characteristics and contributions of hyperandrogenism to insulin resistance and other metabolic profiles in polycystic ovary syndrome.

    Science.gov (United States)

    Huang, Rong; Zheng, Jun; Li, Shengxian; Tao, Tao; Ma, Jing; Liu, Wei

    2015-05-01

    To investigate the different characteristics in Chinese Han women with polycystic ovary syndrome, and to analyze the significance of hyperandrogenism in insulin resistance and other metabolic profiles. A cross-sectional study. Medical university hospital. A total of 229 women with polycystic ovary syndrome aged 18-45 years. Women with polycystic ovary syndrome, diagnosed by Rotterdam criteria, were divided into four groups according to the quartile intervals of free androgen index levels. Comparisons between groups were performed using one-way analysis of variance. Stepwise logistic regression analysis was performed to investigate the association between homeostasis model assessment-insulin resistance and independent variables. Within the four phenotypes, women with phenotype 1 (hyperandrogenism, oligo/anovulation, and polycystic ovaries) exhibited higher total testosterone, free androgen index, androstenedione, low-density lipoprotein, and lower quantitative insulin sensitivity check index (p polycystic ovaries) showed lower total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance, but higher high-density lipoprotein (p < 0.05). The levels of triglycerides, total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance significantly increased, but high-density lipoprotein and quantitative insulin sensitivity check index decreased with the elevation of free androgen index intervals. After adjustment for lipid profiles, free androgen index was significantly associated with homeostasis model assessment-insulin resistance in both lean and overweight/obese women (odds ratio 1.302, p = 0.039 in lean vs. odds ratio 1.132, p = 0.036 in overweight/obese). Phenotypes 1 and 4 represent groups with the most and least severe metabolic profiles, respectively. Hyperandrogenism, particularly with elevated free androgen index, is likely a key contributing factor for insulin resistance and for the aggravation

  8. Polycystic ovary morphology is associated with insulin resistance in women with polycystic ovary syndrome.

    Science.gov (United States)

    Hong, So-Hyeon; Sung, Yeon-Ah; Hong, Young Sun; Jeong, Kyungah; Chung, Hyewon; Lee, Hyejin

    2017-10-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by chronic anovulation, hyperandrogenism, polycystic ovary morphology (PCOM) and metabolic disturbances including insulin resistance and type 2 diabetes mellitus. Although insulin resistance could be associated with PCOM, recent studies have shown controversial results. The aim of this study was to determine the relationship between PCOM and insulin resistance. This was a cross-sectional clinical study. A total of 679 women with PCOS who were diagnosed using the National Institute of Child Health and Human Disease (NICHD) criteria and 272 control women were analysed. We measured fasting glucose and insulin levels, 75 g oral glucose tolerance test-derived glucose and insulin levels, testosterone levels, ovarian volume and follicle number. Polycystic ovary morphology was described in 543 women (80.0%) with PCOS. Women with PCOS had significantly higher 2 hours postload glucose, fasting and 2 hours postload insulin levels, ovarian volume, ovarian follicle numbers and lower insulin sensitivity compared with those of the controls (all P<.01). In women with PCOS, ovarian volume and ovarian follicle number were negatively associated with the quantitative insulin sensitivity check index after adjusting for age, body mass index and total testosterone; however, this association was not observed in the controls. In the logistic regression analysis, increased ovarian follicle number was associated with decreased insulin sensitivity in women with PCOS. In PCOS, enlarged ovarian volume and follicle excess were associated with insulin resistance, and the number of ovarian follicles could be a predictor of insulin resistance. © 2017 John Wiley & Sons Ltd.

  9. Polycystic ovary syndrome (PCOS), insulin resistance and insulin-like growth factors (IGfs)/IGF-binding proteins (IGFBPs).

    Science.gov (United States)

    Wang, Hsin-Shih; Wang, Tzu-Hao

    2003-08-01

    Polycystic ovary syndrome (PCOS) is the most frequent androgen disorder of ovarian function. Hyperinsulinemia with insulin resistance is believed to be a key link in the enigmatic generation of the symptoms of PCOS such as anovulatory infertility and hyperandrogenism. Regression of these symptoms may be achieved by reducing the hyperinsulinemia. A growing body of evidence suggests that PCOS patients with hyperinsulinemia have a higher risk to develop diabetes mellitus, hypertension and cardiovascular disease as compared to age-matched women. Although oral contraceptives, progestins, antiandrogens, and ovulation induction agents remain standard therapies, weight loss should also be vigorously encouraged to ameliorate the metabolic consequences of PCOS. In addition, insulin-sensitizing agents are now being shown to be useful alone or combined with standard therapies to alleviate hyperinsulinemia in PCOS. Finally and most importantly, early identification of patients at risk and prompt initiation of therapies, followed by long-term surveillance and management, may promote the patient's long-term health.

  10. Insulin resistance and its association with the components of the metabolic syndrome among obese children and adolescents

    Directory of Open Access Journals (Sweden)

    Mass-Díaz Eliezer

    2010-06-01

    Full Text Available Abstract Background Insulin resistance is the primary metabolic disorder associated with obesity; yet little is known about its role as a determinant of the metabolic syndrome in obese children. The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among obese children and adolescents. Methods An analytical, cross-sectional and population-based study was performed in forty-four public primary schools in Campeche City, Mexico. A total of 466 obese children and adolescents between 11-13 years of age were recruited. Fasting glucose and insulin concentrations, high density lipoprotein cholesterol, triglycerides, waist circumference, systolic and diastolic blood pressures were measured; insulin resistance and metabolic syndrome were also evaluated. Results Out of the total population studied, 69% presented low values of high density lipoprotein cholesterol, 49% suffered from abdominal obesity, 29% had hypertriglyceridemia, 8% presented high systolic and 13% high diastolic blood pressure, 4% showed impaired fasting glucose, 51% presented insulin resistance and 20% metabolic syndrome. In spite of being obese, 13% of the investigated population did not present any metabolic disorder. For each one of the components of the metabolic syndrome, when insulin resistance increased so did odds ratios as cardiometabolic risk factors. Conclusions Regardless of age and gender an increased degree of insulin resistance is associated with a higher prevalence of disorders in each of the components of the metabolic syndrome and with a heightened risk of suffering metabolic syndrome among obese children and adolescents.

  11. Lean mass and insulin resistance in women with polycystic ovary syndrome.

    Science.gov (United States)

    Comerford, Kevin B; Almario, Rogelio U; Kim, Kyoungmi; Karakas, Sidika E

    2012-09-01

    Insulin resistance is common in women with polycystic ovary syndrome (PCOS). Muscle is the major tissue utilizing glucose while excess adipose tissue relates to insulin resistance. Thus, body composition is likely to be an important regulator of insulin sensitivity. Thirty-nine PCOS patients (age: 29.9±1.0 years; BMI: 33.8±1.2 kg/m(2)) participated in a cross sectional study. Body composition was measured by dual energy x-ray absorptiometry (DEXA). Insulin resistance and secretion were assessed using oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FS-IVGTT). In contrast with the conventional expectations, lean mass correlated directly (Plean mass (52.8±1.8 vs 44.4±1.6 kg), those with higher lean mass had a higher glucose response during OGTT (AUC(Glucose); P=.034). In contrast, 17 pairs matched for lean mass (48.7±1.7 and 48.9±1.6 kg) but discordant for fat mass (43.3±2.6 vs 30.3±8.9 kg) showed no differences in insulin resistance parameters. These novel findings indicate that lean mass relates directly to insulin resistance in PCOS. Published by Elsevier Inc.

  12. Glycated Hemoglobin, Fasting Insulin and the Metabolic Syndrome in Males. Cross-Sectional Analyses of the Aragon Workers' Health Study Baseline.

    Science.gov (United States)

    Saravia, Gabriela; Civeira, Fernando; Hurtado-Roca, Yamilee; Andres, Eva; Leon, Montserrat; Pocovi, Miguel; Ordovas, Jose; Guallar, Eliseo; Fernandez-Ortiz, Antonio; Casasnovas, Jose Antonio; Laclaustra, Martin

    2015-01-01

    Glycated hemoglobin (HbA1c) is currently used to diagnose diabetes mellitus, while insulin has been relegated to research. Both, however, may help understanding the metabolic syndrome and profiling patients. We examined the association of HbA1c and fasting insulin with clustering of metabolic syndrome criteria and insulin resistance as two essential characteristics of the metabolic syndrome. We used baseline data from 3200 non-diabetic male participants in the Aragon Workers' Health Study. We conducted analysis to estimate age-adjusted odds ratios (ORs) across tertiles of HbA1c and insulin. Fasting glucose and Homeostatic model assessment - Insulin Resistance were used as reference. Here we report the uppermost-to-lowest tertile ORs (95%CI). Mean age (SD) was 48.5 (8.8) years and 23% of participants had metabolic syndrome. The ORs for metabolic syndrome criteria tended to be higher across HbA1c than across glucose, except for high blood pressure. Insulin was associated with the criteria more strongly than HbA1c and similarly to Homeostatic model assessment - Insulin Resistance (HOMA-IR). For metabolic syndrome, the OR of HbA1c was 2.68, of insulin, 11.36, of glucose, 7.03, and of HOMA-IR, 14.40. For the clustering of 2 or more non-glycemic criteria, the OR of HbA1c was 2.10, of insulin, 8.94, of glucose, 1.73, and of HOMA-IR, 7.83. All ORs were statistically significant. The areas under the receiver operating characteristics curves for metabolic syndrome were 0.670 (across HbA1c values) and 0.770 (across insulin values), and, for insulin resistance, 0.647 (HbA1c) and 0.995 (insulin). Among non-metabolic syndrome patients, a small insulin elevation identified risk factor clustering. HbA1c and specially insulin levels were associated with metabolic syndrome criteria, their clustering, and insulin resistance. Insulin could provide early information in subjects prone to develop metabolic syndrome.

  13. Retinol-Binding Protein 4 and Insulin Resistance in Polycystic Ovary Syndrome

    OpenAIRE

    Hutchison, Samantha K.; Harrison, Cheryce; Stepto, Nigel; Meyer, Caroline; Teede, Helena J.

    2008-01-01

    OBJECTIVE?Polycystic ovary syndrome (PCOS) is an insulin-resistant state with insulin resistance being an established therapeutic target; however, measurement of insulin resistance remains challenging. We aimed to 1) determine serum retinol-binding protein 4 (RBP4) levels (purported to reflect insulin resistance) in women with PCOS and control subjects, 2) examine the relationship of RBP4 to conventional markers of insulin resistance, and 3) examine RBP4 changes with interventions modulating ...

  14. Insulin receptor degradation is accelerated in cultured lymphocytes from patients with genetic syndromes of extreme insulin resistance

    International Nuclear Information System (INIS)

    McElduff, A.; Hedo, J.A.; Taylor, S.I.; Roth, J.; Gorden, P.

    1984-01-01

    The insulin receptor degradation rate was examined in B lymphocytes that were obtained from peripheral blood of normal subjects and patients with several syndromes of extreme insulin resistance. The insulin receptors were surface labeled using Na 125 I/lactoperoxidase and the cells were returned to incubate in growth media. After varying periods of incubation, aliquots of cells were solubilized and the cell content of labeled receptor subunits were measured by immunoprecipitation with anti-receptor antibodies and NaDodSO4/polyacrylamide gel electrophoresis. In cell lines from four patients in whom the number of insulin receptors was reduced by greater than 90%, the rate of receptor loss was greater than normal (t1/2 equals 3.8 +/- 0.9 h vs. 6.5 +/- 1.2 h; mean +/- SD, P less than 0.01). However, a similar acceleration in receptor degradation was seen in cells from five patients with extreme insulin resistance but low-normal insulin receptor concentration (t1/2 equals 4.4 +/- 0.9 h). Thus, all the patients with genetic syndromes of insulin resistance had accelerated receptor degradation, regardless of their receptor concentration. By contrast, insulin receptors on cultured lymphocytes that were obtained from patients with extreme insulin resistance secondary to autoantibodies to the insulin receptor had normal receptor degradation (t1/2 equals 6.1 +/- 1.9 h). We conclude that (a) accelerated insulin receptor degradation is an additional feature of cells from patients with genetic forms of insulin resistance; (b) that accelerated insulin receptor degradation may explain the low-normal receptor concentrations that were seen in some patients with extreme insulin resistance; and (c) that accelerated degradation does not explain the decreased receptor concentration in patients with very low insulin receptor binding and, therefore, by inference, a defect in receptor synthesis must be present in this subgroup

  15. Obese but not normal-weight women with polycystic ovary syndrome are characterized by metabolic and microvascular insulin resistance.

    Science.gov (United States)

    Ketel, Iris J G; Stehouwer, Coen D A; Serné, Erik H; Korsen, Ted J M; Hompes, Peter G A; Smulders, Yvo M; de Jongh, Renate T; Homburg, Roy; Lambalk, Cornelis B

    2008-09-01

    Polycystic ovary syndrome (PCOS) and obesity are associated with diabetes and cardiovascular disease, but it is unclear to what extent PCOS contributes independently of obesity. The objective of the study was to investigate whether insulin sensitivity and insulin's effects on the microcirculation are impaired in normal-weight and obese women with PCOS. Thirty-five women with PCOS (19 normal weight and 16 obese) and 27 age- and body mass index-matched controls (14 normal weight and 13 obese) were included. Metabolic Insulin sensitivity (isoglycemic-hyperinsulinemic clamp) and microvascular insulin sensitivity [endothelium dependent (acetylcholine [ACh])] and endothelium-independent [sodium nitroprusside (SNP)] vasodilation with laser Doppler flowmetry was assessed at baseline and during hyperinsulinemia. Metabolic insulin sensitivity (M/I value) and the area under the response curves to ACh and SNP curves were measured to assess microcirculatory function at baseline and during insulin infusion (microvascular insulin sensitivity). Obese women were more insulin resistant than normal-weight women (P PCOS women were more resistant than obese controls (P = 0.02). In contrast, normal-weight women with PCOS had similar insulin sensitivity, compared with normal-weight women without PCOS. Baseline responses to ACh showed no difference in the four groups. ACh responses during insulin infusion were significantly greater in normal-weight PCOS and controls than in obese PCOS and controls. PCOS per se had no significant influence on ACh responses during insulin infusion. During hyperinsulinemia, SNP-dependent vasodilatation did not significantly increase, compared with baseline in the four groups. PCOS per se was not associated with impaired metabolic insulin sensitivity in normal-weight women but aggravates impairment of metabolic insulin sensitivity in obese women. In obese but not normal-weight women, microvascular and metabolic insulin sensitivity are decreased, independent

  16. Insulin response to oral glucose in healthy, lean young women and patients with polycystic ovary syndrome.

    Science.gov (United States)

    Kulshreshtha, Bindu; Ganie, Mohammed Ashraf; Praveen, Edavan Pulikkanath; Gupta, Nandita; Lal Khurana, Madan; Seith, Ashu; Dwivedi, Sadanand N; Kumar, Guresh; Ammini, Ariachery C

    2008-11-01

    Insulin resistance and consequent hyperinsulinemia are common among patients with polycystic ovary syndrome (PCOS). Ethnicity and dietary habits affect insulin levels. There is little published information from India on insulin levels in PCOS patients. Thus the present study aimed to determine the insulin response to oral glucose in women with PCOS and healthy women. In a case-control study design, women with PCOS and lean healthy women without a family history of diabetes mellitus underwent oral glucose tolerance testing. Samples were collected at 0, 1 and 2 h after glucose ingestion. Two hundred and eighty-five women with PCOS and 27 lean healthy young women were enrolled into the study. The mean age of controls was 22.8 +/- 4.5 years (range 15-32 years) and their mean body mass index (BMI) was 19.7 +/- 2.6 kg/m(2). Mean blood glucose at 0, 1 and 2 h was 88.2 +/- 7.2, 115.5 +/- 25.5 and 91.8 +/- 20.5 mg/dl, respectively. Corresponding plasma insulin levels were 5.8 +/- 1.1, 32.7 +/- 26.5 and 14.6 +/- 9.6 mIU/l. Peak insulin levels were seen at 1 h and these came down to less than 40% of the peak value by 2 h. Glucose/insulin ratio at 0, 1 and 2 h was 15.6 +/- 3.1, 7.0 +/- 3.1 and 11.4 +/- 7.0. Homeostasis model assessment of insulin resistance (HOMA-IR) was 1.2 +/- 0.2. The age of the PCOS women ranged from 15 to 40 years (mean 23.4 +/- 6.2 years) and their BMI ranged from 16.4 to 50.4 kg/m(2) (mean 27.7 +/- 6.3 kg/m(2)). One hundred and seventy-six (62%) PCOS patients had normal glucose tolerance (NGT), 39 (14%) had impaired fasting glucose (IFG), 49 (17%) had impaired glucose tolerance (IGT) and 21 (7%) had type 2 diabetes mellitus (T2DM). Insulin response was higher in women with PCOS. Peak insulin was observed at 1 h. The difference between 1-h and 2-h post-glucose insulin decreased with worsening glucose tolerance. Both plasma insulin and BMI showed a rising trend from NGT to IFG to IGT. There was no further increase in either insulin or BMI from IGT to T2DM

  17. Influence of functional nutrients on insulin resistance in horses with equine metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Krzysztof Marycz, Eberhard Moll and Jakub Grzesiak

    2014-04-01

    Full Text Available The obesity is a rising health problem both in veterinary and human medicine. In equine medicine excessive body weight is frequently related to insulin resistance and laminitis as is defined as equine metabolic syndrome (EMS. The dietetic management is considered as the crucial part of treatment strategy in the course of EMS. The main feeding recommendation is to administer the low energy diet in order to restore insulin efficiency and to lower body weight. In this study 14 horses of different breed, both sexes and different ages with diagnosed equine metabolic syndrome were fed, concurrently, with oats (3g/kg bw, hay (15g/kg bw and experimental dietary supplement containing selected herbs, aminoacids, butyric acid derivative, biotin and selected dietetic plant like artichoke. The influence of above dietary protocol on body weight, insulin level, and adipose tissue morphometry was investigated in horses from group A. Horses from group B fed only with oats (3g/kg bw and hay (15g/kg bw served as a control. Results of the experiment indicated that tested supplement could improve insulin efficiency and reduce body mass in experimental horses group.

  18. Spectrum of lipid and lipoprotein indices in human subjects with insulin resistance syndrome

    International Nuclear Information System (INIS)

    Khan, S.H.; Khan, F.A.; Mohammad, A.S.

    2008-01-01

    Insulin resistance syndrome or metabolic syndrome is one of the major metabolic threats our recently urbanized society is going to face in near future. The management of this syndrome requires a very effective biochemical marker for screening. The objective of this cross sectional study were to compare various lipid and lipoprotein indices in human subjects with insulin resistance syndrome This study was carried out between April 2004 to January 2006 at the department of chemical pathology and endocrinology, Armed Forces Institute of Pathology, Rawalpindi. A total of forty-seven subjects with metabolic syndrome were selected as per the criteria of National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III) from a target population diagnosed to have impaired glucose regulation at AFIP. Forty-seven age and sex-matched healthy controls were also included in the study. Insulin resistance was calculated by the method of HOMA-IR, using the formula of Mathew's et al. The various lipid and lipoproteins, their ratios and log-transformed versions were evaluated for differences between subjects with metabolic syndrome and controls. Finally the diagnostic performances of these candidate lipid markers were evaluated. Results between subjects with metabolic syndrome and controls were found to be significant for serum triglyceride (p<0.05), HDL-C (p<0.05), triglyceride/HDLC (p<0.01), Log triglyceride/HDL-C (p<0.01), total cholesterol/HDL-C (p<0.01), LDL-C/HDL-C (p<0.01). However there was weak correlation between these lipid based markers and HOMA-IR ((serum triglyceride: r= 0.225), (HDL-C: r= -0.235), (triglyceride/HDL-C: r= 0.333), (total cholesterol/HDL-C: r= 0.239)). The AUCs for the diagnosis of metabolic syndrome remained highest for HOMA-IR (0.727 (95%CI: 0.642-0.812)), followed by triglyceride/HDL-C (0.669 (95%CI: 0.572-0.766)) and LDLC/ HDL-C (0.639 (95%CI: 0.537-0.742)). The differences for lipids and lipoproteins between subjects with metabolic

  19. Correlation Between Insulin, Leptin and Polycystic Ovary Syndrome

    African Journals Online (AJOL)

    Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of fertile age. .... Serum leptin level rises in both studied groups (control and ... resistant group) with high significant difference (P < 0.01).

  20. Therapeutic fasting in patients with metabolic syndrome and impaired insulin resistance.

    Science.gov (United States)

    Stange, Rainer; Pflugbeil, Christine; Michalsen, Andreas; Uehleke, Bernhard

    2013-01-01

    In this study, we evaluated whether a short- to mid-term fasting therapy (7-18 days) might improve insulin resistance according to the homeostasis model assessment for insulin resistance (HOMA-IR), measured during mid-term (80 days) follow-up observation in patients with metabolic syndrome. In this open label observational study in inpatients, criteria of metabolic syndrome were defined. Before medically controlled Buchinger fasting, a wash-out period for hypoglycemic agents was conducted. Further evaluation was carried out on day 80. 25 patients (13 males, 12 females, mean age 61.3 years) were included in this study (mean fasting duration 11.5 days). Out of 16 inpatients with type 2 diabetes, 4 had been treated with metformin, 3 with insulin, and 1 with glimepiride before the intervention. After therapy, body mass index (BMI), fasting insulin, fasting glucose, and HOMA-IR were all significantly reduced. Compared to baseline, HOMA-IR decreased by 33% in all patients, by 38% in patients with type 2 diabetes, and by 23% in patients without diabetes. At day 80, BMI further improved, while other parameters showed complete (insulin) or partial (glucose, HOMA-IR) rebound. At this time, HOMA-IR values showed an only insignificant improvement in 15% of all patients, in 20% of patients with type 2 diabetes, and in 6% of patients without diabetes. There was no correlation between change in BMI and change in HOMA-IR (r(2) = 0.008, baseline minus day 80). No serious side effects were observed. Fasting as a safe and acceptable procedure may cause short- and mid-term improvement of increased insulin resistance (HOMA-IR). Patients with type 2 diabetes benefit more than those without diabetes. A possible clinical significance of this effect should be explored in larger and controlled clinical trials. © 2014 S. Karger GmbH, Freiburg.

  1. Insulin Resistance, Metabolic Syndrome, and Polycystic Ovary Syndrome in Obese Youth.

    Science.gov (United States)

    Platt, Adrienne M

    2015-07-01

    School nurses are well aware of the childhood obesity epidemic in the United States, as one in three youth are overweight or obese. Co-morbidities found in overweight or obese adults were not commonly found in youth three decades ago but are now increasingly "normal" as the obesity epidemic continues to evolve. This article is the second of six related articles discussing the co-morbidities of childhood obesity and discusses the complex association between obesity and insulin resistance, metabolic syndrome, and polycystic ovary syndrome. Insulin resistance increases up to 50% during puberty, which may help to explain why youth are more likely to develop co-morbidities as teens. Treatment of these disorders is focused on changing lifestyle habits, as a child cannot change his or her pubertal progression, ethnicity, or family history. School nurses and other personnel can assist youth with insulin resistance, metabolic syndrome, and polycystic ovary syndrome by supporting their efforts to make changes, reinforcing that insulin resistance is not necessarily type 2 diabetes even if the child is taking medication, and intervening with negative peer pressure. © 2015 The Author(s).

  2. Poor Sleep Quality is Associated with Insulin Resistance in Postmenopausal Women With and Without Metabolic Syndrome.

    Science.gov (United States)

    Kline, Christopher E; Hall, Martica H; Buysse, Daniel J; Earnest, Conrad P; Church, Timothy S

    2018-05-01

    Poor sleep quality has previously been shown to be related to insulin resistance in apparently healthy adults. However, it is unclear whether an association between sleep quality and insulin resistance exists among adults with metabolic syndrome (MetS). Participants included 347 overweight/obese postmenopausal women without type 2 diabetes (age: 57.5 ± 6.5 years; body mass index [BMI]: 31.7 ± 3.7 kg/m 2 ; 54% with MetS). Sleep quality was assessed with the six-item Medical Outcomes Study Sleep Scale; values were categorized into quartiles. Insulin resistance was calculated from fasting glucose and insulin with the homeostasis model assessment of insulin resistance (HOMA2-IR) method. Analysis of covariance models were used to examine the association between sleep quality and HOMA2-IR after accounting for MetS and covariates (e.g., BMI, cardiorespiratory fitness, and energy intake). Women with the worst sleep quality had significantly higher HOMA2-IR values than women in all other quartiles (P ≤ 0.05 for each), and women with MetS had significantly higher HOMA2-IR values than women without MetS (P quality and HOMA2-IR did not differ between those with or without MetS (P = 0.26). Women with MetS in the worst quartile of sleep quality had higher HOMA2-IR values than all other women (P 30 min to fall asleep, frequent restless sleep, and frequent daytime drowsiness were each related to higher HOMA2-IR values (each P quality is an important correlate of insulin resistance in postmenopausal women with and without MetS. Intervention studies are needed to determine whether improving sleep improves insulin resistance in populations at elevated cardiometabolic risk.

  3. Assessment of insulin resistance and impaired glucose tolerance in lean women with polycystic ovary syndrome.

    Science.gov (United States)

    Stovall, Dale William; Bailey, Amelia Purser; Pastore, Lisa M

    2011-01-01

    To analyze insulin resistance (IR) and determine the need for a 2-hour oral glucose tolerance test (OGTT) for the identification of IR and impaired glucose tolerance (IGT) in lean nondiabetic women with polycystic ovary syndrome (PCOS). This was a cross-sectional analysis of treatment-naive women with PCOS who enrolled in a university-based clinical trial. Nondiabetic women with PCOS based on the Eunice Kennedy Shriven National Institute of Child Health and Human Development (NICHD) definition, aged 18-43 years and weighing ≤113 kg, were evaluated. Glucose and insulin levels were assessed at times 0, 30, 60, 90, and 120 minutes after a 75-g glucose load. Lean was defined as body mass index (BMI) women was studied. The prevalence of IR was 0% among lean women vs. 21% among nonlean subjects based on fasting insulin I(0) and 40%-68% based on two different homeostatic model assessment (HOMA) cutoff points (p women with IR had a BMI ≥ 28. Controlling for age and race, BMI explained over 57% of the variation in insulin fasting (I(o)), glucose fasting/Io (G(o)/I(o)), the qualitative insulin sensitivity check index (QUICKI), and HOMA and was a highly significant predictor of these outcomes (p lean PCOS women had IGT based on a 2-hour OGTT, and no lean subjects had IGT based on their fasting blood glucose. Diabetes mellitus, IGT, and IR are far less common in young lean women with PCOS compared with obese women with PCOS. These data imply that it is unnecessary to routinely perform either IR testing or 2-hour OGTT in lean women with PCOS; however, greater subject accumulation is needed to determine if OGTT is necessary in lean women with PCOS. BMI is highly predictive of both insulin and glucose levels in women with PCOS.

  4. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

    International Nuclear Information System (INIS)

    Lin, Yan-Jie; Juan, Chi-Chang; Kwok, Ching-Fai; Hsu, Yung-Pei; Shih, Kuang-Chung; Chen, Chin-Chang; Ho, Low-Tone

    2015-01-01

    Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET A R during insulin resistance, ET A R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET A R expression, but not ET B R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET A R pathway suppressed insulin

  5. Severe hypoglycemia secondary to methimazole-induced insulin autoimmune syndrome in a 16 year old African-American male.

    Science.gov (United States)

    Gomez Cruz, Michelle J; Jabbar, Muhammad; Saini, Natinder; Eng, Donna; Crawford, Brandon; Vazquez, Delia M; Menon, Ram; Chen, Ming

    2012-12-01

    Insulin autoimmune syndrome (IAS) or Hirata's disease is a rare disorder characterized by hypoglycemia secondary to insulin autoantibodies (IAb). Over 200 patients have been described from Japan with significantly less numbers being reported from outside the Orient. IAS is more common in patients older than 40 yr of age with reports in the pediatric age group being notably rarer. Exposure to sulfhydryl group containing medications is implicated in the pathogenesis of this syndrome. In this report, we describe a case of IAS in an African-American adolescent. A 16-yr-old healthy African-American male was diagnosed with Graves' disease and started on Methimazole. Four weeks later, he was found unconscious and hypoglycemic (blood sugar 1.5 mmol/L). Evaluation was negative for insulinoma. Insulin antibodies were positive. Oral glucose tolerance test revealed elevated free insulin concentrations with disproportionately elevated total insulin levels. The patient was started on prednisone, diazoxide, and propranolol for management of IAS and hyperthyroidism. Thyroid radio-ablation was subsequently undertaken. The doses of prednisone and diazoxide were tapered and these medications discontinued after 9 months. The insulin antibody levels decreased gradually and became undetectable in 6 months with resolution of the hypoglycemia. © 2012 John Wiley & Sons A/S.

  6. The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

    OpenAIRE

    Messier, Claude; Teutenberg, Kevin

    2005-01-01

    Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in a...

  7. Insulin resistance, the metabolic syndrome, diabetes, and cardiovascular disease risk in women with PCOS.

    Science.gov (United States)

    Teede, H J; Hutchison, S; Zoungas, S; Meyer, C

    2006-08-01

    Polycystic ovary syndrome is the most common endocrinopathy of reproductive aged women affecting 6-10% of the population. Traditionally considered a reproductive disorder manifesting as chronic anovulation, infertility, and hyperandrogenism, management has primarily focused on short-term reproductive outcomes. Recently, however, significant metabolic aspects in conjunction with longer-term health sequealae of PCOS have been recognized. The metabolic features are primarily related to underlying insulin resistance (IR), which is now understood to play an important role in both the pathogenesis and long-term sequelae of PCOS.

  8. Insulin autoimmune syndrome induced by methimazole in a Korean girl with Graves' disease

    Directory of Open Access Journals (Sweden)

    Sun Hee Lee

    2013-03-01

    Full Text Available Hypoglycemia was detected in a 15-year-old girl due to loss of consciousness. She was diagnosed with Graves' disease and was being treated with methimazole for the past 4 months. A paradoxically increased insulin levels was found when she suffered from the hypoglycemic episode. An imaging study showed no mass lesion in the pancreas, and insulin antibodies were found in the serum. She was diagnosed with insulin autoimmune syndrome. Her HLA typing was performed, and it revealed HLA-DRB1 *04:06. The patient was treated with a corticosteroid for 2 months. After discontinuing the steroid, the insulin antibody titer decreased dramatically, and she did not have any episode of hypoglycemia since. This is the first report of insulin autoimmune syndrome in a Korean girl, and we have revealed the connection between HLA type and insulin autoimmune syndrome in Korea.

  9. Effects of medical therapy on insulin resistance and the cardiovascular system in polycystic ovary syndrome.

    Science.gov (United States)

    Meyer, Caroline; McGrath, Barry P; Teede, Helena Jane

    2007-03-01

    We aimed to determine the impact of medical therapy for symptom management on insulin resistance, metabolic profiles, and surrogate markers of cardiovascular disease in polycystic ovary syndrome (PCOS), an insulin-resistant pre-diabetes condition. One hundred overweight women (BMI >27 kg/m2), average age 31 years, who were nonsmokers, were not pregnant, did not have diabetes, and were off relevant medications for 3 months completed this 6-month open-label controlled trial. Randomization was to a control group (higher-dose oral contraceptive [OCP] 35 microg ethinyl estradiol [EE]/2 mg cyproterone acetate, metformin [1 g b.d.] or low-dose OCP [20 microg EE/100 microg levonorgestrel + aldactone 50 mg b.d.]). Primary outcome measures were insulin resistance (area under curve on oral glucose tolerance test) and surrogate markers of cardiovascular disease including arterial stiffness (pulse wave velocity [PWV]) and endothelial function. All treatments similarly and significantly improved symptoms including hirsutism and menstrual cycle length. Insulin resistance was improved by metformin and worsened by the high-dose OCP. Arterial stiffness worsened in the higher-dose OCP group (PWV 7.46 vs. 8.03 m/s, P insulin resistance. In overweight women with PCOS, metformin and low- and high-dose OCP preparations have similar efficacy but differential effects on insulin resistance and arterial function. These findings suggest that a low-dose OCP preparation may be preferable if contraception is needed and that metformin should be considered for symptomatic management, particularly in women with additional metabolic and cardiovascular risk factors.

  10. A higher score on the Aging Males' Symptoms scale is associated with insulin resistance in middle-aged men.

    Science.gov (United States)

    Hamanoue, Nobuya; Tanabe, Makito; Tanaka, Tomoko; Akehi, Yuko; Murakami, Junji; Nomiyama, Takashi; Yanase, Toshihiko

    2017-05-30

    An age-associated androgen decrease and its pathological conditions are defined as late-onset hypogonadism (LOH). Among the various symptoms associated with LOH, a visceral fat increase is strongly associated with relatively low levels of testosterone. However, few studies have investigated the relationship between the Aging Males' Symptoms (AMS) scores and metabolic abnormalities. Thus, we aimed to clarify this relationship by investigating the relationship between AMS scores and various markers in blood. During routine health examinations in 241 middle-aged males (52.7±7.5 years of age, mean±SD), 150 males (62.2%) displayed higher AMS values than normal. No statistical association was observed between total AMS scores and any testosterone value. All mental, physical and sexual AMS subscales were significantly positively correlated with insulin levels and HOMA-IR. Only sexual subscale scores were significantly inversely associated with free or bioavailable testosterone level. Males with insulin resistance (HOMA-IR≥2.5) demonstrated significantly higher AMS scores than those with normal insulin sensitivity (HOMA-IRinsulin and HOMA-IR values. Interestingly, univariate and multivariate analyses revealed that HOMA-IR≥2.5 was a significant predictor for detection of moderately severe AMS values (AMS≥37), whereas AMS≥37 was not a predictor of metabolic syndrome by International Diabetes Federation (IDF) criterion. In conclusion, almost 60% of healthy male subjects displayed abnormal AMS scores. AMS values were not associated with testosterone values but rather were related to insulin resistance, particularly in subjects with moderately severe AMS values. Insulin resistance-related general unwellness might be reflected by AMS values.

  11. Diamel Therapy in Polycystic Ovary Syndrome Reduces Hyperinsulinaemia, Insulin Resistance, and Hyperandrogenaemia

    Directory of Open Access Journals (Sweden)

    Arturo Hernández-Yero

    2012-01-01

    Full Text Available For to determine the effect of Diamel on the insulin resistance, insulin sensitivity, and sexual hormones results in women with polycystic ovary syndrome (PCOS. A study was carried out on 37 patients with this disorder. A triple-blind clinical trial was designed in which the Diamel food supplement was compared with a placebo. The women with reproductive ages were randomly distributed in two groups, with 18 and 19 women respectively, and they took Diamel or placebo and were followed up during 6 months with clinical and biochemical evaluation. A significant decrease in the HOMA-IR from the initial value at six months was observed in the group with Diamel. The insulin sensitivity improved considerably in this group. The rate of menstrual recovery was higher in the group with Diamel, and two patients from this group obtained pregnancy. The hormone levels shows a significant decrease in testosterone at 3 months in the group with Diamel compared with the control group. The LH also decreases in the same group when comparing the start with 6 months.We concluded that the Diamel decreases insulin resistance and improves sensitivity to this hormone in women with PCOS, with improvement in the levels of LH and testosterone.

  12. Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance.

    Science.gov (United States)

    Barber, Thomas M; Dimitriadis, George K; Andreou, Avgi; Franks, Stephen

    2016-06-01

    Polycystic ovary syndrome (PCOS) is a common condition that typically develops in reproductive-age women. The cardinal clinical and biochemical characteristics of PCOS include reproductive dysfunction and hyperandrogenic features. PCOS is also strongly associated with obesity based on data from epidemiological and genetic studies. Accordingly, PCOS often becomes manifest in those women who carry a genetic predisposition to its development, and who also gain weight. The role of weight gain and obesity in the development of PCOS is mediated at least in part, through worsening of insulin resistance. Compensatory hyperinsulinaemia that develops in this context disrupts ovarian function, with enhanced androgen production and arrest of ovarian follicular development. Insulin resistance also contributes to the strong association of PCOS with adverse metabolic risk, including dysglycaemia, dyslipidaemia and fatty liver. Conversely, modest weight loss of just 5% body weight with improvement in insulin sensitivity, frequently results in clinically meaningful improvements in hyperandrogenic, reproductive and metabolic features. Future developments of novel therapies for obese women with PCOS should focus on promotion of weight loss and improvement in insulin sensitivity. In this context, therapies that complement lifestyle changes such as dietary modification and exercise, particularly during the maintenance phase of weight loss are important. Putative novel targets for therapy in PCOS include human brown adipose tissue. © 2016 Royal College of Physicians.

  13. Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives.

    Science.gov (United States)

    Salzano, Andrea; D'Assante, Roberta; Heaney, Liam M; Monaco, Federica; Rengo, Giuseppe; Valente, Pietro; Pasquali, Daniela; Bossone, Eduardo; Gianfrilli, Daniele; Lenzi, Andrea; Cittadini, Antonio; Marra, Alberto M; Napoli, Raffaele

    2018-03-23

    Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. This review summarises the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population. We searched PubMed, Web of Science, and Scopus for manuscripts published prior to November 2017 using key words "Klinefelter syndrome" AND "insulin resistance" OR "metabolic syndrome" OR "diabetes mellitus" OR "cardiovascular disease" OR "testosterone". Manuscripts were collated, studied and carried forward for discussion where appropriate. Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system. Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS.

  14. Limitations of insulin resistance assessment in polycystic ovary syndrome

    Science.gov (United States)

    Lewandowski, Krzysztof C; Płusajska, Justyna; Horzelski, Wojciech; Bieniek, Ewa; Lewiński, Andrzej

    2018-01-01

    Background Though insulin resistance (IR) is common in polycystic ovary syndrome (PCOS), there is no agreement as to what surrogate method of assessment of IR is most reliable. Subjects and methods In 478 women with PCOS, we compared methods based on fasting insulin and either fasting glucose (HOMA-IR and QUICKI) or triglycerides (McAuley Index) with IR indices derived from glucose and insulin during OGTT (Belfiore, Matsuda and Stumvoll indices). Results There was a strong correlation between IR indices derived from fasting values HOMA-IR/QUICKI, r = −0.999, HOMA-IR/McAuley index, r = −0.849 and between all OGTT-derived IR indices (e.g. r = −0.876, for IRI/Matsuda, r = −0.808, for IRI/Stumvoll, and r = 0.947, for Matsuda/Stumvoll index, P IR indices derived from fasting vs OGTT-derived variables, ranging from r = −0.881 (HOMA-IR/Matsuda), through r = 0.58, or r = −0.58 (IRI/HOMA-IR, IRI/QUICKI, respectively) to r = 0.41 (QUICKI/Stumvoll), and r = 0.386 for QUICKI/Matsuda indices. Detailed comparison between HOMA-IR and IRI revealed that concordance between HOMA and IRI was poor for HOMA-IR/IRI values above 75th and 90th percentile. For instance, only 53% (70/132) women with HOMA-IR >75th percentile had IRI value also above 75th percentile. There was a significant, but weak correlation of all IR indices with testosterone concentrations. Conclusions Significant number of women with PCOS can be classified as being either insulin sensitive or insulin resistant depending on the method applied, as correlation between various IR indices is highly variable. Clinical application of surrogate indices for assessment of IR in PCOS must be therefore viewed with an extreme caution. PMID:29436386

  15. Role of insulin in the hyperandrogenemia of lean women with polycystic ovary syndrome and normal insulin sensitivity.

    Science.gov (United States)

    Baillargeon, Jean-Patrice; Carpentier, André

    2007-10-01

    To determine the effect of reducing insulin secretion on hyperandrogenemia in lean normoinsulinemic women with polycystic ovary syndrome (PCOS) and normal metabolic insulin sensitivity. Transversal assessment at baseline and prospective follow-up of lean PCOS group after 8 days of diazoxide, which reduces insulin secretion, and 1 month of leuprolide, which suppresses LH. Clinical research center of an academic hospital. Nine lean women (body mass index PCOS and normal insulin levels, as well as 17 lean healthy women. Lean PCOS women were reassessed after 8 days of diazoxide and after 1 month of leuprolide, which suppresses LH. Androgen levels and insulin-stimulated glucose disposal (metabolic insulin sensitivity), determined by euglycemic-hyperinsulinemic clamp (M-value). Mean M-value of lean PCOS women (48.5 micromol/kg.min) was similar to lean control subjects (52.9 micromol/kg.min). They also had comparable anthropometric measures, lipids, fibrinogen, and plasminogen activator inhibitor 1. The LH did not change significantly after diazoxide, but was almost suppressed after leuprolide in the PCOS group. Androstenedione decreased significantly after diazoxide and even more after leuprolide. However, free T significantly decreased only after diazoxide in lean PCOS women. Diazoxide also increased SHBG significantly in this group. In women with typical PCOS and normal insulin levels and metabolic insulin sensitivity, reducing insulin secretion significantly decreased androgen and increased SHBG levels. These results suggest that insulin contributes to hyperandrogenemia even in PCOS women with normal metabolic insulin sensitivity, which might be due to increased sensitivity of their androgenic insulin pathway.

  16. Insulin resistance, metabolic syndrome, and lipids in African women ...

    African Journals Online (AJOL)

    HDL, and atherogenic index of plasma; log (TG/HDL) were calculated and compared with IR. Metabolic syndrome was sought for using both the WHO and the harmonized joint criteria. Results: The mean age was 44.4 (13.1) years. Hypertension ...

  17. Central insulin-like growth factor-1 (IGF-1) restores whole-body insulin action in a model of age-related insulin resistance and IGF-1 decline.

    Science.gov (United States)

    Huffman, Derek M; Farias Quipildor, Gabriela; Mao, Kai; Zhang, Xueying; Wan, Junxiang; Apontes, Pasha; Cohen, Pinchas; Barzilai, Nir

    2016-02-01

    Low insulin-like growth factor-1 (IGF-1) signaling is associated with improved longevity, but is paradoxically linked with several age-related diseases in humans. Insulin-like growth factor-1 has proven to be particularly beneficial to the brain, where it confers protection against features of neuronal and cognitive decline. While aging is characterized by central insulin resistance in the face of hyperinsulinemia, the somatotropic axis markedly declines in older humans. Thus, we hypothesized that increasing IGF-1 in the brain may prove to be a novel therapeutic alternative to overcome central insulin resistance and restore whole-body insulin action in aging. Utilizing hyperinsulinemic-euglycemic clamps, we show that old insulin-resistant rats with age-related declines in IGF-1 level demonstrate markedly improved whole-body insulin action, when treated with central IGF-1, as compared to central vehicle or insulin (P IGF-1, but not insulin, suppressed hepatic glucose production and increased glucose disposal rates in aging rats (P IGF-1 action in the brain and periphery provides a 'balance' between its beneficial and detrimental actions. Therefore, we propose that strategies aimed at 'tipping the balance' of IGF-1 action centrally are the optimal approach to achieve healthy aging and longevity in humans. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  18. Maternal and fetal insulin levels at birth in women with polycystic ovary syndrome: data from a randomized controlled study on metformin.

    Science.gov (United States)

    Helseth, Ragnhild; Vanky, Eszter; Stridsklev, Solhild; Vogt, Christina; Carlsen, Sven M

    2014-05-01

    Metformin is suggested to reduce pregnancy complications in women with polycystic ovary syndrome (PCOS). Metformin crosses the placenta and therapeutic concentrations are measured in the fetal circulation. Whether metformin treatment in pregnant PCOS women affects maternal and fetal insulin concentrations at birth is not clarified. To investigate the possible effect of metformin on insulin concentrations in umbilical cord blood and the possible association between maternal and fetal insulin concentrations. Post-hoc analysis of a subgroup of PCOS women participating in a double-blind randomized controlled trial. University hospital setting. Women with PCOS (n=118), aged 19-39 years. Maternal and umbilical cord insulin concentrations immediately after birth. At delivery women randomized to metformin had lower insulin concentrations than those randomized to placebo (259±209 vs 361±261 pmol/l; P=0.020). No difference was found in insulin concentrations in umbilical venous (P=0.95) and arterial (P=0.39) blood between the metformin and placebo groups. The arteriovenous difference was also equal between the groups (P=0.38). Insulin concentrations were higher in the umbilical vein than in the umbilical artery independent of randomization (70±51 vs 45±48 pmol/l; Pmetformin treatment during pregnancy resulted in lower maternal insulin concentrations at delivery. Metformin treatment did not affect fetal insulin concentrations. Higher insulin concentrations in the umbilical vein indicate that the placenta somehow secretes insulin to the fetus. The possibility of placental insulin secretion to the fetus deserves further investigations.

  19. Diabetes, insulin resistance, and metabolic syndrome in horses.

    Science.gov (United States)

    Johnson, Philip J; Wiedmeyer, Charles E; LaCarrubba, Alison; Ganjam, V K; Messer, Nat T

    2012-05-01

    Analogous to the situation in human medicine, contemporary practices in horse management, which incorporate lengthy periods of physical inactivity coupled with provision of nutritional rations characterized by inappropriately high sugar and starch, have led to obesity being more commonly recognized by practitioners of equine veterinary practice. In many of these cases, obesity is associated with insulin resistance (IR) and glucose intolerance. An equine metabolic syndrome (MS) has been described that is similar to the human MS in that both IR and aspects of obesity represent cornerstones of its definition. Unlike its human counterpart, identification of the equine metabolic syndrome (EMS) portends greater risk for development of laminitis, a chronic, crippling affliction of the equine hoof. When severe, laminitis sometimes necessitates euthanasia. Unlike the human condition, the risk of developing type 2 diabetes mellitus and many other chronic conditions, for which the risk is recognized as increased in the face of MS, is less likely in horses. The equine veterinary literature has been replete with reports of scientific investigations regarding the epidemiology, pathophysiology, and treatment of EMS. © 2012 Diabetes Technology Society.

  20. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR): A Better Marker for Evaluating Insulin Resistance Than Fasting Insulin in Women with Polycystic Ovarian Syndrome.

    Science.gov (United States)

    Majid, Hafsa; Masood, Qamar; Khan, Aysha Habib

    2017-03-01

    To assess the utility of HOMA-IR in assessing insulin resistance in patients with polycystic ovary syndrome (PCOS) and compare it with fasting insulin for assessing insulin resistance (IR). Observational study. Section of Clinical Chemistry, Department of Pathology and Laboratory Medicine, The Aga Khan University Hospital, Karachi, from January 2009 to September 2012. Medical chart review of all women diagnosed with PCOS was performed. Of the 400 PCOS women reviewed, 91 met the inclusion criteria. Insulin resistance was assessed by calculating HOMA-IR using the formula (fasting glucose x fasting insulin)/405, taking normal value HOMA-IR of women was 3.1 ±1.7, respectively with IR in 69% (n=63) women, while hyperinsulinemia was present in 60% (n=55) women (fasting Insulin 18.5 ±5.8 µIU/ml). Hyperandrogenism was present in 53.8% (n=49), whereas 38.5% (n=35) women had primary infertility or subfertility, while 65.9% (n=60) had menstrual irregularities; and higher frequencies were observed in women with IR. Eight subjects with IR and endocrine abnormalities were missed by fasting insulin. Insulin resistance is common in PCOS and it is likely a pathogenic factor for development of PCOS. HOMAIR model performed better than hyperinsulinemia alone for diagnosing IR.

  1. Elevated serum levels of free insulin-like growth factor I in polycystic ovary syndrome

    NARCIS (Netherlands)

    H.J. Thierry van Dessel; P.D.K. Lee (Philip); G. Faessen; B.C.J.M. Fauser (Bart); L.C. Giudice

    1999-01-01

    textabstractPolycystic ovary syndrome (PCOS) is the most common cause of anovulation in women. Previous studies suggest that the pathogenesis of PCOS may involve interrelated abnormalities of the insulin-like growth factor (IGF) and ovarian steroidogenesis systems. We

  2. Efficacy of 2-hour post glucose insulin levels in predicting insulin resistance in polycystic ovarian syndrome with infertility

    Directory of Open Access Journals (Sweden)

    Pikee Saxena

    2011-01-01

    Full Text Available Background : Insulin resistance (IR is central to the pathogenesis of polycystic ovarian syndrome (PCOS, but tests for determining IR are elaborate, tedious and expensive. Aims : To evaluate if "2-hour post-glucose insulin level" is an effective indicator of IR and can aid in diagnosing IR in infertile PCOS women. Settings and Design : Observational study at infertility clinic of a tertiary care center. Materials and Methods : 50 infertile women with PCOS and 20 females with tubal/male factor infertility were evaluated for the presence of IR, as defined by the fasting/2-hour post-glucose insulin levels cutoffs of >25/>41 μU/mL, respectively. The clinical, metabolic and endocrinologic profile was determined in both the groups. Statistical Analysis : Statistical analysis was performed using SPSS (Chicago, IL, USA. Results : Body mass index, post load glucose, insulin, glucose/insulin ratio, area under curve (AUC of glucose and insulin and insulinogenic index were significantly lower in the controls as compared to the PCOS group. "2-hour post-glucose insulin levels" were elevated in 88% of PCOS individuals but were normal in all females not suffering from PCOS. These levels significantly correlated with AUC of glucose and insulin, and insulinogenic index and inversely correlated with 2-hour glucose to insulin ratio (r=0.827, 0.749 and −0.732, respectively. Conclusions : "2-hour post-glucose insulin levels" appears to be a good indicator of IR. It can be a useful tool, especially in low resource setting where a single sample can confirm the diagnosis, thus reducing cost and repeat visits.

  3. Insulin action in women with polycystic ovary syndrome and its relation to gestational diabetes

    NARCIS (Netherlands)

    De Wilde, Marlieke A.; Goverde, Angelique J.; Veltman-Verhulst, Susanne M.; Eijkemans, Marinus J C; Franx, Arie; Fauser, Bart C J M; Koster, Maria P H

    2015-01-01

    STUDY QUESTION: How does insulin action change during pregnancy in women with polycystic ovary syndrome (PCOS) who develop gestational diabetes (GDM) compared with women with PCOS who do not? SUMMARY ANSWER: Women with PCOS who develop GDM already show disturbed insulin action early in pregnancy.

  4. Relationship of hypovitaminosis d and insulin resistance in patients with coronary heart disease and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    V. F. Orlovsky

    2013-08-01

    Full Text Available BACKGROUND: Insulin resistance (IR - is one of the predictors of cardiovascular disease and progression of atherosclerosis, regardless of major classical risk factors. IR has become a global epidemic. Experimental data indicate that low concentration of vitamin D associated with IR, diabetes mellitus type 2, by reducing the sensitivity of peripheral tissues to insulin and dysfunction of β-pancreatic cells. Randomized studies showed that vitamin D supplements have a preventive role in the development of type 2 diabetes mellitus (DM. The present study aims to examine the association between serum vitamin D concentrations and indicators of carbohydrate metabolism, indexes of insulin resistance and insulin sensitivity in the patients with coronary artery disease. METHODS: This study included 135 patients with CHD stable angina pectoris class II – III. The mean age was 64,7±0,97 years, 40% were women (n = 54. Patients were divided into two groups: I – with isolated CHD (70 patients and II - CHD combined with MS (65 patients. MS was diagnosed according to the criteria of the International Diabetes Federation (IDF, 2005. The study did not include patients who received vitamin D2, D3 and multivitamins containing these vitamins for last 6 months, patients with malabsorption fat syndrome, acute and chronic liver disease, chronic renal failure, nephrotic syndrome, urolithiasis, and primary hyperparathyroidism. Also excluded from the study were patients with DM type 1 and type 2 taking glucose-lowering drugs. Serum 25(OHD and insulin were measured by enzyme immunoassay (25-OH Vitamin D Immunodiagnostics Systems Limited (UK; DRG (USA. RESULT: Vitamin D deficiency or insufficiency was present in 91,9 % of the tested patients. Among subnormal values prevailed insufficiency in 51,9 % (70 pers., deficit diagnosed in 40.0% of patients (54 pers.. Established that patients with CHD associated with MS have a significantly more pronounced hypovitaminosis D

  5. Effects of growth hormone and insulin-like growth factor 1 deficiency on ageing and longevity.

    Science.gov (United States)

    Laron, Zvi

    2002-01-01

    Present knowledge on the effects of growth hormone (GH)/insulin-like growth hormone (IGF)1 deficiency on ageing and lifespan are reviewed. Evidence is presented that isolated GH deficiency (IGHD), multiple pituitary hormone deficiencies (MPHD) including GH, as well as primary IGE1 deficiency (GH resistance, Laron syndrome) present signs of early ageing such as thin and wrinkled skin, obesity, hyperglycemia and osteoporosis. These changes do not seem to affect the lifespan, as patients reach old age. Animal models of genetic MPHD (Ames and Snell mice) and GH receptor knockout mice (primary IGF1 deficiency) also have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting large amounts of GH have premature death. In conclusion longstanding GH/IGF1 deficiency affects several parameters of the ageing process without impairing lifespan, and as shown in animal models prolongs longevity. In contrast high GH/IGF1 levels accelerate death.

  6. Prevalence of insulin resistance and its association with metabolic syndrome criteria among Bolivian children and adolescents with obesity

    Directory of Open Access Journals (Sweden)

    Rodriguez Susana

    2008-08-01

    Full Text Available Abstract Background Obesity is a one of the most common nutritional disorder worldwide, clearly associated with the metabolic syndrome, condition with implications for the development of many chronic diseases. In the poorest countries of Latin America, malnourishment is still the most prevalent nutritional problem, but obesity is emerging in alarming rates over the last 10 years without a predictable association with metabolic syndrome. The objective of our study was to determine the association between insulin-resistance and components of the metabolic syndrome in a group of Bolivian obese children and adolescents. The second objective was determining the relation of acanthosis nigricans and insulin-resistance. Methods We studied 61 obese children and adolescents aged between 5 and 18 years old. All children underwent an oral glucose tolerance test and fasting blood sample was also obtained to measure insulin, HDL, LDL and triglycerides serum level. The diagnosis of metabolic syndrome was defined according to National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP III criteria adapted for children. Results Metabolic syndrome was found in 36% of the children, with a higher rate among males (40% than females (32.2% (p = 0.599. The prevalence of each of the components was 8.2% in impaired glucose tolerance, 42.6% for high triglyceride level, 55.7% for low levels of high-density lipoprotein cholesterol, and 24.5% for high blood pressure. Insulin resistance (HOMA-IR > 3.5 was found in 39.4% of the children, with a higher rate in males (50% than females (29%. A strong correlation was found between insulin resistance and high blood pressure (p = 0.0148 and high triglycerides (p = 0.002. No statistical significance was found between the presence of acanthosis nigricans and insulin resistance. Conclusion Metabolic syndrome has a prevalence of 36% in children and adolescent population in the study. Insulin resistance was very common among

  7. Insulin Responsiveness in Metabolic Syndrome after Eight Weeks of Cycle Training

    Science.gov (United States)

    Stuart, Charles A.; South, Mark A.; Lee, Michelle L.; McCurry, Melanie P.; Howell, Mary E. A.; Ramsey, Michael W.; Stone, Michael H.

    2013-01-01

    Introduction Insulin resistance in obesity is decreased after successful diet and exercise. Aerobic exercise training alone was evaluated as an intervention in subjects with the metabolic syndrome. Methods Eighteen non-diabetic, sedentary subjects, eleven with the metabolic syndrome, participated in eight weeks of increasing intensity stationary cycle training. Results Cycle training without weight loss did not change insulin resistance in metabolic syndrome subjects or sedentary control subjects. Maximal oxygen consumption (VO2max), activated muscle AMP-dependent kinase, and muscle mitochondrial marker ATP synthase all increased. Strength, lean body mass, and fat mass did not change. Activated mammalian target of rapamycin was not different after training. Training induced a shift in muscle fiber composition in both groups but in opposite directions. The proportion of 2x fibers decreased with a concomitant increase in 2a mixed fibers in the control subjects, but in metabolic syndrome, 2x fiber proportion increased and type 1 fibers decreased. Muscle fiber diameters increased in all three fiber types in metabolic syndrome subjects. Muscle insulin receptor expression increased in both groups and GLUT4 expression increased in the metabolic syndrome subjects. Excess phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser337 in metabolic syndrome muscle tended to increase further after training in spite of a decrease in total IRS-1. Conclusion In the absence of weight loss, cycle training of metabolic syndrome subjects resulted in enhanced mitochondrial biogenesis, and increased expression of insulin receptors and GLUT4 in muscle, but did not decrease the insulin resistance. The failure for the insulin signal to proceed past IRS-1 tyrosine phosphorylation may be related to excess serine phosphorylation at IRS-1 Ser337 and this is not ameliorated by eight weeks of endurance exercise training. PMID:23669880

  8. Insulin resistance in non-obese women with polycystic ovary syndrome: relation to byproducts of oxidative stress.

    Science.gov (United States)

    Macut, D; Simic, T; Lissounov, A; Pljesa-Ercegovac, M; Bozic, I; Djukic, T; Bjekic-Macut, J; Matic, M; Petakov, M; Suvakov, S; Damjanovic, S; Savic-Radojevic, A

    2011-07-01

    To get more insight into molecular mechanisms underlying oxidative stress and its link with insulin resistance, oxidative stress parameters, as well as, antioxidant enzyme activities were studied in young, non-obese women with polycystic ovary syndrome (PCOS). Study was performed in 34 PCOS women and 23 age and body mass index (BMI)-matched healthy controls. Plasma nitrotyrosine and malondialdehyde (MDA), representative byproducts of protein and lipid oxidative damage, were determined by enzyme immunoassay. Antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPX) were studied spectrophotometrically. Insulin resistance was calculated using homeostasis assessment model (HOMA-IR). Plasma nitrotyrosine and MDA were increased, but only nitrotyrosine was significantly higher (p PCOS women compared to controls. Uric acid (surrogate marker of × antine oxidase) was also significantly elevated in PCOS (p PCOS and controls. Indices of insulin resistance (insulin and HOMAIR) were significantly higher in PCOS group and positively correlated with level of MDA (r = 0.397 and r = 0.523, respectively; p insulin resistance could be responsible for the existence of subtle form of oxidative stress in young, nonobese PCOS women. Hence, presence of insulin resistance, hyperinsulinemia and oxidative damage are likely to accelerate slow development of cardiovascular disease in PCOS. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

  9. Clinical significance of changes of serum leptin and insulin levels in patients with polycystic ovary syndrome

    International Nuclear Information System (INIS)

    Chen Zhaojun; Zhang Lahong; Gao Ying; Ren Xiaohua

    2007-01-01

    Objective: To explore the relationship between the serum leptin, insulin levels and development of polycystic ovary syndrome (PCOS). Methods: Serum leptin and insulin levels (with RIA) were determined in 34 patients with PCOS and 30 controls. Results: The serum leptin and insulin levels in the 34 PCOS patients were significantly higher than those in controls (P<0. 01), and those in obese patients (n=22) were significantly higher than those in non-obese ones (n=12) too(P<0.01). Conclusion: Changes of serum leptin and insulin levels were closely related to the development of PCOS and leptin might be used as a diagnostic indicator for PCOS. (authors)

  10. Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training

    Science.gov (United States)

    Roberts, Christian K.; Hevener, Andrea L.; Barnard, R. James

    2014-01-01

    Metabolic syndrome (MS) is a collection of cardiometabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia. Although there has been significant debate regarding the criteria and concept of the syndrome, this clustering of risk factors is unequivocally linked to an increased risk of developing type 2 diabetes and cardiovascular disease. Regardless of the true definition, based on current population estimates, nearly 100 million have MS. It is often characterized by insulin resistance, which some have suggested is a major underpinning link between physical inactivity and MS. The purpose of this review is to: (i) provide an overview of the history, causes and clinical aspects of MS, (ii) review the molecular mechanisms of insulin action and the causes of insulin resistance, and (iii) discuss the epidemiological and intervention data on the effects of exercise on MS and insulin sensitivity. PMID:23720280

  11. Insulin-resistant glucose metabolism in patients with microvascular angina--syndrome X

    DEFF Research Database (Denmark)

    Vestergaard, H; Skøtt, P; Steffensen, R

    1995-01-01

    Studies in patients with microvascular angina (MA) or the cardiologic syndrome X have shown a hyperinsulinemic response to an oral glucose challenge, suggesting insulin resistance and a role for increased serum insulin in coronary microvascular dysfunction. The aim of the present study was to exa......Studies in patients with microvascular angina (MA) or the cardiologic syndrome X have shown a hyperinsulinemic response to an oral glucose challenge, suggesting insulin resistance and a role for increased serum insulin in coronary microvascular dysfunction. The aim of the present study...... was to examine whether patients with MA are insulin-resistant. Nine patients with MA and seven control subjects were studied. All were sedentary and glucose-tolerant. Coronary arteriography was normal in all participants, and exercise-induced coronary ischemia was demonstrated in all MA patients. A euglycemic...... metabolism (8.4 +/- 0.9 v 12.5 +/- 1.3 mg.kg FFM-1.min-1, P

  12. Study on the relationship between the serum adiponectin and insulin levels in patients with polycystic ovary syndrome (PCOS)

    International Nuclear Information System (INIS)

    Wang Ying; Yang Wen

    2010-01-01

    Objective: To study the relationship between the serum adiponectin and insulin levels in patients with polycystic ovary syndrome (PCOS). Methods: Levels of serum adiponectin and insulin were detected with RIA in 36 patients with polycystic ovary syndrome and 35 controls. Results: In the patients, the serum adiponectin levels were significantly lower than those in controls (P <0.01), while the serum insulin levels were significantly higher (P <0.01). Serum adiponectin and insulin levels were mutually negatively correlated (r =-0.5034, P < 0.01). Conclusion: There is a close relationship between the serum adiponectin and insulin levels in patients with polycystic ovary syndrome. (authors)

  13. Novel adiponectin-resistin (AR and insulin resistance (IRAR indexes are useful integrated diagnostic biomarkers for insulin resistance, type 2 diabetes and metabolic syndrome: a case control study

    Directory of Open Access Journals (Sweden)

    Muniandy Sekaran

    2011-01-01

    Full Text Available Abstract Background Adiponectin and resistin are adipokines which modulate insulin action, energy, glucose and lipid homeostasis. Meta-analyses showed that hypoadiponectinemia and hyperresistinemia are strongly associated with increased risk of insulin resistance, type 2 diabetes (T2DM, metabolic syndrome (MS and cardiovascular disease. The aim of this study was to propose a novel adiponectin-resistin (AR index by taking into account both adiponectin and resistin levels to povide a better indicator of the metabolic homeostasis and metabolic disorders. In addition, a novel insulin resistance (IRAR index was proposed by integration of the AR index into an existing insulin resistance index to provide an improved diagnostic biomarker of insulin sensitivity. Methods In this case control study, anthropometric clinical and metabolic parameters including fasting serum total adiponectin and resistin levels were determined in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS whose ages ranged between 40-70 years old. Significant differences in continuous variables among subject groups were confirmed by ANCOVA or MANCOVA test using 1,000 stratified bootstrap samples with bias corrected and accelerated (BCa 95% CI. Spearman's rho rank correlation test was used to test the correlation between two variables. Results The AR index was formulated as 1+log10(R0-log10(A0. The AR index was more strongly associated with increased risk of T2DM and MS than hypoadiponectinemia and hyperresistinemia alone. The AR index was more strongly correlated with the insulin resistance indexes and key metabolic endpoints of T2DM and MS than adiponectin and resistin levels alone. The AR index was also correlated with a higher number of MS components than adiponectin and resistin levels alone. The IRAR index was formulated as log10(I0G0+log10(I0G0log10(R0/A0. The normal reference range of the IRAR index for insulin sensitive individuals was

  14. Serum zonulin is elevated in women with polycystic ovary syndrome and correlates with insulin resistance and severity of anovulation.

    Science.gov (United States)

    Zhang, Dongmei; Zhang, Li; Yue, Fangzhi; Zheng, Yingying; Russell, Ryan

    2015-01-01

    Evidence suggests that increased gut permeability may be associated with polycystic ovary syndrome (PCOS). Human zonulin is currently the only physiological mediator known to reversibly regulate gut permeability by disassembling intestinal tight junctions. So far, no data on serum zonulin levels in patients with PCOS are available. This study aimed to determine circulating serum zonulin levels in women with PCOS and discuss the relationship between zonulin, insulin resistance, and menstrual disorders in this group. A case-control study. The study includes 78 women recently diagnosed with PCOS and 63 age-matched healthy controls recruited. Serum zonulin levels were determined by ELISA. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda and DeFronzo's insulin sensitivity index (ISI). PCOS women had higher serum zonulin levels (P=0.022). After adjustment for age and BMI, zonulin levels significantly correlated with HOMA-IR and ISI. Furthermore, PCOS women with more severe menstrual disorders had significantly higher zonulin levels and displayed an inverse correlation between zonulin and the number of menstrual cycles per year (r=-0.398, Pzonulin, a biomarker for gut permeability, is increased in PCOS women and correlates with insulin resistance and severity of menstrual disorders. It suggests that alterations in gut permeability may play a role in the pathophysiology of PCOS, and serum zonulin might be used as a biomarker for both risk stratification and therapeutic outcomes in PCOS women. © 2015 European Society of Endocrinology.

  15. Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yan-Jie [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Juan, Chi-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Kwok, Ching-Fai [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hsu, Yung-Pei [Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Shih, Kuang-Chung [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Chen, Chin-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Ho, Low-Tone, E-mail: ltho@vghtpe.gov.tw [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China)

    2015-05-08

    Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET{sub A}R during insulin resistance, ET{sub A}R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET{sub A}R expression, but not ET{sub B}R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET{sub A}R pathway

  16. Insulin resistance in obesity as the underlying cause for the metabolic syndrome.

    Science.gov (United States)

    Gallagher, Emily J; Leroith, Derek; Karnieli, Eddy

    2010-01-01

    The metabolic syndrome affects more than a third of the US population, predisposing to the development of type 2 diabetes and cardiovascular disease. The 2009 consensus statement from the International Diabetes Federation, American Heart Association, World Heart Federation, International Atherosclerosis Society, International Association for the Study of Obesity, and the National Heart, Lung, and Blood Institute defines the metabolic syndrome as 3 of the following elements: abdominal obesity, elevated blood pressure, elevated triglycerides, low high-density lipoprotein cholesterol, and hyperglycemia. Many factors contribute to this syndrome, including decreased physical activity, genetic predisposition, chronic inflammation, free fatty acids, and mitochondrial dysfunction. Insulin resistance appears to be the common link between these elements, obesity and the metabolic syndrome. In normal circumstances, insulin stimulates glucose uptake into skeletal muscle, inhibits hepatic gluconeogenesis, and decreases adipose-tissue lipolysis and hepatic production of very-low-density lipoproteins. Insulin signaling in the brain decreases appetite and prevents glucose production by the liver through neuronal signals from the hypothalamus. Insulin resistance, in contrast, leads to the release of free fatty acids from adipose tissue, increased hepatic production of very-low-density lipoproteins and decreased high-density lipoproteins. Increased production of free fatty acids, inflammatory cytokines, and adipokines and mitochondrial dysfunction contribute to impaired insulin signaling, decreased skeletal muscle glucose uptake, increased hepatic gluconeogenesis, and β cell dysfunction, leading to hyperglycemia. In addition, insulin resistance leads to the development of hypertension by impairing vasodilation induced by nitric oxide. In this review, we discuss normal insulin signaling and the mechanisms by which insulin resistance contributes to the development of the metabolic

  17. The incidence of metabolic syndrome in obese Czech children: the importance of early detection of insulin resistance using homeostatic indexes HOMA-IR and QUICKI.

    Science.gov (United States)

    Pastucha, D; Filipčíková, R; Horáková, D; Radová, L; Marinov, Z; Malinčíková, J; Kocvrlich, M; Horák, S; Bezdičková, M; Dobiáš, M

    2013-01-01

    Common alimentary obesity frequently occurs on a polygenic basis as a typical lifestyle disorder in the developed countries. It is associated with characteristic complex metabolic changes, which are the cornerstones for future metabolic syndrome development. The aims of our study were 1) to determine the incidence of metabolic syndrome (based on the diagnostic criteria defined by the International Diabetes Federation for children and adolescents) in Czech obese children, 2) to evaluate the incidence of insulin resistance according to HOMA-IR and QUICKI homeostatic indexes in obese children with and without metabolic syndrome, and 3) to consider the diagnostic value of these indexes for the early detection of metabolic syndrome in obese children. We therefore performed anthropometric and laboratory examinations to determine the incidence of metabolic syndrome and insulin resistance in the group of 274 children with obesity (128 boys and 146 girls) aged 9-17 years. Metabolic syndrome was found in 102 subjects (37 %). On the other hand, the presence of insulin resistance according to QUICKI HOMA-IR >3.16 in 53 % of obese subjects. This HOMA-IR limit was exceeded by 70 % children in the MS(+) group, but only by 43 % children in the MS(-) group (p<0.0001). However, a relatively high incidence of insulin resistance in obese children without metabolic syndrome raises a question whether the existing diagnostic criteria do not falsely exclude some cases of metabolic syndrome. On the basis of our results we suggest to pay a preventive attention also to obese children with insulin resistance even if they do not fulfill the actual diagnostic criteria for metabolic syndrome.

  18. Prevalence and clinical profile of insulin resistance in young women of poly cystic ovary syndrome: A study from Pakistan.

    Science.gov (United States)

    Tabassum, Rumina; Imtiaz, Fouzia; Sharafat, Shaheen; Shukar-Ud-Din, Shazia; Nusrat, Uzma

    2013-04-01

    The aim was to estimate the prevalence of Insulin Resistance (IR) in Poly Cystic Ovary Syndrome (PCOS) and analyze its clinical parameters. This observational study was conducted at Dow University Hospital during June 2011 till May 2012. Patients of PCOS were selected, an anthropometric measurement, examination and fasting blood test for sugar (FBS) and insulin was performed. Data was collected on pre designed questionnaire, was analyzed by SPSS version 16. Forty-six cases of PCOS were included in the study. Prevalence of IR was 34.78%. Mean age of patients was 23.72 ± 4.37 years. Waist Hip Ratio (WHR) was raised in 42 (91.30%), acanthosis was found in 26(56.50%), impaired FBS was seen in 9 (19.6%) and raised fasting insulin in 16 (34.8%) patients. There was significant association between acanthosis and WHR (0.044) and between acanthosis and FBS (0.008). Correlation studies between parameters showed a significant correlation between Waist & Hips (0.93), similarly Waist & WHR showed positive correlation (0.59), at p< 0.01. Significant positive correlation was also found between waist and FBS (0.32) and FBS & WHR (0.378). Acanthosis nigrican, raised WHR and FBS are significant parameters for insulin resistance in cases of Poly Cystic Ovary Syndrome (PCOS).

  19. Insulin resistance determined by Homeostasis Model Assessment (HOMA) and associations with metabolic syndrome among Chinese children and teenagers.

    Science.gov (United States)

    Yin, Jinhua; Li, Ming; Xu, Lu; Wang, Ying; Cheng, Hong; Zhao, Xiaoyuan; Mi, Jie

    2013-11-15

    The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among Chinese children and adolescents. Moreover, to determine the cut-off values for homeostasis model assessment of insulin resistance (HOMA-IR) at MS risk. 3203 Chinese children aged 6 to 18 years were recruited. Anthropometric and biochemical parameters were measured. Metabolic syndrome (MS) was identified by a modified Adult Treatment Panel III (ATP III) definition. HOMA-IR index was calculated and the normal reference ranges were defined from the healthy participants. Receiver operating characteristic (ROC) analysis was used to find the optimal cutoff of HOMA-IR for diagnosis of MS. With the increase of insulin resistance (quintile of HOMA-IR value), the ORs of suffering MS or its related components were significantly increased. Participants in the highest quintile of HOMA-IR were about 60 times more likely to be classified with metabolic syndrome than those in the lowest quintile group. Similarly, the mean values of insulin and HOMA-IR increased with the number of MS components. The present HOMA-IR cutoff point corresponding to the 95th percentile of our healthy reference children was 3.0 for whole participants, 2.6 for children in prepubertal stage and 3.2 in pubertal period, respectively. The optimal point for diagnosis of MS was 2.3 in total participants, 1.7 in prepubertal children and 2.6 in pubertal adolescents, respectively, by ROC curve, which yielded high sensitivity and moderate specificity for a screening test. According to HOMA-IR > 3.0, the prevalence of insulin resistance in obese or MS children were 44.3% and 61.6% respectively. Our data indicates insulin resistance is common among Chinese obese children and adolescents, and is strongly related to MS risk, therefore requiring consideration early in life. As a reliable measure of insulin resistance and assessment of MS risk, the optimal HOMA-IR cut

  20. IGF-1 receptor haploinsufficiency leads to age-dependent development of metabolic syndrome.

    Science.gov (United States)

    Thakur, Sachin; Garg, Neha; Zhang, Ning; Hussey, Sophie E; Musi, Nicolas; Adamo, Martin L

    2017-05-13

    Individuals born small for gestational age (SGA) are at a higher risk of developing the metabolic syndrome later in life. IGF-1 resistance has been reported in placentae from SGA births and mutations in the Igf1 receptor gene have been reported in several cohorts of SGA subjects. We have used the Igf1r heterozygous (Igf1r +/- ) male mouse as a model to investigate the mechanisms by which Igf1r haploinsufficiency leads to insulin resistance. Despite exhibiting IGF-1 resistance, insulin signaling is enhanced in young Igf1r +/- mice but is attenuated in the muscle of old Igf1r +/- mice. Although smaller than WT (wild type) mice, old-aged Igf1r +/- had increased adiposity and exhibit increased lipogenesis. We hypothesize that IGF-1 resistance initially causes a transient increase in insulin signaling thereby promoting a lipogenic phenotype, which subsequently leads to insulin resistance. Copyright © 2017. Published by Elsevier Inc.

  1. The effects of insulin sensitizers on the cardiovascular risk factors in women with polycystic ovary syndrome.

    Science.gov (United States)

    Kassi, E; Diamanti-Kandarakis, E

    2008-12-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in pre-menopausal women characterized by menstrual cycle disturbances, chronic anovulation, and clinical and/or biochemical hyperandrogenism. Although, the primary etiology of PCOS remains unknown, insulin resistance/hyperinsulinemia plays a pivotal role in the pathogenesis of the syndrome. A growing body of recent data support that women with PCOS have displayed an increased prevelance of cardiovascular disease (CVD) risk factors putting potentially at a hight risk for heart disease. Most of these CVD risk factors are etiologically correlated with insulin resistance/hyperinsulinemia, highlighting the role of insulin sensitizers in the therapeutic quiver for the chronic treatment of PCOS. In this review, we discuss the current literature on the CVD risk factors in PCOS and the influence of insulin sensitizers upon these risk factors.

  2. Insulin Signaling, Resistance, and the Metabolic Syndrome: Insights from Mouse Models to Disease Mechanisms

    Science.gov (United States)

    Guo, Shaodong

    2014-01-01

    Insulin resistance is a major underlying mechanism for the “metabolic syndrome”, which is also known as insulin resistance syndrome. Metabolic syndrome is increasing at an alarming rate, becoming a major public and clinical problem worldwide. Metabolic syndrome is represented by a group of interrelated disorders, including obesity, hyperglycemia, hyperlipidemia, and hypertension. It is also a significant risk factor for cardiovascular disease and increased morbidity and mortality. Animal studies demonstrate that insulin and its signaling cascade normally control cell growth, metabolism and survival through activation of mitogen-activated protein kinases (MAPKs) and phosphotidylinositide-3-kinase (PI3K), of which activation of PI-3K-associated with insulin receptor substrate-1 and -2 (IRS1, 2) and subsequent Akt→Foxo1 phosphorylation cascade has a central role in control of nutrient homeostasis and organ survival. Inactivation of Akt and activation of Foxo1, through suppression IRS1 and IRS2 in different organs following hyperinsulinemia, metabolic inflammation, and over nutrition may provide the underlying mechanisms for metabolic syndrome in humans. Targeting the IRS→Akt→Foxo1 signaling cascade will likely provide a strategy for therapeutic intervention in the treatment of type 2 diabetes and its complications. This review discusses the basis of insulin signaling, insulin resistance in different mouse models, and how a deficiency of insulin signaling components in different organs contributes to the feature of the metabolic syndrome. Emphasis will be placed on the role of IRS1, IRS2, and associated signaling pathways that couple to Akt and the forkhead/winged helix transcription factor Foxo1. PMID:24281010

  3. Ghrelin receptor null mice have reduced visceral fat and improved insulin sensitivity during aging

    Science.gov (United States)

    Aging is associated with a higher incidence of Type 2 diabetes; one in five Americans over age 65 has diabetes. Loss of lean mass and accumulation of fat, particularly visceral fat, during aging result in increased insulin resistance. Insulin resistance is a major pathogenic factor for Type 2 diabet...

  4. Understanding and managing disturbances in insulin metabolism and body weight in women with polycystic ovary syndrome.

    Science.gov (United States)

    Moran, L; Norman, R J

    2004-10-01

    Polycystic ovary syndrome (PCOS) is a common clinical and metabolic condition in women of reproductive age. It is associated with short-term reproductive and long-term metabolic dysfunction. Treatment has traditionally focused on fertility and hormonal therapy. However, general obesity, central obesity and insulin resistance are strongly implicated in its aetiology and improving these factors has proved highly successful in some clinical situations, reducing the need for costly assisted reproduction. A low-fat, high-carbohydrate diet is thought to improve insulin sensitivity, aid in weight loss and reduction of metabolic and reproductive symptoms and improve the long-term maintenance of a reduced weight. However, there has been recent community interest in adopting a protocol advocating a moderate increase in dietary protein for improving weight loss and PCOS symptoms. Altering the glycaemic index of the diet has also received considerable attention as a regime for promoting satiety and reducing metabolic risk factors for type 2 diabetes mellitus and cardiovascular disease. Exercise and other lifestyle changes are essential for altering the short- and long-term effects of PCOS. It is vital that the efficacy of these strategies is assessed so that accurate medical and dietetic advice can be given both to patients and to the health-care community.

  5. A Cross-Sectional Study of the Phenotypes of Obesity and Insulin Resistance in Adults with Down Syndrome

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    Diego Real de Asua

    2014-12-01

    Full Text Available BackgroundDespite the confluence of multiple cardiovascular risk factors, subclinical atherosclerotic damage and cardiovascular events remain extremely rare in adults with Down syndrome (DS. We aim to determine the prevalence of obesity and metabolic disorders in an adult cohort with DS and to compare our findings with adults without DS.MethodsCross-sectional study of 51 consecutively selected adults with DS living in the community and 51 healthy controls in an outpatient clinic of a tertiary care hospital in Madrid, Spain. Epidemiological data (age and gender, anthropometric data (body mass index and waist-to-height ratio, coexisting clinical conditions, and laboratory data (fasting glucose, insulin, glycated hemoglobin, creatinine, thyroid hormones, vitamins, and lipid profile were measured and compared between the groups.ResultsAdults with DS were significantly younger and more often men with a higher prevalence of overweight and obesity than controls. Their waist-to-height ratio was higher, and they more frequently had abdominal obesity. The results of an analysis adjusted for age and gender revealed no differences in fasting insulin levels, homeostatic model assessment indexes, or lipid profile between adults with DS and controls.ConclusionAdults with DS presented a high prevalence of overweight and obesity. However, we found no differences in lipid profile, prevalence of insulin resistance, or metabolic syndrome between adults with DS and controls.

  6. Effect of meal frequency on glucose and insulin levels in women with polycystic ovary syndrome: a randomised trial.

    Science.gov (United States)

    Papakonstantinou, E; Kechribari, I; Mitrou, P; Trakakis, E; Vassiliadi, D; Georgousopoulou, E; Zampelas, A; Kontogianni, M D; Dimitriadis, G

    2016-05-01

    The aim of the study was to compare the effect of two-meal patterns (three vs six meals per day) on glucose and insulin levels in women with polycystic ovary syndrome (PCOS). In a randomised, crossover, 24-week study, 40 women with PCOS, aged 27±6 years, body mass index 27±6 kg/m(2), followed a weight maintenance diet (% carbohydrates:protein:fat, 40:25:35), consumed either as a three- or a six-meal pattern, with each intervention lasting for 12 weeks. Anthropometric measurements, diet compliance and subjective hunger, satiety and desire to eat were assessed biweekly. All women underwent an oral glucose tolerance test (OGTT) with 75 g glucose for measurement of plasma glucose and insulin at the beginning and end of each intervention. HaemoglobinA1c (HbA1c), blood lipids and hepatic enzymes were measured at the beginning and end of each intervention. Body weight remained stable throughout the study. Six meals decreased significantly fasting insulin (P=0.014) and post-OGTT insulin sensitivity (Matsuda index, P=0.039) vs three meals. After incorporation of individual changes over time, with adjustment for potential confounders, the only variable that remained significant was the Matsuda index, which was then used in multivariate analysis and general linear models. Six meals improved post-OGTT insulin sensitivity independently of age and body weight vs three meals (P=0.012). No significant differences were found between six and three meals for glucose, HbA1c, blood lipids, hepatic enzymes, subjective desire to eat and satiety. Six meals had a more favourable effect on post-OGTT insulin sensitivity in women with PCOS compared with isocaloric three meals.

  7. Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women

    OpenAIRE

    Baldani, Dinka Pavicic; Skrgatic, Lana; Ougouag, Roya

    2015-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity...

  8. Aging in Rare Intellectual Disability Syndromes

    Science.gov (United States)

    Dykens, Elisabeth M.

    2013-01-01

    This review highlights several methodological challenges involved in research on aging, health, and mortality in adults with rare intellectual disability syndromes. Few studies have been performed in this area, with research obstacles that include: the ascertainment of older adults with genetic versus clinical diagnoses; likelihood that adults…

  9. Insulin resistance and endocrine-metabolic abnormalities in polycystic ovarian syndrome: Comparison between obese and non-obese PCOS patients.

    Science.gov (United States)

    Layegh, Parvin; Mousavi, Zohreh; Farrokh Tehrani, Donya; Parizadeh, Seyed Mohammad Reza; Khajedaluee, Mohammad

    2016-04-01

    Insulin resistance has an important role in pathophysiology of polycystic ovarian syndrome (PCOS). Yet there are certain controversies regarding the presence of insulin resistance in non-obese patients. The aim was to compare the insulin resistance and various endocrine and metabolic abnormalities in obese and non-obese PCOS women. In this cross-sectional study which was performed from 2007-2010, 115 PCOS patients, aged 16-45 years were enrolled. Seventy patients were obese (BMI ≥25) and 45 patients were non-obese (BMI 2.3) between two groups (p=0.357). Waist circumference (pPCOS patients. There was no significant difference in total testosterone (p=0.634) and androstenedione (p=0.736) between groups whereas Dehydroepiandrotendione sulfate (DHEAS) was significantly higher in non-obese PCOS women (p=0.018). There was no case of fatty liver and metabolic syndrome in non-obese patients, whereas they were seen in 31.3% and 39.4% of obese PCOS women, respectively. Our study showed that metabolic abnormalities are more prevalent in obese PCOS women, but adrenal axis activity that is reflected in higher levels of DHEAS was more commonly pronounced in our non-obese PCOS patients.

  10. Polycystic ovary syndrome and insulin: our understanding in the past, present and future.

    Science.gov (United States)

    Mayer, Stéphanie B; Evans, William S; Nestler, John E

    2015-03-01

    Insulin resistance is prevalent in women with polycystic ovary syndrome (PCOS), and plays a critical pathophysiologic role in both the metabolic and reproductive complications of PCOS. This review focuses on the contribution of insulin resistance to anovulation in PCOS and to the high risk for Type 2 diabetes, metabolic syndrome and early cardiovasular disease. Key points for clinicians emphasized by this review are the following: PCOS is a clinical diagnosis and alternative diagnoses must be excluded; PCOS carries an inherent risk of insulin resistance and, hence, metabolic consequences for which women with PCOS should be screened regardless of BMI or degree of obesity; and PCOS is associated with infertility and this should be discussed early on in care of women diagnosed with PCOS, recognizing that there are several possible strategies to address infertility in women with PCOS, each with its own risks and benefits.

  11. Associations of Prenatal Growth with Metabolic Syndrome, Insulin Resistance, and Nutritional Status in Chilean Children

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    Francisco Mardones

    2014-01-01

    Full Text Available Introduction. The association of prenatal growth with nutritional status, metabolic syndrome (MS, and insulin resistance (IR was studied in school-age children. Methods. A retrospective cohort study was designed linking present data of children with perinatal records. 3325 subjects were enrolled. Anthropometry, blood pressure (BP, and pubertal status were assessed. Blood lipids, glucose, and insulin were measured. Linear associations were assessed using the Cochran-Armitage test. Odds ratios and nonlinear associations were computed. Results. 3290 children (52% females, mean age of 11.4 ± 1 years were analyzed. Prevalence of obesity, stunting, MS, and IR was 16.0%, 3.6%, 7.3%, and 25.5%, respectively. The strongest positive association was between birth weight (BW and obesity (OR 2.97 (95% CI 2.01–4.40 at BW ≥ 4,000 g compared to BW 2,500–2,999. The strongest inverse association was between birth length (BL and stunting (OR 8.70 (95% CI 3.66–20.67 at BL < 48 cm compared to BL 52-53 cm. A U-shaped association between BL and BP ≥ 90th percentile was observed. Significant ORs were also found for MS and IR. Adjustments for present fat mass increased or maintained the most prenatal growth influences. Conclusions. Prenatal growth influences MS, IR, and nutritional status. Prenatal growth was more important than present body composition in determining these outcomes.

  12. Insulin Resistance and the Polycystic Ovary Syndrome Revisited: An Update on Mechanisms and Implications

    Science.gov (United States)

    Diamanti-Kandarakis, Evanthia

    2012-01-01

    Polycystic ovary syndrome (PCOS) is now recognized as an important metabolic as well as reproductive disorder conferring substantially increased risk for type 2 diabetes. Affected women have marked insulin resistance, independent of obesity. This article summarizes the state of the science since we last reviewed the field in the Endocrine Reviews in 1997. There is general agreement that obese women with PCOS are insulin resistant, but some groups of lean affected women may have normal insulin sensitivity. There is a post-binding defect in receptor signaling likely due to increased receptor and insulin receptor substrate-1 serine phosphorylation that selectively affects metabolic but not mitogenic pathways in classic insulin target tissues and in the ovary. Constitutive activation of serine kinases in the MAPK-ERK pathway may contribute to resistance to insulin's metabolic actions in skeletal muscle. Insulin functions as a co-gonadotropin through its cognate receptor to modulate ovarian steroidogenesis. Genetic disruption of insulin signaling in the brain has indicated that this pathway is important for ovulation and body weight regulation. These insights have been directly translated into a novel therapy for PCOS with insulin-sensitizing drugs. Furthermore, androgens contribute to insulin resistance in PCOS. PCOS may also have developmental origins due to androgen exposure at critical periods or to intrauterine growth restriction. PCOS is a complex genetic disease, and first-degree relatives have reproductive and metabolic phenotypes. Several PCOS genetic susceptibility loci have been mapped and replicated. Some of the same susceptibility genes contribute to disease risk in Chinese and European PCOS populations, suggesting that PCOS is an ancient trait. PMID:23065822

  13. Heart type fatty acid binding protein response and subsequent development of atherosclerosis in insulin resistant polycystic ovary syndrome patients.

    Science.gov (United States)

    Cakir, Evrim; Ozbek, Mustafa; Sahin, Mustafa; Cakal, Erman; Gungunes, Askin; Ginis, Zeynep; Demirci, Taner; Delibasi, Tuncay

    2012-12-18

    Women with polycystic ovary syndrome (PCOS) have higher risk for cardiovascular disease (CVD). Heart type fatty acid binding protein (HFABP) has been found to be predictive for myocardial ischemia.Wet ested whether HFABP is the predictor for CVD in PCOS patients, who have an increased risk of cardiovascular disease. This was a prospective, cross sectional controlled study conducted in a training and research hospital.The study population consisted of 46 reproductive-age PCOS women and 28 control subjects. We evaluated anthropometric and metabolic parameters, carotid intima media thickness and HFABP levels in both PCOS patients and control group. Mean fasting insulin, homeostasis model assessment insulin resistance index (HOMA-IR), triglyceride, total cholesterol, low density lipoprotein cholesterol, free testosterone, total testosterone, carotid intima media thickness (CIMT) levels were significantly higher in PCOS patients. Although HFABP levels were higher in PCOS patients, the difference did not reach statistically significant in early age groups. After adjustment for age and body mass index, HFABP level was positive correlated with hsCRP, free testosterone levels, CIMT and HOMA-IR. Heart type free fatty acid binding protein appeared to have an important role in metabolic response and subsequent development of atherosclerosis in insulin resistant, hyperandrogenemic PCOS patients.

  14. Heart type fatty acid binding protein response and subsequent development of atherosclerosis in insulin resistant polycystic ovary syndrome patients

    Directory of Open Access Journals (Sweden)

    Cakir Evrim

    2012-12-01

    Full Text Available Abstract Background Women with polycystic ovary syndrome (PCOS have higher risk for cardiovascular disease (CVD. Heart type fatty acid binding protein (HFABP has been found to be predictive for myocardial ischemia.Wet ested whether HFABP is the predictor for CVD in PCOS patients, who have an increased risk of cardiovascular disease. Methods This was a prospective, cross sectional controlled study conducted in a training and research hospital.The study population consisted of 46 reproductive-age PCOS women and 28 control subjects. We evaluated anthropometric and metabolic parameters, carotid intima media thickness and HFABP levels in both PCOS patients and control group. Results Mean fasting insulin, homeostasis model assessment insulin resistance index (HOMA-IR, triglyceride, total cholesterol, low density lipoprotein cholesterol, free testosterone, total testosterone, carotid intima media thickness (CIMT levels were significantly higher in PCOS patients. Although HFABP levels were higher in PCOS patients, the difference did not reach statistically significant in early age groups. After adjustment for age and body mass index, HFABP level was positive correlated with hsCRP, free testosterone levels, CIMT and HOMA-IR. Conclusions Heart type free fatty acid binding protein appeared to have an important role in metabolic response and subsequent development of atherosclerosis in insulin resistant, hyperandrogenemic PCOS patients.

  15. Relationship between Serum Lipoprotein Ratios and Insulin Resistance in Polycystic Ovary Syndrome

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    Shou-Kui Xiang

    2012-01-01

    Full Text Available Objective. To investigate the association between serum lipoprotein ratios and insulin resistance in women with polycystic ovarian syndrome (PCOS. Methods. 105 PCOS patients and 109 controls were randomly enrolled in the study. Serum levels of luteinizing hormone (LH, follicle-stimulating hormone (FSH, estradiol (E2, total testosterone (T, fasting glucose (FBG, fasting insulin (FINS, serum triglycerides (TG, total cholesterol (TC, high-density lipoprotein (HDL-C, and low-density lipoprotein (LDL-C levels were checked, and then TG/HDL-C ratio, TC/HDL-C, ratio and LDL-C/HDL-C ratio were calculated. The homeostasis model assessment of insulin resistance (HOMA-IR was used to calculate the insulin resistance. Results. All lipoprotein ratios were significantly higher in PCOS patients as compared to healthy controls (<0.05. TG/HDL-C ratio, TC/HDL-C ratio, and LDL-C/HDL-C ratio were significantly correlated with HOMA-IR (<0.05. The ROC curve demonstrated that TC/HDL-C ratio had higher sensitivity and specificity in diagnosing PCOS with insulin resistance. Conclusion. This study demonstrates that serum lipoprotein ratio significantly correlates with insulin resistance and can be used as the marker of insulin resistance in PCOS patients.

  16. Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

    Science.gov (United States)

    Lauretta, Rosa; Lanzolla, Giulia; Vici, Patrizia; Mariani, Luciano; Moretti, Costanzo

    2016-01-01

    Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis. PMID:27725832

  17. Obese adolescent girls with polycystic ovary syndrome (PCOS) have more severe insulin resistance measured by HOMA-IR score than obese girls without PCOS.

    Science.gov (United States)

    Sawathiparnich, Pairunyar; Weerakulwattana, Linda; Santiprabhob, Jeerunda; Likitmaskul, Supawadee

    2005-11-01

    The prevalence of obesity in Thai children is increasing. These individuals are at increased risks of metabolic syndrome that includes insulin resistance, type 2 diabetes mellitus (T2DM), polycystic ovary syndrome (PCOS), dyslipidemia and hypertension. PCOS has been known to be associated with insulin resistance. To compare the insulin sensitivity between obese adolescent girls with PCOS and those without PCOS. We reviewed demographic and hormonal data of 6 obese adolescent girls with PCOS and compared with 6 age, weight and BMI-matched non-PCOS controls. Each subject underwent an oral glucose tolerance test. Homeostasis model assessment of insulin resistance score (HOMA-IR score) in obese adolescent girls with PCOS was significantly higher than in girls without PCOS with median and range as follows (16.5 [3.8, 21.8] vs. 4.1 [3.3, 6.9], p = 0.04). Our study demonstrates that obese adolescent girls with PCOS have more severe insulin resistance measured by HOMA-IR score than girls without PCOS independent of the degree of obesity. Since insulin resistance is a metabolic precursor of future cardiovascular diseases, obese adolescent girls with PCOS might be at greater risk of developing cardiovascular disease in later adulthood than their non-PCOS counterparts.

  18. Effects of the insulin sensitizer pioglitazone on menstrual irregularity, insulin resistance and hyperandrogenism in young women with polycystic ovary syndrome.

    Science.gov (United States)

    Stabile, Gaspare; Borrielli, Irene; Artenisio, Alfredo Carducci; Bruno, Lucia Maria; Benvenga, Salvatore; Giunta, Loretta; La Marca, Antonio; Volpe, Annibale; Pizzo, Alfonsa

    2014-06-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine cause of menstrual irregularities, hirsutism and acne. Women with PCOS present elevated plasma insulin levels, both fasting and after a glucose load, as an indirect evidence of insulin resistance. PCOS women may also present hypertension, low levels of HDL cholesterol, hypertriglyceridemia, visceral obesity and a higher level of CRP and fibrinogen that can predict an atherosclerotic risk. This study was carried out on 15 young women with PCOS selected according to the 2003 diagnostic criteria of The Rotterdam Consensus Statement and 15 Control women. PCOS women were treated with pioglitazone 30 mg/day and at the beginning and after 6 months of treatment were evaluated: menstrual cycle trend, hirsutism and acne, total cholesterolemia and HDL, triglyceridemia, fibrinogenemia, C-reactive protein, oral glucose tolerance test, glycated hemoglobin, FSH, LH, 17OH-progesterone, 17β-estradiol, free and total testosterone, SHBG, DHEA-S, Δ4-androstenedione and adiponectin. Treatment with pioglitazone improves the irregularities of menses and hirsutism. Six months of treatment modify other parameters linked with a higher risk of type 2 diabetes mellitus and cardiovascular diseases: adiponectin increased with reduction of insulin resistance while fibrinogen and CRP levels decreased. Copyright © 2014 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  19. Activin signaling targeted by insulin/dFOXO regulates aging and muscle proteostasis in Drosophila.

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    Hua Bai

    2013-11-01

    Full Text Available Reduced insulin/IGF signaling increases lifespan in many animals. To understand how insulin/IGF mediates lifespan in Drosophila, we performed chromatin immunoprecipitation-sequencing analysis with the insulin/IGF regulated transcription factor dFOXO in long-lived insulin/IGF signaling genotypes. Dawdle, an Activin ligand, is bound and repressed by dFOXO when reduced insulin/IGF extends lifespan. Reduced Activin signaling improves performance and protein homeostasis in muscles of aged flies. Activin signaling through the Smad binding element inhibits the transcription of Autophagy-specific gene 8a (Atg8a within muscle, a factor controlling the rate of autophagy. Expression of Atg8a within muscle is sufficient to increase lifespan. These data reveal how insulin signaling can regulate aging through control of Activin signaling that in turn controls autophagy, representing a potentially conserved molecular basis for longevity assurance. While reduced Activin within muscle autonomously retards functional aging of this tissue, these effects in muscle also reduce secretion of insulin-like peptides at a distance from the brain. Reduced insulin secretion from the brain may subsequently reinforce longevity assurance through decreased systemic insulin/IGF signaling.

  20. Insulin sensitivity affects corticolimbic brain responses to visual food cues in polycystic ovary syndrome patients.

    Science.gov (United States)

    Alsaadi, Hanin M; Van Vugt, Dean A

    2015-11-01

    This study examined the effect of insulin sensitivity on the responsiveness of appetite regulatory brain regions to visual food cues. Nineteen participants diagnosed with polycystic ovary syndrome (PCOS) were divided into insulin-sensitive (n=8) and insulin-resistant (n=11) groups based on the homeostatic model assessment of insulin resistance (HOMA2-IR). Subjects underwent functional magnetic resonance imaging (fMRI) while viewing food pictures following water or dextrose consumption. The corticolimbic blood oxygen level dependent (BOLD) responses to high-calorie (HC) or low-calorie (LC) food pictures were compared within and between groups. BOLD responses to food pictures were reduced during a glucose challenge in numerous corticolimbic brain regions in insulin-sensitive but not insulin-resistant subjects. Furthermore, the degree of insulin resistance positively correlated with the corticolimbic BOLD response in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate and ventral tegmental area (VTA) in response to HC pictures, and in the dorsolateral prefrontal cortex (DLPFC), mPFC, anterior cingulate, and insula in response to LC pictures following a glucose challenge. BOLD signal in the OFC, midbrain, hippocampus, and amygdala following a glucose challenge correlated with HOMA2-IR in response to HC-LC pictures. We conclude that the normal inhibition of corticolimbic brain responses to food pictures during a glucose challenge is compromised in insulin-resistant subjects. The increase in brain responsiveness to food pictures during postprandial hyperinsulinemia may lead to greater non-homeostatic eating and perpetuate obesity in insulin-resistant subjects.

  1. Dihydrotestosterone deteriorates cardiac insulin signaling and glucose transport in the rat model of polycystic ovary syndrome.

    Science.gov (United States)

    Tepavčević, Snežana; Vojnović Milutinović, Danijela; Macut, Djuro; Žakula, Zorica; Nikolić, Marina; Božić-Antić, Ivana; Romić, Snježana; Bjekić-Macut, Jelica; Matić, Gordana; Korićanac, Goran

    2014-05-01

    It is supposed that women with polycystic ovary syndrome (PCOS) are prone to develop cardiovascular disease as a consequence of multiple risk factors that are mostly related to the state of insulin resistance and consequent hyperinsulinemia. In the present study, we evaluated insulin signaling and glucose transporters (GLUT) in cardiac cells of dihydrotestosterone (DHT) treated female rats as an animal model of PCOS. Expression of proteins involved in cardiac insulin signaling pathways and glucose transporters, as well as their phosphorylation or intracellular localization were studied by Western blot analysis in DHT-treated and control rats. Treatment with DHT resulted in increased body mass, absolute mass of the heart, elevated plasma insulin concentration, dyslipidemia and insulin resistance. At the molecular level, DHT treatment did not change protein expression of cardiac insulin receptor and insulin receptor substrate 1, while phosphorylation of the substrate at serine 307 was increased. Unexpectedly, although expression of downstream Akt kinase and its phosphorylation at threonine 308 were not altered, phosphorylation of Akt at serine 473 was increased in the heart of DHT-treated rats. In contrast, expression and phosphorylation of extracellular signal regulated kinases 1/2 were decreased. Plasma membrane contents of GLUT1 and GLUT4 were decreased, as well as the expression of GLUT4 in cardiac cells at the end of androgen treatment. The obtained results provide evidence for alterations in expression and especially in functional characteristics of insulin signaling molecules and glucose transporters in the heart of DHT-treated rats with PCOS, indicating impaired cardiac insulin action. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Relationship between serum insulin level and age and sex in 980 patients with essential hypertension

    International Nuclear Information System (INIS)

    Cai Jianlin; Ji Naijun; Mei Yubin; Wang Chengyao; Fan Bifu; Chen Donghai; Guan Li; Tong Lijun; Li Fuyuan; Gao Meiying

    2004-01-01

    Objective: To investigate the change of serum insulin level in essential hypertension patients and its relationship with age and sex. Methods: The levels of serum insulin were determined with radioimmunoassay in 980 essential hypertension patients and 120 controls. Results: The levels of serum insulin in the essential hypertension patients were significantly higher than those in the controls (t=4.280, P<0.01). However, there were no significant differences among the levels in different sex and age groups. The same held true for women before and after menopause as well as different stages of hypertension. Conclusion: The average serum insulin level in EH patients was significantly higher than the level in controls, and had positive correlation to mean arterial pressure. But no significant differences were found among different sex and age groups, so serum insulin could be a new independent risk factor of essential hypertension

  3. Metabolic syndrome criteria as predictors of insulin resistance, inflammation and mortality in chronic hemodialysis patients.

    Science.gov (United States)

    Vogt, Barbara Perez; Souza, Priscilla L; Minicucci, Marcos Ferreira; Martin, Luis Cuadrado; Barretti, Pasqual; Caramori, Jacqueline Teixeira

    2014-10-01

    Abstract Background: Chronic kidney disease (CKD) and metabolic syndrome are characterized by overlapping disorders, including glucose intolerance, hypertension, dyslipidemia, and, in some cases, obesity. However, there are no specific criteria for the diagnosis of metabolic syndrome in CKD. Metabolic syndrome can also be associated with increased risk of mortality. Some traditional risk factors may protect dialysis patients from mortality, known as "reverse epidemiology." Metabolic syndrome might undergo reverse epidemiology. The objectives were to detect differences in frequency and metabolic characteristics associated with three sets of diagnostic criteria for metabolic syndrome, to evaluate the accuracy of insulin resistance (IR) and inflammation to identify patients with metabolic syndrome, and to investigate the effects of metabolic syndrome by three sets of diagnostic criteria on mortality in chronic hemodialysis patients. An observational study was conducted. Diagnostic criteria for metabolic syndrome proposed by National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), International Diabetes Federation (IDF), and Harmonizing the Metabolic Syndrome (HMetS) statement were applied to 98 hemodialysis patients. The prevalence of metabolic syndrome was 51%, 66.3%, and 75.3% according to NCEP ATP III, IDF, and HMetS criteria, respectively. Diagnosis of metabolic syndrome by HMetS was simultaneously capable of revealing both inflammation and IR, whereas NCEP ATP III and IDF criteria were only able to identify IR. Mortality risk increased in the presence of metabolic syndrome regardless of the criteria used. The prevalence of metabolic syndrome in hemodialysis varies according to the diagnostic criteria used. IR and inflammation predict metabolic syndrome only when diagnosed by HMetS criteria. HMetS was the diagnostic criteria that can predict the highest risk of mortality.

  4. Brain Insulin Administration Triggers Distinct Cognitive and Neurotrophic Responses in Young and Aged Rats.

    Science.gov (United States)

    Haas, Clarissa B; Kalinine, Eduardo; Zimmer, Eduardo R; Hansel, Gisele; Brochier, Andressa W; Oses, Jean P; Portela, Luis V; Muller, Alexandre P

    2016-11-01

    Aging is a major risk factor for cognitive deficits and neurodegenerative disorders, and impaired brain insulin receptor (IR) signaling is mechanistically linked to these abnormalities. The main goal of this study was to investigate whether brain insulin infusions improve spatial memory in aged and young rats. Aged (24 months) and young (4 months) male Wistar rats were intracerebroventricularly injected with insulin (20 mU) or vehicle for five consecutive days. The animals were then assessed for spatial memory using a Morris water maze. Insulin increased memory performance in young rats, but not in aged rats. Thus, we searched for cellular and molecular mechanisms that might account for this distinct memory response. In contrast with our expectation, insulin treatment increased the proliferative activity in aged rats, but not in young rats, implying that neurogenesis-related effects do not explain the lack of insulin effects on memory in aged rats. Furthermore, the expression levels of the IR and downstream signaling proteins such as GSK3-β, mTOR, and presynaptic protein synaptophysin were increased in aged rats in response to insulin. Interestingly, insulin treatment increased the expression of the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) receptors in the hippocampus of young rats, but not of aged rats. Our data therefore indicate that aged rats can have normal IR downstream protein expression but failed to mount a BDNF response after challenge in a spatial memory test. In contrast, young rats showed insulin-mediated TrkB/BDNF response, which paralleled with improved memory performance.

  5. HOMA1-IR and HOMA2-IR indexes in identifying insulin resistance and metabolic syndrome - Brazilian Metabolic Syndrome Study (BRAMS)

    OpenAIRE

    Geloneze, B; Vasques, ACJ; Stabe, CFC; Pareja, JC; Rosado, LEFPD; de Queiroz, EC; Tambascia, MA

    2009-01-01

    Objective: To investigate cut-off values for HOMA1-IR and HOMA2-IR to identify insulin resistance (IR) and metabolic syndrome (MS), and to assess the association of the indexes with components of the MS. Methods: Nondiabetic subjects from the Brazilian Metabolic Syndrome Study were studied (n = 1,203, 18 to 78 years). The cut-off values for IR were determined from the 9011 percentile in the healthy group (n = 297) and, for MS, a ROC curve was generated for the total sample. Results: In the he...

  6. Insulin

    Science.gov (United States)

    ... For Consumers Home For Consumers Consumer Information by Audience For Women Women's Health Topics Insulin Share Tweet ... I start having side effects? What is my target blood sugar level? How often should I check ...

  7. Associations of vitamin D with insulin resistance, obesity, type 2 diabetes, and metabolic syndrome.

    Science.gov (United States)

    Wimalawansa, Sunil J

    2018-01-01

    The aim of this study is to determine the relationships of vitamin D with diabetes, insulin resistance obesity, and metabolic syndrome. Intra cellular vitamin D receptors and the 1-α hydroxylase enzyme are distributed ubiquitously in all tissues suggesting a multitude of functions of vitamin D. It plays an indirect but an important role in carbohydrate and lipid metabolism as reflected by its association with type 2 diabetes (T2D), metabolic syndrome, insulin secretion, insulin resistance, polycystic ovarian syndrome, and obesity. Peer-reviewed papers, related to the topic were extracted using key words, from PubMed, Medline, and other research databases. Correlations of vitamin D with diabetes, insulin resistance and metabolic syndrome were examined for this evidence-based review. In addition to the well-studied musculoskeletal effects, vitamin D decreases the insulin resistance, severity of T2D, prediabetes, metabolic syndrome, inflammation, and autoimmunity. Vitamin D exerts autocrine and paracrine effects such as direct intra-cellular effects via its receptors and the local production of 1,25(OH) 2 D 3 , especially in muscle and pancreatic β-cells. It also regulates calcium homeostasis and calcium flux through cell membranes, and activation of a cascade of key enzymes and cofactors associated with metabolic pathways. Cross-sectional, observational, and ecological studies reported inverse correlations between vitamin D status with hyperglycemia and glycemic control in patients with T2D, decrease the rate of conversion of prediabetes to diabetes, and obesity. However, no firm conclusions can be drawn from current studies, because (A) studies were underpowered; (B) few were designed for glycemic outcomes, (C) the minimum (or median) serum 25(OH) D levels achieved are not measured or reported; (D) most did not report the use of diabetes medications; (E) some trials used too little (F) others used too large, unphysiological and infrequent doses of vitamin D; and

  8. Effect of Ursolic Acid on Metabolic Syndrome, Insulin Sensitivity, and Inflammation.

    Science.gov (United States)

    Ramírez-Rodríguez, Alejandra M; González-Ortiz, Manuel; Martínez-Abundis, Esperanza; Acuña Ortega, Natalhie

    2017-09-01

    To evaluate the effect of ursolic acid on metabolic syndrome, insulin sensitivity, and inflammation, a randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients (30-60 years) with a diagnosis of metabolic syndrome without treatment. They were randomly assigned to two groups of 12 patients, each to receive orally 150 mg of ursolic acid or homologated placebo once a day for 12 weeks. Before and after the intervention, the components of metabolic syndrome, insulin sensitivity (Matsuda index), and inflammation profile (interleukin-6 and C-reactive protein) were evaluated. After ursolic acid administration, the remission of metabolic syndrome occurred in 50% of patients (P = .005) with significant differences in body weight (75.7 ± 11.5 vs. 71 ± 11 kg, P = .002), body mass index (BMI) (29.9 + 3.6 vs. 24.9 ± 1.2 kg/m 2 , P = .049), waist circumference (93 ± 8.9 vs. 83 + 8.6 cm, P = .008), fasting glucose (6.0 ± 0.5 vs. 4.7 ± 0.4 mmol/L, P = .002), and insulin sensitivity (3.1 ± 1.1 vs. 4.2 ± 1.2, P = .003). Ursolic acid administration leads to transient remission of metabolic syndrome, reducing body weight, BMI, waist circumference and fasting glucose, as well as increasing insulin sensitivity.

  9. Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance.

    Science.gov (United States)

    Castellano, Christian-Alexandre; Baillargeon, Jean-Patrice; Nugent, Scott; Tremblay, Sébastien; Fortier, Mélanie; Imbeault, Hélène; Duval, Julie; Cunnane, Stephen C

    2015-01-01

    To investigate whether cerebral metabolic rate of glucose (CMRglu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance. Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function. The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group. The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

  10. Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance.

    Directory of Open Access Journals (Sweden)

    Christian-Alexandre Castellano

    Full Text Available To investigate whether cerebral metabolic rate of glucose (CMRglu is altered in normal weight young women with polycystic ovary syndrome (PCOS who exhibit mild insulin resistance.Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR. A battery of cognitive tests was administered to evaluate working memory, attention and executive function.The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035 compared to the Controls. The PCOS group had 9-14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018. A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05. Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group.The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer's disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted.

  11. Association of PPARG Pro12Ala polymorphism with insulin sensitivity and body mass index in patients with polycystic ovary syndrome.

    Science.gov (United States)

    Baldani, Dinka Pavicic; Skrgatic, Lana; Cerne, Jasmina Z; Ferk, Polonca; Simunic, Velimir; Gersak, Ksenija

    2014-03-01

    Insulin resistance is one of the key factors in the pathogenesis of polycystic ovary syndrome (PCOS). The peroxisome proliferator-activated receptor gamma (PPARG) plays a role in the regulation of insulin sensitivity. The aim of the present study was to establish a possible association of the PPARG Pro12Ala polymorphism with PCOS and its effect on family and personal history, as well as on the metabolic and endocrine parameters in PCOS patients. A total of 151 PCOS patients and 179 healthy women of reproductive age were enrolled. History, body mass index (BMI), waist-to-hip ratio and the presence of phenotypic hyperandrogenism were recorded. Hormonal, metabolic and biochemical profiles were assessed. A molecular analysis for the genetic polymorphism was performed. One third (29.8%) of the PCOS patients were found to be carriers of at least one variant of the Ala allele (X/Ala), while 70.2% carried two wild-type Pro alleles (Pro/Pro), with an equal distribution observed in the control group. The PCOS patients carrying the X/Ala alleles exhibited lower serum fasting insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR) and BMI compared to Pro/Pro carriers. This finding was significant only in the lean PCOS group. The polymorphic genotype exerted no effect on history, hormonal and clinical hyperandrogenism, lipid status or C-reactive protein, leptin, adiponectin, resistin and ghrelin serum levels in women with PCOS. In conclusion, although the PPARG Pro12Ala polymorphism is not a major determinant of PCOS in the Croatian population, it may exert a positive effect on insulin sensitivity and BMI. As these associations were recorded exclusively in the lean group of patients with PCOS, this polymorphism potentially contributes to a protective role against hyperinsulinemia and obesity.

  12. Correlation of Serum Lipoprotein Ratios with Insulin Resistance in Infertile Women with Polycystic Ovarian Syndrome: A Case Control Study.

    Science.gov (United States)

    Ghaffarzad, Aisa; Amani, Reza; Mehrzad Sadaghiani, Mahzad; Darabi, Masoud; Cheraghian, Bahman

    2016-01-01

    Dyslipidemia and insulin resistance (IR), occurring in most infertile women with polycystic ovarian syndrome (PCOS), increase the risk of cardiovascular disease (CVD) and type 2 diabetes. This study aimed to assess the relationships between lipoprotein ratios and IR in PCOS women. Thirty six infertile women with PCOS selected based on Androgen Excess Society (AES) criteria and 29 healthy women matched for age were recruited to this case-control study. After physical measurements, fasting serum glucose (Glu), insulin and lipid profile levels [triglycerides (TGs), total cholesterol (TC), low-density lipoproteincholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C)] were measured, while lipoprotein ratios (TC/HDL-C, LDL-C/HDL-C, TG/HDL-C) were calculated. IR was also calculated using homeostasis model assessment (HOMA)-IR. The optimal cutoffs of lipoprotein ratios in relation to HOMA-IR were calculated based on the Receiver Operating Characteristics (ROC) curve analysis using the area under curve (AUC). Waist circumference (WC), insulin levels, HOMA-IR, TG levels, and all lipoprotein ratios were significantly higher, while HDL-C was lower in PCOS group as compared to healthy controls. All lipoprotein ratios, TG levels, and WC are significantly correlated with insulin levels and HOMA-IR. Among lipoprotein ratios, the highest AUC of the ROC belonged to TG/HDL-C ratio with sensitivity of 63.6% and specificity of 84.4% (TG/HDL-C>3.19) as a marker of IR in infertile PCOS women. Lipoprotein ratios, particularly TG/HDL-C, are directly correlated with insulin levels and can be used as a marker of IR (HOMA-IR) in infertile PCOS patients.

  13. Glucose intolerance, insulin resistance and cardiovascular risk factors in first degree relatives of women with polycystic ovary syndrome.

    Science.gov (United States)

    Yilmaz, Murat; Bukan, Neslihan; Ersoy, Reyhan; Karakoç, Ayhan; Yetkin, Ilhan; Ayvaz, Göksun; Cakir, Nuri; Arslan, Metin

    2005-09-01

    The aim of the present study was to evaluate insulin resistance (IR), glucose tolerance status and cardiovascular risk factors in first degree relatives of patients with polycystic ovary syndrome (PCOS). A total of 120 family members [Mothers(PCOS) (n = 40), Fathers(PCOS) (n = 38), Sisters(PCOS) (n = 25) and Brothers(PCOS) (n = 17)] of 55 patients with PCOS and 75 unrelated healthy control subjects without a family history of diabetes or PCOS (four age- and weight-matched subgroups, i.e. Control(Mothers), Control(Fathers), Control(Sisters) and Control(Brothers)) were studied. IR was assessed by homeostatic model assessment (HOMA IR), log HOMA, insulin sensivity index (ISI), the quantitative insulin sensitivity check index (QUICKI) and area under the curve for insulin during the oral glucose tolerance test (AUCI, AUCG) in with normal glucose tolerance (NGT) subjects and controls. Serum adiponectin, resistin, homocysteine and lipid levels were measured. The prevalence of any degree of glucose intolerance was 40% in Mothers(PCOS) and 52% in Fathers(PCOS). In total, six (15%) glucose tolerance disorders were identified in the Control(Mothers) and Control(Fathers) in first degree relatives of control subjects. The first degree relatives of PCOS patients had significantly higher serum fasting insulin, HOMA-IR, Log HOMA and AUCI levels in all subgroups than the control subjects. The control subjects had significantly elevated QUCKI, ISI levels and serum adiponectin levels compared to the first degree relatives of PCOS subjects in all subgroups. The serum Hcy and resistin levels increased significantly in both Fathers(PCOS) and Mothers(PCOS) groups but not Brothers(PCOS) and Sister(PCOS). The results of the present study support the finding that the first degree relatives of PCOS patients carry an increased risk of cardiovascular disease, as do PCOS patients.

  14. Correlation of Serum Lipoprotein Ratios with Insulin Resistance in Infertile Women with Polycystic Ovarian Syndrome: A Case Control Study

    Directory of Open Access Journals (Sweden)

    Aisa Ghaffarzad

    2016-05-01

    Full Text Available Background: Dyslipidemia and insulin resistance (IR, occurring in most infertile women with polycystic ovarian syndrome (PCOS, increase the risk of cardiovascular disease (CVD and type 2 diabetes. This study aimed to assess the relationships between lipoprotein ratios and IR in PCOS women. Materials and Methods: Thirty six infertile women with PCOS selected based on Androgen Excess Society (AES criteria and 29 healthy women matched for age were recruited to this case-control study. After physical measurements, fasting serum glucose (Glu, insulin and lipid profile levels [triglycerides (TGs, total cholesterol (TC, low-density lipoproteincholesterol (LDL-C and high-density lipoprotein-cholesterol (HDL-C] were measured, while lipoprotein ratios (TC/HDL-C, LDL-C/HDL-C, TG/HDL-C were calculated. IR was also calculated using homeostasis model assessment (HOMA-IR. The optimal cutoffs of lipoprotein ratios in relation to HOMA-IR were calculated based on the Receiver Operating Characteristics (ROC curve analysis using the area under curve (AUC. Results: Waist circumference (WC, insulin levels, HOMA-IR, TG levels, and all lipoprotein ratios were significantly higher, while HDL-C was lower in PCOS group as compared to healthy controls. All lipoprotein ratios, TG levels, and WC are significantly correlated with insulin levels and HOMA-IR. Among lipoprotein ratios, the highest AUC of the ROC belonged to TG/HDL-C ratio with sensitivity of 63.6% and specificity of 84.4% (TG/HDL-C>3.19 as a marker of IR in infert ile PCOS women. Conclusion: Lipoprotein ratios, particularly TG/HDL-C, are directly correlated with insulin levels and can be used as a marker of IR (HOMA-IR in infertile PCOS patients.

  15. Age-related changes in Serum Growth Hormone, Insulin-like Growth Factor-1 and Somatostatin in System Lupus Erythematosus

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    Malemud Charles J

    2004-10-01

    Full Text Available Abstract Background Systemic lupus erythematosus is an age- and gender-associated autoimmune disorder. Previous studies suggested that defects in the hypothalamic/pituitary axis contributed to systemic lupus erythematosus disease progression which could also involve growth hormone, insulin-like growth factor-1 and somatostatin function. This study was designed to compare basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels in female systemic lupus erythematosus patients to a group of normal female subjects. Methods Basal serum growth hormone, insulin-like growth factor-1 and somatostatin levels were measured by standard radioimmunoassay. Results Serum growth hormone levels failed to correlate with age (r2 = 3.03 in the entire group of normal subjects (i.e. 20 – 80 years. In contrast, serum insulin-like growth factor-1 levels were inversely correlated with age (adjusted r2 = 0.092. Of note, serum growth hormone was positively correlated with age (adjusted r2 = 0.269 in the 20 – 46 year range which overlapped with the age range of patients in the systemic lupus erythematosus group. In that regard, serum growth hormone levels were not significantly higher compared to either the entire group of normal subjects (20 – 80 yrs or to normal subjects age-matched to the systemic lupus erythematosus patients. Serum insulin-like growth factor-1 levels were significantly elevated (p 55 yrs systemic lupus erythematosus patients. Conclusions These results indicated that systemic lupus erythematosus was not characterized by a modulation of the growth hormone/insulin-like growth factor-1 paracrine axis when serum samples from systemic lupus erythematosus patients were compared to age- matched normal female subjects. These results in systemic lupus erythematosus differ from those previously reported in other musculoskeletal disorders such as rheumatoid arthritis, osteoarthritis, fibromyalgia, diffuse idiopathic skeletal

  16. Ginseng Berry Extract Supplementation Improves Age-Related Decline of Insulin Signaling in Mice

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    Eunhui Seo

    2015-04-01

    Full Text Available The aim of this study was to evaluate the effects of ginseng berry extract on insulin sensitivity and associated molecular mechanisms in aged mice. C57BL/6 mice (15 months old were maintained on a regular diet (CON or a regular diet supplemented with 0.05% ginseng berry extract (GBD for 24 or 32 weeks. GBD-fed mice showed significantly lower serum insulin levels (p = 0.016 and insulin resistance scores (HOMA-IR (p = 0.012, suggesting that GBD improved insulin sensitivity. Pancreatic islet hypertrophy was also ameliorated in GBD-fed mice (p = 0.007. Protein levels of tyrosine phosphorylated insulin receptor substrate (IRS-1 (p = 0.047, and protein kinase B (AKT (p = 0.037, were up-regulated in the muscle of insulin-injected GBD-fed mice compared with CON-fed mice. The expressions of forkhead box protein O1 (FOXO1 (p = 0.036 and peroxisome proliferator-activated receptor gamma (PPARγ (p = 0.032, which are known as aging- and insulin resistance-related genes, were also increased in the muscle of GBD-fed mice. We conclude that ginseng berry extract consumption might increase activation of IRS-1 and AKT, contributing to the improvement of insulin sensitivity in aged mice.

  17. Insulin resistance and its association with the components of the metabolic syndrome among obese children and adolescents

    OpenAIRE

    Mass-Díaz Eliezer; Madrigal-Azcárate Adrián; Medina-Bravo Patricia; Klünder-Klünder Miguel; Juárez-López Carlos; Flores-Huerta Samuel

    2010-01-01

    Abstract Background Insulin resistance is the primary metabolic disorder associated with obesity; yet little is known about its role as a determinant of the metabolic syndrome in obese children. The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among obese children and adolescents. Methods An analytical, cross-sectional and population-based study was performed in forty-four public primary schools ...

  18. Intranasal insulin to improve developmental delay in children with 22q13 deletion syndrome: an exploratory clinical trial

    OpenAIRE

    Schmidt, Heinrich; Giese, Renate; Enders, Angelika; Kern, W.; Hallschmid, M.

    2009-01-01

    Background: The 22q13 deletion syndrome (Phelan– McDermid syndrome) is characterised by a global developmental delay, absent or delayed speech, generalised hypotonia, autistic behaviour and characteristic phenotypic features. Intranasal insulin has been shown to improve declarative memory in healthy adult subjects and in patients with Alzheimer disease. Aims: To assess if intranasal insulin is also able to improve the developmental delay in children with 22q13 delet...

  19. Infection of growing swine with porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae — Effects on growth, serum metabolites, and insulin-like growth factor-I.

    OpenAIRE

    Roberts, N. Elizabeth; Almond, Glen W.

    2003-01-01

    This study evaluated the influence of concomitant infections with porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae on growth performance, serum metabolite concentrations, and serum insulin-like growth factor-I (IGF-I) in growing pigs. Twenty-two barrows (10 weeks of age) were treated with either an intranasal administration of PRRSV and an intratracheal infusion of M. hyopneumoniae (treatment; n = 8) or a sham inoculation with medium (sham; n = 8), or w...

  20. Zinc and homocysteine levels in polycystic ovarian syndrome patients with insulin resistance.

    Science.gov (United States)

    Guler, Ismail; Himmetoglu, Ozdemir; Turp, Ahmet; Erdem, Ahmet; Erdem, Mehmet; Onan, M Anıl; Taskiran, Cagatay; Taslipinar, Mine Yavuz; Guner, Haldun

    2014-06-01

    In this study, our objective was to evaluating the value of serum zinc levels as an etiologic and prognostic marker in patients with polycystic ovarian syndrome. We conducted a prospective study, including 53 women with polycystic ovarian syndrome and 33 healthy controls. We compared serum zinc levels, as well as clinical and metabolic features, of the cases. We also compared serum zinc levels between patients with polycystic ovarian syndrome with insulin resistance. Mean zinc levels were found to be significantly lower in patients with polycystic ovarian syndrome than healthy controls. Multiple logistic regression analysis of significant metabolic variables between polycystic ovarian syndrome and control groups (serum zinc level, body mass index, the ratio of triglyceride/high-density lipoprotein cholesterol, and homocysteine) revealed that zinc level was the most significant variable to predict polycystic ovarian syndrome. Mean serum zinc levels tended to be lower in patients with polycystic ovarian syndrome with impaired glucose tolerance than patients with normal glucose tolerance, but the difference was not statistically significant. In conclusion, zinc deficiency may play a role in the pathogenesis of polycystic ovarian syndrome and may be related with its long-term metabolic complications.

  1. Ovarian SAHA syndrome is associated with a more insulin-resistant profile and represents an independent risk factor for glucose abnormalities in women with polycystic ovary syndrome: a prospective controlled study.

    Science.gov (United States)

    Dalamaga, Maria; Papadavid, Evangelia; Basios, Georgios; Vaggopoulos, Vassilios; Rigopoulos, Dimitrios; Kassanos, Dimitrios; Trakakis, Eftihios

    2013-12-01

    SAHA syndrome is characterized by the tetrad: seborrhea, acne, hirsutism, and androgenetic alopecia. No previous study has examined the prevalence of glucose abnormalities in ovarian SAHA and explored whether it may be an independent risk factor for glucose abnormalities. In a prospective controlled study, we investigated the spectrum of glucose abnormalities in ovarian SAHA and explored whether it is associated with a more insulin-resistant profile. In all, 316 patients with a diagnosis of polycystic ovary syndrome (PCOS) (56 with SAHA) and 102 age-matched healthy women were examined and underwent a 2-hour oral glucose tolerance test. Serum glucose homeostasis parameters, hormones, and adipokines were determined. SAHA prevalence was 17.7% in patients with PCOS and predominance of the severe PCOS phenotype. Ovarian SAHA was independently associated with a more insulin-resistant profile (higher homeostatic model assessment of insulin resistance score, lower quantitative insulin sensitivity check index [QUICKI] and MATSUDA indices, and relative hypoadiponectinemia), and represented an independent risk factor for glucose abnormalities regardless of anthropometric features, age, and PCOS phenotype. There was no performance of skin biopsies. The prompt recognition of SAHA syndrome in women with PCOS permits an earlier diagnosis and surveillance of metabolic abnormalities, especially in Mediterranean PCOS population exhibiting a lower prevalence of glucose abnormalities. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  2. Insulin resistance according to β-cell function in women with polycystic ovary syndrome and normal glucose tolerance.

    Science.gov (United States)

    Song, Do Kyeong; Hong, Young Sun; Sung, Yeon-Ah; Lee, Hyejin

    2017-01-01

    Polycystic ovary syndrome (PCOS) is associated with insulin resistance (IR) and compensatory hyperinsulinemia. IR is recognized as a major risk factor for the development of type 2 diabetes mellitus. However, few studies have investigated IR in women with PCOS and normal glucose tolerance. The objective of this study was to evaluate IR and β-cell function in women with PCOS and normal glucose tolerance. Additionally, we sought to evaluate the usefulness of oral glucose tolerance test (OGTT)-derived IR indices in lean women with PCOS. We recruited 100 women with PCOS and normal glucose tolerance and 100 age- and BMI-matched women as controls. IR and insulin secretory indices, including the homeostasis-model assessment (HOMA)-IR, HOMA-M120, HOMA-F and the Stumvoll index, were calculated from an OGTT. Increased β-cell function was defined as>75th percentile for the HOMA-F in control women. Women with PCOS had higher values for post-load 2-hour glucose, fasting insulin, post-load 2-hour insulin, HOMA-IR, HOMA-M120, HOMA-F and lower values for the Stumvoll index than the controls (all PsWomen with PCOS and increased β-cell function showed lower Stumvoll index values than the matched controls (Plean women with PCOS (all PsWomen with PCOS and normal glucose tolerance showed higher IR than controls matched for age, BMI, and β-cell function. β-cell function was increased in women with PCOS when compared to the matched controls, but not when the lean subjects were compared to the matched controls separately. Therefore, early evaluation of IR in women with PCOS and normal glucose tolerance may be needed.

  3. Effects of androgens on insulin action in women: is androgen excess a component of female metabolic syndrome?

    Science.gov (United States)

    Corbould, A

    2008-10-01

    Hyperinsulinemia as a consequence of insulin resistance causes hyperandrogenemia in women. The objective was to review evidence for the converse situation, i.e. whether androgens adversely influence insulin action. Androgen excess could potentially contribute to the pathogenesis of insulin resistance in women with polycystic ovary syndrome (PCOS), metabolic syndrome/type 2 diabetes, and in obese peripubertal girls. An Entrez-PubMed search was conducted to identify studies addressing the relationship of androgens with metabolic syndrome/type 2 diabetes in women. Studies reporting outcomes of androgen administration, interventions to reduce androgen effects in hyperandrogenemic women, and basic studies investigating androgen effects on insulin target tissues were reviewed. Multiple studies showed associations between serum testosterone and insulin resistance or metabolic syndrome/type 2 diabetes risk in women, but their cross-sectional nature did not allow conclusions about causality. Androgen administration to healthy women was associated with development of insulin resistance. Intervention studies in women with hyperandrogenism were limited by small subject numbers and use of indirect methods for assessing insulin sensitivity. However, in three of the seven studies using euglycemic hyperinsulinemic clamps, reduction of androgen levels or blockade of androgen action improved insulin sensitivity. Testosterone administration to female rats caused skeletal muscle insulin resistance. Testosterone induced insulin resistance in adipocytes of women in vitro. In conclusion, the metabolic consequences of androgen excess in women have been under-researched. Studies of long-term interventions that lower androgen levels or block androgen effects in young women with hyperandrogenism are needed to determine whether these might protect against metabolic syndrome/type 2 diabetes in later life. Copyright (c) 2008 John Wiley & Sons, Ltd.

  4. The Distribution of Stroma and Antral Follicles Differs between Insulin-Resistance and Hyperandrogenism-Related Polycystic Ovarian Syndrome

    Directory of Open Access Journals (Sweden)

    Carlo Alviggi

    2017-05-01

    Full Text Available IntroductionAlthough insulin resistance plays an important pathogenetic role in polycystic ovary syndrome (PCOS, no correlation between ultrasound PCOS pattern and insulin resistance has yet been reported. The aim of this retrospective observational study was to assess whether the ovarian ultrasonographic parameter differed between PCOS women with insulin resistance and those with a hyperandrogenic profile.Materials and methodsWomen who fulfilled the Rotterdam criteria for PCOS were retrospectively studied. Anthropometric, biochemical, and clinical data were recorded. Women were divided into two groups based on specific transvaginal ultrasound parameters: subjects with more than half of the follicles measuring between 5 and 9 mm in diameter, an ultrasonographic determined stroma/total area (S/A > 0.34 and a “necklace” sign of antral follicles (Group A; and subjects with more than half of the antral follicles measuring between 2 and 4 mm in diameter, an S/A ≤ 0.34; no “necklace” sign but ubiquitously distributed follicles determined by ultrasound (Group B. The association between these ultrasound patterns and the presence of insulin resistance was also evaluated.ResultsSeventy-eight patients were enrolled: 33 with ultrasound sound pattern A and 45 with pattern B. The latter pattern had a sensitivity of 88% and a specificity of 78% in predicting PCOS women with insulin resistance. There were no differences in age, Ferriman–Gallwey score, and serum gonadotropin or androgen levels between the two groups. Body mass index, the waist-to-hip ratio, and homeostasis model assessment were significantly higher in group B than in group A (p < 0.05. Conversely, sex hormone binding globulin levels and ovarian volume were significantly higher in group A (p < 0.05. Insulin resistance was more frequent in group B than in group A (36/41, 87.8% versus 7/32, 21.8%; p < 0.05.ConclusionThese results suggest that insulin resistance

  5. Polycystic Ovary Syndrome, Insulin Resistance, and Obesity: Navigating the Pathophysiologic Labyrinth

    Science.gov (United States)

    Rojas, Joselyn; Chávez, Mervin; Olivar, Luis; Rojas, Milagros; Morillo, Jessenia; Mejías, José; Calvo, María; Bermúdez, Valmore

    2014-01-01

    Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome. PMID:25763405

  6. Polycystic Ovary Syndrome, Insulin Resistance, and Obesity: Navigating the Pathophysiologic Labyrinth

    Directory of Open Access Journals (Sweden)

    Joselyn Rojas

    2014-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR, and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.

  7. Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth.

    Science.gov (United States)

    Rojas, Joselyn; Chávez, Mervin; Olivar, Luis; Rojas, Milagros; Morillo, Jessenia; Mejías, José; Calvo, María; Bermúdez, Valmore

    2014-01-01

    Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.

  8. The brain response to peripheral insulin declines with age: a contribution of the blood-brain barrier?

    Science.gov (United States)

    Sartorius, Tina; Peter, Andreas; Heni, Martin; Maetzler, Walter; Fritsche, Andreas; Häring, Hans-Ulrich; Hennige, Anita M

    2015-01-01

    It is a matter of debate whether impaired insulin action originates from a defect at the neural level or impaired transport of the hormone into the brain. In this study, we aimed to investigate the effect of aging on insulin concentrations in the periphery and the central nervous system as well as its impact on insulin-dependent brain activity. Insulin, glucose and albumin concentrations were determined in 160 paired human serum and cerebrospinal fluid (CSF) samples. Additionally, insulin was applied in young and aged mice by subcutaneous injection or intracerebroventricularly to circumvent the blood-brain barrier. Insulin action and cortical activity were assessed by Western blotting and electrocorticography radiotelemetric measurements. In humans, CSF glucose and insulin concentrations were tightly correlated with the respective serum/plasma concentrations. The CSF/serum ratio for insulin was reduced in older subjects while the CSF/serum ratio for albumin increased with age like for most other proteins. Western blot analysis in murine whole brain lysates revealed impaired phosphorylation of AKT (P-AKT) in aged mice following peripheral insulin stimulation whereas P-AKT was comparable to levels in young mice after intracerebroventricular insulin application. As readout for insulin action in the brain, insulin-mediated cortical brain activity instantly increased in young mice subcutaneously injected with insulin but was significantly reduced and delayed in aged mice during the treatment period. When insulin was applied intracerebroventricularly into aged animals, brain activity was readily improved. This study discloses age-dependent changes in insulin CSF/serum ratios in humans. In the elderly, cerebral insulin resistance might be partially attributed to an impaired transport of insulin into the central nervous system.

  9. Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

    Directory of Open Access Journals (Sweden)

    Hahner Stefanie

    2008-07-01

    Full Text Available Abstract Background Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity. Methods We investigated the role of the -2221Msp(C/T and -23HphI(A/T polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317, Addison's disease (AD, n = 107 or Hashimoto's thyroiditis (HT, n = 61], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62 as well as in healthy controls (HC, n = 275. Results T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T and "AA" -23HphI(A/T polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively. The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion We demonstrate that the allele "C" of the -2221Msp(C/T and "A" -23HphI(A/T insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.

  10. Metabolic consequences of obesity and insulin resistance in polycystic ovary syndrome: diagnostic and methodological challenges.

    Science.gov (United States)

    Jeanes, Yvonne M; Reeves, Sue

    2017-06-01

    Women with polycystic ovary syndrome (PCOS) have a considerable risk of metabolic dysfunction. This review aims to present contemporary knowledge on obesity, insulin resistance and PCOS with emphasis on the diagnostic and methodological challenges encountered in research and clinical practice. Variable diagnostic criteria for PCOS and associated phenotypes are frequently published. Targeted searches were conducted to identify all available data concerning the association of obesity and insulin resistance with PCOS up to September 2016. Articles were considered if they were peer reviewed, in English and included women with PCOS. Obesity is more prevalent in women with PCOS, but studies rarely reported accurate assessments of adiposity, nor split the study population by PCOS phenotypes. Many women with PCOS have insulin resistance, though there is considerable variation reported in part due to not distinguishing subgroups known to have an impact on insulin resistance as well as limited methodology to measure insulin resistance. Inflammatory markers are positively correlated with androgen levels, but detailed interactions need to be identified. Weight management is the primary therapy; specific advice to reduce the glycaemic load of the diet and reduce the intake of pro-inflammatory SFA and advanced glycation endproducts have provided promising results. It is important that women with PCOS are educated about their increased risk of metabolic complications in order to make timely and appropriate lifestyle modifications. Furthermore, well-designed robust studies are needed to evaluate the mechanisms behind the improvements observed with dietary interventions.

  11. The correlation of plasma omentin-1 with insulin resistance in non-obese polycystic ovary syndrome.

    Science.gov (United States)

    Yang, Hai-Yan; Ma, Yan; Lu, Xin-Hong; Liang, Xing-Huan; Suo, Ying-Jun; Huang, Zhen-Xing; Lu, De-Cheng; Qin, Ying-Fen; Luo, Zuo-Jie

    2015-10-01

    Aberrant circulating adipokines are considered to be related to the pathological mechanism of polycystic ovary syndrome (PCOS). This study aims to evaluate the relationship between plasma omentin-1 levels, metabolic and hormonal parameters in the setting of non-obese Chinese women with PCOS. This was a case-controlled, cross-sectional study of 153 non-obese (BMIovary volume were analyzed in all subjects. Plasma omentin-1 levels of non-obese PCOS individuals were significantly lower than in healthy non-obese controls. Body Mass Index (BMI), homeostasis model of assessment for insulin resistance index (HOMA-IR), levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), LH/FSH ratio and ovary volume (OV) were significantly higher in subjects with PCOS than controls. In the HOMA-IR stratified subgroups, PCOS individuals with insulin resistance had lower omentin-1 than those without insulin resistance after BMI adjustment. Omentin-1 was negatively correlated with BMI, HOMA-IR and fasting insulin. Multiple linear regressions revealed that BMI contributed to omentin-1 levels. Ovary volume was negatively correlated to HOMA-IR but had no correlation with omentin-1. Plasma omentin-1 concentrations were decreased in the non-obese PCOS group. Insulin resistance could further decrease plasma omentin-1 in non-obese individuals with PCOS independent of BMI status. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  12. Genetic variation in exon 17 of INSR is associated with insulin resistance and hyperandrogenemia among lean Indian women with polycystic ovary syndrome.

    Science.gov (United States)

    Mukherjee, Srabani; Shaikh, Nuzhat; Khavale, Sushma; Shinde, Gayatri; Meherji, Pervin; Shah, Nalini; Maitra, Anurupa

    2009-05-01

    Polycystic ovary syndrome (PCOS) is a multigenic disorder, and insulin resistance is one of its hallmark features. Polymorphisms in exon 17 of insulin receptor (INSR) gene are reported to be associated with PCOS. We investigated this association in Indian women and its putative relationship with PCOS associated traits, which has not been explored so far. In this case control study, the polymorphisms were investigated by direct sequencing in 180 women with PCOS and 144 age matched controls. Clinical, anthropometric, biochemical, and hormonal parameters were also estimated. The silent C/T polymorphism at His1058 in exon 17 of INSR was found to be present in our study population. The polymorphic genotype (CT+TT) was significantly associated with PCOS in lean women (chi(2)=8.493, df=1, P=0.004). It showed association with higher fasting insulin levels (P=0.02), homeostasis model assessment of insulin resistance (P=0.005), free androgen index (P=0.03), and lower quantitative insulin sensitivity check index (P=0.004) in lean PCOS women. No other novel or known polymorphism was identified in exon 17 in this cohort. The study shows significant association of C/T polymorphism at His1058 of INSR with PCOS in the lean rather than obese Indian women. Its association with indices of insulin resistance and hyperandrogenemia is also seen in the same group. The findings strengthen the concept that pathogenesis of PCOS is different in lean and obese women.

  13. INSULIN LIKE GROWTH FACTOR 1 POSSIBLE DEPENDENCE IN PATIENTS WITH METABOLIC SYNDROME OF NODULAR PATHOLOGY OF THE THYROID GLAND.

    Science.gov (United States)

    Rekvava, M; Dundua, T; Kobulia, M; Javashvili, L; Giorgadze, E

    2017-09-01

    Metabolic syndrome and nodular pathology of the thyroid gland is a widespread problem nowadays. Recently there has been a notable coincidence between metabolic syndrome and nodular pathology of thyroid gland. Hence, it is interesting to reveal the connection between these two diseases. It is possible that insulin-like growth factor system (IGF), namely IGF 1 is connecting link between metabolic syndrome and nodular pathology of thyroid gland, because IGF1 stimulates growth and proliferation of cells in the body. We have investigated18-82 years of age 71 patients. group 1 n27- subjects with thyroid nodular disease, and metabolic syndrome, group 2 n31- subjects with thyroid nodular disease and without metabolic syndrome. group 3 n13 - subjects with metabolic syndrome and no thyroid pathology. In all groups were assessed thyroid structural data, defined parameters of carbohydrate metabolism, thyroid function and blood concentration of IGF1. In patients with hyperinsulinemia IGF 1 was noted in normal or reduced concentration. In I group IGF1 was normal in 70,4% (n=19), decreased in 29,6% (n=8), In II group was normal in 77,4 % (n=24), decreased in 22,6% (n=7) and in III group was normal in 76,9% (n=10), decreased in 23,1% (n=3). Increase of IGF 1 in patients with thyroid nodular disease patients was not noted. Statistically significant connection between IGF1 and thyroid nodules was not revealed. For the further investigation of this connection we plan to measure IGF1 in the thyroid histological samples in the future studies.

  14. Altered expression of genes involved in mitochondrial oxidative phosphorylation and insulin signaling in skeletal muscle of obese women with polycystic ovary syndrome (PCOS)

    DEFF Research Database (Denmark)

    Skov, Vibe

    be of similar importance for insulin resistance in the polycystic ovary syndrome (PCOS).   Materials and methods: Using the HG-U133 Plus 2.0 expression array from Affymetrix, we analyzed gene expression in skeletal muscle from obese women with PCOS (n=16) and age- and body mass index-matched control women (n=13...... a sum statistic and conducting a permutation test. Subsequently, we performed biological pathway analysis using Gene Set Enrichment Analysis (GSEA) and Gene Microarray Pathway Profiler (GenMAPP).   Results: Women with PCOS were characterized by fasting hyperinsulinemia and impaired insulin...... validated by quantitative real-time PCR and immunoblot analyses.   Conclusion: Our results, for the first time, provide evidence for an association between insulin resistance and impaired mitochondrial oxidative metabolism in skeletal muscle in women with PCOS. Furthermore, differential expression of genes...

  15. Effect of rosiglitazone on insulin resistance, growth factors, and reproductive disturbances in women with polycystic ovary syndrome.

    Science.gov (United States)

    Belli, Susana H; Graffigna, Mabel N; Oneto, Adriana; Otero, Patricia; Schurman, Leon; Levalle, Oscar A

    2004-03-01

    To evaluate the effects of rosiglitazone on insulin resistance, growth factors, and reproductive disturbances in women with polycystic ovary syndrome (PCOS). Prospective study. Women with PCOS attending as outpatients of the Endocrine Division, Hospital Durand, Buenos Aires. Twenty-four insulin-resistant women with PCOS. Hormonal evaluations and a standardized oral glucose tolerance test before and after a 3-month trial of 4 mg of rosiglitazone daily. Serum LH, FSH, T, IGF-1, IGFBP-1, IGFBP-3, leptin, 17alpha-hydroxyprogesterone, insulin, and glucose concentrations. The area under insulin curve (AUC-insulin), the HOMA index (insulin resistance), the QUICKI index (insulin sensitivity), and the beta-cell function were calculated. Body mass index (BMI) and the waist/hip ratio were evaluated. A significant decrease was observed in serum fasting insulin, AUC insulin, HOMA index, beta-cell function, IGF-1, LH, and waist/hip ratio. The QUICKI index and IGFBP-1 increased significantly. Serum sex hormone-binding globulin, androgens, leptin, IGFBP-3, and BMI remained unchanged. Twenty-two of 23 females had their menses restored, and three patients became pregnant. One patient was excluded because she became pregnant at the second month. Associated with the decrease in LH, rosiglitazone improved insulin-resistance parameters and normalized the menstrual cycle, which suggests that this drug could improve the endocrine-reproductive condition in insulin-resistant women with PCOS.

  16. Temporary reversal by topotecan of marked insulin resistance in a patient with myelodysplastic syndrome: case report and possible mechanism for tumor necrosis factor alpha (TNF-alpha)-induced insulin resistance.

    Science.gov (United States)

    Huntington, M O; Krell, K E; Armour , W E; Liljenquist, J E

    2001-06-01

    Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity of the insulin receptor. We report here a remarkable degree of insulin resistance in a patient with adult respiratory distress syndrome and myelodysplasia.

  17. Body fat and insulin resistance independently predict increased serum C-reactive protein in hyperandrogenic women with polycystic ovary syndrome.

    Science.gov (United States)

    Tosi, Flavia; Dorizzi, Romolo; Castello, Roberto; Maffeis, Claudio; Spiazzi, Giovanna; Zoppini, Giacomo; Muggeo, Michele; Moghetti, Paolo

    2009-11-01

    Increased serum C-reactive protein (CRP), an independent predictor of coronary heart disease, was reported in women with polycystic ovary syndrome (PCOS). It remains unclear whether this finding is due to the association between PCOS and either insulin resistance, obesity, or androgen excess, which are all common features of this condition. The aims of this study were to assess whether increased serum CRP is a specific feature of PCOS and to investigate the mechanisms underlying this association. Serum high-sensitivity CRP (hs-CRP) was measured in 86 hyperandrogenic women (age 21.6+/-4.2 years, body mass index (BMI) 23.6+/-3.5 kg/m2), 50 with PCOS and 36 with idiopathic hyperandrogenism (HA). Thirty-five BMI-matched healthy women were also studied as controls. In these subjects, endocrine and metabolic profiles were assessed. In all hyperandrogenic subjects and 14 controls, insulin sensitivity was measured by the glucose clamp technique. Body fat was measured by bioelectrical impedance. Hs-CRP concentrations were higher in PCOS women (3.43+/-2.01 mg/l) than in HA subjects and healthy women (2.43+/-1.04, PPCOS). In multiple regression analyses, increased serum hs-CRP was independently predicted by higher body fat and lower insulin sensitivity. However, in lean women, serum-free testosterone was an additional, negative, predictive variable. PCOS is accompanied by a low-grade chronic inflammation. Body fat appears the main determining factor of this finding, which is only partly explained by insulin resistance. At least in lean women, androgen excess per se seems to play an additional, possibly protective, role in this association.

  18. Effects of vitamin D supplementation on insulin sensitivity and androgen levels in vitamin-D-deficient polycystic ovary syndrome patients.

    Science.gov (United States)

    Karadağ, Cihan; Yoldemir, Tevfik; Yavuz, Dilek Gogas

    2018-02-01

    The aim of this study was to identify the effects of vitamin D supplementation on insulin sensitivity and androgen levels in vitamin-D-deficient polycystic ovary syndrome (PCOS) patients. Sixty-seven vitamin-D-deficient (25-hydroxyvitamin D [25(OH)D] levels below 20 ng/mL) PCOS patients and 54 vitamin-D-deficient non-PCOS volunteer subjects matched for age and body mass index were enrolled to this prospective study. All participants were given 50 000 IU/week cholecalciferol orally for 8 weeks and 1500 IU/day for 4 weeks. Insulin sensitivity was calculated with the Matsuda insulin sensitivity index (ISI) based on an oral glucose tolerance test. Matsuda ISI, gonadal hormones (estrogen, testosterone, androstenedione), and 25(OH)D levels were studied before and at the end of the 12th week of vitamin D load. After vitamin D supplementation, serum androstenedione levels had decreased significantly (P = 0.007) and Matsuda ISI values had increased significantly (P = 0.001) in the PCOS group but no significant changes were seen in those parameters in controls. We observed positive correlations between 25(OH)D levels and Matsuda ISI (r = 0.307; P < 0.01), and negative correlations between 25(OH)D levels and total testosterone (r = -0.306; P < 0.01) and androstenedione (r = -0.275; P < 0.01) levels in the PCOS group. Vitamin D supplementation increased insulin sensitivity and decreased androgen levels in vitamin-D-deficient women with PCOS but did not have any effect in vitamin-D-deficient non-PCOS women. These results may indicate the possible role of vitamin D in the complex pathogenesis of PCOS. © 2017 Japan Society of Obstetrics and Gynecology.

  19. Aging and insulin signaling differentially control normal and tumorous germline stem cells.

    Science.gov (United States)

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-02-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  20. Metabolic syndrome, insulin resistance and other cardiovascular risk factors in university students.

    Science.gov (United States)

    Barbosa, José Bonifácio; dos Santos, Alcione Miranda; Barbosa, Marcelo Mesquita; Barbosa, Márcio Mesquita; de Carvalho, Carolina Abreu; Fonseca, Poliana Cristina de Almeida; Fonseca, Jessica Magalhães; Barbosa, Maria do Carmo Lacerda; Bogea, Eduarda Gomes; da Silva, Antônio Augusto Moura

    2016-04-01

    A cross-sectional population-based study using questionnaire and anthropometric data was conducted on 968 university students of São Luís, Brazil, from which 590 showed up for blood collection. In the statistical analysis the Student t-test, Mann-Whitney and chi-square tests were used. The prevalence of metabolic syndrome by the Joint Interim Statement (JIS) criteria was 20.5%, almost three times more prevalent in men (32.2%) than in women (13.5%) (P University students of private institutions had higher prevalences of sedentary lifestyle, obesity, abdominal obesity, elevated triglycerides and metabolic syndrome than students from public institutions. High prevalences of metabolic syndrome, insulin resistance and other cardiovascular risk factors were found in this young population. This suggests that the burden of these diseases in the future will be increased.

  1. [Mechanism of action of insulin sensitizer agents in the treatment of polycystic ovarian syndrome].

    Science.gov (United States)

    Galindo García, Carlos G; Vega Arias, Maria de Jesús; Hernández Marín, Imelda; Ayala, Aquiles R

    2007-03-01

    Polycystic ovarian disease (PCOD) is the most important endocrine abnormality that affects women in reproductive age. It is characterized by chronic anovulation and hyperandrogenemia probably secondary to insulin resistance. Hence insulin sensitizers agents had been used in PCOD. Metformin is a biguanide used in the treatment of PCOD via decrease of hepatic gluconeogenesis and insulinemia; improvement peripheral glucose utilization, oxidative glucose metabolism, nonoxidative glucose metabolism and intracellular glucose transport. Such effects, when this drug is administered alone during 3 to 6 months, increase sex hormone binding globulin (SHBG), reduce free androgens index and hirsutism, decrease insulin resistance, and regulate menses in 60 to 70% of cases. Thiazolidinodiones are drugs that decrease insulin resistance in the liver with hepatic glucose production. Their mechanism of action is through the peroxisome proliferator-activated receptors gamma (PPAR-gamma), that help to decrease plasmatic concentrations of free fatty acids, pre and postprandial glucose, insulin, triglycerides, increased HDL cholesterol and decreased LDL, menses return to normality, with improvement of ovulation and decreased hirsutism. It seems that by modulation and attenuation of insulin resistance, hypoglucemic agents such as metfomin and thiazolidinodiones can be used effectively to treat anovulation, infertility and hyperandrogenemia.

  2. Recurrent pregnancy loss in polycystic ovary syndrome: role of hyperhomocysteinemia and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Pratip Chakraborty

    Full Text Available Recurrent pregnancy loss (RPL in polycystic ovary syndrome (PCOS, which occurs in ∼50% of total pregnancies is a frequent obstetric complication. Among the several hypotheses, insulin resistance (IR, obesity and hyperhomocysteinemia (HHcy play significant role/s in RPL. This study was conducted to assess the link between elevated levels of homocysteine and IR in PCOS-associated women with RPL in Kolkata, India. A retrospective study was conducted of one hundred and twenty six PCOS women (<30 years who experienced two or more spontaneous abortions during the first trimester presenting to Institute of Reproductive Medicine (IRM in Kolkata during the period of March 2008 through February 2011. One hundred and seventeen non-PCOS subjects with matching age range were randomly chosen as controls. Incidence of HHcy and IR was 70.63% (n = 89 and 56.34% (n = 71, respectively, in RPL-affected PCOS population which was significantly higher (p<0.04; p<0.0001 when compared to the non-PCOS set (HHcy: 57.26%; IR: 6.83%. Rates of miscarriage were significantly higher (p<0.008; p<0.03 in hyperhomocysteinemia-induced miscarriage when compared to the normohomocysteinemic segment (PCOS: 70.63% vs.29.36% & non-PCOS: 57.26% vs. 42.73% along with the insulin resistant (p<0.04; p<0.0001 population (PCOS: 70.63% vs. 56.34% & non-PCOS: 57.26% vs. 6.83% in both groups. A probabilistic causal model evaluated HHcy as the strongest plausible factor for diagnosis of RPL. A probability percentage of 43.32% in the cases of HHcy- mediated RPL suggests its increased tendency when compared to IR mediated miscarriage (37.29%, further supported by ROC-AUC (HHcy: 0.778vs. IR: 0.601 values. Greater susceptibility towards HHcy may increase the incidence for miscarriage in women in India and highlights the need to combat the condition in RPL control programs in the subcontinent.

  3. Epicardial adipose tissue is associated with visceral fat, metabolic syndrome, and insulin resistance in menopausal women.

    Science.gov (United States)

    Fernández Muñoz, María J; Basurto Acevedo, Lourdes; Córdova Pérez, Nydia; Vázquez Martínez, Ana Laura; Tepach Gutiérrez, Nayive; Vega García, Sara; Rocha Cruz, Alberto; Díaz Martínez, Alma; Saucedo García, Renata; Zárate Treviño, Arturo; González Escudero, Eduardo Alberto; Degollado Córdova, José Antonio

    2014-06-01

    Epicardial adipose tissue has been associated with several obesity-related parameters and with insulin resistance. Echocardiographic assessment of this tissue is an easy and reliable marker of cardiometabolic risk. However, there are insufficient studies on the relationship between epicardial fat and insulin resistance during the postmenopausal period, when cardiovascular risk increases in women. The objective of this study was to examine the association between epicardial adipose tissue and visceral adipose tissue, waist circumference, body mass index, and insulin resistance in postmenopausal women. A cross sectional study was conducted in 34 postmenopausal women with and without metabolic syndrome. All participants underwent a transthoracic echocardiogram and body composition analysis. A positive correlation was observed between epicardial fat and visceral adipose tissue, body mass index, and waist circumference. The values of these correlations of epicardial fat thickness overlying the aorta-right ventricle were r = 0.505 (P < .003), r = 0.545 (P < .001), and r = 0.515 (P < .003), respectively. Epicardial adipose tissue was higher in postmenopausal women with metabolic syndrome than in those without this syndrome (mean [standard deviation], 544.2 [122.9] vs 363.6 [162.3] mm(2); P = .03). Epicardial fat thickness measured by echocardiography was associated with visceral adipose tissue and other obesity parameters. Epicardial adipose tissue was higher in postmenopausal women with metabolic syndrome. Therefore, echocardiographic assessment of epicardial fat may be a simple and reliable marker of cardiovascular risk in postmenopausal women. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  4. Relationship between Serum Lipids and Insulin Resistance among Women with Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    H Rashidi

    2016-12-01

    Full Text Available Background and aim:  Polycystic ovary syndrome is a common endocrine disorder that is associated with lipid disorders and obesity with an increased risk of cardiovascular disease. The aim of this study was to determine the association between lipid profile and fasting blood sugar levels and insulin resistance among women with polycystic ovary syndrome. Methods: The present case-control study was conducted on 153 women with PCOS and 449 healthy women as controls. Data was extracted from data center of Diabetes Research Center of Ahvaz University of Medical Sciences including women from 4 cities of Khuzestan province (Ahwaz, Behbahan, Abadan, and Khorramshahr. Serum lipids, fasting blood sugar, and serum insulin levels along with Body Mass Index (BMI, Homeostatic Model Assessment Insulin Resistance (HOMA IR, Lipid Accumulation Product (LAP, and Body Adiposity Index in two groups were analyzed by independent t-tests, chi-square and Fisher exact test. Results:  The frequency of low HDL and high total cholesterol was higher in women with PCOS than control group (p =0.032, and p =0.001, respectively. No significant difference was seen between No two groups in the mean levels of total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, fasting blood sugar, HOMA IR, LAP, and PA (p >0.05. In women with BMI30. In women with BMI>30, the mean triglyceride and glucose levels was higher in PCOS group than control group (p=0.029, and p=0.010. Conclusion:  In the present study, in obese women, triglyceride and fasting glucose levels were higher in patients with polycystic ovary syndrome than healthy women. In non-obese women, however, the total cholesterol level was higher in patients with polycystic ovary syndrome than healthy women.  

  5. ROLE OF INSULIN SENSITIZERS ON CARDIOVASCULAR RISK FACTORS IN POLYCYSTIC OVARIAN SYNDROME: A META-ANALYSIS.

    Science.gov (United States)

    Thethi, Tina K; Katalenich, Bonnie; Nagireddy, Prathima; Chabbra, Pankdeep; Kuhadiya, Nitesh; Fonseca, Vivian

    2015-06-01

    Polycystic ovarian syndrome (PCOS) is associated with an increase in cardiovascular (CV) risk factors such as insulin resistance, with accompanying hyperinsulinemia and hyperlipidemia, which are predisposing factors for type 2 diabetes mellitus and CV disease. The aim of this meta-analysis is to examine the effect of insulin sensitizers on clinical and biochemical features of PCOS and risk factors for CV disease. A systematic literature review was conducted, and randomized controlled clinical trials were identified by a search of bibliographic databases: Medline database (from 1966 forward), EMBASE (January 1985 forward), and Cochrane Central Register of Controlled Trials. Reviews of reference lists further identified candidate trials. Data was independently abstracted in duplicate by 2 investigators using a standardized data-collection form. Articles without a comparison group and randomization allocation were excluded. Reviewers worked independently and in duplicate to determine the methodological quality of trials, then collected data on patient characteristics, interventions, and outcomes. Of 455 studies, 44 trials were eligible. A random effects model was used. Significant unadjusted results favoring treatment with insulin sensitizers were obtained for body mass index (BMI) (effect size [ES] of 0.58), waist to hip ratio (WHR) (ES of 0.02), low-density-lipoprotein cholesterol (LDL-C) (ES of 0.11), fasting insulin (ES of 2.82), fasting glucose (ES of 0.10), free testosterone (ES of 1.88), and androstenedione level (ES of 0.76). Treatment with insulin sensitizers in women with PCOS results in improvement in CV factors such as BMI, WHR, LDL-C, fasting insulin, glucose, free testosterone, and androstenedione.

  6. Insulin Signaling in the Aging of Healthy and Proteotoxically Stressed Mechanosensory Neurons

    Directory of Open Access Journals (Sweden)

    Courtney eScerbak

    2014-07-01

    Full Text Available Insulin signaling is central to cellular metabolism and organismal aging. However, the role of insulin signaling in natural and proteotoxically stressed aging neurons has yet to be fully described. We studied aging of Caenorbaditis elegans mechanosensory neurons expressing a neurotoxic expanded polyglutamine transgene (polyQ128, or lacking this proteotoxicity stressor (polyQ0, under conditions in which the insulin signaling pathway was disrupted by RNA interference (RNAi. We describe specific changes in lifespan, mechanosensory neuronal morphologies, and mechansensory function following RNAi treatment targeting the insulin signaling pathway. Overall, we confirmed that transcription factor DAF-16 is neuroprotective in the proteotoxically stressed model, though not strikingly in the naturally aging model. Decreased insulin signaling through daf-2 RNAi improved mechanosensory function in both models and decreased protein aggregation load in polyQ128, yet showed opposing effects on accumulation of neuronal aberrations in both strains. Decreased daf-2 signaling slightly enhanced mechanosensation while greatly enhancing branching of the mechanosensory neuron axons and dendrites in polyQ0 animals, suggesting that branching is an adaptive response in natural aging. These effects in polyQ0 did not appear to involve DAF-16, suggesting the existence of a non-canonical DAF-2 pathway for the modulation of morphological adaptation. However, in polyQ128 animals, decreased daf-2 signaling significantly enhanced mechanosensation while decreasing neuronal aberrations. Unlike other interventions that reduce the strength of insulin signaling, daf-2 RNAi dramatically redistributed large polyQ128 aggregates to the cell body, away from neuronal processes. Our results suggest that insulin signaling strength can differentially affect specific neurons aging naturally or under proteotoxic stress.

  7. Impaired genome maintenance suppresses the growth hormone--insulin-like growth factor 1 axis in mice with Cockayne syndrome.

    Directory of Open Access Journals (Sweden)

    Ingrid van der Pluijm

    2007-01-01

    Full Text Available Cockayne syndrome (CS is a photosensitive, DNA repair disorder associated with progeria that is caused by a defect in the transcription-coupled repair subpathway of nucleotide excision repair (NER. Here, complete inactivation of NER in Csb(m/m/Xpa(-/- mutants causes a phenotype that reliably mimics the human progeroid CS syndrome. Newborn Csb(m/m/Xpa(-/- mice display attenuated growth, progressive neurological dysfunction, retinal degeneration, cachexia, kyphosis, and die before weaning. Mouse liver transcriptome analysis and several physiological endpoints revealed systemic suppression of the growth hormone/insulin-like growth factor 1 (GH/IGF1 somatotroph axis and oxidative metabolism, increased antioxidant responses, and hypoglycemia together with hepatic glycogen and fat accumulation. Broad genome-wide parallels between Csb(m/m/Xpa(-/- and naturally aged mouse liver transcriptomes suggested that these changes are intrinsic to natural ageing and the DNA repair-deficient mice. Importantly, wild-type mice exposed to a low dose of chronic genotoxic stress recapitulated this response, thereby pointing to a novel link between genome instability and the age-related decline of the somatotroph axis.

  8. Insulin resistance in young adults born small for gestational age (SGA).

    Science.gov (United States)

    Putzker, Stephanie; Bechtold-Dalla Pozza, Susanne; Kugler, Karl; Schwarz, Hans P; Bonfig, Walter

    2014-03-01

    This work aimed to assess glucose metabolism and insulin sensitivity in young adults born small for gestational age (SGA) as well as to measure the body composition and adipocytokines of these subjects. A total of 108 out of 342 SGA-born participants were invited for reexamination from the former Bavarian Longitudinal Study (BLS), in which 7505 risk-newborns of the years 1985 to 1986 were prospectively followed. Of these, 76 (34 female/42 male) participants at the age of 19.7±0.5 years were enrolled. Clinical examination and oral glucose tolerance testing (oGTT) was performed with assessment of insulin resistance indices, HbA1c, body mass index (BMI), adipocytokines, and body composition by bioimpedance analysis (BIA). A total of 25 out of 76 (32.9%) patients had abnormal fasting and/or glucose-stimulated insulin levels. Glucose values measured during oGTT showed no abnormalities, except one participant who had impaired glucose tolerance. Homeostasis model assessment insulin resistance index (HOMA-IR) was 1.92±4.2, and insulin sensitivity index by Matsuda (ISI(Matsuda)) showed mean values of 7.85±4.49. HOMA-IR>2.5 was found in 8 patients (10.5%), and 20 patients (26.3%) had an ISI(Matsuda)range for both genders and correlated significantly with BMI (r=0.465, p0.001), but not with adiponectin. Insulin resistance correlated with change in weight-for-height Z-score during the first 3 months of age, indicating that weight gain during that early phase might be a risk factor for the development of insulin resistance in children born SGA. A high percentage of insulin-resistant subjects were reconfirmed in a large German cohort of young adults born SGA. Therefore, regular screening for disturbances in glucose metabolism is recommended in these subjects.

  9. Insulin is Differentially Related to Cognitive Decline and Atrophy in Alzheimer’s Disease and Aging

    Science.gov (United States)

    Burns, Jeffrey M.; Honea, Robyn A.; Vidoni, Eric D.; Hutfles, Lewis; Brooks, William M.; Swerdlow, Russell H.

    2012-01-01

    We assessed the relationship of insulin resistance with cognitive decline and brain atrophy over two years in early Alzheimer’s disease (AD, n=48) and nondemented controls (n=61). Intravenous glucose tolerance tests were conducted at baseline to determine insulin area-under-the-curve (AUC). A standard battery of cognitive tasks and MRI were conducted at baseline and 2-year follow-up. In nondemented controls, higher baseline insulin AUC was associated with 2-year decline in global cognitive performance (beta=−0.36, p=0.005). In early AD, however, higher insulin AUC was associated with less decline in global cognitive performance (beta=0.26, p=0.06), slower global brain atrophy (beta=0.40, p=0.01) and less regional atrophy in the bilateral hippocampi and cingulate cortices. While insulin resistance is associated with cognitive decline in nondemented aging, higher peripheral insulin may have AD-specific benefits or insulin signaling may be affected by systemic physiologic changes associated with AD. PMID:21745566

  10. Leukocytosis in women with polycystic ovary syndrome (PCOS) is incompletely explained by obesity and insulin resistance.

    LENUS (Irish Health Repository)

    Phelan, N

    2012-06-20

    OBJECTIVES: Low-grade chronic inflammation predicts cardiovascular outcomes and is observed in women with polycystic ovary syndrome (PCOS). Whether this is entirely a cause or consequence of insulin resistance (IR) is unknown. METHODS: Seventy pairs of women with and without PCOS, matched for age, BMI and IR (HOMA, QUICKI and Avignon index), were generated from a larger cohort of 103 women with and 104 BMI-matched women without PCOS. Women with PCOS were studied in the follicular phase of the menstrual cycle. White cell count (WCC), high-sensitivity CRP (hsCRP) and a series of 12 cytokines and growth factors were measured. These inflammatory markers were also compared between women with PCOS and 10 normal women studied in the follicular, peri-ovulatory and luteal stages. RESULTS: When all subjects were compared, WCC (6.75 x 10(9) vs 5.60 x 10(9) g\\/l, p<0.005), hsCRP (4.04 vs 2.90 mg\\/l, p<0.05), and IL-6 (1.11 vs 0.72 pg\\/ml, p<0.05) were greater in women with PCOS. Pair-matching for IR eliminated between-group differences in hsCRP and cytokines but did not alter the difference in WCC (6.60 x 10(9) vs 5.60 x 10(9) g\\/l, p<0.005). WCC was greater in PCOS compared to normal women at all stages of the menstrual cycle. CONCLUSIONS: Low-grade inflammation occurs in PCOS. Increased hsCRP and cytokines are associated with IR but increased WCC is observed even when IR is accounted for. The explanation for this and its clinical significance is unknown. © 2012 Blackwell Publishing Ltd.

  11. Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels.

    Science.gov (United States)

    Panidis, Dimitrios; Farmakiotis, Dimitrios; Rousso, David; Kourtis, Anargyros; Katsikis, Ilias; Krassas, Gerassimos

    2008-04-01

    To investigate the combined effect of diet and orlistat, for 24 weeks, on anthropometric features, hormonal parameters, and indices of insulin resistance in obese women with polycystic ovary syndrome (PCOS) and in obese women without the syndrome. Prospective clinical study. Department of obstetrics and gynecology in a major university in Greece. Eighteen selected women with PCOS were matched for age and body mass index with 14 obese control women. Subjects were prescribed an energy-restricted diet, and orlistat (120 mg, 3 times per d) was administered to all subjects for 24 weeks. At baseline, week 12, and week 24, after an overnight fast, blood samples were collected, and serum levels of FSH, LH, PRL, T, Delta(4)A, DHEAS, 17 alpha-hydroxyprogesterone, sex hormone-binding globulin, glucose, and insulin were measured. Testosterone levels were significantly decreased with treatment in women with PCOS; this decrease was attributed to the first trimester, whereas T levels did not change during the second 12-week period. In women with PCOS, insulin levels and HOMA-IR values were decreased during the first 12 weeks, whereas no significant change was observed during the second trimester. Orlistat administration, combined with diet, for 24 weeks, resulted in significant weight loss and improvement of insulin resistance in obese women, with or without PCOS. Moreover, T levels were significantly decreased in women with PCOS. There appears to be a trend during the first 12-week period for greater improvement of metabolic and hormonal parameters in women with PCOS.

  12. Metabolic syndrome, insulin resistance and other cardiovascular risk factors in university students

    Directory of Open Access Journals (Sweden)

    José Bonifácio Barbosa

    2016-04-01

    Full Text Available Abstract A cross-sectional population-based study using questionnaire and anthropometric data was conducted on 968 university students of São Luís, Brazil, from which 590 showed up for blood collection. In the statistical analysis the Student t-test, Mann-Whitney and chi-square tests were used. The prevalence of metabolic syndrome by the Joint Interim Statement (JIS criteria was 20.5%, almost three times more prevalent in men (32.2% than in women (13.5% (P < 0.001. The prevalence of insulin resistance was 7.3% and the prevalence of low HDL-cholesterol was high (61.2%, both with no statistically significant differences by sex. Men showed a higher percentage of smoking, overweight, high blood pressure, high blood glucose and increased fasting hypertriglyceridemia. Women were more sedentary. University students of private institutions had higher prevalences of sedentary lifestyle, obesity, abdominal obesity, elevated triglycerides and metabolic syndrome than students from public institutions. High prevalences of metabolic syndrome, insulin resistance and other cardiovascular risk factors were found in this young population. This suggests that the burden of these diseases in the future will be increased.

  13. Distribution of Serum Total Homocysteine and Its Association with Diabetes and Cardiovascular Risk Factors of the Insulin Resistance Syndrome in Mexican American Men: The Third National Health and Nutrition Examination Survey

    Directory of Open Access Journals (Sweden)

    Gillum Richard

    2003-08-01

    Full Text Available Abstract Background Few data have been published on the association of variables of the insulin resistance syndrome and serum total homocysteine (tHcy, a putative risk factor for cardiovascular morbidity, in representative samples of total populations or in Hispanic Americans. Methods To describe the distributions of serum tHcy concentration and variables associated with insulin resistance in Mexican American men and to assess their association, data from a cross-sectional survey of a large national sample, the Third National Health and Nutrition Examination Survey were analyzed. Analyses were restricted to Mexican American men aged 40–74 years with data on glycated hemoglobin (%, body mass index (BMI, body fat distribution, HDL cholesterol, fasting serum insulin, serum triglycerides and serum tHcy concentrations. Results Cumulative distributions of serum tHcy shifted to the right with increasing age. Log serum tHcy was not associated with prevalence of diagnosed diabetes mellitus or glycated hemoglobin percent or other risk factors other than age. Log serum tHcy concentration showed borderline significant (p = 0.049 positive association with fasting serum insulin concentration independent of age and BMI, only in men aged 60–74. Conclusion No consistent association of tHcy with diabetes prevalence or variables of the insulin resistance syndrome were found in Mexican American men aged 40–74 years. Further research is needed on the associations of serum tHcy concentration with insulin resistance and other components of the insulin resistance syndrome in persons of varying ethnicity.

  14. Epigenetic oxidative redox shift (EORS) theory of aging unifies the free radical and insulin signaling theories

    OpenAIRE

    Brewer, Gregory J.

    2009-01-01

    Harman’s free radical theory of aging posits that oxidized macromolecules accumulate with age to decrease function and shorten life-span. However, nutritional and genetic interventions to boost antioxidants have generally failed to increase life-span. Furthermore, the free radical theory fails to explain why exercise causes higher levels of oxyradical damage, but generally promotes healthy aging. The separate anti-aging paradigms of genetic or caloric reductions in the insulin signaling pathw...

  15. IMPACT OF ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM ON THE DEVELOPMENT OF INSULIN RESISTANCE SYNDROME

    Directory of Open Access Journals (Sweden)

    G. E. Roitberg

    2013-01-01

    Full Text Available Objective: to analyze the distribution of components of insulin resistance (IR syndrome and to study the frequency of their combinations in relation to the genotypes and allelic variants of the angiotensin-converting enzyme (ACE gene.Subjects and methods. A group of clinically healthy patients (50 women and 42 men with different genotypes of the ACE gene was examined.The distribution of IR syndrome components and the frequency of their combinations were analyzed in relation to the genotypes and allelicvariants of the ACE gene.Results. A group of D allele carriers compared to A allele ones showed a pronounced tendency for the frequency of IR to reduce due to thehigher proportion of patients with complete IR syndrome. This observation becomes statistically significant in the assessment of homozygous variants of the ACE gene. At the same time dyslipidemia and hypertension in the presence of IR significantly more frequently occurred in patients with the DD genotype than in those with genotype II.Conclusion. There was a marked predominance of the manifestations of IR syndrome with a complete set of components in the DD genotypicgroup, which confirms the significant strong association between ACE gene polymorphism and IR syndrome.

  16. Glucose but not insulin or insulin resistance is associated with memory performance in middle-aged non-diabetic women: a cross sectional study.

    Science.gov (United States)

    Backeström, Anna; Eriksson, Sture; Nilsson, Lars-Göran; Olsson, Tommy; Rolandsson, Olov

    2015-01-01

    Elevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population. We linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 ± 8.0 years). Episodic and semantic memory functions were tested, and fasting plasma insulin, fasting plasma glucose, and 2-hour glucose were analysed along with other potential influencing factors on memory function. Since men and women display different results on memory functions they were analysed separately. Insulin resistance was calculated using the HOMA-IR method. A higher fasting plasma glucose concentration was associated with lower episodic memory in women (r = -0.08, 95% CI -0.14; -0.01), but not in men. Plasma insulin levels and insulin resistance were not associated with episodic or semantic memory in women or in men after adjustments for age, fasting glucose, 2-hour glucose, BMI, education, smoking, cardiovascular disease, hypertension, cholesterol, and physical activity. This indicates that fasting glucose but not insulin, might have impact on episodic memory in middle-aged women.

  17. Oxidative stress and metabolic syndrome: Effects of a natural antioxidants enriched diet on insulin resistance.

    Science.gov (United States)

    Mancini, Antonio; Martorana, Giuseppe Ettore; Magini, Marinella; Festa, Roberto; Raimondo, Sebastiano; Silvestrini, Andrea; Nicolotti, Nicola; Mordente, Alvaro; Mele, Maria Cristina; Miggiano, Giacinto Abele Donato; Meucci, Elisabetta

    2015-04-01

    Oxidative stress (OS) could play a role in metabolic syndrome-related manifestations contributing to insulin resistance (IR). The aim of the present study was to gain insight the relationships between OS, IR and other hormones involved in caloric balance, explaining the effects of a natural antioxidant-enriched diet in patients affected by metabolic syndrome. We investigated the effects of dietary antioxidants on IR, studying 53 obese (20 males and 33 females, 18-66 years old, BMI 36.3 ± 5.5 kg/m 2 ), with IR evaluated by Homeostasis Model Assessment (HOMA)-index, comparing 4 treatments: hypocaloric diet alone (group A) or plus metformin 1000 mg/daily (group B), natural antioxidants-enriched hypocaloric diet alone (group C) or plus metformin (group D). A personalized program, with calculated antioxidant intake of 800-1000 mg/daily, from fruit and vegetables, was administered to group C and D. The glycemic and insulinemic response to oral glucose load, and concentrations of total-, LDL- and HDL-cholesterol, triglycerides, uric acid, C reactive protein, fT3, fT4, TSH, insulin-like growth factor 1 were evaluated before and after 3-months. Plasma Total antioxidant capacity was determined by H 2 O 2 -metmyoglobin system, which interacting with the chromogen ABTS generates a radical with latency time (LAG) proportional to antioxidant content. Despite a similar BMI decrease, we found a significant decrease of HOMA and insulin peak only in group B and D. Insulin response (AUC) showed the greatest decrease in group D (25.60  ±  8.96%) and was significantly lower in group D vs B. No differences were observed in glucose response, lipid metabolism and TAC (expressed as LAG values). TSH values were significantly suppressed in group D vs B. These data suggest that dietary antioxidants ameliorate insulin-sensitivity in obese subjects with IR by enhancing the effect of insulin-sensitizing drugs albeit with molecular mechanisms which remain yet to be elucidated

  18. Low serum uric acid concentration augments insulin effects on the prevalence of metabolic syndrome.

    Science.gov (United States)

    Porchia, Leonardo M; Gonzalez-Mejia, M Elba; Torres-Rasgado, Enrique; Ruiz-Vivanco, Guadalupe; Pérez-Fuentes, Ricardo

    2018-05-01

    Insulin and uric acid were shown affect the prevalence of Metabolic Syndrome (MetS), but no studies examine their interaction. Therefore, we conducted this study to determine their biological interaction in subjects from central Mexico. 433 subjects were enrolled for a cross-sectional study. MetS was defined according to the Harmonizing Definition. Hyperuricemia was defined as ≥7.0 mg/dL in males and ≥5.8 mg/dL in females. Hyperinsulinemia was defined as ≥11.0 μU/mL. Pearson correlation coefficient (r) was calculated to determine the association between uric acid or insulin and MetS. Logistic regression was used to determine the risk (odds ratio) of developing MetS. Biological interactions were determined by the PROCESS Macro and Anderson's method. Insulin and uric acid levels were elevated in MetS positive group (p uric acid and insulin was associated with the number of MetS components (PROCESS Model 1, interaction coefficient = -0.009, 95%CI: -0.017 to -0.001, p = .036). Johnson-Neyman analysis suggests the interaction is lost when uric acid concentration increased >7.0 mg/dL. When the cohort was separated by hyperinsulinemia and hyperuricemia, there was a significant risk of developing MetS for subjects with hyperuricemia (odds ratio = 2.3; 95%CI: 1.1-4.8, p uric acid and insulin augments the prevalence of MetS; however, no biological interaction was determined for hyperuricemia and hyperinsulinemia. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  19. [Current options of insulin resistence correction in patients with metabolic syndrome].

    Science.gov (United States)

    Demidova, T Iu; Ametov, A S; Titova, O I

    2006-01-01

    To study thiasolidindion drug pioglitazone for efficacy in metabolic syndrome (MS). Twenty patients with MS were examined at baseline and after 12 week therapy with pioglitazone. The examination included estimation of fasting and postprandial glycemia, insulin resistance index, HOMA-IR index, HbAlc, lipid profile, microalbuminuria (MAU), blood pressure, endothelium-related vasodilation. Pioglitazone therapy for 12 weeks significantly reduced HbAlc, fasting and postprandial glycemia, insulinemia, HOMA-IR, improved blood lipid spectrum, reduced visceral obesity. Positive effects were also achieved on blood pressure, MAU and endothelium-related vasodilation.

  20. Age of First Arrhythmic Event in Brugada Syndrome

    DEFF Research Database (Denmark)

    Milman, Anat; Andorin, Antoine; Gourraud, Jean-Baptiste

    2017-01-01

    BACKGROUND: Data on the age at first arrhythmic event (AE) in Brugada syndrome are from limited patient cohorts. The aim of this study is 2-fold: (1) to define the age at first AE in a large cohort of patients with Brugada syndrome, and (2) to assess the influence of the mode of AE documentation,...

  1. Acupuncture treatment for insulin sensitivity of women with polycystic ovary syndrome and insulin resistance: a study protocol for a randomized controlled trial.

    Science.gov (United States)

    Li, Juan; Ng, Ernest Hung Yu; Stener-Victorin, Elisabet; Hu, Zhenxing; Shao, Xiaoguang; Wang, Haiyan; Li, Meifang; Lai, Maohua; Xie, Changcai; Su, Nianjun; Yu, Chuyi; Liu, Jia; Wu, Taixiang; Ma, Hongxia

    2017-03-09

    Our prospective pilot study of acupuncture affecting insulin sensitivity on polycystic ovary syndrome (PCOS) combined with insulin resistance (IR) showed that acupuncture had a significant effect on improving the insulin sensitivity of PCOS. But there is still no randomized controlled trial to determine the effect of acupuncture on the insulin sensitivity in women with PCOS and IR. In this article, we present the protocol of a randomized controlled trial to compare the effect of true acupuncture on the insulin sensitivity of these patients compared with metformin and sham acupuncture. Acupuncture may be an effective therapeutic alternative that is superior to metformin and sham acupuncture in improving the insulin sensitivity of PCOS combined with IR. This study is a multi-center, controlled, double-blind, and randomized clinical trial aiming to evaluate the effect of acupuncture on the insulin sensitivity in PCOS combined with IR. In total 342 patients diagnosed with PCOS and IR will be enrolled. Participants will be randomized to one of the three groups: (1) true acupuncture + metformin placebo; (2) sham acupuncture + metformin, and (3) sham acupuncture + metformin placebo. Participants and assessors will be blinded. The acupuncture intervention will be given 3 days per week for a total of 48 treatment sessions during 4 months. Metformin (0.5 g per pill) or placebo will be given, three times per day, and for 4 months. Primary outcome measures are changes in homeostasis model assessment of insulin resistance (HOMA-IR) and improvement rate of HOMA-IR by oral glucose tolerance test (OGTT) and insulin releasing test (Ins). Secondary outcome measures are homeostasis model assessment-β (HOMA-β), area under the curve for glucose and insulin, frequency of regular menstrual cycles and ovulation, body composition, metabolic profile, hormonal profile, questionnaires, side effect profile, and expectation and credibility of treatment. Outcome measures are

  2. Insulin resistance according to β-cell function in women with polycystic ovary syndrome and normal glucose tolerance.

    Directory of Open Access Journals (Sweden)

    Do Kyeong Song

    Full Text Available Polycystic ovary syndrome (PCOS is associated with insulin resistance (IR and compensatory hyperinsulinemia. IR is recognized as a major risk factor for the development of type 2 diabetes mellitus. However, few studies have investigated IR in women with PCOS and normal glucose tolerance. The objective of this study was to evaluate IR and β-cell function in women with PCOS and normal glucose tolerance. Additionally, we sought to evaluate the usefulness of oral glucose tolerance test (OGTT-derived IR indices in lean women with PCOS.We recruited 100 women with PCOS and normal glucose tolerance and 100 age- and BMI-matched women as controls. IR and insulin secretory indices, including the homeostasis-model assessment (HOMA-IR, HOMA-M120, HOMA-F and the Stumvoll index, were calculated from an OGTT. Increased β-cell function was defined as>75th percentile for the HOMA-F in control women.Women with PCOS had higher values for post-load 2-hour glucose, fasting insulin, post-load 2-hour insulin, HOMA-IR, HOMA-M120, HOMA-F and lower values for the Stumvoll index than the controls (all Ps<0.05. Women with PCOS and increased β-cell function showed lower Stumvoll index values than the matched controls (P<0.05. The HOMA-F was significantly associated with the HOMA-M120 and Stumvoll index when adjusted for age and BMI in a multiple regression analysis (all Ps<0.05. The HOMA-M120 was positively correlated with triglycerides and free testosterone, and the Stumvoll index was negatively correlated with triglycerides and free testosterone in lean women with PCOS (all Ps<0.05.Women with PCOS and normal glucose tolerance showed higher IR than controls matched for age, BMI, and β-cell function. β-cell function was increased in women with PCOS when compared to the matched controls, but not when the lean subjects were compared to the matched controls separately. Therefore, early evaluation of IR in women with PCOS and normal glucose tolerance may be needed.

  3. Ovarian morphology is associated with insulin resistance in women with polycystic ovary syndrome: a cross sectional study.

    Science.gov (United States)

    Reid, Sara Pittenger; Kao, Chia-Ning; Pasch, Lauri; Shinkai, Kanade; Cedars, Marcelle I; Huddleston, Heather G

    2017-01-01

    Polycystic ovary syndrome (PCOS) is a very common disorder well known to be associated with insulin resistance and metabolic disease. Insulin resistance is likely involved in the promotion of the PCOS reproductive phenotype and may mediate some of the ovarian morphology seen in the disorder. The phenotype of each individual woman with PCOS can vary widely as can her metabolic risk. This is a cross-sectional study of patients seen in a multidisciplinary PCOS clinic at the University of California at San Francisco between 2006 and 2014. All participants underwent systematic evaluation with anthropometric measurements, comprehensive skin exam, transvaginal ultrasound and laboratory studies at the time of their initial visit to the clinic. Serum samples were stored and androgen studies were carried out on all stored samples at the University of Virginia. Logistic regression was employed to evaluate the association between ovarian volume or follicle number and metabolic parameters (fasting insulin, HOMA-IR, fasting glucose, 2 h glucose, waist circumference) and hyperandrogenism (free testosterone, total testosterone, DHEAS, acanthosis nigricans), controlling for age. Three-hundred thirteen patients seen during the study period met Rotterdam criteria for PCOS and had sufficient measurements for inclusion in our analysis. The odds ratio of elevated HOMA-IR for patients with a maximum ovarian volume >10 cc was 1.9 compared to those with a maximum ovarian volume of ≤10 cc (95% CI 1.0-3.4). The odds ratio of abnormal fasting insulin for patients with higher ovarian volume was 1.8 (95% CI 1.0-3.4) compared with those with lower ovarian volume. Follicle number was not significantly associated with any metabolic parameters. Increased ovarian volume is associated with markers of insulin resistance in PCOS. In concordance with prior studies, we did not find follicle number to be predictive of metabolic risk. Ovarian volume may serve as a useful tool to aid clinicians in

  4. Effects of aging and insulin resistant states on protein anabolic responses in older adults.

    Science.gov (United States)

    Morais, Jose A; Jacob, Kathryn Wright; Chevalier, Stéphanie

    2018-07-15

    Insulin is the principal postprandial anabolic hormone and resistance to its action could contribute to sarcopenia. We developed different types of hyperinsulinemic clamp protocols to measure simultaneously glucose and protein metabolism in insulin resistant states (older adults, obesity, diabetes, etc.). To define effects of healthy aging in response to insulin, we employed the hyperinsulinemic, euglycemic and isoaminoacidemic (HYPER-1) clamp. The net whole-body anabolic (protein balance) response to hyperinsulinemia was lower in the elderly vs young (p = 0.007) and was highly correlated with the clamp glucose rate of disposal (r = 0.671, p anabolism compared with young ones. As most of the anabolism occurs during feeding, we studied the fed-state metabolic responses with aging using the hyperinsulinemic, hyperglycemic and hyperaminoacidemic clamp, including muscle biopsies. Older women showed comparable whole-body protein anabolic responses and stimulation of mixed-muscle protein synthesis by feeding to the young. The responses of skeletal muscle insulin signaling through the Akt-mTORC1 pathway were also unaltered, and therefore consistent with muscle protein synthesis results. Given that type 2 diabetes infers insulin resistance of protein metabolism with aging, we studied 10 healthy, 8 obese, and 8 obese type 2 diabetic elderly women using the HYPER-1 clamp. When compared to the group of young lean women to define the effects of obesity and diabetes with aging, whole-body change in net protein balance with hyperinsulinemia was similarly blunted in obese and diabetic older women. However, only elderly obese women with diabetes had lower net balance than lean older women. We conclude that with usual aging, the blunted whole-body anabolic response in elderly subjects is mediated by the failure of insulin to stimulate protein synthesis to the same extent as in the young, especially in men. This blunted response can be overcome at the whole-body and muscle

  5. Clinical Significance of Inflammatory Markers in Polycystic Ovary Syndrome: Their Relationship to Insulin Resistance and Body Mass Index

    Directory of Open Access Journals (Sweden)

    Nervana Samy

    2009-01-01

    Full Text Available Background: Women with polycystic ovary syndrome (PCOS have an increased prevalence of insulin resistance (IR and related disorders. Elevated serum levels of high sensitivity CRP (hs-CRP, interleukin-6 (IL-6 and tumor necrosis factor α (TNF-α reflect low-grade chronic inflammation and have been associated with several insulin-resistant states; they are useful cardiovascular risk markers. The objective of this study was to investigate whether soluble inflammatory markers are altered in PCOS focusing on its relationship with obesity and indexes of insulin resistance.

  6. Beneficial effects of viscous dietary fiber from Konjac-mannan in subjects with the insulin resistance syndrome: results of a controlled metabolic trial.

    Science.gov (United States)

    Vuksan, V; Sievenpiper, J L; Owen, R; Swilley, J A; Spadafora, P; Jenkins, D J; Vidgen, E; Brighenti, F; Josse, R G; Leiter, L A; Xu, Z; Novokmet, R

    2000-01-01

    Dietary fiber has recently received recognition for reducing the risk of developing diabetes and heart disease. The implication is that it may have therapeutic benefit in prediabetic metabolic conditions. To test this hypothesis, we investigated the effect of supplementing a high-carbohydrate diet with fiber from Konjac-mannan (KJM) on metabolic control in subjects with the insulin resistance syndrome. We screened 278 free-living subjects between the ages of 45 and 65 years from the Canadian-Maltese Diabetes Study. A total of 11 (age 55+/-4 years, BMI 28+/-1.5 kg/m2) were recruited who satisfied the inclusion criteria: impaired glucose tolerance, reduced HDL cholesterol, elevated serum triglycerides, and moderate hypertension. After an 8-week baseline, they were randomly assigned to take either KJM fiber-enriched test biscuits (0.5 g of glucomannan per 100 kcal of dietary intake or 8-13 g/day) or wheat bran fiber (WB) control biscuits for two 3-week treatment periods separated by a 2-week washout. The diets were isoenergetic, metabolically controlled, and conformed to National Cholesterol Education Program Step 2 guidelines. Serum lipids, glycemic control, and blood pressure were the outcome measures. Decreases in serum cholesterol (total, 12.4+/-3.1%, PFasting blood glucose, insulin, triglycerides, HDL cholesterol, and body weight remained unchanged. A diet rich in high-viscosity KJM improves glycemic control and lipid profile, suggesting a therapeutic potential in the treatment of the insulin resistance syndrome.

  7. Lipoprotein subclass patterns in women with polycystic ovary syndrome (PCOS) compared with equally insulin-resistant women without PCOS.

    LENUS (Irish Health Repository)

    Phelan, N

    2012-02-01

    OBJECTIVES: Women with polycystic ovary syndrome (PCOS) are more insulin resistant and display an atherogenic lipid profile compared with normal women of similar body mass index (BMI). Insulin resistance (IR) at least partially underlies the dyslipidemia of PCOS, but it is unclear whether PCOS status per se confers additional risk. RESEARCH DESIGN AND METHODS: Using a case-control design, we compared plasma lipids and lipoprotein subclasses (using polyacrylamide gel tube electrophoresis) in 70 women with PCOS (National Institutes of Health criteria) and 70 normal women pair matched for age, BMI, and IR (homeostasis model assessment-IR, quantitative insulin sensitivity check index, and the Avignon Index). Subjects were identified as having a (less atherogenic) type A pattern consisting predominantly of large low-density lipoprotein (LDL) subfractions or a (more atherogenic) non-A pattern consisting predominantly of small-dense LDL subfractions. RESULTS: Total, high-density lipoprotein, or LDL cholesterol, or triacylglycerol did not differ between the groups, but very low-density lipoprotein levels (P<0.05) were greater in women with PCOS, whereas a non-A LDL profile was seen in 12.9% compared with 2.9% of controls (P<0.05, chi2). Multiple regression analysis revealed homeostasis model assessment-IR and waist circumference to be independent predictors of very low-density lipoprotein together explaining 40.2% of the overall variance. Logistic regression revealed PCOS status to be the only independent determinant of a non-A LDL pattern (odds ratio 5.48 (95% confidence interval 1.082-27.77; P<0.05). CONCLUSIONS: Compared with women matched for BMI and IR, women with PCOS have potentially important differences in lipid profile with greater very low-density lipoprotein levels and increased rates of a more atherogenic non-A LDL pattern.

  8. Sex steroids, insulin sensitivity and sympathetic nerve activity in relation to affective symptoms in women with polycystic ovary syndrome.

    Science.gov (United States)

    Jedel, Elizabeth; Gustafson, Deborah; Waern, Margda; Sverrisdottir, Yrsa Bergmann; Landén, Mikael; Janson, Per Olof; Labrie, Fernand; Ohlsson, Claes; Stener-Victorin, Elisabet

    2011-11-01

    Affective symptoms are poorly understood in polycystic ovary syndrome (PCOS). Clinical signs of hyperandrogenism and high serum androgens are key features in PCOS, and women with PCOS are more likely to be overweight or obese, as well as insulin resistant. Further, PCOS is associated with high sympathetic nerve activity. To elucidate if self-reported hirsutism, body mass index (BMI) and waistline, circulating sex steroids, sex hormone-binding globulin (SHBG), insulin sensitivity and sympathetic nerve activity are associated with depression and anxiety-related symptoms in women with PCOS. Seventy-two women with PCOS, aged 21-37 years, were recruited from the community. Hirsutism was self-reported using the Ferriman-Gallway score. Serum estrogens, sex steroid precursors, androgens and glucuronidated androgen metabolites were analyzed by gas and liquid chromatography/mass spectroscopy (GC-MS/LC-MS/MS) and SHBG by chemiluminiscent microparticle immunoassay (CMIA). Insulin sensitivity was measured with euglycemic hyperinsulinemic clamp. Sympathetic nerve activity was measured with microneurography. Symptoms of depression and anxiety were self-reported using the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Brief Scale for Anxiety (BSA-S). Circulating concentrations of testosterone (T) (P=0.026), free T (FT) (P=0.025), and androstane-3α 17β-diol-3glucuronide (3G) (P=0.029) were lower in women with depression symptoms of potential clinical relevance (MADR-S≥11). The odds of having a MADRS-S score ≥11 were higher with lower FT and 3G. No associations with BSA-S were noted. Lower circulating FT and 3G were associated with worse self-reported depression symptoms. The relationship between mental health, sex steroids and corresponding metabolites in PCOS requires further investigation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Neck circumference as a new anthropometric indicator for prediction of insulin resistance and components of metabolic syndrome in adolescents: Brazilian Metabolic Syndrome Study

    Directory of Open Access Journals (Sweden)

    Cleliani de Cassia da Silva

    2014-06-01

    Full Text Available OBJECTIVE: To evaluate the correlation between neck circumference and insulin resistance and components of metabolic syndrome in adolescents with different adiposity levels and pubertal stages, as well as to determine the usefulness of neck circumference to predict insulin resistance in adolescents.METHODS:Cross-sectional study with 388 adolescents of both genders from ten to 19 years old. The adolescents underwent anthropometric and body composition assessment, including neck and waist circumferences, and biochemical evaluation. The pubertal stage was obtained by self-assessment, and the blood pressure, by auscultation. Insulin resistance was evaluated by the Homeostasis Model Assessment-Insulin Resistance. The correlation between two variables was evaluated by partial correlation coefficient adjusted for the percentage of body fat and pubertal stage. The performance of neck circumference to identify insulin resistance was tested by Receiver Operating Characteristic Curve.RESULTS: After the adjustment for percentage body fat and pubertal stage, neck circumference correlated with waist circumference, blood pressure, triglycerides and markers of insulin resistance in both genders.CONCLUSIONS: The results showed that the neck circumference is a useful tool for the detection of insulin resistance and changes in the indicators of metabolic syndrome in adolescents. The easiness of application and low cost of this measure may allow its use in Public Health services.

  10. Hibiscus sabdariffa calyx palliates insulin resistance, hyperglycemia, dyslipidemia and oxidative rout in fructose-induced metabolic syndrome rats.

    Science.gov (United States)

    Ajiboye, Taofeek O; Raji, Hikmat O; Adeleye, Abdulwasiu O; Adigun, Nurudeen S; Giwa, Oluwayemisi B; Ojewuyi, Oluwayemisi B; Oladiji, Adenike T

    2016-03-30

    The effect of Hibiscus sabdariffa calyx extract was evaluated in high-fructose-induced metabolic syndrome rats. Insulin resistance, hyperglycemia, dyslipidemia and oxidative rout were induced in rats using high-fructose diet. High-fructose diet-fed rats were administered 100 and 200 mg kg(-1) body weight of H. sabdariffa extract for 3 weeks, starting from week 7 of high-fructose diet treatment. High-fructose diet significantly (P Hibiscus extract. Overall, aqueous extract of H. sabdariffa palliates insulin resistance, hyperglycemia, dyslipidemia and oxidative rout in high-fructose-induced metabolic syndrome rats. © 2015 Society of Chemical Industry.

  11. Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome

    Science.gov (United States)

    Lai, Yerui; Chen, Jinhua; Li, Ling; Yin, Jingxia; He, Junying; Yang, Mengliu; Jia, Yanjun; Liu, Dongfang; Liu, Hua; Liao, Yong; Yang, Gangyi

    2016-01-01

    The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women. PMID:27180914

  12. Polycystic ovarian syndrome and low milk supply: Is insulin resistance the missing link?

    Directory of Open Access Journals (Sweden)

    Lora Stanka Kirigin Biloš

    2017-06-01

    Full Text Available Despite the known maternal and infant benefits of breastfeeding, only about two-fifths of infants are exclusively breastfed for the first 6 months of life, with low milk supply among the most commonly cited reasons for breastfeeding cessation. Although anecdotal reports from lactation consultants indicate that polycystic ovarian syndrome (PCOS interferes with lactation, very few studies have examined this relationship, and the association between PCOS and lactation dysfunction remains poorly understood. Moreover, studies have reported conflicting results when examining breastfeeding success in women with PCOS, and divergence of the PCOS phenotype may be responsible for the heterogeneous results to date. Specifically, insulin resistance may have an aggravating or even essential role in the pathogenesis of low milk supply. Recently, protein tyrosine phosphatase, receptor type, F has been identified as a potential biomarker linking insulin resistance with insufficient milk supply. Accordingly, interventions targeting insulin action have been recognized as potentially promising strategies toward the treatment of lactation dysfunction. This review will highlight studies linking PCOS with low milk supply and explore potential mechanisms that contribute to lactation dysfunction in these women.

  13. Correlation analysis of sex hormone level and insulin resistance in patients with polycystic ovarian syndrome

    International Nuclear Information System (INIS)

    Yuan Xiongzhou; Yuan Guofu; Zhang Xinying; Li Xiufen; Lv Huihui; Sun Zhiru

    2012-01-01

    Objective: To explore the etiology and mechanisms of polycystic ovarian syndrome (PCOS). Methods: The levels of serum LH, FSH, E 2 , P and T in patients with PCOS were detected by ECLIA. The insulin release test was detected by RIA and the glucose tolerance test by enzymatic method. Results: It showed that 28.2% patients only insulin resistance (IR), 13.1% patients also existed of IR and glucose tolerance damage, 5.5% patients only had glucose tolerance damage. Pure IR in the obese accounted for 35.7%; Pure impaired glucose tolerance, fat person accounted for 36.3%; IR with impaired glucose tolerance, fat person accounted for 34.6%. There were no significant differences on LH, LH/FSH, E 2 , T levels between the obese group and the non-obese group (P> 0.05), but there was a significant difference on fasting blood glucose and fasting insulin levels between them (P<0.05). The menstrual cycle and follicular number between the obese group and the non-obese group had significantly differences (P<0.05). Conclusion: There exist different degrees of IR and glucose tolerance damage in most of PCOS patients. The obese people account for higher proportion in patients with IR and glucose tolerance. The obesity can promote the formation of IR and increase reproductive dysfunction. (authors)

  14. Remission of insulin autoimmune syndrome in a patient with Grave's disease by treatment with methimazole.

    Science.gov (United States)

    Okabe, R; Inaba, M; Hosoi, M; Ishimura, E; Kumeda, Y; Nishizawa, Y; Morii, H

    1999-06-01

    The patient, a 24-year-old man, had suffered from hunger, sweating, tachycardia and palpitation for three years. He was diagnosed as having Graves' disease (GD) and treated with methimazole (MMI) for 3 months. He noted that palpitation and perspiration seemed to particularly occur when he was hungry, and thus he was examined to determine whether these symptoms were caused by hypoglycemia. As a markedly elevated immunoreactive insulin level and the presence of insulin antibody in serum were found, he was diagnosed as having insulin autoimmune syndrome (IAS). HLA typing revealed the patient to be positive for group Bw62/Cw4/DR4, which is reportedly a specific HLA type in MMI-treated euthyoroid GD patients with IAS. In spite of the continuation of MMI treatment, the % binding of IRI decreased and the hypoglycemic episode disappeared. In contrast to the previously reported MMI induced IAS in GD cases, MMI is unlikely to have exacerbated IAS in the present case, although his HLA combination is identical to that of the previous cases.

  15. Intranasal insulin to improve developmental delay in children with 22q13 deletion syndrome: an exploratory clinical trial.

    Science.gov (United States)

    Schmidt, H; Kern, W; Giese, R; Hallschmid, M; Enders, A

    2009-04-01

    The 22q13 deletion syndrome (Phelan-McDermid syndrome) is characterised by a global developmental delay, absent or delayed speech, generalised hypotonia, autistic behaviour and characteristic phenotypic features. Intranasal insulin has been shown to improve declarative memory in healthy adult subjects and in patients with Alzheimer disease. To assess if intranasal insulin is also able to improve the developmental delay in children with 22q13 deletion syndrome. We performed exploratory clinical trials in six children with 22q13 deletion syndrome who received intranasal insulin over a period of 1 year. Short-term (during the first 6 weeks) and long-term effects (after 12 months of treatment) on motor skills, cognitive functions, or autonomous functions, speech and communication, emotional state, social behaviour, behavioural disorders, independence in daily living and education were assessed. The children showed marked short-term improvements in gross and fine motor activities, cognitive functions and educational level. Positive long-term effects were found for fine and gross motor activities, nonverbal communication, cognitive functions and autonomy. Possible side effects were found in one patient who displayed changes in balance, extreme sensitivity to touch and general loss of interest. One patient complained of intermittent nose bleeding. We conclude that long-term administration of intranasal insulin may benefit motor development, cognitive functions and spontaneous activity in children with 22q13 deletion syndrome.

  16. Effect on Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator during Weight Loss in Obese Women with and without Polycystic Ovary Syndrome

    OpenAIRE

    Cheang, Kai I.; Sistrun, Sakita N.; Morel, Kelley S.; Nestler, John E.

    2016-01-01

    Background. A deficiency of D-chiro-inositol-inositolphosphoglycan mediator (DCI-IPG) may contribute to insulin resistance in polycystic ovary syndrome (PCOS). Whether the relationship between impaired DCI-IPG release and insulin resistance is specific to PCOS rather than obesity is unknown. We assessed insulin-released DCI-IPG and its relationship to insulin sensitivity at baseline and after weight loss in obese women with and without PCOS. Methods. Obese PCOS (n = 16) and normal (n = 15) wo...

  17. Chronic Kidney Disease in Non-Diabetic Older Adults: Associated Roles of the Metabolic Syndrome, Inflammation, and Insulin Resistance.

    Directory of Open Access Journals (Sweden)

    Andrea R Zammit

    Full Text Available The aims of the study were to examine the association between CKD and the metabolic syndrome (MetS and its components in older adults. We also explored two possible pathways linking the metabolic syndrome with CKD: inflammation as measured by high sensitivity C-Reactive Protein (hsCRP and insulin resistance as measured by HOMA-IR.Community-dwelling non-diabetic 70+ adults from the Einstein Aging Study participated in the study. We defined CKD as eGFR below 60mL/min/1.73m2. MetS was defined according to recent guidelines from the National Cholesterol Education Program. Binary logistic regressions were used to assess the association between the metabolic syndrome, its components and CKD with adjustments for demographics, HOMA-IR and hsCRP.Of 616 participants (mean age = 79.3 years, 65.5% female, 25% had MetS and 26.5% had CKD. Participants with CKD had a significantly higher prevalence of the MetS than individuals without CKD (34.4% vs. 24.3%. Binary logistic regression models showed that CKD was associated with MetS (OR = 1.72, 95%CI = 1.13-2.61. The association was unaltered by adjustment for hsCRP but altered by adjustment for HOMA-IR. As the number of MetS components increased the relative odds of CKD also increased. None of the individual components was independently associated with CKD.MetS is associated with CKD in non-diabetic older adults. Results showed that as the number of MetS components increased so did the odds for CKD. HOMA-IR seems to be in the casual pathway linking MetS to CKD.

  18. The first long-lived mutants: discovery of the insulin/IGF-1 pathway for ageing

    OpenAIRE

    Kenyon, Cynthia

    2011-01-01

    Inhibiting insulin/IGF-1 signalling extends lifespan and delays age-related disease in species throughout the animal kingdom. This life-extension pathway, the first to be defined, was discovered through genetic studies in the small roundworm Caenorhabditis elegans. This discovery is described here.

  19. Biomarkers and insulin sensitivity in women with Polycystic Ovary Syndrome: Characteristics and predictive capacity.

    Science.gov (United States)

    Cassar, Samantha; Teede, Helena J; Harrison, Cheryce L; Joham, Anju E; Moran, Lisa J; Stepto, Nigel K

    2015-07-01

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with metabolic complications. Metabolic biomarkers with roles in obesity, glycaemic control and lipid metabolism are potentially relevant in PCOS. The aim was to investigate metabolic biomarkers in lean and overweight women with and without PCOS and to determine whether any biomarker was able to predict insulin resistance in PCOS. Cross-sectional study. Eighty-four women (22 overweight and 22 lean women with PCOS, 18 overweight and 22 lean women without PCOS) were recruited from the community and categorized based on PCOS and BMI status. Primary outcomes were metabolic biomarkers [ghrelin, resistin, visfatin, glucagon-like peptide-1 (GLP-1), leptin, plasminogen activator inhibitor -1 (PAI-1), glucose-dependent insulinotropic polypeptide (GIP) and C-Peptide] measured using the Bio-Plex Pro Diabetes assay and insulin sensitivity as assessed by glucose infusion rate on euglycaemic-hyperinsulinaemic clamp. The biomarkers C-peptide, leptin, ghrelin and visfatin were different between overweight and lean women, irrespective of PCOS status. The concentration of circulating biomarkers did not differ between women with PCOS diagnosed by the Rotterdam criteria or National Institute of Health criteria. PAI-1 was the only biomarker that significantly predicted insulin resistance in both control women (P = 0.04) and women with PCOS (P = 0.01). Biomarkers associated with metabolic diseases appear more strongly associated with obesity rather than PCOS status. PAI-1 may also be a novel independent biomarker and predictor of insulin resistance in women with and without PCOS. © 2014 John Wiley & Sons Ltd.

  20. Quercetin Decreases Insulin Resistance in a Polycystic Ovary Syndrome Rat Model by Improving Inflammatory Microenvironment.

    Science.gov (United States)

    Wang, Zhenzhi; Zhai, Dongxia; Zhang, Danying; Bai, Lingling; Yao, Ruipin; Yu, Jin; Cheng, Wen; Yu, Chaoqin

    2017-05-01

    Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepiandrosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor κB (NF-κB) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1β, IL-6, and tumor necrosis factor α. Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-κB in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-κB signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.

  1. Fluvastatin increases insulin-like growth factor-1 gene expression in rat model of metabolic syndrome

    International Nuclear Information System (INIS)

    Mansy, Wael H.; Sourour, Doaa A.; Shaker, Olfat G.; Mahfouz, Mahmoud M.

    2008-01-01

    Insulin-like growth factor-1 (IGF-1) was found to have a role in both glucose homeostasis and cardiovascular diseases. The present study was designed to compare the effects of fluvastatin and metformin on IGF-1 mRNA expression within the liver and other individual components of the metabolic syndrome induced in rats by high fructose feeding. Rats fed 60% fructose in diet for 6 weeks were treated daily with fluvastatin (3.75 mg/kg/day) during the last two weeks and were compared with untreated fructose fed group. Fasting levels of plasma cholesterol, triglyceride, glucose, insulin, nitric oxide products, IGF-1 mRNA within the liver as well as systolic blood pressure and body weight were determined. Compared to control rats, the fructose fed group developed hypertension, hyperlipidemia, hyperinsulinemia, hyperglycemia and endothelial dysfunction as well as decreased levels of plasma IGF-1 and its mRNA within the liver. Fructose fed rats treated with fluvastatin or metformin for 2 weeks showed significant decrease in plasma cholesterol, triglyceride, insulin and glucose levels compared to untreated fructose fed group. Also, both drugs increased significantly plasma levels of nitric oxide products and IGF-1 together with significant increase in IGF-1 mRNA within the liver. However, only metformin treated rats showed significant decrease in systolic blood pressure compared to fructose fed group. This study showed that in a rat model of insulin resistance, fluvastatin improves the metabolic profile and increases plasma level of IGF-1 and its gene expression as effective as metformin. (author)

  2. Obstructive sleep apnoea is independently associated with the metabolic syndrome but not insulin resistance state

    Directory of Open Access Journals (Sweden)

    Sithole J

    2006-11-01

    Full Text Available Abstract Obstructive sleep apnoea (OSA is a cardio-metabolic disorder. Whether metabolic syndrome (MS, insulin resistance (IR and albuminuria are independently associated with OSA is unclear, but defining the interactions between OSA and various cardiovascular (CV risk factors independent of obesity facilitates the development of therapeutic strategies to mitigate their increased CV risks. We prospectively recruited 38 subjects with OSA and 41 controls. Anthropometric measurements, glucose, lipids, insulin and blood pressure (BP were measured after an overnight fast. IR state was defined as homeostasis model assessment (HOMA value >3.99 and MS diagnosed according to the International Diabetes Federation (IDF criteria. Subjects with OSA were more obese, more insulin resistant, more hyperglycaemic, had higher Epworth score (measure of day time somnolence and systolic blood pressure levels. The prevalence of MS was higher in OSA compared with non-OSA subjects (74% vs 24%, p 103 cm would predict MS in patients with OSA at 75–78% sensitivity and 61–64% specificity. The agreement between MS and IR state in this cohort is poor. Thus, OSA is associated with MS independent of obesity predominantly due to increased triglyceride, glucose and Epworth score values but not IR or microalbuminuria status. This observation suggests an alternative pathogenic factor mediating the increased cardiovascular risk in patients with OSA and MS, other than that due to IR. The independent link between Epworth score and MS in patients with OSA implicates the role of daytime sleepiness and chronic hypoxia as a potential mediator. Given the discordant between MS and IR state, measurement of waist is useful for predicting mainly MS but not insulin resistance status in patients with OSA. Appropriate pharmacological intervention targeting these independent factors is important in reducing the increased CV risks among patients with OSA.

  3. Adolescent oligomenorrhea in a biracial schoolgirl cohort: a simple clinical parameter predicting impaired fasting glucose plus type 2 diabetes mellitus, insulin, glucose, insulin resistance, and centripetal obesity from age 19 to 25 years.

    Science.gov (United States)

    Morrison, John A; Glueck, Charles J; Daniels, Stephen; Wang, Ping; Stroop, Davis

    2011-09-01

    We hypothesized that adolescent oligomenorrhea (ages 14-19) would independently predict impaired fasting glucose (IFG; ≥110 to fasting glucose + T2DM at ages 19 to 24 were more common in girls having 1 (6%), 2 (11%), and ≥3 (38%) oligomenorrhea reports from ages 14 to 19 than in girls without oligomenorrhea (3%; P = .0003). Positive explanatory variables (all Ps ≤ .05) for homeostasis model assessment of IR at ages 19 to 24 included age 14 waist (partial R(2) = 30.1%), oligomenorrhea with hyperandrogenism (polycystic ovary syndrome; partial R(2) = 4.1%), black race (3.8%), and oligomenorrhea frequency during ages 14 to 19 (0.8%); sex hormone binding globulin was a negative explanatory variable (0.7%). This is the first prospective study to report an independent association of adolescent oligomenorrhea with young adult IFG + T2DM, with insulin and glucose levels, and with IR. Age 14 waist circumference, oligomenorrhea with hyperandrogenism (polycystic ovary syndrome), black race, oligomenorrhea frequency at ages 14 to 19, and age 14 sex hormone binding globulin were independently associated with IR at ages 19 to 24, potentially facilitating primary prevention of IFG, T2DM, and hyperinsulinemia. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Effect of the Aged Garlic Extract on Cardiovascular Function in Metabolic Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Israel Pérez-Torres

    2016-10-01

    Full Text Available The antioxidant properties of aged garlic extract (AGE on cardiovascular functioning (CF in metabolic syndrome (MS remains poorly studied. Here we study the AGE effects on CF in a rat model of MS. Control rats plus saline solution (C + SS, MS rats (30% sucrose in drinking water from weaning plus saline solution (MS + SS, control rats receiving AGE (C + AGE 125 mg/Kg/12 h and MS rats with AGE (MS + AGE were studied. MS + SS had increased triglycerides, systolic blood pressure, insulin, leptin, HOMA index, and advanced glycation end products. AGE returned their levels to control values (p < 0.01. Cholesterol was decreased by AGE (p = 0.05. Glutathion and GPx activity were reduced in MS + SS rats and increased with AGE (p = 0.05. Lipid peroxidation was increased in MS + SS and AGE reduced it (p = 0.001. Vascular functioning was deteriorated by MS (increased vasocontraction and reduced vasodilation and AGE improved it (p = 0.001. Coronary vascular resistance was increased in MS rats and AGE decreased it (p = 0.001. Cardiac performance was not modified by MS but AGE increased it. NO measured in the perfusate liquid from the heart and serum citrulline, nitrites/nitrates were decreased in MS and AGE increased them (p < 0.01. In conclusion, AGE reduces MS-induced cardiovascular risk, through its anti-oxidant properties.

  5. Overexpression of Lnk in the Ovaries Is Involved in Insulin Resistance in Women With Polycystic Ovary Syndrome.

    Science.gov (United States)

    Hao, Meihua; Yuan, Feng; Jin, Chenchen; Zhou, Zehong; Cao, Qi; Xu, Ling; Wang, Guanlei; Huang, Hui; Yang, Dongzi; Xie, Meiqing; Zhao, Xiaomiao

    2016-10-01

    Polycystic ovary syndrome (PCOS) progression involves abnormal insulin signaling. SH2 domain-containing adaptor protein (Lnk) may be an important regulator of the insulin signaling pathway. We investigated whether Lnk was involved in insulin resistance (IR). Thirty-seven women due to receive laparoscopic surgery from June 2011 to February 2012 were included from the gynecologic department of the Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Samples of polycystic and normal ovary tissues were examined by immunohistochemistry. Ovarian cell lines underwent insulin stimulation and Lnk overexpression. Expressed Lnk underwent coimmunoprecipitation tests with green fluorescent protein-labeled insulin receptor and His-tagged insulin receptor substrate 1 (IRS1), and their colocalization in HEK293T cells was examined. Ovarian tissues from PCOS patients with IR exhibited higher expression of Lnk than ovaries from normal control subjects and PCOS patients without IR; mainly in follicular granulosa cells, the follicular fluid and plasma of oocytes in secondary follicles, and atretic follicles. Lnk was coimmunoprecipitated with insulin receptor and IRS1. Lnk and insulin receptor/IRS1 locations overlapped around the nucleus. IR, protein kinase B (Akt), and ERK1/2 activities were inhibited by Lnk overexpression and inhibited further after insulin stimulation, whereas IRS1 serine activity was increased. Insulin receptor (Tyr1150/1151), Akt (Thr308), and ERK1/2 (Thr202/Tyr204) phosphorylation was decreased, whereas IRS1 (Ser307) phosphorylation was increased with Lnk overexpression. In conclusion, Lnk inhibits the phosphatidylinositol 3 kinase-AKT and MAPK-ERK signaling response to insulin. Higher expression of Lnk in PCOS suggests that Lnk probably plays a role in the development of IR.

  6. The insulin-like growth factor I system: physiological and pathophysiological implication in cardiovascular diseases associated with metabolic syndrome.

    Science.gov (United States)

    Ren, Jun; Anversa, Piero

    2015-02-15

    Metabolic syndrome is a cluster of risk factors including obesity, dyslipidemia, hypertension, and insulin resistance. A number of theories have been speculated for the pathogenesis of metabolic syndrome including impaired glucose and lipid metabolism, lipotoxicity, oxidative stress, interrupted neurohormonal regulation and compromised intracellular Ca(2+) handling. Recent evidence has revealed that adults with severe growth hormone (GH) and insulin-like growth factor I (IGF-1) deficiency such as Laron syndrome display increased risk of stroke and cardiovascular diseases. IGF-1 signaling may regulate contractility, metabolism, hypertrophy, apoptosis, autophagy, stem cell regeneration and senescence in the heart to maintain cardiac homeostasis. An inverse relationship between plasma IGF-1 levels and prevalence of metabolic syndrome as well as associated cardiovascular complications has been identified, suggesting the clinical promises of IGF-1 analogues or IGF-1 receptor activation in the management of metabolic and cardiovascular diseases. However, the underlying pathophysiological mechanisms between IGF-1 and metabolic syndrome are still poorly understood. This mini-review will discuss the role of IGF-1 signaling cascade in the prevalence of metabolic syndrome in particular the susceptibility to overnutrition and sedentary life style-induced obesity, dyslipidemia, insulin resistance and other features of metabolic syndrome. Special attention will be dedicated in IGF-1-associated changes in cardiac responses in various metabolic syndrome components such as insulin resistance, obesity, hypertension and dyslipidemia. The potential risk of IGF-1 and IGF-1R stimulation such as tumorigenesis is discussed. Therapeutic promises of IGF-1 and IGF-1 analogues including mecasermin, mecasermin rinfabate and PEGylated IGF-1 will be discussed. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin.

    Science.gov (United States)

    Yuan, Hong; Weng, Chunyan; Yang, Youbo; Huang, Lihua; Xing, Xiaowei

    2013-12-01

    The metabolic syndrome (MS) is a cluster of metabolic disorders arising from insulin resistance, characterized by the presence of central obesity, impaired fasting glucose level, dyslipidemia and hypertension. As the first-line medication, metformin is commonly used for MS to reduce insulin resistance. Comparing with rosiglitazone, metformin does not increase cardiovascular mortality risk in patients with MS. However, metformin is not good enough in improving insulin sensitivity. Its molecular mechanism is still not clear. Recent studies have demonstrated that resistin, an adipokine, could induce IR by both AMPK-dependent and AMPK-independent pathways. Though there were conflicting findings of resistin in metabolic syndrome or type 2 diabetes mellitus in different studies, resistin was significant decreased in the rosiglitazone treated patients than in the metformin-treated patients in most of studies. Here, we hypothesized that resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin. This hypothesis could explain why rosiglitazone is superior to metformin in enhancement of insulin sensitivity. Copyright © 2013. Published by Elsevier Ltd.

  8. Glucose but not insulin or insulin resistance is associated with memory performance in middle-aged non-diabetic women : a cross sectional study

    OpenAIRE

    Backeström, Anna; Eriksson, Sture; Nilsson, Lars-Göran; Olsson, Tommy; Rolandsson, Olov

    2015-01-01

    Background: Elevated concentrations of plasma glucose appear to play a role in memory impairment, and it has been suggested that insulin might also have a negative effect on cognitive function. Our aim was to study whether glucose, insulin or insulin resistance are associated with episodic or semantic memory in a non-diabetic and non-demented population.  Methods: We linked and matched two population-based data sets identifying 291 participants (127 men and 164 women, mean age of 50.7 +/- 8.0...

  9. A Challenging Form of Non-autoimmune Insulin-Dependent Diabetes in a Wolfram Syndrome Patient with a Novel Sequence Variant.

    Science.gov (United States)

    Paris, Liliana P; Usui, Yoshihiko; Serino, Josefina; Sá, Joaquim; Friedlander, Martin

    2015-06-01

    Wolfram syndrome type 1 is a rare, autosomal recessive, neurodegenerative disorder that is diagnosed when insulin-dependent diabetes of non-auto-immune origin and optic atrophy are concomitantly present. Wolfram syndrome is also designated by DIDMOAD that stands for its most frequent manifestations: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. With disease progression, patients also commonly develop severe neurological and genito-urinary tract abnormalities. When compared to the general type 1 diabetic population, patients with Wolfram Syndrome have been reported to have a form of diabetes that is more easily controlled and with less microvascular complications, such as diabetic retinopathy. We report a case of Wolfram syndrome in a 16-year-old male patient who presented with progressive optic atrophy and severe diabetes with very challenging glycemic control despite intensive therapy since diagnosis at the age of 6. Despite inadequate metabolic control he did not develop any diabetic microvascular complications during the 10-year follow-up period. To further investigate potential causes for this metabolic idiosyncrasy, we performed genetic analyses that revealed a novel combination of homozygous sequence variants that are likely the cause of the syndrome in this family. The identified genotype included a novel sequence variant in the Wolfram syndrome type 1 gene along with a previously described one, which had initially been associated with isolated low frequency sensorineural hearing loss (LFSNHL). Interestingly, our patient did not show any abnormal findings with audiometry testing.

  10. A Challenging Form of Non-autoimmune Insulin-Dependent Diabetes in a Wolfram Syndrome Patient with a Novel Sequence Variant

    Science.gov (United States)

    Paris, Liliana P; Usui, Yoshihiko; Serino, Josefina; Sá, Joaquim; Friedlander, Martin

    2015-01-01

    Wolfram syndrome type 1 is a rare, autosomal recessive, neurodegenerative disorder that is diagnosed when insulin-dependent diabetes of non-auto-immune origin and optic atrophy are concomitantly present. Wolfram syndrome is also designated by DIDMOAD that stands for its most frequent manifestations: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. With disease progression, patients also commonly develop severe neurological and genito-urinary tract abnormalities. When compared to the general type 1 diabetic population, patients with Wolfram Syndrome have been reported to have a form of diabetes that is more easily controlled and with less microvascular complications, such as diabetic retinopathy. We report a case of Wolfram syndrome in a 16-year-old male patient who presented with progressive optic atrophy and severe diabetes with very challenging glycemic control despite intensive therapy since diagnosis at the age of 6. Despite inadequate metabolic control he did not develop any diabetic microvascular complications during the 10-year follow-up period. To further investigate potential causes for this metabolic idiosyncrasy, we performed genetic analyses that revealed a novel combination of homozygous sequence variants that are likely the cause of the syndrome in this family. The identified genotype included a novel sequence variant in the Wolfram syndrome type 1 gene along with a previously described one, which had initially been associated with isolated low frequency sensorineural hearing loss (LFSNHL). Interestingly, our patient did not show any abnormal findings with audiometry testing. PMID:26819810

  11. Effect of berberine on insulin resistance in women with polycystic ovary syndrome: study protocol for a randomized multicenter controlled trial.

    Science.gov (United States)

    Li, Yan; Ma, Hongli; Zhang, Yuehui; Kuang, Hongying; Ng, Ernest Hung Yu; Hou, Lihui; Wu, Xiaoke

    2013-07-18

    Insulin resistance and hyperinsulinemia play a key role in the pathogenesis of polycystic ovary syndrome (PCOS), which is characterized by hyperandrogenism, ovulatory dysfunction, and presence of polycystic ovaries on pelvic scanning. Insulin resistance is significantly associated with the long-term risks of metabolic syndrome and cardiovascular disease. Berberine has effects on insulin resistance but its use in women with PCOS has not been fully investigated. In this paper, we present a research design evaluating the effects of berberine on insulin resistance in women with PCOS. This is a multicenter, randomized, placebo-controlled and double-blind trial. A total of 120 patients will be enrolled in this study and will be randomized into two groups. Berberine or placebo will be taken orally for 12 weeks. The primary outcome is the whole body insulin action assessed with the hyperinsulinemic-euglycemic clamp. We postulate that women with PCOS will have improved insulin resistance following berberine administration. This study is registered at ClinicalTrials.gov, NCT01138930.

  12. Wfs1- deficient rats develop primary symptoms of Wolfram syndrome: insulin-dependent diabetes, optic nerve atrophy and medullary degeneration.

    Science.gov (United States)

    Plaas, Mario; Seppa, Kadri; Reimets, Riin; Jagomäe, Toomas; Toots, Maarja; Koppel, Tuuliki; Vallisoo, Tuuli; Nigul, Mait; Heinla, Indrek; Meier, Riho; Kaasik, Allen; Piirsoo, Andres; Hickey, Miriam A; Terasmaa, Anton; Vasar, Eero

    2017-08-31

    Wolfram syndrome (WS) is a rare autosomal-recessive disorder that is caused by mutations in the WFS1 gene and is characterized by juvenile-onset diabetes, optic atrophy, hearing loss and a number of other complications. Here, we describe the creation and phenotype of Wfs1 mutant rats, in which exon 5 of the Wfs1 gene is deleted, resulting in a loss of 27 amino acids from the WFS1 protein sequence. These Wfs1-ex5-KO232 rats show progressive glucose intolerance, which culminates in the development of diabetes mellitus, glycosuria, hyperglycaemia and severe body weight loss by 12 months of age. Beta cell mass is reduced in older mutant rats, which is accompanied by decreased glucose-stimulated insulin secretion from 3 months of age. Medullary volume is decreased in older Wfs1-ex5-KO232 rats, with the largest decreases at the level of the inferior olive. Finally, older Wfs1-ex5-KO232 rats show retinal gliosis and optic nerve atrophy at 15 months of age. Electron microscopy revealed axonal degeneration and disorganization of the myelin in the optic nerves of older Wfs1-ex5-KO232 rats. The phenotype of Wfs1-ex5-KO232 rats indicates that they have the core symptoms of WS. Therefore, we present a novel rat model of WS.

  13. A novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia linked to a mutation in the human insulin receptor gene

    DEFF Research Database (Denmark)

    Højlund, Kurt; Hansen, Torben; Lajer, Maria

    2004-01-01

    a missense mutation (Arg1174Gln) in the tyrosine kinase domain of the insulin receptor gene that cosegregated with the disease phenotype (logarithm of odds [LOD] score 3.21). In conclusion, we report a novel syndrome of autosomal-dominant hyperinsulinemic hypoglycemia. The findings demonstrate...

  14. Ordovas-Oxidized LDL is associated with metabolic syndrome traits independently of central obesity and insulin resistance

    Science.gov (United States)

    This study assesses whether oxidative stress, using oxidized LDL (ox-LDL) as a proxy, is associated with metabolic syndrome (MS), whether ox-LDL mediates the association between central obesity and MS, and whether insulin resistance mediates the association between ox-LDL and MS. We examined baselin...

  15. Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition

    DEFF Research Database (Denmark)

    Kootte, Ruud S.; Levin, Evgeni; Salojärvi, Jarkko

    2017-01-01

    be predicted based on baseline fecal microbiota composition. Kootte et al. show that fecal microbiota transplantation from lean donors to obese patients with metabolic syndrome improves insulin sensitivity, a transient effect associated with changes in microbiota composition and fasting plasma metabolites...

  16. Insulin-resistance and metabolic syndrome are related to executive function in women in a large family-based study

    NARCIS (Netherlands)

    M. Schuur (Maaike); P. Henneman (Peter); J.C. van Swieten (John); M.C. Zillikens (Carola); I. de Koning (Inge); A.C.J.W. Janssens (Cécile); J.C.M. Witteman (Jacqueline); Y.S. Aulchenko (Yurii); R.R. Frants (Rune); B.A. Oostra (Ben); J.A.P. Willems van Dijk (Ko); C.M. van Duijn (Cornelia)

    2010-01-01

    textabstractWhile type 2 diabetes is well-known to be associated with poorer cognitive performance, few studies have reported on the association of metabolic syndrome (MetS) and contributing factors, such as insulin-resistance (HOMA-IR), low adiponectin-, and high C-reactive protein (CRP)- levels.

  17. The relationship of adrenal androgen level and insulin resistance in polycystic ovary syndrome patients

    International Nuclear Information System (INIS)

    Tan Qingling; Zhang Hui; Chen Biling

    2011-01-01

    Objective: To investigate the relationship between adrenal androgen level and insulin resistance in polycystic ovary syndrome (PCOS) patients. Methods: Twenty-two healthy women and 85 PCOS patients were underwent adrenocorticptropic hormone (ACTH) stimulation test, and 85 PCOS patients were divided into high response-polycystic ovary syndrome (HR-PCOS) group and normal response-polycystic ovary syndrome (NR-PCOS) group. The ratio of serum luteinizing hormone to follicle stimulating hormone (LH/FSH), estradiol (E 2 ), testosterone (T) and progestin (P) were tested by radioimmunoassay method. 17-hydroxy-progesterone (17-OHP), dehydroepiandros-teronesulfate (DHEAS) and androsterone (AD) was tested at 0 and 60 min after an ACTH stimulation test. Body mass index (BMI), waist-to-hip-circumference radio (WHR) and homeostasis modes of assessment for insulin resistence index (HOMA-IR) were also measured. Results: There were 20 cases that 17-OHP levels were higher than normal (HR-PCOS), the other 65 cases were NR-PCOS group. MBI and WHR(MBI: χ 2 =13.874, 14.512, WHR: χ 2 =12.607, 15.153, P all 2 =4.801, 5.326, P all>0.05). HR-PCOS group and NR-PCOS group were significantly higher than the control group for LH/FSH and estradiol (LH/FSH: χ 2 =18.226, 16.327, E2: χ 2 =17.334, 19.261, P all 2 =12.274, P 2 =20.314, 18.492, P all 2 =18.063, 19.214, DHEAS: χ 2 =17.358, 19.355, P all 2 =4.109, 4.362, P all>0.05). AD of HR-PCOS group and NR-PCOS group were higher than control group before and after the ACTH stimulation test (χ 2 =14.062, 16.549, P all 2 =5.541, P>0.05) between the two PCOS groups. Serum cortisol was no difference between HR-PCOS, NR-PCOS and control groups before and after stimulation test. HOMA-IR of HR-PCOS group and NR-PCOS group were higher than control group (χ 2 =19.263, 21.482, P all 2 =13.582, P<0.05). Conclusions: There have significantly higher basal and ACTH-stimulated level of adrenal androgen hyperresponsiveness in PCOS patients. Adrenal androgen

  18. Effects of vitamin D supplementation on insulin resistance and cardiometabolic risk factors in children with metabolic syndrome: a triple-masked controlled trial.

    Science.gov (United States)

    Kelishadi, Roya; Salek, Shadi; Salek, Mehdi; Hashemipour, Mahin; Movahedian, Mahsa

    2014-01-01

    This triple-masked controlled trial aimed to assess the effects of vitamin D supplementation on insulin resistance and cardiometabolic risk factors in obese children and adolescents. The study comprised 50 participants, aged 10 to 16 years, who were randomly assigned into two groups of equal number. In this 12-week trial, one group received oral vitamin D (300,000 IU) and the other group received placebo. Cardiometabolic risk factors, insulin resistance, and a continuous value of metabolic syndrome (cMetS) were determined. Statistical analysis was conducted after adjustment for covariate interactions. Overall, 21 patients in the vitamin D group and 22 in the placebo group completed the trial. No significant difference was observed in the baseline characteristics of the two groups. After the trial, in the vitamin D group, serum insulin and triglyceride concentrations, as well as HOM -IR and C-MetS decreased significantly, both when compared with the baseline and with the placebo group. No significant difference was observed when comparing total cholesterol, LDL-C, HDL-C, fasting blood glucose, and blood pressure. The present findings support the favorable effects of vitamin D supplementation on reducing insulin resistance and cardiometabolic risk factors in obese children. Copyright © 2013 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  19. [Relationship between the triglyceride/high-density lipoprotein-cholesterol ratio, insulin resistance index and cardiometabolic risk factors in women with polycystic ovary syndrome].

    Science.gov (United States)

    Roa Barrios, Marlene; Arata-Bellabarba, Gabriela; Valeri, Lenin; Velázquez-Maldonado, Elsy

    2009-02-01

    To evaluate the relationship between the triglyceride/high density lipoprotein cholesterol (TG/HDL-c) ratio, insulin resistance index and cardiometabolic risk factors in women with polycystic ovary syndrome (PCOS). The present crosssectional study analyzed 62 women with PCOS and 48 healthy women (control group) aged 17- 35 years old. Body mass index (BMI), waist circumference (WC) and blood pressure were registered. Plasma concentrations of glucose, insulin, triglycerides, total cholesterol and HDL-c were measured. TheTG/HDL-c ratio, homeostasis model assessment for insulin resistance (HOMA(IR)) and quantitative insulin sensitivity check index (QUICKI) were calculated. Women with PCOS showed significantly higher values of the TG/HDL-c ratio and HOMA(IR), and a significantly lower QUICKI value. These differences were related to BMI and WC, with the highest values being observed in obese patients. The 50th percentile for the TG/HDL-c ratio was 3.64; the TG/cHDL ratio was positively correlated with BMI, WC and HOMA(IR) (r=0.48, pglucose > 100 mg/dl (10% vs 3%; ptriglycerides>150 mg/dl (55% vs 20%; p80 cm (82.3% vs 43.8%; pindexes (HOMA(IR), QUICKI). The TG/HDL-c ratio could be considered as a useful and practical method to identify an increased risk of cardiovascular disease in patients with PCOS.

  20. Effects of vitamin D supplementation on insulin resistance and cardiometabolic risk factors in children with metabolic syndrome: a triple-masked controlled trial

    Directory of Open Access Journals (Sweden)

    Roya Kelishadi

    2014-01-01

    Full Text Available OBJECTIVE: this triple-masked controlled trial aimed to assess the effects of vitamin D supplementation on insulin resistance and cardiometabolic risk factors in obese children and adolescents. METHODS: the study comprised 50 participants, aged 10 to16 years, who were randomly assigned into two groups of equal number. In this 12-week trial, one group received oral vitamin D (300,000 IU and the other group received placebo. Cardiometabolic risk factors, insulin resistance, and a continuous value of metabolic syndrome (cMetS were determined. Statistical analysis was conducted after adjustment for covariate interactions. RESULTS: overall, 21 patients in the vitamin D group and 22 in the placebo group completed the trial. No significant difference was observed in the baseline characteristics of the two groups. After the trial, in the vitamin D group, serum insulin and triglyceride concentrations, as well as HOM -IR and C-MetS decreased significantly, both when compared with the baseline and with the placebo group. No significant difference was observed when comparing total cholesterol, LDL-C, HDL-C, fasting blood glucose, and blood pressure. CONCLUSION: the present findings support the favorable effects of vitamin D supplementation on reducing insulin resistance and cardiometabolic risk factors in obese children.

  1. Differences in low-grade chronic inflammation and insulin resistance in women with previous gestational diabetes mellitus and women with polycystic ovary syndrome.

    Science.gov (United States)

    Thomann, Robert; Rossinelli, Nadia; Keller, Ulrich; Tirri, Brigitte Frey; De Geyter, Christian; Ruiz, Juan; Kränzlin, Marius; Puder, Jardena J

    2008-04-01

    Polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) are both characterized by an increase in insulin resistance. Our goal in the present study was to measure insulin resistance (as estimated by homeostasis model assessment, sex hormone-binding globulin (SHBG) and adiponectin concentrations) and parameters of low-grade inflammation in non-diabetic, non-hyperandrogenic ovulatory women with previous GDM (pGDM) and in non-diabetic women with classic PCOS, characterized by hyperandrogenism and oligo/anovulation. We evaluated 20 women with PCOS, 18 women with pGDM and 19 controls, all matched according to body mass index (BMI). Fasting blood samples were drawn in all women 3-6 days after spontaneous or dydrogesterone-induced withdrawal bleeding. Body fat distribution was assessed using dual-energy X-ray absorptiometry in all women. After adjusting for age and percent body fat, measures of insulin resistance such as SHBG and adiponectin concentrations were decreased and central obesity was increased in women with PCOS and pGDM compared with controls (all p PCOS compared with BMI-matched controls (all p insulin resistance are increased in both women with PCOS and women with pGDM, while low-grade inflammation is increased only in PCOS. PCOS and GDM might represent specific phenotypes of one disease entity with an increased risk of cardiovascular disease, whereby women with PCOS demonstrate an augmented cardiovascular risk profile.

  2. Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome.

    Science.gov (United States)

    Aye, Myint Myint; Kilpatrick, Eric S; Aburima, Ahmed; Wraith, Katie S; Magwenzi, Simbarashe; Spurgeon, B; Rigby, Alan S; Sandeman, Derek; Naseem, Khalid M; Atkin, Stephen L

    2014-02-28

    Atherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in young women with PCOS. Following overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20% intralipid for 5 hours on separate days. Insulin sensitivity was measured using a hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion. Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were measured by flow cytometric analysis of platelet fibrinogen binding and P-selectin expression using whole blood taken during each infusion (at 2 hours) and at the end of each clamp. Lipid infusion increased triglycerides and reduced insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3, 6.48] versus 2.60 [0.88, 3.88] mg kg(-1) min(-1), P<0.001) and PCOS (3.15 [2.94, 3.85] versus 1.06 [0.72, 1.43] mg kg(-1) min(-1), P<0.001). Platelet activation by ADP was enhanced and ability to suppress platelet activation by PGI2 diminished during lipid infusion in both groups when compared to saline. Importantly, insulin infusion decreased lipid-induced platelet hyperactivity by decreasing their response to 1 μmol/L ADP (78.7% [67.9, 82.3] versus 62.8% [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 μmol/L PGI2 (67.6% [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS. Acute hypertriglyceridemia induced IR, and increased platelet activation in both groups that was not reversed by insulin in PCOS subjects compared to controls. This suggests that platelet hyperactivity induced by acute hypertriglyceridemia and IR could contribute athero-thrombotic risk. www.isrctn.org. Unique Identifier: ISRCTN42448814.

  3. Galantamine alleviates inflammation and insulin resistance in patients with metabolic syndrome in a randomized trial.

    Science.gov (United States)

    Consolim-Colombo, Fernanda M; Sangaleti, Carine T; Costa, Fernando O; Morais, Tercio L; Lopes, Heno F; Motta, Josiane M; Irigoyen, Maria C; Bortoloto, Luiz A; Rochitte, Carlos Eduardo; Harris, Yael Tobi; Satapathy, Sanjaya K; Olofsson, Peder S; Akerman, Meredith; Chavan, Sangeeta S; MacKay, Meggan; Barnaby, Douglas P; Lesser, Martin L; Roth, Jesse; Tracey, Kevin J; Pavlov, Valentin A

    2017-07-20

    Metabolic syndrome (MetS) is an obesity-driven condition of pandemic proportions that increases the risk of type 2 diabetes and cardiovascular disease. Pathophysiological mechanisms are poorly understood, though inflammation has been implicated in MetS pathogenesis. The aim of this study was to assess the effects of galantamine, a centrally acting acetylcholinesterase inhibitor with antiinflammatory properties, on markers of inflammation implicated in insulin resistance and cardiovascular risk, and other metabolic and cardiovascular indices in subjects with MetS. In this randomized, double-blind, placebo-controlled trial, subjects with MetS (30 per group) received oral galantamine 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo. The primary outcome was inflammation assessed through plasma levels of cytokines and adipokines associated with MetS. Secondary endpoints included body weight, fat tissue depots, plasma glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol (total, HDL, LDL), triglycerides, BP, heart rate, and heart rate variability (HRV). Galantamine resulted in lower plasma levels of proinflammatory molecules TNF (-2.57 pg/ml [95% CI -4.96 to -0.19]; P = 0.035) and leptin (-12.02 ng/ml [95% CI -17.71 to -6.33]; P < 0.0001), and higher levels of the antiinflammatory molecules adiponectin (2.71 μg/ml [95% CI 1.93 to 3.49]; P < 0.0001) and IL-10 (1.32 pg/ml, [95% CI 0.29 to 2.38]; P = 0.002) as compared with placebo. Galantamine also significantly lowered plasma insulin and HOMA-IR values, and altered HRV. Low-dose galantamine alleviates inflammation and insulin resistance in MetS subjects. These findings support further study of galantamine in MetS therapy. ClinicalTrials.gov, number NCT02283242. Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, and the NIH.

  4. The utility of metformin therapy in reproductive-aged women with polycystic ovary syndrome (PCOS).

    Science.gov (United States)

    Nathan, Nisha; Sullivan, Shannon D

    2014-01-01

    Metformin, an insulin-sensitizing drug commonly used to treat Type 2 Diabetes Mellitus (T2DM), has been increasingly used off-label for the treatment of polycystic ovary syndrome (PCOS), which affects at least 5-10% of reproductive- age women. With very little risk associated with its use, metformin provides many important benefits to women with PCOS, including regulating menstrual cycles, improving clinical signs of hyperandrogenism, ameliorating metabolic syndrome, inducing ovulation, improving pregnancy rates and pregnancy outcomes, preventing gestational diabetes, and preventing progression to T2DM. Here, we review the indications for metformin in women with PCOS, with a focus on the use of metformin during pre-conception and pregnancy.

  5. HOMA1-IR and HOMA2-IR indexes in identifying insulin resistance and metabolic syndrome: Brazilian Metabolic Syndrome Study (BRAMS).

    Science.gov (United States)

    Geloneze, Bruno; Vasques, Ana Carolina Junqueira; Stabe, Christiane França Camargo; Pareja, José Carlos; Rosado, Lina Enriqueta Frandsen Paez de Lima; Queiroz, Elaine Cristina de; Tambascia, Marcos Antonio

    2009-03-01

    To investigate cut-off values for HOMA1-IR and HOMA2-IR to identify insulin resistance (IR) and metabolic syndrome (MS), and to assess the association of the indexes with components of the MS. Nondiabetic subjects from the Brazilian Metabolic Syndrome Study were studied (n = 1,203, 18 to 78 years). The cut-off values for IR were determined from the 90th percentile in the healthy group (n = 297) and, for MS, a ROC curve was generated for the total sample. In the healthy group, HOMA-IR indexes were associated with central obesity, triglycerides and total cholesterol (p 2.7 and HOMA2-IR > 1.8; and, for MS were: HOMA1-IR > 2.3 (sensitivity: 76.8%; specificity: 66.7%) and HOMA2-IR > 1.4 (sensitivity: 79.2%; specificity: 61.2%). The cut-off values identified for HOMA1-IR and HOMA2-IR indexes have a clinical and epidemiological application for identifying IR and MS in Westernized admixtured multi-ethnic populations.

  6. Crucial roles of Nox2-derived oxidative stress in deteriorating the function of insulin receptors and endothelium in dietary obesity of middle-aged mice.

    Science.gov (United States)

    Du, Junjie; Fan, Lampson M; Mai, Anna; Li, Jian-Mei

    2013-11-01

    Systemic oxidative stress associated with dietary calorie overload plays an important role in the deterioration of vascular function in middle-aged patients suffering from obesity and insulin resistance. However, effective therapy is still lacking. In this study, we used a mouse model of middle-aged obesity to investigate the therapeutic potential of pharmaceutical inhibition (apocynin, 5 mM supplied in the drinking water) or knockout of Nox2, an enzyme generating reactive oxygen species (ROS), in high-fat diet (HFD)-induced obesity, oxidative stress, insulin resistance and endothelial dysfunction. Littermates of C57BL/6J wild-type (WT) and Nox2 knockout (KO) mice (7 months old) were fed with a HFD (45% kcal fat) or normal chow diet (NCD, 12% kcal fat) for 16 weeks and used at 11 months of age. Compared to NCD WT mice, HFD WT mice developed obesity, insulin resistance, dyslipidaemia and hypertension. Aortic vessels from these mice showed significantly increased Nox2 expression and ROS production, accompanied by significantly increased ERK1/2 activation, reduced insulin receptor expression, decreased Akt and eNOS phosphorylation and impaired endothelium-dependent vessel relaxation to acetylcholine. All these HFD-induced abnormalities (except the hyperinsulinaemia) were absent in apocynin-treated WT or Nox2 KO mice given the same HFD. In conclusion, Nox2-derived ROS played a key role in damaging insulin receptor and endothelial function in dietary obesity after middle-age. Targeting Nox2 could represent a valuable therapeutic strategy in the metabolic syndrome. © 2013 The British Pharmacological Society.

  7. Serum visfatin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome.

    Science.gov (United States)

    Kowalska, Irina; Straczkowski, Marek; Nikolajuk, Agnieszka; Adamska, Agnieszka; Karczewska-Kupczewska, Monika; Otziomek, Elzbieta; Wolczynski, Slawomir; Gorska, Maria

    2007-07-01

    Visfatin, a protein secreted by adipose tissue, is suggested to play a role in pathogenesis of insulin resistance. In polycystic ovary syndrome (PCOS), insulin resistance might be involved in the development of endocrine and metabolic abnormalities. The aim of the study was to asses the relation between serum visfatin concentration and insulin sensitivity and markers of hyperandrogenism in lean and obese PCOS patients. The study group consisted of 70 women with PCOS (23 lean and 47 obese) and 45 healthy women (25 lean and 20 obese). Euglycemic hyperinsulinemic clamp and the measurements of serum visfatin, sex hormones were performed. The PCOS group had lower insulin sensitivity (P=0.00049) and higher serum visfatin (P=0.047) in comparison to the control group. The decrease in insulin sensitivity was present in both the lean (P=0.019) and obese (P=0.0077) PCOS subjects, whereas increase in serum visfatin was observed only in lean PCOS subjects (P=0.012). In the whole group, serum visfatin was negatively correlated with insulin sensitivity (r=-0.27, P=0.004). This relationship was also observed in the subgroup of lean (r=-0.30, P=0.038), but not obese women. Additionally, in lean women, visfatin was associated with serum testosterone (r=0.47, P=0.002) and free androgen index (r=0.48, P=0.002), independently of other potential confounding factors. Visfatin is associated with insulin resistance and markers of hyperandrogenism in lean PCOS patients.

  8. Nutrition, insulin resistance and dysfunctional adipose tissue determine the different components of metabolic syndrome

    Science.gov (United States)

    Paniagua, Juan Antonio

    2016-01-01

    Obesity is an excessive accumulation of body fat that may be harmful to health. Today, obesity is a major public health problem, affecting in greater or lesser proportion all demographic groups. Obesity is estimated by body mass index (BMI) in a clinical setting, but BMI reports neither body composition nor the location of excess body fat. Deaths from cardiovascular diseases, cancer and diabetes accounted for approximately 65% of all deaths, and adiposity and mainly abdominal adiposity are associated with all these disorders. Adipose tissue could expand to inflexibility levels. Then, adiposity is associated with a state of low-grade chronic inflammation, with increased tumor necrosis factor-α and interleukin-6 release, which interfere with adipose cell differentiation, and the action pattern of adiponectin and leptin until the adipose tissue begins to be dysfunctional. In this state the subject presents insulin resistance and hyperinsulinemia, probably the first step of a dysfunctional metabolic system. Subsequent to central obesity, insulin resistance, hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, hypertension and fatty liver are grouped in the so-called metabolic syndrome (MetS). In subjects with MetS an energy balance is critical to maintain a healthy body weight, mainly limiting the intake of high energy density foods (fat). However, high-carbohydrate rich (CHO) diets increase postprandial peaks of insulin and glucose. Triglyceride-rich lipoproteins are also increased, which interferes with reverse cholesterol transport lowering high-density lipoprotein cholesterol. In addition, CHO-rich diets could move fat from peripheral to central deposits and reduce adiponectin activity in peripheral adipose tissue. All these are improved with monounsaturated fatty acid-rich diets. Lastly, increased portions of ω-3 and ω-6 fatty acids also decrease triglyceride levels, and complement the healthy diet that is recommended in patients with MetS. PMID

  9. Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome.

    Science.gov (United States)

    Rosa, Damiana D; Grześkowiak, Łukasz M; Ferreira, Célia L L F; Fonseca, Ana Carolina M; Reis, Sandra A; Dias, Mariana M; Siqueira, Nathane P; Silva, Leticia L; Neves, Clóvis A; Oliveira, Leandro L; Machado, Alessandra B F; Peluzio, Maria do Carmo G

    2016-08-10

    There is growing evidence that kefir can be a promising tool in decreasing the risk of many diseases, including metabolic syndrome (MetS). The aim of the present study was to evaluate the effect of kefir supplementation in the diet of Spontaneously Hypertensive Rats (SHR) in which MetS was induced with monosodium glutamate (MSG), and to determine its effect on metabolic parameters, inflammatory and oxidation marker expression and glycemic index control. Thirty animals were used in this experiment. For the induction of MetS, twenty two-day-old male SHR received five consecutive intradermal injections of MSG. For the Negative Control, ten newborn male SHR received intradermal injections of saline solution (0.9% saline solution). After weaning, animals received standard diet and water ad libitum until reaching 3 months old, for the development of MetS. They were then divided into three groups (n = 10): negative control (NC, 1 mL saline solution per day), positive control (PC, 1 mL saline solution per day) and the Kefir group (1 mL kefir per day). Feeding was carried out by gavage for 10 weeks and the animals received standard food and water ad libitum. Obesity, insulin resistance, pro- and anti-inflammatory markers, and the histology of pancreatic and adipose tissues were among the main variables evaluated. Compared to the PC group, kefir supplementation reduced plasma triglycerides, liver lipids, liver triglycerides, insulin resistance, fasting glucose, fasting insulin, thoracic circumference, abdominal circumference, products of lipid oxidation, pro-inflammatory cytokine expression (IL-1β) and increased anti-inflammatory cytokine expression (IL-10). The present findings indicate that kefir has the potential to benefit the management of MetS.

  10. Nutrition, insulin resistance and dysfunctional adipose tissue determine the different components of metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    Juan; Antonio; Paniagua[1,2

    2016-01-01

    Obesity is an excessive accumulation of body fat that may be harmful to health. Today, obesity is a major public health problem, affecting in greater or lesser proportion all demographic groups. Obesity is estimated by body mass index (BMI) in a clinical setting, but BMI reports neither body composition nor the location of excess body fat.Deaths from cardiovascular diseases, cancer and diabetes accounted for approximately 65% of all deaths, and adiposity and mainly abdominal adiposity are associated with all these disorders. Adipose tissue could expand to inflexibility levels. Then, adiposity is associated with a state of low-grade chronic inflammation, with increased tumor necrosis factor-α and interleukin-6 release, which interfere with adipose cell differentiation, and the action pattern of adiponectin and leptin until the adipose tissue begins to be dysfunctional. In this state the subject presents insulin resistance and hyperinsulinemia, probably the first step of a dysfunctional metabolic system. Subsequent to central obesity, insulin resistance, hyperglycemia,hypertriglyceridemia, hypoalphalipoproteinemia, hypertension and fatty liver are grouped in the so-called metabolic syndrome (MetS). In subjects with MetS an energy balance is critical to maintain a healthy body weight, mainly limiting the intake of high energy density foods (fat). However, high-carbohydrate rich (CHO) diets increase postprandial peaks of insulin and glucose.Triglyceride-rich lipoproteins are also increased, which interferes with reverse cholesterol transport lowering highdensity lipoprotein cholesterol. In addition, CHO-rich diets could move fat from peripheral to central deposits and reduce adiponectin activity in peripheral adipose tissue. All these are improved with monounsaturated fatty acid-rich diets. Lastly, increased portions of ω-3 and ω-6 fatty acids also decrease triglyceride levels, and complement the healthy diet that is recommended in patients with MetS.

  11. Admission Glycaemia and Acute Insulin Resistance in Heart Failure Complicating Acute Coronary Syndrome.

    Science.gov (United States)

    Lazzeri, Chiara; Valente, Serafina; Chiostri, Marco; D'Alfonso, Maria Grazia; Spini, Valentina; Angelotti, Paola; Gensini, Gian Franco

    2015-11-01

    Few data are so far available on the relation between increased glucose values and insulin resistance and mortality at short-term in patients with acute heart failure (AHF). The present investigation, performed in 409 consecutive patients with AHF complicating acute coronary syndrome (ACS), was aimed at assessing the prognostic role of admission glycaemia and acute insulin resistance (as indicated by the Homeostatic Model Assessment - HOMA index) for death during Intensive Cardiac Care (ICCU) stay. Admission glucose tertiles were considered. In our series, diabetic patients accounted for the 33%. Patients in the third glucose tertiles exhibited the lowest LVEF (both on admission and at discharge), a higher use of mechanical ventilation, intra-aortic balloon pump and inotropic drugs and the highest in-ICCU mortality rate. In the overall population, hyperglycaemic patients (both diabetic and non diabetic) were 227 (227/409, 55.5%). Admission glycaemia was an independent predictor of in-ICCU mortality, together with admission LVEF and eGFR, while acute insulin resistance (as indicated by HOMA-index) was not associated with early death. The presence of admission hyperglycaemia in non-diabetic patients was independently associated with in-ICCU death while hyperglycaemia in diabetic patients was not. According to our results, hyperglycaemia is a common finding in patients with ACS complicated by AHF and it is an independent predictor of early death. Non-diabetic patients with hyperglycaemia are the subgroup with the highest risk of early death. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  12. Assessment of insulin resistance in lean women with polycystic ovary syndrome.

    Science.gov (United States)

    Morciano, Andrea; Romani, Federica; Sagnella, Francesca; Scarinci, Elisa; Palla, Carola; Moro, Francesca; Tropea, Anna; Policola, Caterina; Della Casa, Silvia; Guido, Maurizio; Lanzone, Antonio; Apa, Rosanna

    2014-07-01

    To develop and validate a specific simple measure of insulin sensitivity using oral glucose tolerance test (OGTT) values for lean polycystic ovary syndrome (PCOS) women. Retrospective study. Gynecologic Outpatient Clinic of University Hospital, affiliated with Unit of Gynecologic Endocrinology. Totals of 201 lean and 198 overweight/obese (ov-ob) nondiabetic PCOS patients were retrospectively selected. None. All patients underwent OGTT, euglycemic-hyperinsulinemic clamp, and androgenic and biochemical assays. The predictive performance of each insulin resistance (IR) index was analyzed with the use of receiver operating characteristic (ROC) curves. Higher correlation coefficients with clamp studies were obtained with the Belfiore Area (RS=0.579) and the homeostasis-model assessment (HOMA)-M120 (RS=-0.576) in lean PCOS patients and with the Sib (RS=0.697) in ov-ob PCOS patients. The best predictive index of IR in lean PCOS was a HOMA-M120 value of ≥12.8 or more (area under the ROC curve [AUC] 92.4%). In the ov-ob PCOS population, the best predictive performance was obtained by a Sib of ≤10.2 or less (AUC 85.7%). IR should be assessed in all PCOS women, both lean and ov-ob subjects. The HOMA-M120 resulted as a very simple tool, validated specifically for the lean PCOS woman whose cardiometabolic impairment is more frequently misunderstood. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Hepatic steatosis in young lean insulin resistant women with polycystic ovary syndrome.

    Science.gov (United States)

    Markou, Athina; Androulakis, Ioannis I; Mourmouris, Christos; Tsikkini, Ageliki; Samara, Christianna; Sougioultzis, Stavros; Piaditis, George; Kaltsas, Gregory

    2010-03-01

    To investigate the presence of nonalcoholic fatty liver disease (NAFLD) in young lean women with polycystic ovary syndrome (PCOS) and insulin resistance (IR). Case control study. Women with PCOS and healthy controls in a metabolic day ward. Seventeen young lean women with PCOS and 17 matched controls were studied prospectively. Fasting blood and a glucose tolerance test. Ovarian and liver ultrasonography, and computed tomography (CT) of the liver (women with PCOS only). Anthropometric variables, biochemical and hormonal parameters, and several IR indices were determined. Hepatic lipid content was assessed with ultrasonography and CT of the liver. Women with PCOS had higher androgen levels, and the IR indices, glucose and insulin area under the curve, QUICKI, MATSUDA, and HOMA, compared to controls. In addition to IR, women with PCOS had normal aminotransferase levels, and higher, although within the normal range, alkaline phosphatase levels compared with controls. Women with PCOS had no evidence of NAFLD by either ultrasonography or CT of the liver. Young lean women with PCOS and IR do not have evidence of NAFLD. Because of the presence of IR, follow-up is required to determine whether they are at risk of developing NAFLD. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  14. Therapeutic actions of an insulin receptor activator and a novel peroxisome proliferator-activated receptor gamma agonist in the spontaneously hypertensive obese rat model of metabolic syndrome X.

    Science.gov (United States)

    Velliquette, Rodney A; Friedman, Jacob E; Shao, J; Zhang, Bei B; Ernsberger, Paul

    2005-07-01

    Insulin resistance clusters with hyperlipidemia, impaired glucose tolerance, and hypertension as metabolic syndrome X. We tested a low molecular weight insulin receptor activator, demethylasterriquinone B-1 (DMAQ-B1), and a novel indole peroxisome proliferator-activated receptor gamma agonist, 2-(2-(4-phenoxy-2-propylphenoxy)ethyl)indole-5-acetic acid (PPEIA), in spontaneously hypertensive obese rats (SHROB), a genetic model of syndrome X. Agents were given orally for 19 days. SHROB showed fasting normoglycemia but impaired glucose tolerance after an oral load, as shown by increased glucose area under the curve (AUC) [20,700 mg x min/ml versus 8100 in lean spontaneously hypertensive rats (SHR)]. Insulin resistance was indicated by 20-fold excess fasting insulin and increased insulin AUC (6300 ng x min/ml versus 990 in SHR). DMAQ-B1 did not affect glucose tolerance (glucose AUC = 21,300) but reduced fasting insulin 2-fold and insulin AUC (insulin AUC = 4300). PPEIA normalized glucose tolerance (glucose AUC = 9100) and reduced insulin AUC (to 3180) without affecting fasting insulin. PPEIA also increased food intake, fat mass, and body weight gain (81 +/- 12 versus 45 +/- 8 g in untreated controls), whereas DMAQ-B1 had no effect on body weight but reduced subscapular fat mass. PPEIA but not DMAQ-B1 reduced blood pressure. In skeletal muscle, insulin-stimulated phosphorylation of the insulin receptor and insulin receptor substrate protein 1-associated phosphatidylinositol 3-kinase activity were decreased by 40 to 55% in SHROB relative to lean SHR. PPEIA, but not DMAQ-B1, enhanced both insulin actions. SHROB also showed severe hypertriglyceridemia (355 +/- 42 mg/dl versus 65 +/- 3 in SHR) attenuated by both agents (DMAQ-B1, 228 +/- 18; PPEIA, 79 +/- 3). Both these novel antidiabetic agents attenuate insulin resistance and hypertriglyceridemia associated with metabolic syndrome but via distinct mechanisms.

  15. Relationships between lipid profiles and metabolic syndrome, insulin resistance and serum high molecular adiponectin in Japanese community-dwelling adults

    Directory of Open Access Journals (Sweden)

    Takayama Shuzo

    2011-05-01

    Full Text Available Abstract Background There are few studies to demonstrate the associations between newly addressed lipid profiles and metabolic syndrome (MetS-associated variables. Methods Study participants without medications for hypertension, diabetes, or dyslipidemia {614 men aged 58 ± 14 (mean ± standard deviation; range, 20-89 years and 779 women aged 60 ± 12 (range, 21-88 years} were randomly recruited from a single community at the time of their annual health examination. The association between lipid profiles (total cholesterol (T-C, triglycerides (TG, low-density lipoprotein cholesterol (LDL-C, high-density lipoprotein cholesterol (HDL-C, non-HDL-C, T-C/HDL-C, TG/HDL-C, LDL-C/HDL-C ratio and MetS, Insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR, and serum HMW adiponectin were analyzed. Results In multiple linear regression analysis, TG/HDL-C and T-C/HDL-C ratios as well as TG showed significantly strong associations with all three MetS-associated variables in both men and women. In men, the ROC curve analyses showed that the best marker for these variables was TG/HDL-C ratio, with the AUC for presence of MetS (AUC, 0.82; 95% CI, 0.77-0.87, HOMA-IR (AUC, 0.75; 95% CI, 0.70-0.80, and serum HMW adiponectin (AUC, 0.67; 95% CI, 0.63-0.71, respectively. The T-C/HDL-C ratio, TG, HDL-C, LDL-C/HDL-C ratio, and non-HDL-C also discriminated these markers; however all their AUC estimates were lower than TG/HDL-C ratio. These results were similar in women. Conclusion In Japanese community-dwelling adults, lipid ratios of TG/HDL-C, T-C/HDL-C, LDL-C/HDL-C as well as TG and HDL-C were consistently associated with MetS, insulin resistance and serum HMW adiponectin. Lipid ratios may be used as reliable markers.

  16. Prevalence of insulin resistance and prediction of glucose intolerance and type 2 diabetes mellitus in women with polycystic ovary syndrome.

    Science.gov (United States)

    Vrbikova, Jana; Dvorakova, Katerina; Grimmichova, Tereza; Hill, Martin; Stanicka, Sona; Cibula, David; Bendlova, Bela; Starka, Luboslav; Vondra, Karel

    2007-01-01

    Diabetes mellitus type 2 (DM2) affects 10% of women with polycystic ovary syndrome (PCOS). We evaluated the sensitivity and specificity of clinical and fasting biochemical parameters in screening for impaired glucose tolerance (IGT) and DM2. Women with PCOS [n=244, age 27.4+/-7.5 years, body mass index (BMI) 27.5+/-6.9 kg/m(2)] and healthy women (n=57, age 26.8+/-5.8 years, BMI 21.3+/-2.1 kg/m(2)) underwent basal blood sampling and an oral glucose tolerance test (oGTT). Insulin resistance was identified in 40.2% of PCOS women. Impaired fasting glucose (5.6-6.9 mmol/L) was found in 30 subjects (12.3%), but the oGTT revealed IGT in only six of these cases and DM2 in one subject. IGT was found in 23 (9.4%) and DM2 in four (1.6%) of the women with PCOS. The conventional upper limits for total cholesterol, triglycerides, systolic and diastolic blood pressure and fasting glucose revealed low sensitivity for the identification of impaired glucose metabolism. No single parameter nor any combination of them showed an accuracy sufficient for screening of IGT or DM2 in PCOS patients. All PCOS patients should be screened using an oGTT to identify disturbances in glucose metabolism.

  17. Clopidogrel-Induced Insulin Autoimmune Syndrome: A Newly Recognized Cause of Hypoglycemia in a Patient Without Diabetes.

    Science.gov (United States)

    Rajpal, Aman; Kassem, Laure Sayyed; Moscoso-Cordero, Maria; Arafah, Baha M

    2017-09-01

    Insulin autoimmune syndrome (IAS), defined as hyperinsulinemic hypoglycemia with high titers of anti-insulin antibodies, is frequently reported in Japanese patients but rarely observed in whites. We report in this study on a 79-year-old white male without diabetes who developed IAS following exposure to clopidogrel, a drug not previously known to cause hypoglycemia. The patient presented with recurrent symptomatic hypoglycemia. During one episode, serum glucose was 45 mg/dL, whereas insulin and C-peptide levels were 40,000 mIU/mL and 40 ng/mL, respectively. Additional studies revealed no intake of insulin or its secretagogues, whereas anti-insulin antibody titer was high (59.3 nmol/L). Although total insulin levels were consistently high, free insulin concentrations (polyethylene glycol precipitation) were appropriate for ambient glycemia. The patient was found to have HLA-DRB1*0404, a feature often reported in Japanese patients with IAS. Three weeks prior to symptom onset, he was started on clopidogrel, a drug that does not have a sulfhydryl group, but its active metabolite does. Clopidogrel was switched to a nonsulfhydryl antiplatelet agent, and glucocorticoid therapy was initiated. Shortly thereafter, the frequency of hypoglycemic episodes decreased, and glucocorticoids were tapered over the ensuing 3 months. No hypoglycemic episodes were noted during 6 months of observation after discontinuing glucocorticoids, whereas the total insulin and anti-insulin antibody levels normalized. The data indicate that IAS should be considered in the differential diagnosis of hyperinsulinemic hypoglycemia in seemingly well individuals, even when no drugs known to cause IAS were used. Clinical suspicion of IAS can avoid expensive imaging and unnecessary surgery in affected patients.

  18. Insulin Resistance Is Associated With Smaller Cortical Bone Size in Nondiabetic Men at the Age of Peak Bone Mass.

    Science.gov (United States)

    Verroken, Charlotte; Zmierczak, Hans-Georg; Goemaere, Stefan; Kaufman, Jean-Marc; Lapauw, Bruno

    2017-06-01

    In type 2 diabetes mellitus, fracture risk is increased despite preserved areal bone mineral density. Although this apparent paradox may in part be explained by insulin resistance affecting bone structure and/or material properties, few studies have investigated the association between insulin resistance and bone geometry. We aimed to explore this association in a cohort of nondiabetic men at the age of peak bone mass. Nine hundred ninety-six nondiabetic men aged 25 to 45 years were recruited in a cross-sectional, population-based sibling pair study at a university research center. Insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR), with insulin and glucose measured from fasting serum samples. Bone geometry was assessed using peripheral quantitative computed tomography at the distal radius and the radial and tibial shafts. In age-, height-, and weight-adjusted analyses, HOMA-IR was inversely associated with trabecular area at the distal radius and with cortical area, periosteal and endosteal circumference, and polar strength strain index at the radial and tibial shafts (β ≤ -0.13, P insulin-like growth factor 1, or sex steroid levels. In this cohort of nondiabetic men at the age of peak bone mass, insulin resistance is inversely associated with trabecular and cortical bone size. These associations persist after adjustment for body composition, muscle size or function, or sex steroid levels, suggesting an independent effect of insulin resistance on bone geometry. Copyright © 2017 Endocrine Society

  19. The Biased G-Protein-Coupled Receptor Agonism Bridges the Gap between the Insulin Receptor and the Metabolic Syndrome

    Science.gov (United States)

    Liauchonak, Iryna; Dawoud, Fady; Riat, Yatin; Sambi, Manpreet; Jain, Justin; Kalaydina, Regina-Veronicka; Mendonza, Nicole; Bajwa, Komal

    2018-01-01

    Insulin signaling, as mediated through the insulin receptor (IR), plays a critical role in metabolism. Aberrations in this signaling cascade lead to several pathologies, the majority of which are classified under the umbrella term “metabolic syndrome”. Although many of these pathologies are associated with insulin resistance, the exact mechanisms are not well understood. One area of current interest is the possibility of G-protein-coupled receptors (GPCRs) influencing or regulating IR signaling. This concept is particularly significant, because GPCRs have been shown to participate in cross-talk with the IR. More importantly, GPCR signaling has also been shown to preferentially regulate specific downstream signaling targets through GPCR agonist bias. A novel study recently demonstrated that this GPCR-biased agonism influences the activity of the IR without the presence of insulin. Although GPCR-IR cross-talk has previously been established, the notion that GPCRs can regulate the activation of the IR is particularly significant in relation to metabolic syndrome and other pathologies that develop as a result of alterations in IR signaling. As such, we aim to provide an overview of the physiological and pathophysiological roles of the IR within metabolic syndrome and its related pathologies, including cardiovascular health, gut microflora composition, gastrointestinal tract functioning, polycystic ovarian syndrome, pancreatic cancer, and neurodegenerative disorders. Furthermore, we propose that the GPCR-biased agonism may perhaps mediate some of the downstream signaling effects that further exacerbate these diseases for which the mechanisms are currently not well understood. PMID:29462993

  20. Age and body weight effects on glucose and insulin tolerance in colony cats maintained since weaning on high dietary carbohydrate.

    Science.gov (United States)

    Backus, R C; Cave, N J; Ganjam, V K; Turner, J B M; Biourge, V C

    2010-12-01

    High dietary carbohydrate is suggested to promote development of diabetes mellitus in cats. Glucose tolerance, insulin sensitivity, and insulin secretion were assessed in young [0.8-2.3 (median = 1.1) years, n = 13] and mature [4.0-7.0 (median 5.8) years, n = 12] sexually intact females of a large (n ≅ 700) feline colony in which only dry-type diets (35% metabolizable energy as carbohydrate) were fed from weaning. Insulin sensitivity was assessed from the 'late-phase' (60-120 min) plasma insulin response of intravenous glucose tolerance tests (IVGTTs) and from fractional change in glycaemia from baseline 15 min after an insulin bolus (0.1 U/kg, i.v.). Insulin secretion was assessed from the 'early-phase' (0-15 min) plasma insulin response of IVGTTs. Compared to the young cats, the mature cats had greater body weights [2.3-3.8 (median = 2.9) vs. 3.0-6.3 (median = 4.0) kg, p < 0.01], greater late-phase insulin responses (p < 0.05), lower insulin-induced glycaemic changes (p = 0.06), lower early-phase insulin responses (p < 0.05), and non-significantly different rates of glucose disposal. The late-phase insulin response was correlated with body weight and age (p < 0.05). When group assignments were balanced for body weight, the age-group differences and correlations became non-significant. The findings indicate that body weight gain is more likely than dry-type diets to induce the pre-diabetic conditions of insulin resistance and secretion dysfunction. © 2010 The Authors. Journal of Animal Physiology and Animal Nutrition © 2010 Blackwell Verlag GmbH.

  1. Changes of Heart Structure and Function in Terms of Insulin Resistance at Thyrotoxicosis Syndrome

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    T.Yu. Yuzvenko

    2014-08-01

    Full Text Available The article presents the findings of the study on the effect of increased thyroid function on the background of insulin resistance on the performance of the structure and function of the heart. It has been found that in increased thyroid function, main nosological form of myocardial damage in patients without concomitant cardiovascular disease is the development of metabolic endocrine cardiomyopathy. Feature of heart disorder in thyrotoxicosis syndrome is an absence of cardosclerotic, myocarditic and ischemic processes. Features of clinical, instrumental and laboratory changes in patients with elevated thyroid function are subjective manifestation, trend towards the development of systolic hypertension, expressed hypolipidemia, tendency to hyperglycemia. Manifestations of electrical dysfunction of the myocardium in hyperthyroidism are increased heart rate, expressed trend towards increase of arrhythmogenesis (mainly ventricular type, disturbance of ventricular repolarization and the prevalence of electrical inhomogeneity of the myocardium of both atria and ventricles. Morphofunctional changes of the heart in thyrotoxicosis syndrome manifest by increase in the size of its cavities, left ventricular mass, rapid relaxation of the latter. Heart disease in thyrotoxicosis is characterized by an increase in the duration and dispersion of QTc interval, which indicates a violation of myocardial repolarization, and increase in its electrical inhomogeneity, which can be a predictor of the risk of ventricular arrhythmias. Changes in cardiac function at thyrotoxicosis in male patients are characterized by greater severity of electrophysiological and morphofunctional changes in the myocardium compared to female patients.

  2. Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications.

    Science.gov (United States)

    Vernochet, Cecile; Damilano, Federico; Mourier, Arnaud; Bezy, Olivier; Mori, Marcelo A; Smyth, Graham; Rosenzweig, Anthony; Larsson, Nils-Göran; Kahn, C Ronald

    2014-10-01

    Mitochondrial dysfunction in adipose tissue occurs in obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this dysfunction contributes to or is the result of these disorders is unknown. To investigate the physiological consequences of severe mitochondrial impairment in adipose tissue, we generated mice deficient in mitochondrial transcription factor A (TFAM) in adipocytes by using mice carrying adiponectin-Cre and TFAM floxed alleles. These adiponectin TFAM-knockout (adipo-TFAM-KO) mice had a 75-81% reduction in TFAM in the subcutaneous and intra-abdominal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), causing decreased expression and enzymatic activity of proteins in complexes I, III, and IV of the electron transport chain (ETC). This mitochondrial dysfunction led to adipocyte death and inflammation in WAT and a whitening of BAT. As a result, adipo-TFAM-KO mice were resistant to weight gain, but exhibited insulin resistance on both normal chow and high-fat diets. These lipodystrophic mice also developed hypertension, cardiac hypertrophy, and cardiac dysfunction. Thus, isolated mitochondrial dysfunction in adipose tissue can lead a syndrome of lipodystrophy with metabolic syndrome and cardiovascular complications. © FASEB.

  3. A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals

    Directory of Open Access Journals (Sweden)

    Dorian S Houser

    2013-11-01

    Full Text Available Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris, which fasts from food and water for periods of up to three months. During this time, ~90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7-3.2 mM. All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures

  4. A non-traditional model of the metabolic syndrome: the adaptive significance of insulin resistance in fasting-adapted seals.

    Science.gov (United States)

    Houser, Dorian S; Champagne, Cory D; Crocker, Daniel E

    2013-11-01

    Insulin resistance in modern society is perceived as a pathological consequence of excess energy consumption and reduced physical activity. Its presence in relation to the development of cardiovascular risk factors has been termed the metabolic syndrome, which produces increased mortality and morbidity and which is rapidly increasing in human populations. Ironically, insulin resistance likely evolved to assist animals during food shortages by increasing the availability of endogenous lipid for catabolism while protecting protein from use in gluconeogenesis and eventual oxidation. Some species that incorporate fasting as a predictable component of their life history demonstrate physiological traits similar to the metabolic syndrome during prolonged fasts. One such species is the northern elephant seal (Mirounga angustirostris), which fasts from food and water for periods of up to 4 months. During this time, ∼90% of the seals metabolic demands are met through fat oxidation and circulating non-esterified fatty acids are high (0.7-3.2 mM). All life history stages of elephant seal studied to date demonstrate insulin resistance and fasting hyperglycemia as well as variations in hormones and adipocytokines that reflect the metabolic syndrome to some degree. Elephant seals demonstrate some intriguing adaptations with the potential for medical advancement; for example, ketosis is negligible despite significant and prolonged fatty acid oxidation and investigation of this feature might provide insight into the treatment of diabetic ketoacidosis. The parallels to the metabolic syndrome are likely reflected to varying degrees in other marine mammals, most of which evolved on diets high in lipid and protein content but essentially devoid of carbohydrate. Utilization of these natural models of insulin resistance may further our understanding of the pathophysiology of the metabolic syndrome in humans and better assist the development of preventative measures and therapies.

  5. Leptin and insulin growth factor 1: diagnostic markers of the refeeding syndrome and mortality.

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    Elnenaei, Manal O; Alaghband-Zadeh, Jamshid; Sherwood, Roy; Awara, Mahmoud A; Moniz, Caje; le Roux, Carel W

    2011-09-01

    Refeeding syndrome is difficult to diagnose since the guidelines for identifying those at risk are largely based on subjective clinical parameters and there are no predictive biochemical markers. We examined the suitability of insulin-like growth factor 1 (IGF1) and leptin as markers to identify patients at risk of the refeeding syndrome before initiation of parenteral nutrition (PN). A total of thirty-five consecutive patients referred for commencement of PN were included. Serum leptin and IGF1 were measured before starting PN. Electrolytes, liver and renal function tests were conducted before and daily for 1 week after initiating PN. The primary outcome was a decrease in phosphate 12-36 h after initiating PN. 'Refeeding index' (RI) was defined as leptin × IGF1 divided by 2800 to produce a ratio of 1·0 in patients who are well nourished. RI had better sensitivity (78 %; 95 % CI 40, 97 %) and specificity (78 %; 95 % CI 40, 97 %) with a likelihood ratio of 3·4, at a cut-off value of 0·19 for predicting a ≥ 30 % decrease in phosphate concentration within 12-36 h after starting PN, compared with IGF1 or leptin alone. However, IGF1 was a better predictor of mortality than either leptin or the RI. The present study is the first to derive and test the 'RI', and find that it is a sensitive and specific predictor of the refeeding syndrome in hospitalised patients before starting PN.

  6. Serum concentrations of fibroblast growth factors 19 and 21 in women with gestational diabetes mellitus: association with insulin resistance, adiponectin, and polycystic ovary syndrome history.

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    Dongyu Wang

    Full Text Available BACKGROUND: Fibroblast growth factor 19 (FGF19 and FGF21 are considered to be novel adipokines that improve glucose tolerance and insulin sensitivity. In the current study, we investigated serum FGF19 and FGF21 levels in patients with gestational diabetes mellitus (GDM and explored their relationships with anthropometric and endocrine parameters. METHOD: Serum FGF19 and FGF21 levels were determined by enzyme-linked immunosorbent assay (ELISA in patients with GDM (n = 30 and healthy pregnant controls (n = 60 matched for maternal and gestational age. Serum FGF19 and FGF21 levels were correlated with anthropometric, metabolic, and endocrine parameters. RESULTS: Circulating levels of FGF19 were significantly reduced in patients with GDM relative to healthy pregnant subjects, whereas FGF21 levels were increased in GDM patients. Serum FGF19 levels independently and inversely correlated with insulin resistance (increased homeostasis model assessment of insulin resistance, HOMA-IR and were positively related to serum adiponectin in both groups. In contrast, serum FGF21 levels independently and positively correlated with insulin resistance and serum triglycerides and were inversely related to serum adiponectin. In addition, in the combined population of both groups, those women with preconception polycystic ovary syndrome (PCOS history had the lowest levels of FGF19, which were significantly lower than those in GDM patients without PCOS history and those in controls without PCOS history. CONCLUSIONS: Circulating FGF19 levels are reduced in GDM patients, in contrast with FGF21 levels. Both serum FGF19 and FGF21 levels are strongly related to insulin resistance and serum levels of adiponectin. Considering the different situation between FGF19 and FGF21, we suggest that reduced serum FGF19 levels could be involved in the pathophysiology of GDM, while increased serum FGF21 levels could be in a compensatory response to this disease.

  7. Serum concentrations of fibroblast growth factors 19 and 21 in women with gestational diabetes mellitus: association with insulin resistance, adiponectin, and polycystic ovary syndrome history.

    Science.gov (United States)

    Wang, Dongyu; Zhu, Wenjing; Li, Jieming; An, Chongyou; Wang, Zilian

    2013-01-01

    Fibroblast growth factor 19 (FGF19) and FGF21 are considered to be novel adipokines that improve glucose tolerance and insulin sensitivity. In the current study, we investigated serum FGF19 and FGF21 levels in patients with gestational diabetes mellitus (GDM) and explored their relationships with anthropometric and endocrine parameters. Serum FGF19 and FGF21 levels were determined by enzyme-linked immunosorbent assay (ELISA) in patients with GDM (n = 30) and healthy pregnant controls (n = 60) matched for maternal and gestational age. Serum FGF19 and FGF21 levels were correlated with anthropometric, metabolic, and endocrine parameters. Circulating levels of FGF19 were significantly reduced in patients with GDM relative to healthy pregnant subjects, whereas FGF21 levels were increased in GDM patients. Serum FGF19 levels independently and inversely correlated with insulin resistance (increased homeostasis model assessment of insulin resistance, HOMA-IR) and were positively related to serum adiponectin in both groups. In contrast, serum FGF21 levels independently and positively correlated with insulin resistance and serum triglycerides and were inversely related to serum adiponectin. In addition, in the combined population of both groups, those women with preconception polycystic ovary syndrome (PCOS) history had the lowest levels of FGF19, which were significantly lower than those in GDM patients without PCOS history and those in controls without PCOS history. Circulating FGF19 levels are reduced in GDM patients, in contrast with FGF21 levels. Both serum FGF19 and FGF21 levels are strongly related to insulin resistance and serum levels of adiponectin. Considering the different situation between FGF19 and FGF21, we suggest that reduced serum FGF19 levels could be involved in the pathophysiology of GDM, while increased serum FGF21 levels could be in a compensatory response to this disease.

  8. Circulating osteoprotegerin and soluble receptor activator of nuclear factor κB ligand in polycystic ovary syndrome: relationships to insulin resistance and endothelial dysfunction.

    Science.gov (United States)

    Pepene, Carmen Emanuela; Ilie, Ioana Rada; Marian, Ioan; Duncea, Ileana

    2011-01-01

    There is plenty of evidence that osteoprotegerin (OPG) is linked to subclinical vascular damage and predicts cardiovascular disease in high-risk populations. Our aim is to investigate the relationships of OPG/free soluble receptor activator of nuclear factor κB ligand (sRANKL) to insulin resistance, brachial artery flow-mediated vasodilation (FMD), and the carotid artery intima-media thickness (CIMT) in polycystic ovary syndrome (PCOS), a disorder characterized by hyperandrogenism, impaired glucose control, and endothelial injury. A cross-sectional, observational study. Hormonal and metabolic profiles, FMD, CIMT, serum OPG, and ampli-sRANKL were assessed in 64 young PCOS patients and 20 controls of similar age. Body composition was measured by dual energy X-ray absorptiometry. OPG was significantly lower in PCOS and related negatively to free testosterone and positively to estradiol (E(2)) levels. In multivariate analysis, OPG but not ampli-sRANKL correlated positively to fasting insulin, insulin sensitivity indices, and FMD. Neither OPG nor ampli-sRANKL was associated with CIMT. Significantly lower adjusted FMD values were demonstrated in women in the upper OPG quartile group (>2.65 pmol/l) compared with all other quartile groups together (P=0.012). In PCOS, multiple regression analysis retained E(2)/sex hormone-binding globulin ratio, fat mass, and homeostasis model assessment of insulin resistance as independent predictors of OPG. In PCOS, circulating OPG is related to both endothelial dysfunction and insulin resistance, independent of obesity and androgen excess, suggesting OPG as a useful biomarker of these effects. Further studies are needed to evaluate OPG in relation to cardiovascular events and cardiovascular mortality in PCOS.

  9. Utility of the modified ATP III defined metabolic syndrome and severe obesity as predictors of insulin resistance in overweight children and adolescents: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Agarwalla Vipin

    2007-02-01

    Full Text Available Abstract Background The rising prevalence of obesity and metabolic syndrome (MetS has received increased attention since both place individuals at risk for Type II diabetes and cardiovascular disease. Insulin resistance (IR has been implicated in the pathogenesis of obesity and MetS in both children and adults and is a known independent cardiovascular risk factor. However measures of IR are not routinely performed in children while MetS or severe obesity when present, are considered as clinical markers for IR. Objective The study was undertaken to assess the utility of ATPIII defined metabolic syndrome (MetS and severe obesity as predictors of insulin resistance (IR in a group of 576 overweight children and adolescents attending a pediatric obesity clinic in Brooklyn. Methods Inclusion criteria were children ages 3–19, and body mass index > 95th percentile for age. MetS was defined using ATP III criteria, modified for age. IR was defined as upper tertile of homeostasis model assessment (HOMA within 3 age groups (3–8, n = 122; 9–11, n = 164; 12–19, n = 290. Sensitivity, specificity, positive predictive values and odds ratios (OR with 95% confidence intervals (CI were calculated within age groups for predicting IR using MetS and severe obesity respectively. Results MetS was present in 45%, 48% and 42% of the respective age groups and significantly predicted IR only in the oldest group (OR = 2.0, 95% CI 1.2, 3.4; p = .006. Sensitivities were Conclusion The expression of IR in overweight children and adolescents is heterogeneous and MetS or severe obesity may not be sufficiently sensitive and specific indicators of insulin resistance. In addition to screening for MetS in overweight children markers for IR should be routinely performed. Further research is needed to establish threshold values of insulin measures in overweight children who may be at greater associated risk of adverse outcomes whether or not MetS is present.

  10. Defective insulin signaling and the protective effects of dimethyldiguanide during follicular development in the ovaries of polycystic ovary syndrome.

    Science.gov (United States)

    Wang, Fan; Wang, Shaobing; Zhang, Zhenghong; Lin, Qingqiang; Liu, Yiping; Xiao, Yijun; Xiao, Kaizhuan; Wang, Zhengchao

    2017-12-01

    It is established that the physiological effects of insulin are primarily mediated by the insulin signaling pathway. However, a defective insulin signaling is closely associated with the clinical manifestations of polycystic ovary syndrome (PCOS), which include excess androgen levels, insulin resistance and anovulation, and is involved in the pathophysiology of PCOS at the molecular level. Dimethyldiguanide (DMBG) has been widely employed to alleviate reproduction dysfunction in women with PCOS, however, the exact mechanism of this effect remains unclear. The objective of the present study was to investigate the effects of DMBG on the expression of the insulin signaling pathway in the ovaries of rats with PCOS, and to identify the potential underlying molecular mechanisms of these effects in PCOS. In the present study, a PCOS rat model was induced by letrozole, and successful establishment of the model was confirmed by examining ovarian histology and determining serum testosterone levels, by hematoxylin and eosin staining and ELISA, respectively. Subsequently, the expression of two key elements of insulin signaling, insulin receptor substrate (IRS)‑2 and phosphatidylinositol 3‑kinase (PI3K), was determined by immunohistochemistry and western blot analysis. The results demonstrated that IRS‑2 and PI3K expression was markedly decreased in PCOS ovaries, which was rescued by DMBG treatment. These results indicate that IRS‑2/PI3K signaling may be involved in the development of PCOS and the therapeutic effects of DMBG on PCOS. To further confirm the effects of DMBG on insulin signaling expression during this process, the expression of an additional two downstream proteins, phosphoinositide‑dependent kinase‑1 (PDK‑1) and the mammalian target of rapamycin (mTOR), was also investigated in the present study, and the results demonstrated that the expression of PDK‑1 and mTOR was significantly reduced in PCOS ovaries and increased following DMBG treatment

  11. Over-stimulation of insulin/IGF-1 signaling by western diet may promote diseases of civilization: lessons learnt from laron syndrome

    OpenAIRE

    Schmitz Gerd; John Swen; Melnik Bodo C

    2011-01-01

    Abstract The insulin/insulin-like growth factor-1 (IGF-1) pathway drives an evolutionarily conserved network that regulates lifespan and longevity. Individuals with Laron syndrome who carry mutations in the growth hormone receptor (GHR) gene that lead to severe congenital IGF-1 deficiency with decreased insulin/IGF-1 signaling (IIS) exhibit reduced prevalence rates of acne, diabetes and cancer. Western diet with high intake of hyperglycemic carbohydrates and insulinotropic dairy over-stimulat...

  12. [Physiological patterns of intestinal microbiota. The role of dysbacteriosis in obesity, insulin resistance, diabetes and metabolic syndrome].

    Science.gov (United States)

    Halmos, Tamás; Suba, Ilona

    2016-01-03

    The intestinal microbiota is well-known for a long time, but due to newly recognized functions, clinician's attention has turned to it again in the last decade. About 100 000 billion bacteria are present in the human intestines. The composition of bacteriota living in diverse parts of the intestinal tract is variable according to age, body weight, geological site, and diet as well. Normal bacteriota defend the organism against the penetration of harmful microorganisms, and has many other functions in the gut wall integrity, innate immunity, insulin sensitivity, metabolism, and it is in cross-talk with the brain functions as well. It's a recent recognition, that intestinal microbiota has a direct effect on the brain, and the brain also influences the microbiota. This two-way gut-brain axis consists of microbiota, immune and neuroendocrine system, as well as of the autonomic and central nervous system. Emerging from fermentation of carbohydrates, short-chain fatty acids develop into the intestines, which produce butyrates, acetates and propionates, having favorable effects on different metabolic processes. Composition of the intestinal microbiota is affected by the circadian rhythm, such as in shift workers. Dysruption of circadian rhythm may influence intestinal microbiota. The imbalance between the microbiota and host organism leads to dysbacteriosis. From the membrane of Gram-negative bacteria lipopolysacharides penetrate into the blood stream, via impaired permeability of the intestinal mucosa. These processes induce metabolic endotoxaemia, inflammation, impaired glucose metabolism, insulin resistance, obesity, and contribute to the development of metabolic syndrome, type 2 diabetes, inflammarory bowel diseases, autoimmunity and carcinogenesis. Encouraging therapeutic possibility is to restore the normal microbiota either using pro- or prebiotics, fecal transplantation or bariatric surgery. Human investigations seem to prove that fecal transplant from lean

  13. Serum insulin-like growth factor 1 in the aging horse

    DEFF Research Database (Denmark)

    Lygren, Tone; Hansen, Sanni; Langberg, Henning

    2014-01-01

    BACKGROUND: Insulin-like growth factor 1 (IGF-1) has important roles in anabolic processes in the musculoskeletal system and has been reported to decrease with age in both people and horses. OBJECTIVES: The objective of this study was to determine serum IGF-1 levels in the aging horse from early...... was found between serum IGF-1 levels and age in the cross-sectional study. In the longitudinal study, a latent variable model fitted to the data revealed that horses in general experienced a 5.2% increase of serum IGF-1 levels over a 5-year period, but horses crossing a change point around 9 years of age...... between the 2 samples experienced an 11.0% decrease. CONCLUSIONS: In this study, there was no evidence for aging being a factor in changes of IGF-1 levels in an adult and old horse population....

  14. Insulin-resistance and metabolic syndrome are related to executive function in women in a large family-based study.

    Science.gov (United States)

    Schuur, M; Henneman, P; van Swieten, J C; Zillikens, M C; de Koning, I; Janssens, A C J W; Witteman, J C M; Aulchenko, Y S; Frants, R R; Oostra, B A; van Dijk, K Willems; van Duijn, C M

    2010-08-01

    While type 2 diabetes is well-known to be associated with poorer cognitive performance, few studies have reported on the association of metabolic syndrome (MetS) and contributing factors, such as insulin-resistance (HOMA-IR), low adiponectin-, and high C-reactive protein (CRP)-levels. We studied whether these factors are related to cognitive function and which of the MetS components are independently associated. The study was embedded in an ongoing family-based cohort study in a Dutch population. All participants underwent physical examinations, biomedical measurements, and neuropsychological testing. Linear regression models were used to determine the association between MetS, HOMA-IR, adiponectin levels, CRP, and cognitive test scores. Cross-sectional analyses were performed in 1,898 subjects (mean age 48 years, 43% men). People with MetS had significantly higher HOMA-IR scores, lower adiponectin levels, and higher CRP levels. MetS and high HOMA-IR were associated with poorer executive function in women (P = 0.03 and P = 0.009). MetS and HOMA-IR are associated with poorer executive function in women.

  15. Effects of exercise on insulin resistance and body composition in overweight and obese women with and without polycystic ovary syndrome.

    Science.gov (United States)

    Hutchison, Samantha K; Stepto, Nigel K; Harrison, Cheryce L; Moran, Lisa J; Strauss, Boyd J; Teede, Helena J

    2011-01-01

    Polycystic ovary syndrome (PCOS) is an insulin-resistant (IR) state. Visceral fat (VF) is independently associated with IR. The objectives of the study were to explore mechanisms underpinning IR by assessing the effect of exercise training on IR and body composition in overweight PCOS and non-PCOS women. This was a prospective exercise intervention study. The study was conducted at an academic medical center. Participants included 20 overweight PCOS and 14 overweight non-PCOS women. The intervention included 12 wk of intensified aerobic exercise (3 h/wk). IR on euglycemic hyperinsulinemic clamp, body composition including abdominal visceral and sc fat distribution by computer tomography and lipids was measured. PCOS subjects were more IR (P = 0.02) and had more VF (P = 0.04 age adjusted) than non-PCOS women. In PCOS women, IR correlated with VF (r = -0.78, P cardiometabolic risk factors including IR, triglycerides, and VF in PCOS were observed without significant weight loss and if confirmed in future controlled trials, suggest weight loss should not be the sole focus of exercise programs.

  16. The impact of insulin resistance on clinical, hormonal and metabolic parameters in lean women with polycystic ovary syndrome.

    Science.gov (United States)

    Yildizhan, Begum; Anik Ilhan, Gokce; Pekin, Tanju

    2016-10-01

    This study was performed to assess insulin resistance (IR) in lean women with polycystic ovary syndrome (PCOS). Retrospective analysis of 100 consecutive lean (body mass index PCOS subjects was performed. Subjects were divided into two groups according to homeostasis model assessment IR index (HOMA-IR), as IR + and IR-. A HOMA-IR value >2.5 was used to indicate IR. A total of 100 lean PCOS subjects were enrolled in the study, of which 47% were insulin resistant. Comparison of group means showed significantly higher values for waist-to-hip ratio (WHR), diastolic blood pressure and Ferriman-Gallwey score (FGS) in IR + group. HOMA-IR values were found to be positively correlated with WHR (r = 0.500, p PCOS subjects, the insulin resistant group should be separated as unique and IR should also be evaluated in lean women with PCOS.

  17. Epigenetic oxidative redox shift (EORS) theory of aging unifies the free radical and insulin signaling theories.

    Science.gov (United States)

    Brewer, Gregory J

    2010-03-01

    Harman's free radical theory of aging posits that oxidized macromolecules accumulate with age to decrease function and shorten life-span. However, nutritional and genetic interventions to boost anti-oxidants have generally failed to increase life-span. Furthermore, the free radical theory fails to explain why exercise causes higher levels of oxyradical damage, but generally promotes healthy aging. The separate anti-aging paradigms of genetic or caloric reductions in the insulin signaling pathway is thought to slow the rate of living to reduce metabolism, but recent evidence from Westbrook and Bartke suggests metabolism actually increases in long-lived mice. To unify these disparate theories and data, here, we propose the epigenetic oxidative redox shift (EORS) theory of aging. According to EORS, sedentary behavior associated with age triggers an oxidized redox shift and impaired mitochondrial function. In order to maintain resting energy levels, aerobic glycolysis is upregulated by redox-sensitive transcription factors. As emphasized by DeGrey, the need to supply NAD(+) for glucose oxidation and maintain redox balance with impaired mitochondrial NADH oxidoreductase requires the upregulation of other oxidoreductases. In contrast to the 2% inefficiency of mitochondrial reduction of oxygen to the oxyradical, these other oxidoreductases enable glycolytic energy production with a deleterious 100% efficiency in generating oxyradicals. To avoid this catastrophic cycle, lactate dehydrogenase is upregulated at the expense of lactic acid acidosis. This metabolic shift is epigenetically enforced, as is insulin resistance to reduce mitochondrial turnover. The low mitochondrial capacity for efficient production of energy reinforces a downward spiral of more sedentary behavior leading to accelerated aging, increased organ failure with stress, impaired immune and vascular functions and brain aging. Several steps in the pathway are amenable to reversal for exit from the vicious

  18. Association of mean platelet volume with androgens and insulin resistance in nonobese patients with polycystic ovary syndrome.

    Science.gov (United States)

    Dogan, Bercem Aycicek; Arduc, Ayse; Tuna, Mazhar Muslum; Karakılıc, Ersen; Dagdelen, Iffet; Tutuncu, Yasemin; Berker, Dilek; Guler, Serdar

    2014-10-01

    Mean platelet volume (MPV) is generally accepted as a new marker of cardiovascular disease risk in several studies. This study aimed to determine the association of MPV with androgen hormones and insulin resistance (IR) in nonobese patients with polycystic ovary syndrome (PCOS). A total of 136 patients with newly diagnosed reproductive-age PCOS (regarding the criteria of new PCOS phenotypes, based on the Rotterdam criteria) who were nonobese with the mean age of 25 years (25.39 ± 5.51) and mean body mass index (BMI) of 21 kg/m(2) (22.07 ± 2.13) were included. In addition, 59 healthy subjects with mean age of 26 years (22.07 ± 2.13) and mean BMI of 22 kg/m(2) (21.52 ± 3.84) were recruited as control. Total blood count (including MPV), total testosterone, free testosterone, dehydroepiandrosterone-sulfate (DHEAS), and androstenedione levels were recorded. IR was calculated from blood chemistry measurements of fasting insulin and glucose according to updated homeostasis model assessment. No differences were observed in mean MPV values between patients and control group (9.02 fL (8.5-10.1) and 8.9 fL (7.7-9.1), respectively; P = 0.777). MPV values were similar among nonobese patients with and without IR and control subjects (P > 0.05). We detected significantly lower values of MPV in patients with hyperandrogenemia in comparison to patients with normal androgen levels (8.7 and 9.5 fL, P = 0.012). There was a negative correlation between total testosterone, DHEAS, and MPV (P = 0.016, r = -0.229; and P = 0.006, r = -0.261, respectively). Multiple logistic regression analyses confirmed the independence of these associations. Our study revealed that nonobese women with and without PCOS have similar MPV values. While IR does not have any effect on MPV, elevated androgen levels are associated with a low MPV in nonobese patients with PCOS.

  19. Silymarin ameliorates fructose induced insulin resistance syndrome by reducing de novo hepatic lipogenesis in the rat.

    Science.gov (United States)

    Prakash, Prem; Singh, Vishal; Jain, Manish; Rana, Minakshi; Khanna, Vivek; Barthwal, Manoj Kumar; Dikshit, Madhu

    2014-03-15

    High dietary fructose causes insulin resistance syndrome (IRS), primarily due to simultaneous induction of genes involved in glucose, lipid and mitochondrial oxidative metabolism. The present study evaluates effect of a hepatoprotective agent, silymarin (SYM) on fructose-induced metabolic abnormalities in the rat and also assessed the associated thrombotic complications. Wistar rats were kept on high fructose (HFr) diet throughout the 12-week study duration (9 weeks of HFr feeding and subsequently 3 weeks of HFr plus SYM oral administration [once daily]). SYM treatment significantly reduced the HFr diet-induced increase expression of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α/β, peroxisome proliferator-activated receptor (PPAR)-α, forkhead box protein O1 (FOXO1), sterol regulatory element binding protein (SREBP)-1c, liver X receptor (LXR)-β, fatty acid synthase (FAS) and PPARγ genes in rat liver. SYM also reduced HFr diet mediated increase in plasma triglycerides (TG), non-esterified fatty acids (NEFA), uric acid, malondialdehyde (MDA), total nitrite and pro-inflammatory cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-gamma [IFN-γ] and tumor necrosis factor [TNF]) levels. Moreover, SYM ameliorated HFr diet induced reduction in glucose utilization and endothelial dysfunction. Additionally, SYM significantly reduced platelet activation (adhesion and aggregation), prolonged ferric chloride-induced blood vessel occlusion time and protected against exacerbated myocardial ischemia reperfusion (MI-RP) injury. SYM treatment prevented HFr induced mRNA expression of hepatic PGC-1α/β and also its target transcription factors which was accompanied with recovery in insulin sensitivity and reduced propensity towards thrombotic complications and aggravated MI-RP injury. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Impact of Roux-en-Y Gastric Bypass on Metabolic Syndrome and Insulin Resistance Parameters

    Science.gov (United States)

    Gestic, Martinho Antonio; Utrini, Murillo Pimentel; Machado, Ricardo Rossetto; Geloneze, Bruno; Pareja, José Carlos; Chaim, Elinton Adami

    2014-01-01

    Abstract Background: Metabolic syndrome (MetS) is a complex association of clustering metabolic factors that increase risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease. Surgical treatment has become an important tool to achieve its control. The aim of this study was to evaluate the impact of Roux-en-Y gastric bypass (RYGB) on MetS and its individual components, clinical characteristics, and biochemical features. Subjects and Methods: The study is a retrospective cohort of 96 subjects with MetS who underwent RYGB and were evaluated at baseline and after surgery. Clinical and biochemical features were analyzed. Results: After surgery, significant rates of resolution for MetS (88.5%), T2DM (90.6%), hypertension (85.6%), and dyslipidemias (54.2%) were found. Significant decreases in levels of fasting glucose, fasting insulin, hemoglobin A1c, low-density lipoprotein, and triglycerides and an increase in high-density lipoprotein level were also shown. The decrease in insulin resistance evaluated by homeostasis model assessment (HOMA-IR) was consistent. MetS resolution was associated with postoperative glycemic control, decreases in levels of fasting glucose, hemoglobin A1c, HOMA-IR, and triglycerides and in antihypertensive usage, and percentage weight loss. Conclusions: This study found high rates of resolution for MetS, T2DM, hypertension, and dyslipidemias after RYGB in obese patients. This finding was consistent with current literature. Hence RYGB should be largely indicated for this group of subjects as it is a safe and powerful tool to achieve MetS control. PMID:24299427

  1. Polycystic ovary syndrome: insight into pathogenesis and a common association with insulin resistance

    OpenAIRE

    Barber, TM; Dimitriadis, GK; Andreou, A; Franks, S

    2015-01-01

    Polycystic ovary syndrome (PCOS) is a common condition that typically develops in reproductive-age women. The cardinal clinical and biochemical characteristics of PCOS include reproductive dysfunction and hyperandrogenic features. PCOS is also strongly associated with obesity based on data from epidemiological and genetic studies. Accordingly, PCOS often becomes manifest in those women who carry a genetic predisposition to its development, and who also gain weight. The role of weight gain and...

  2. Postprandial changes in glucose oxidation and insulin sensitivity in metabolic syndrome: Influence of fibroblast growth factor 21 and vitamin D status.

    Science.gov (United States)

    Pathak, Kaveri; Soares, Mario J; Zhao, Yun; James, Anthony P; Sherriff, Jillian L; Newsholme, Philip

    2017-05-01

    Metabolic inflexibility due to insulin resistance has been reported in metabolic syndrome (MetS). Fibroblast growth factor 21 (FGF21) and vitamin D status may improve insulin sensitivity. The aim of this study was to investigate glucose-induced thermogenesis and oxidation in MetS, and to examine whether changes in FGF21 or prevailing vitamin D status modulated defined metabolic parameters. Forty-eight overweight and obese older adults (14 men, 34 women; ages 51 ± 15 y) were studied. Resting metabolic rate (RMR) and respiratory quotient (RQ) were measured before and intermittently for 2 h after an oral glucose tolerance test (OGTT). The total area under the curve (TAUC) was calculated. Insulin sensitivity index (ISI) was determined as 10 4 /(insulin × glucose) for fasting and 2 h venous blood. Fat mass (FM) and fat free mass (FFM) were measured by dual-energy x-ray absorptiometry. Participants were grouped by metabolic syndrome (MetS+ for disease presence; MetS- when no disease was present) and by median 25 hydroxyvitamin D (OHD) concentration as VD_low and VD_high. 25 OHD was also tested as a continuous variable. A parsimonious 2 × 2 analysis of variance included age, FM, FFM and MetS × sex interaction. Adjusted RMR was similar between groups but an interactive effect of MetS and sex was noted. Fasting RQ was significantly different between vitamin groups (VD_low: 0.835 ± 0.008 versus VD_high: 0.810 ± 0.008; P = 0.024) and fasting ISI was significantly greater in MetS- compared with MetS+ (P = 0.037). Postglucose increases in thermogenesis, RQ, and FGF21 were significant, but ISI decreased. Adjusted postprandial TAUC_RQ (VD_low: 1.71 ± 0.01; VD_high: 1.74 ± 0.001; P = 0.041) and ISI_2 h (VD_low: 35.41 ± 0.21; VD_high: 101.90 ± 0.21; P = 0.001) were significantly different. Adjusted FGF21 was similar across all comparisons before and after OGTT. Higher vitamin D status, but not FGF21, was associated with greater postprandial

  3. The relationship between maternal insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and IGFBP-3 to gestational age and preterm delivery.

    LENUS (Irish Health Repository)

    Cooley, Sharon M

    2010-05-01

    To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational age at delivery.

  4. Parental-age effects in Down syndrome

    Indian Academy of Sciences (India)

    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Introduction .... currence risk for younger women, by the age of 40, the re- currence risk is not ..... Published on the Web: 30 March 2009. Journal of Genetics ...

  5. Prevalence, incidence, and age at diagnosis in Marfan Syndrome

    DEFF Research Database (Denmark)

    Groth, Kristian A; Hove, Hanne; Kyhl, Kasper

    2015-01-01

    Background: Marfan syndrome is a genetic disorder with considerable morbidity and mortality. Presently, clinicians use the 2010 revised Ghent nosology, which includes optional genetic sequencing of the FBN1 gene, to diagnose patients. So far, only a few studies based on older diagnostic criteria...... have reported a wide range of prevalence and incidence. Our aim was to study prevalence, incidence, and age at diagnosis in patients with Marfan syndrome. Method: Using unique Danish patient-registries, we identified all possible Marfan syndrome patients recorded by the Danish healthcare system (1977......-2014). Following, we confirmed or rejected the diagnosis according to the 2010 revised Ghent nosology. Results: We identified a total of 1628 persons with possible Marfan syndrome. We confirmed the diagnosis in 412, whereof 46 were deceased, yielding a maximum prevalence of 6.5/100,000 at the end of 2014...

  6. Insulin resistance improvement by cinnamon powder in polycystic ovary syndrome: A randomized double-blind placebo controlled clinical trial.

    Science.gov (United States)

    Hajimonfarednejad, Mahdie; Nimrouzi, Majid; Heydari, Mojtaba; Zarshenas, Mohammad Mehdi; Raee, Mohammad Javad; Jahromi, Bahia Namavar

    2018-02-01

    Our aim is to assess the effect of cinnamon powder capsules on insulin resistance, anthropometric measurements, glucose and lipid profiles, and androgens of women with polycystic ovarian syndrome (PCOS). Out of 80 women that were diagnosed as PCOS by Rotterdam Criteria, 66 were enrolled in this randomized double-blind placebo-controlled clinical trial. All of the PCOS women were taking medroxy progesterone acetate 10 mg/day for the last 10 days of their menstrual cycles. The cases were randomly allocated to 2 groups. The women in the first group were treated by cinnamon powder capsules 1.5 g/day in 3 divided doses for 12 weeks and the second group by similar placebo capsules. Anthropometric measurements, fasting blood sugar, fasting insulin, blood glucose 2 hr after taking 75 g oral glucose, HbA1c, testosterone, dehydroepiandrosterone sulphate, homeostatic model assessment for insulin resistance, triglyceride, and cholesterol (low-density lipoprotein, high-density lipoprotein, and total) before and after the intervention were evaluated and compared as outcome measures. Fasting insulin (p = .024) and homeostatic model assessment for insulin resistance (p = .014) were reduced after 12 weeks in the cinnamon group compared with the placebo. There was also a significant decrease in low-density lipoprotein in cinnamon group (p = .004) as compared with baseline that caused significant difference with placebo (p = .049). However, changes in other outcome measurements did not lead to statistically significant difference with placebo. The present results suggest that complementary supplementation of cinnamon significantly reduced fasting insulin and insulin resistance in women with PCOS. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Association Between Omentin, Visfatin and Insulin-Like Growth Factor-1 in Women With Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Goodarzi

    2014-12-01

    Full Text Available Background Adipokines that are produced by adipose tissue have extensive effects on carbohydrate and lipid metabolism and also on the pathogenesis of the metabolic syndrome (MetS. Objectives This study aimed to measure the concentrations of omentin-1, visfatin and insulin-like growth factor-1 (IGF-1 as likely markers of metabolic syndrome and also to demonstrate their associations in women with MetS. Materials and Methods Eighty women with MetS and eighty healthy women as controls participated in this study. Blood pressure, waist circumference, body mass index (BMI, and serum biochemical parameters were determined in all subjects. The serum level of IGF-1, omentin-1 and visfatin were assessed using the enzyme linked immunosorbent assay (ELISA. The association between omentin, visfatin and IGF-1 was also determined in these women. Results Significantly lower levels of omentin-1 and IGF-1 were observed in MetS subjects compared to the controls (P = 0.009 and < 0.001 respectively. However, a significant difference was not observed in visfatin concentration between the two studied groups (P = 0.67. A positive association was observed between omentin-1, visfatin and IGF-1 in the MetS group. Conclusions Our findings indicated a lower level of both omentin-1 and IGF-1 in women with MetS; this might play a role in the pathogenesis of MetS. Furthermore, the main finding of the current investigation was the association between omentin, visfatin and IGF-1; however determining the molecular mechanism of the observed relationships needs further studies.

  8. Impaired insulin signaling and spatial learning in middle-aged rats: The role of PTP1B.

    Science.gov (United States)

    Kuga, Gabriel Keine; Muñoz, Vitor Rosetto; Gaspar, Rafael Calais; Nakandakari, Susana Castelo Branco Ramos; da Silva, Adelino Sanchez Ramos; Botezelli, José Diego; Leme, José Alexandre Curiacos de Almeida; Gomes, Ricardo José; de Moura, Leandro Pereira; Cintra, Dennys Esper; Ropelle, Eduardo Rochete; Pauli, José Rodrigo

    2018-04-01

    The insulin and Brain-Derived Neurotrophic Factor (BDNF) signaling in the hippocampus promotes synaptic plasticity and memory formation. On the other hand, aging is related to the cognitive decline and is the main risk factor for Alzheimer's Disease (AD). The Protein-Tyrosine Phosphatase 1B (PTP1B) is related to several deleterious processes in neurons and emerges as a promising target for new therapies. In this context, our study aims to investigate the age-related changes in PTP1B content, insulin signaling, β-amyloid content, and Tau phosphorylation in the hippocampus of middle-aged rats. Young (3 months) and middle-aged (17 months) Wistar rats were submitted to Morris-water maze (MWM) test, insulin tolerance test, and molecular analysis in the hippocampus. Aging resulted in increased body weight, and insulin resistance and decreases learning process in MWM. Interestingly, the middle-aged rats have higher levels of PTP-1B, lower phosphorylation of IRS-1, Akt, GSK3β, mTOR, and TrkB. Also, the aging process increased Tau phosphorylation and β-amyloid content in the hippocampus region. In summary, this study provides new evidence that aging-related PTP1B increasing, contributing to insulin resistance and the onset of the AD. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Impaired insulin activation and dephosphorylation of glycogen synthase in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Nicoline Resen

    2008-01-01

    CONTEXT: Insulin resistance is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). The molecular mechanisms underlying reduced insulin-mediated glycogen synthesis in skeletal muscle of patients with PCOS have not been established. SUBJECTS AND METHODS: We...... metabolically characterized by euglycemic-hyperinsulinemic clamps and indirect calorimetry. RESULTS: Reduced insulin-mediated glucose disposal (P .... No significant abnormalities in GSK-3alpha or -3beta were found in PCOS subjects. Pioglitazone treatment improved insulin-stimulated glucose metabolism and GS activity in PCOS (all P

  10. Fragile X Syndrome: An Aging Perspective

    Science.gov (United States)

    Schneider, Andrea; Ligsay, Andrew; Hagerman, Randi J.

    2013-01-01

    Cognitive and behavioral correlates of molecular variations related to the FMR1 gene have been studied rather extensively, but research about the long-term outcome in individuals with fragile X spectrum disorders remains sparse. In this review, we present an overview of aging research and recent findings in regard to cellular and clinical…

  11. [Effect of insulin on burn wound healing in aging diabetes mellitus rats].

    Science.gov (United States)

    Wu, Jian; Xue, Xiaodong; Liu, Junling; Si, Xiaoqiang; Yang, Guohu

    2009-12-01

    To investigate the effect of topical application of insulin on the burn wound healing in aging diabetes mellitus (DM) rats and to explore its mechanism. Seventy-five SPF Wistar rats (female and/or male), aged 12-24 months and weighing 300-350 g, were selected and randomly divided into group A (burn control group, n=25), group B (DM burn control group, n=25), and group C (DM insulin treatment group, n=25). The rats in group B and group C were fed with high-fat, high-protein, and high-sugar forage for 1 month and received intraperitoneal injection of streptozotocin (STZ) to establish experimental model of aging DM. The rats were fed with high-fat, high-protein, and high-sugar forage for another 8 weeks. Then, the deep second-degree burn model was established in the rats of group B and group C. The wounds in group A and B underwent local subcutaneous injection of 2 mL isotonic saline and group C received local subcutaneous injection of 0.1 U insulin. The rate of wound healing was calculated 7, 14, and 21 days after burn injury. At 1, 3, 7, 14, and 21 days after burn injury, HE staining observation, immunohistochemistry staining for CD34, detection of sugar and hydroxyproline (HOP) content in wound tissue, and microvessel density (MVD) calculation were performed. At 7, 14, and 21 days after burn injury, the wound healing rates of group A and group C was significantly higher than that of group B (P 0.05). Histology observation at 21 days after burn injury: in group A, certain degree of epithelization was evident in the wound epithelium; in group B, large quantity of necrotic tissue was evident; in group C, complete epithelization occurred in the wound epithelium with better epithelial cell differentiation and more neonatal collagen. For the sugar content in the wound tissue, group A was significantly lower than group B or group C at 1, 3, 7, 14, and 21 days (P wound tissue and the MVD count, group A or group C was significantly higher than group B (P 0.05). CD34

  12. Home-based exercise may not decrease the insulin resistance in individuals with metabolic syndrome.

    Science.gov (United States)

    Chen, Chiao-Nan; Chuang, Lee-Ming; Korivi, Mallikarjuna; Wu, Ying-Tai

    2015-01-01

    This study investigated the differences in exercise self-efficacy, compliance, and effectiveness of home-based exercise in individuals with and without metabolic syndrome (MetS). One hundred and ten individuals at risk for diabetes participated in this study. Subjects were categorized into individuals with MetS and individuals without MetS. Metabolic risk factors and exercise self-efficacy were evaluated for all subjects before and after 3 months of home-based exercise. Univariate analysis of variance was used to compare the effectiveness of a home-based exercise program between individuals with and without MetS. The home-based exercise program improved body mass index and lipid profile in individuals at risk for diabetes, regardless of MetS status at baseline. Individuals without MetS had higher exercise self-efficacy at baseline and performed greater exercise volume compared with individuals with MetS during the intervention. The increased exercise volume in individuals without MetS may contribute to their better control of insulin resistance than individuals with MetS. Furthermore, baseline exercise self-efficacy was correlated with exercise volume executed by subjects at home. We conclude that home-based exercise programs are beneficial for individuals at risk for diabetes. However, more intensive and/or supervised exercise intervention may be needed for those with MetS.

  13. Disruption of insulin signalling preserves bioenergetic competence of mitochondria in ageing Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Vanfleteren Jacques R

    2010-06-01

    Full Text Available Abstract Background The gene daf-2 encodes the single insulin/insulin growth factor-1-like receptor of Caenorhabditis elegans. The reduction-of-function allele e1370 induces several metabolic alterations and doubles lifespan. Results We found that the e1370 mutation alters aerobic energy production substantially. In wild-type worms the abundance of key mitochondrial proteins declines with age, accompanied by a dramatic decrease in energy production, although the mitochondrial mass, inferred from the mitochondrial DNA copy number, remains unaltered. In contrast, the age-dependent decrease of both key mitochondrial proteins and bioenergetic competence is considerably attenuated in daf-2(e1370 adult animals. The increase in daf-2(e1370 mitochondrial competence is associated with a higher membrane potential and increased reactive oxygen species production, but with little damage to mitochondrial protein or DNA. Together these results point to a higher energetic efficiency of daf-2(e1370 animals. Conclusions We conclude that low daf-2 function alters the overall rate of ageing by a yet unidentified mechanism with an indirect protective effect on mitochondrial function.

  14. The phenotype of polycystic ovary syndrome ameliorates with aging

    NARCIS (Netherlands)

    Brown, Zoe A.; Louwers, Yvonne V.; Fong, Sharon Lie; Valkenburg, Olivier; Birnie, Erwin; de Jong, Frank H.; Fauser, Bart C. J. M.; Laven, Joop S. E.

    2011-01-01

    Objective: To assess the effects of aging on the features of polycystic ovary syndrome (PCOS). Design: Retrospective longitudinal follow-up study. Setting: Tertiary care center. Patient(s): Patients with PCOS, diagnosed according to the 2003 Rotterdam criteria, who visited the outpatient clinic on

  15. Chronic Glucocorticoid Hypersecretion in Cushing's Syndrome Exacerbates Cognitive Aging

    Science.gov (United States)

    Michaud, Kathy; Forget, Helene; Cohen, Henri

    2009-01-01

    Cumulative exposure to glucocorticoid hormones (GC) over the lifespan has been associated with cognitive impairment and may contribute to physical and cognitive degeneration in aging. The objective of the present study was to examine whether the pattern of cognitive deficits in patients with Cushing's syndrome (CS), a disorder characterized by…

  16. The effect of vitamin D supplementation on insulin resistance, visceral fat and adiponectin in vitamin D deficient women with polycystic ovary syndrome: a randomized placebo-controlled trial.

    Science.gov (United States)

    Seyyed Abootorabi, Maryam; Ayremlou, Parvin; Behroozi-Lak, Tahereh; Nourisaeidlou, Sakineh

    2018-06-01

    Low plasma 25-hydroxy-vitamin D (25OHD) is associated with polycystic ovary syndrome (PCOS). Vitamin D deficiency may contribute to the development of insulin resistance, visceral fat and low level of adiponectin which are common feature in PCOS women. This study aimed to evaluate the effect of vitamin D supplementation on insulin resistance, visceral fat, and adiponectin in hypovitaminosis D women with polycystic ovary syndrome. In this randomized, placebo-controlled clinical trial, 44 PCOS women aged 20-38 years with plasma 25OHD D3 once weekly in the intervention group or placebo. The visceral adipose tissue, Insulin resistance (HOMA-IR), HOMA-B, QUICKI, and circulating adiponectin were compared before and after the intervention within groups using paired tests and the mean changes were analyzed between two groups by independent t-test. Of 44 eligible participates, 36 patients (81.8%) completed the study. After 8 week intervention, vitamin D supplementation compared to the placebo group significantly decreased fasting plasma glucose (FPG) (7.67 ± 7.66 versus 1.71 ± 7.50 mg/dL, p = .001) and significantly increased homeostasis model of assessment-estimated B cell function (HOMA-B) (129.76 ± 121.02 versus 48.32 ± 128.35, p = .014), Adiponectin (5.17 ± 8.09 versus -5.29 ± 8.64 mg/dL, p = .001), and serum vitamin D level (28.24 ± 6.47 versus 3.55 ± 4.25 ng/mL, p = .001). Vitamin D supplementation in vitamin D deficient women with PCOS, improved the FPG, HOMA-B, Adiponectin, and serum vitamin D level.

  17. Prevalence, incidence, and age at diagnosis in Marfan Syndrome.

    Science.gov (United States)

    Groth, Kristian A; Hove, Hanne; Kyhl, Kasper; Folkestad, Lars; Gaustadnes, Mette; Vejlstrup, Niels; Stochholm, Kirstine; Østergaard, John R; Andersen, Niels H; Gravholt, Claus H

    2015-12-02

    Marfan syndrome is a genetic disorder with considerable morbidity and mortality. Presently, clinicians use the 2010 revised Ghent nosology, which includes optional genetic sequencing of the FBN1 gene, to diagnose patients. So far, only a few studies based on older diagnostic criteria have reported a wide range of prevalence and incidence. Our aim was to study prevalence, incidence, and age at diagnosis in patients with Marfan syndrome. Using unique Danish patient-registries, we identified all possible Marfan syndrome patients recorded by the Danish healthcare system (1977-2014). Following, we confirmed or rejected the diagnosis according to the 2010 revised Ghent nosology. We identified a total of 1628 persons with possible Marfan syndrome. We confirmed the diagnosis in 412, whereof 46 were deceased, yielding a maximum prevalence of 6.5/100,000 at the end of 2014. The annual median incidence was 0.19/100,000 (range: 0.0-0.7) which increased significantly with an incidence rate ratio of 1.03 (95% CI: 1.02-1.04, p Marfan syndrome during the study period is possibly due to build-up of a registry. Since early diagnosis is essential in preventing aortic events, diagnosing Marfan syndrome remains a task for both pediatricians and physicians caring for adults.

  18. Immotile cilia syndrome in an aged dog

    International Nuclear Information System (INIS)

    Killingsworth, C.R.; Slocombe, R.F.; Wilsman, N.J.

    1987-01-01

    An 11-year-old Dalmatian was examined and treated for bilateral nasal discharge and cough of 6 months' duration. Response to medical treatment and surgical intervention was unsatisfactory. Histologic examination of lung tissue revealed chronic severe catarrhal bronchitis and bronchiolitis with bronchiectasis. Histologic findings and barium sulfate bronchography indicated abnormal mucociliary clearance in the respiratory tract. Electron microscopy revealed abnormalities or deletions of outer and/or inner dynein arms in 26% of the ciliary profiles from the affected dog. Similar abnormalities were not found in 500 ciliary profiles from age- and gender-matched control dogs

  19. Carbohydrate modified diet & insulin sensitizers reduce body weight & modulate metabolic syndrome measures in EMPOWIR (enhance the metabolic profile of women with insulin resistance: a randomized trial of normoglycemic women with midlife weight gain.

    Directory of Open Access Journals (Sweden)

    Harriette R Mogul

    Full Text Available Progressive midlife weight gain is associated with multiple adverse health outcomes and may represent an early manifestation of insulin resistance in a distinct subset of women. Emerging data implicate hyperinsulinema as a proximate cause of weight gain and support strategies that attenuate insulin secretion.To assess a previously reported novel hypocaloric carbohydrate modified diet alone (D, and in combination with metformin (M and metformin plus low-dose rosiglitazone (MR, in diverse women with midlife weight gain (defined as >20lbs since the twenties, normal glucose tolerance, and hyperinsulinemia.46 women, mean age 46.6±1.0, BMI 30.5±0.04 kg/m2, 54.5% white, 22.7% black, 15.9% Hispanic, at 2 university medical centers.A dietary intervention designed to reduce insulin excursions was implemented in 4 weekly nutritional group workshops prior to randomization.Change in 6-month fasting insulin. Pre-specified secondary outcomes were changes in body weight, HOMA-IR, metabolic syndrome (MS measures, leptin, and adiponectin.Six-month fasting insulin declined significantly in the M group: 12.5 to 8.0 µU/ml, p = .026. Mean 6-month weight decreased significantly and comparably in D, M, and MR groups: 4.7, 5.4, and 5.5% (p's.049, .002, and.032. HOMA-IR decreased in M and MR groups (2.5 to 1.6 and 1.9 to 1.3, p's = .054, .013. Additional improvement in MS measures included reduced waist circumference in D and MR groups and increased HDL in the D and M groups. Notably, mean fasting leptin did not decline in a subset of subjects with weight loss (26.15±2.01 ng/ml to 25.99±2.61 ng/ml, p = .907. Adiponectin increased significantly in the MR group (11.1±1.0 to 18.5±7.4, p<.001 Study medications were well tolerated.These findings suggest that EMPOWIR's easily implemented dietary interventions, alone and in combination with pharmacotherapies that target hyperinsulinemia, merit additional investigation in larger, long-term studies

  20. Down Syndrome and the aging process: a systematic review

    Directory of Open Access Journals (Sweden)

    Bruno Sousa Lopes

    2015-05-01

    Full Text Available The study aimed to identify and update the knowledge about older people with Down Syndrome (DS, and to understand the peculiarities of the aging process in this population. Bibliographical research conducted by Portal de Periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and High Wire portal. Inclusion criteria were articles published in the last ten years with the words “Down Syndrome" and “Elderly”.  

  1. Alternative splicing of exon 17 and a missense mutation in exon 20 of the insulin receptor gene in two brothers with a novel syndrome of insulin resistance (congenital fiber-type disproportion myopathy)

    DEFF Research Database (Denmark)

    Vorwerk, P; Christoffersen, C T; Müller, J

    1999-01-01

    The insulin receptor (IR) in two brothers with a rare syndrome of congenital muscle fiber type disproportion myopathy (CFTDM) associated with diabetes and severe insulin resistance was studied. By direct sequencing of Epstein-Barr virus-transformed lymphocytes both patients were found...... either of the two mutated receptors lacked basal or stimulated IR beta-subunit autophosphorylation. A third brother who inherited both normal alleles has an normal muscle phenotype and insulin sensitivity, suggesting a direct linkage of these IR mutations with the CFTDM phenotype....

  2. Mice lacking the p43 mitochondrial T3 receptor become glucose intolerant and insulin resistant during aging.

    Directory of Open Access Journals (Sweden)

    Christelle Bertrand

    Full Text Available Thyroid hormones (TH play an important regulatory role in energy expenditure regulation and are key regulators of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine (T3 receptor (p43 which acts as a mitochondrial transcription factor of the organelle genome, which leads in vitro and in vivo, to a stimulation of mitochondrial biogenesis. Recently, we generated mice carrying a specific p43 invalidation. At 2 months of age, we reported that p43 depletion in mice induced a major defect in insulin secretion both in vivo and in isolated pancreatic islets, and a loss of glucose-stimulated insulin secretion. The present study was designed to determine whether p43 invalidation influences life expectancy and modulates blood glucose and insulin levels as well as glucose tolerance or insulin sensitivity during aging. We report that from 4 months old onwards, mice lacking p43 are leaner than wild-type mice. p43-/- mice also have a moderate reduction of life expectancy compared to wild type. We found no difference in blood glucose levels, excepted at 24 months old where p43-/- mice showed a strong hyperglycemia in fasting conditions compared to controls animals. However, the loss of glucose-stimulated insulin secretion was maintained whatever the age of mice lacking p43. If up to 12 months old, glucose tolerance remained unchanged, beyond this age p43-/- mice became increasingly glucose intolerant. In addition, if up to 12 months old p43 deficient animals were more sensitive to insulin, after this age we observed a loss of this capacity, culminating in 24 months old mice with a decreased sensitivity to the hormone. In conclusion, we demonstrated that during aging the depletion of the mitochondrial T3 receptor p43 in mice progressively induced an increased glycemia in the fasted state, glucose intolerance and an insulin-resistance several features of type-2 diabetes.

  3. Impaired insulin-stimulated phosphorylation of Akt and AS160 in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment

    DEFF Research Database (Denmark)

    Højlund, Kurt; Glintborg, Dorte; Andersen, Nicoline R

    2008-01-01

    , and we examined the effect of 16 weeks of treatment with pioglitazone in PCOS patients. RESULTS: Impaired insulin-mediated total (R(d)) oxidative and nonoxidative glucose disposal (NOGD) was paralleled by reduced insulin-stimulated Akt phosphorylation at Ser473 and Thr308 and AS160 phosphorylation......OBJECTIVE: Insulin resistance in skeletal muscle is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). However, the molecular mechanisms underlying skeletal muscle insulin resistance and the insulin-sensitizing effect of thiazolidinediones in PCOS in vivo...... are less well characterized. RESEARCH DESIGN AND METHODS: We determined molecular mediators of insulin signaling to glucose transport in skeletal muscle biopsies of 24 PCOS patients and 14 matched control subjects metabolically characterized by euglycemic-hyperinsulinemic clamps and indirect calorimetry...

  4. Reduced expression of nuclear-encoded genes involved in mitochondrial oxidative metabolism in skeletal muscle of insulin-resistant women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Skov, Vibe; Glintborg, Dorte; Knudsen, Steen

    2007-01-01

    Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). In patients with type 2 diabetes, insulin resistance in skeletal muscle is associated with abnormalities in insulin signaling, fatty acid metabolism......, and mitochondrial oxidative phosphorylation (OXPHOS). In PCOS patients, the molecular mechanisms of insulin resistance are, however, less well characterized. To identify biological pathways of importance for the pathogenesis of insulin resistance in PCOS, we compared gene expression in skeletal muscle...... of metabolically characterized PCOS patients (n = 16) and healthy control subjects (n = 13) using two different approaches for global pathway analysis: gene set enrichment analysis (GSEA 1.0) and gene map annotator and pathway profiler (GenMAPP 2.0). We demonstrate that impaired insulin-stimulated total, oxidative...

  5. Aging and Immunopathology in Primary Sjögren's Syndrome.

    Science.gov (United States)

    Bouma, Hjalmar R; Bootsma, Hendrika; van Nimwegen, Jolien F; Haacke, Erlin A; Spijkervet, Fred K; Vissink, Arjan; Kroese, Frans G M

    2015-01-01

    Sicca complaints (sensation of dry mouth and/or eyes) are present in about a quarter of the individuals above the age of 65 years old and are mainly due to medication. However, physiological changes that occur during aging might also lead to a diminished glandular function. These age-related changes are, at least in part, to be the consequence of decreased androgen levels. In addition to these physiological effects that occur during normal aging, sicca complaints can also be caused by Sjögren's syndrome (SS): a systemic auto-inflammatory disorder mainly affecting exocrine glands. Genetic factors, lowered levels of gonadal hormones and (viral) infections appear to contribute to the etiology of the syndrome. The incidence of SS is higher among aged individuals, which might be due to earlier diagnosis, as the onset of SS in an individual with age-related exocrine gland dysfunction lowers the threshold for sicca complaints. On the other hand, physiological aging might be considered as a risk factor for development of SS, resulting in a faster development of the syndrome. Differentiating physiological sicca complaints from SS in the elderly can be challenging, since apparently healthy individuals might present with auto-antibodies and lymphocytic infiltrates in salivary glands might be present as well. The drop in the level of androgens and estrogens upon aging, immunosenescence and pro-inflammatory features of the aging immune system may all contribute to the etiology of pSS in the elderly. In this review, we describe the physiological effects of aging and the influence of SS on exocrine gland morphology and function.

  6. Insulin resistance and the metabolic syndrome are related to the severity of steatosis in the pediatric population with obesity

    Directory of Open Access Journals (Sweden)

    Esther Ubiña-Aznar

    Full Text Available Background: To determine the factors associated with an increased risk for severe steatosis (SS and establish the Homeostatic Model Assessment-Insulin Resistance (HOMA-IR as a screening tool. Methods: A cross-sectional study was performed in obese children to assess the relationship between the metabolic syndrome (MetS and glucose metabolism alterations (GMA and the risk for severe steatosis. Results: A total of 94 children (51 males aged from six to 14 years were included. Thirteen children (14.8% had severe steatosis (SS. The anthropometric variables associated with SS included body mass index (BMI (SS 34.1 vs non-SS 29.7, p = 0.005, waist circumference (cm (100 vs 92.5, p = 0.015 and hip circumference (cm (108 vs 100, p = 0.018. The blood parameters included alanine aminotransferase (ALT (UI/dl (27 vs 21, p = 0.002, gamma-glutamil transpeptidase (GGT (UI/dl (16 vs 15, p = 0.017, fasting glycemia (mg/dl (96 vs 88, p = 0.006, fasting insulin (UI/dl (25 vs 15.3, p < 0.001 and HOMA-IR score (7.1 vs 3.7, p < 0.001. Eighteen children with MetS were found to be at an increased risk for severe steatosis (odds ratio [OR] 11.36, p < 0.001. After receiver operating characteristic (ROC curve analysis, the best area under the curve (AUC was obtained for HOMA-R of 0.862. The HOMA-R 4.9 cut-off value had a 100% sensitivity (CI 95%: 96.2-100 and 67.9% specificity (CI 95%: 57.1-78.7 for severe steatosis. Conclusions: The presence of MetS and glucose metabolism alterations are risk factors for severe steatosis. The 4.9 cut-off value for HOMA-IR may be a risk factor for severe steatosis in obese children.

  7. Evaluation of the correlation between insulin like factor 3, polycystic ovary syndrome, and ovarian maldescent.

    Science.gov (United States)

    Seyam, Emaduldin; Hefzy, Enas

    2018-06-01

    The aim of this study was to investigate a proposed correlation between the incidentally discovered undescended ovaries and their confirmed diagnosis as a polycystic ovary disease (PCOD) for all cases included, and to evaluate the role of estimated insulin like factor 3 (INSL3) circulating level in the pathogenesis of both abnormal findings. The study group (A) comprised 35 women whose ovaries had been incidentally found to be undescended during the routine laparoscopy for infertility causes, and all had been diagnosed as PCOD. The control category included two subgroups; subgroup (B) included 35 women group, diagnosed as PCOD but with normally allocated ovaries in the true pelvis, and subgroup (C) included 35 healthy women with regular menses and no signs of hyperandrogenism. Correlations between the level of INSL3 and other PCOD relevant biochemical tests: [e.g. BMI, waist-to-hip ratio (WHR), LH, FSH, androstendione (A), total and free testosterone (T & Ft), DHEA-S, and SHBG] had been also investigated. INSL3 levels were significantly higher in PCOD groups (A) and (B) compared to the healthy fertile control subgroup (C) (80.5 ± 29.4, 65.11 ± 15.6, and 41.11 ± 10.2 pg/mL, respectively), and was highest in group (A). Moreover, we identified a strong correlation between INSL3 and androstenedione (r = 0.42, p = 0.0012), and free (r = 0.42, p = .0123) and total testosterone (r = 0.41, p = .004) in the PCOD (A) and (B) subgroup compared to the levels in subgroup (C). LH was significantly higher in all PCOD women in groups (A&B) (12. 3 ± 3.4, and 11.2 ± 1.4 mIU/L, respectively) compared to those in group (A) (5.7 ± 2.5 mIU/L), with a fair correlation with INSL3. However, there was no statistically significant correlation between INSL3 and FSH, DHEA-S, glucose, basal insulin concentration or HOMA-IR in all PCOD women. The strong positive correlation between INSL3, and high ovarian androgens levels in all PCOD women

  8. Association of abdominal obesity, insulin resistance, and oxidative stress in adipose tissue in women with polycystic ovary syndrome.

    Science.gov (United States)

    Chen, Li; Xu, Wen Ming; Zhang, Dan

    2014-10-01

    To study the expression of insulin signaling-related genes and oxidative stress markers in the visceral adipose tissue obtained from polycystic ovary syndrome (PCOS) patients and healthy control subjects and to investigate the relationships among abdominal obesity, insulin resistance, and oxidative stress at the tissue level. Case-control study. University teaching hospital. In total, 30 PCOS patients and 30 healthy control subjects, who underwent laparoscopic surgery, were included in the study. Abdominal obesity was defined based on waist circumference (WC). The homeostasis model index was used to assess insulin resistance (HOMA-IR). Gene expression of glucose transporter 4 (GLUT4) and insulin receptor substrate 1 (IRS1) in visceral adipose tissue (VAT) and the parameters of oxidative stress, such as superoxide dismutase, enzyme glutathione reductase, and dimethylarginine, were measured, and the expression of protein oxidative damage product 3-nitro-tyrosine residues (nitrotyrosine) in VAT was identified with the use of immunohistochemistry. PCOS was associated with lower expression of GLUT4 and IRS1 and a higher level of oxidative stress in VAT, which was strongly correlated with WC and HOMA-IR. Presence of abdominal obesity further intensified the correlations observed in our measurements. The nitrotyrosine expression in VAT was stronger in PCOS patients. The strong correlation of insulin resistance with oxidative stress at the VAT level suggests that local oxidative stress and abnormalities of insulin signaling in adipose tissue play critical roles in the pathogenesis of PCOS. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Association of MEP1A gene variants with insulin metabolism in central European women with polycystic ovary syndrome.

    Science.gov (United States)

    Lam, Uyen D P; Lerchbaum, Elisabeth; Schweighofer, Natascha; Trummer, Olivia; Eberhard, Katharina; Genser, Bernd; Pieber, Thomas R; Obermayer-Pietsch, Barbara

    2014-03-10

    Polycystic ovary syndrome (PCOS) shows not only hyperandrogenemia, hirsutism and fertility problems, but also metabolic disturbances including obesity, cardiovascular events and type-2 diabetes. Accumulating evidence suggests some degree of inflammation associated with prominent aspects of PCOS. We aimed to investigate the association of genetic variants 3'UTR rs17468190 (G/T) of the inflammation-associated gene MEP1A (GenBank ID: NM_005588.2) with metabolic disturbances in PCOS and healthy control women. Genetic variants rs17468190 (G/T) of MEP1A gene were analyzed in 576 PCOS women and 206 controls by using the Taqman fluorogenic 5'-exonuclease assay. This polymorphism was tested for association with anthropometric, metabolic, hormonal, and functional parameters of PCOS. There was a borderline significant difference in genotype distribution between PCOS and control women (p=0.046). In overweight/obese PCOS patients, the variants rs17468190 (G/T) in the MEP1A gene are associated with glucose and insulin metabolism. In a dominant model, the GG genotype of the MEP1A gene was more strongly associated with insulin metabolism in overweight/obese PCOS women (body mass index, BMI>25 kg/m(2)), than in GT+TT genotypes. The MEP1A GG-carriers showed a significantly increased homeostatic model assessment - insulin resistance (HOMA-IR) (p=0.003), elevation of fasting insulin (p=0.004) and stimulated insulin (30 min, pdisease modification in PCOS. It might contribute to the abnormalities of glucose metabolism and insulin sensitivity and serve as a diagnostic or therapeutic target gene for PCOS. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9 to 13 Years.

    Science.gov (United States)

    Kindler, Joseph M; Pollock, Norman K; Laing, Emma M; Oshri, Assaf; Jenkins, Nathan T; Isales, Carlos M; Hamrick, Mark W; Ding, Ke-Hong; Hausman, Dorothy B; McCabe, George P; Martin, Berdine R; Hill Gallant, Kathleen M; Warden, Stuart J; Weaver, Connie M; Peacock, Munro; Lewis, Richard D

    2017-07-01

    IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

  11. Relationships between the pituitary-adrenal hormones, insulin, and glucose in middle-aged men: moderating influence of psychosocial stress.

    Science.gov (United States)

    Keltikangas-Järvinen, L; Ravaja, N; Räikkönen, K; Hautanen, A; Adlercreutz, H

    1998-12-01

    We examined whether the relationships between the pituitary-adrenal hormones (corticotropin [ACTH) and cortisol), insulin, and glucose differ as a function of psychosocial stress defined in terms of vital exhaustion (VE) and depressive behavior (DB). The participants were 69 normotensive and 21 unmedicated borderline hypertensive (BH) middle-aged men whose work is stressful. Hormonal and metabolic variables were measured during an oral glucose tolerance test (OGTT), and the cortisol response to dexamethasone (DXM) suppression and intravenous ACTH stimulation was also measured. We found that the basal ACTH level during the OGTT was positively associated with the cortisol response to ACTH at 60 minutes, the fasting insulin level, and the insulin to glucose ratio among exhausted and high DB men, while the reverse was true for nonexhausted and low DB men. Also, a high cortisol response to ACTH, a low cortisol level during the OGTT, and a high ratio of these cortisol determinations (cortisol ratio) were associated with high fasting insulin and glucose levels, the summed insulin values, and the insulin to glucose ratio only among nonexhausted and low DB men; among exhausted and high DB men, these associations were less pronounced, absent, or in the opposite direction. The findings suggest that VE and DB have a moderating influence on the relationships among the hormonal and metabolic parameters studied. Psychosocial stress may affect the pituitary-adrenocortical system in complex ways, contributing thereby to insulin resistance, hyperinsulinemia, and coronary heart disease (CHD) risk.

  12. Analysis of IRS-1-mediated phosphatidylinositol 3-kinase activation in the adipose tissue of polycystic ovary syndrome patients complicated with insulin resistance

    Energy Technology Data Exchange (ETDEWEB)

    Yongli, Chu [Yantai Yuhuangding Hospital, Yantai (China). Dept. of Obstetrics and Gynecology; Hongyu, Qiu; Yongyu, Sun; Min, Li; Hongfa, Li

    2004-04-01

    Objective: To investigate the insulin receptor substance-1 (IRS-1)-mediated phosphatidylinositol-3 (PI-3) kinase activity in adipose tissue of polycystic ovary syndrome (PCOS) patients, and to explore molecular mechanisms of insulin resistance of PCOS. Methods: Blood and adipose tissue samples from patients with PCOS with insulin resistance (n=19), PCOS without insulin resistance (n=10) and controls (n=15) were collected. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T) were measured by chemiluminescence assay. Fasting insulin (FIN) was measured by radioimmunoassay. Fasting plasma glucose (FPG) was measured by oxidase assay. Insulin resistance index (IR) was calculated using homeostasis model assessment (HOMA) to analyze the relationship between these markers and insulin resistance. The tyrosine phosphorylation of IRS-1 was measured by immunoprecipitation and enhanced chemiluminescent immunoblotting technique. PI-3 kinase activity was detected by immunoprecipitation, thin-layer chromatography and gamma scintillation counting. The results were analyzed by statistical methods. Results: 1) The levels of serum LH, LH/FSH, T, FIN and HOMA-IR in PCOS without insulin resistance were significantly higher than those of control group (all P<0.05); the levels of serum LH, LH/FSH, T, FIN and HOMA-IR in PCOS with insulin resistance were significantly higher than those of PCOS without insulin resistance (all P<0.05). 2) The tyrosine phosphorylation analysis of IRS-1 showed that IRS-1 tyrosine phosphorylation was significantly decreased in PCOS with insulin resistance compared to that of PCOS without insulin resistance and control groups (P<0.01). 3) PI-3 kinase activity was significantly decreased (P<0.01) and negatively correlated with HOMA-IR. Conclusion: In consequence of the weaker signal caused by the change of upper stream signal molecule IRS-1 tyrosine phosphorylation, PI-3 kinase activity decreased, it affects the insulin signal

  13. Analysis of IRS-1-mediated phosphatidylinositol 3-kinase activation in the adipose tissue of polycystic ovary syndrome patients complicated with insulin resistance

    International Nuclear Information System (INIS)

    Chu Yongli; Qiu Hongyu; Sun Yongyu; Li Min; Li Hongfa

    2004-01-01

    Objective: To investigate the insulin receptor substance-1 (IRS-1)-mediated phosphatidylinositol-3 (PI-3) kinase activity in adipose tissue of polycystic ovary syndrome (PCOS) patients, and to explore molecular mechanisms of insulin resistance of PCOS. Methods: Blood and adipose tissue samples from patients with PCOS with insulin resistance (n=19), PCOS without insulin resistance (n=10) and controls (n=15) were collected. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T) were measured by chemiluminescence assay. Fasting insulin (FIN) was measured by radioimmunoassay. Fasting plasma glucose (FPG) was measured by oxidase assay. Insulin resistance index (IR) was calculated using homeostasis model assessment (HOMA) to analyze the relationship between these markers and insulin resistance. The tyrosine phosphorylation of IRS-1 was measured by immunoprecipitation and enhanced chemiluminescent immunoblotting technique. PI-3 kinase activity was detected by immunoprecipitation, thin-layer chromatography and gamma scintillation counting. The results were analyzed by statistical methods. Results: 1) The levels of serum LH, LH/FSH, T, FIN and HOMA-IR in PCOS without insulin resistance were significantly higher than those of control group (all P<0.05); the levels of serum LH, LH/FSH, T, FIN and HOMA-IR in PCOS with insulin resistance were significantly higher than those of PCOS without insulin resistance (all P<0.05). 2) The tyrosine phosphorylation analysis of IRS-1 showed that IRS-1 tyrosine phosphorylation was significantly decreased in PCOS with insulin resistance compared to that of PCOS without insulin resistance and control groups (P<0.01). 3) PI-3 kinase activity was significantly decreased (P<0.01) and negatively correlated with HOMA-IR. Conclusion: In consequence of the weaker signal caused by the change of upper stream signal molecule IRS-1 tyrosine phosphorylation, PI-3 kinase activity decreased, it affects the insulin signal

  14. Effects of Eight-Weeks of Aerobic Training on Resistin Levels and Insulin Resistance in Sedentary Middle-Aged Women

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    Bahram Abedi

    2017-11-01

    Full Text Available Introduction: Resistin is an adipocyte-specific hormone secreted from adipose tissue which plays a significant role in the energy homeostasis and regulation of energy metabolism. The purpose of this study was to examine the effects of eight weeks of aerobic training on the resistin levels and insulin resistance in sedentary middle-aged women. Methods: In this quasi-experimental research, 20 sedentary women were randomly selected and assigned to two groups: experimental group, n=10, aged 47.70±5.35; and control, n=10, age 41.30±3.02, respectively. The participants in the training group performed an exercise protocol three times per week with the goal of 55 to 65 per cent of maximum heart rate. Before and after the completion, the resistin, insulin, glucose and insulin resistance levels were measured after 12 h of overnight fasting. Data were analyzed before and after the intervention by t-test. The significant level was defined as P≤0.05. Results: Aerobic training in compared with the control group showed significant effect in decreasing resistin levels (P=0.012, BMI (P=0.01, insulin resistance (P=0.01, and increasing VO2 max (P=0.004. Conclusion: It appears that eight weeks of aerobic training significantly changes the level of resistin and the insulin resistance index in sedentary middle-aged women. Plasma resistin may be associated with insulin resistance in sedentary women. In general, according to the results, we may say that an eight-week aerobic training with a significant reduction in plasma resistin has a preventive effect as a new and effective training method on insulin resistance in middle-aged sedentary women.

  15. Insulin signaling and dietary restriction differentially influence the decline of learning and memory with age.

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    Amanda L Kauffman

    2010-05-01

    Full Text Available Of all the age-related declines, memory loss is one of the most devastating. While conditions that increase longevity have been identified, the effects of these longevity-promoting factors on learning and memory are unknown. Here we show that the C. elegans Insulin/IGF-1 receptor mutant daf-2 improves memory performance early in adulthood and maintains learning ability better with age but, surprisingly, demonstrates no extension in long-term memory with age. By contrast, eat-2 mutants, a model of Dietary Restriction (DR, exhibit impaired long-term memory in young adulthood but maintain this level of memory longer with age. We find that crh-1, the C. elegans homolog of the CREB transcription factor, is required for long-term associative memory, but not for learning or short-term memory. The expression of crh-1 declines with age and differs in the longevity mutants, and CREB expression and activity correlate with memory performance. Our results suggest that specific longevity treatments have acute and long-term effects on cognitive functions that decline with age through their regulation of rate-limiting genes required for learning and memory.

  16. AGE AND GENDER MAY INFLUENCE THE RESULTS OF ROUX-EN-Y GASTRIC BYPASS? Metabolic syndrome parameters

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    Stephan Garcia ANDRADE-SILVA

    2014-09-01

    Full Text Available Context Severe obesity affects the body favoring the development of serious diseases, including hypertension, diabetes mellitus, atherosclerosis and non alcoholic fatty liver disease. Bariatric procedures increased in Brazil in the last decade. Objectives The purpose of this study was to verify if gender and age in date of procedure resulted significant differences in metabolic syndrome parameters after surgery. Methods The study involved 205 medical records of adult patients undergoing Roux-en-Y gastric bypass, stratified by gender and age groups and followed one year by a multidisciplinary team. Results It was observed significant decrease in body mass index, fasting glucose and insulin at all ages and both genders. Lipid profile showed significant improvements except high density lipoprotein cholesterol. Ectopic fat in the liver has decreased after 6 months in patients classified with steatosis at baseline. Patients classified as hypertensive blood pressure levels decreased 6 months after surgical intervention. Conclusions Roux-en-Y gastric bypass proved to be an important tool in remission of metabolic syndrome parameters. The reduction of body mass accompanied to decrease in insulin resistance resulted in lower prevalence of comorbidities associated with obesity. The benefits were similar and extended both genders and all age groups between 18 and 65 years old.

  17. Associations between genetic polymorphisms of insulin-like growth factor axis genes and risk for age-related macular degeneration

    Science.gov (United States)

    Purpose: Our objective was to investigate if insulin-like growth factor (IGF) axis genes affect the risk for age-related macular degeneration (AMD). Methods: 864 Caucasian non-diabetic participants from the Age-Related Eye Disease Study (AREDS) Genetic Repository were used in this case control st...

  18. Central arterial stiffness and diastolic dysfunction are associated with insulin resistance and abdominal obesity in young women but polycystic ovary syndrome does not confer additional risk.

    Science.gov (United States)

    Rees, E; Coulson, R; Dunstan, F; Evans, W D; Blundell, H L; Luzio, S D; Dunseath, G; Halcox, J P; Fraser, A G; Rees, D A

    2014-09-01

    Are arterial stiffness, carotid intima-media thickness and diastolic dysfunction increased in young women with polycystic ovary syndrome (PCOS) independently of the effects of obesity? Insulin resistance and central obesity are associated with subclinical cardiovascular dysfunction in young women, but a diagnosis of PCOS does not appear to confer additional risk at this age. Some studies have shown that young women with PCOS may have increased measures of cardiovascular risk, including arterial stiffness, carotid intima-media thickness and myocardial dysfunction. However, it is difficult to establish how much of this risk is due to PCOS per se and how much is due to obesity and insulin resistance, which are common in PCOS and themselves associated with greater vascular risk. This cross-sectional study comprised 84 women with PCOS and 95 healthy volunteers, aged 16-45 years. The study was conducted in a university hospital. Subjects underwent a comprehensive assessment of body composition (including computed tomography (CT) assessment of visceral fat; VF), measurements of arterial stiffness (aortic pulse wave velocity; aPWV), common carotid intima-media thickness (ccIMT), diastolic function (longitudinal tissue velocity; e':a') and endocrinological measures. A sample size of 80 in each group gave 80% power for detecting a difference of 0.45 m/s in aPWV or a difference of 0.25 in e':a'. After adjustment for age and body mass index (BMI), PCOS subjects had a greater insulin response (insulin area under the curve-IAUC) following glucose challenge (adjusted difference [AD] 35 900 pmol min/l, P insulin resistance were only partly attenuated by adjusting for logVF. There was no significant relationship between aPWV or e':a' and either testosterone or adiponectin. The study recruited young women meeting the Rotterdam criteria for PCOS diagnosis; hence our findings may not be generalizable to older patients or those meeting other definitions of the syndrome. Biochemical

  19. Prevalence of the metabolic syndrome, insulin resistance index, leptin and thyroid hormone levels in the general population of Merida (Venezuela).

    Science.gov (United States)

    Uzcátegui, Euderruh; Valery, Lenin; Uzcátegui, Lilia; Gómez Pérez, Roald; Marquina, David; Baptista, Trino

    2015-06-01

    The metabolic syndrome (MetSyn) is a significant risk factor for cardiovascular events, but scarce information exists about its frequency in Venezuela. In this cross-sectional study, we quantified the prevalence of the MetSyn in a probabilistic, stratified sample of 274 subjects aged > or =18 years from the Libertador district in Merida, Venezuela. Secondary outcomes were the measurement of thyroid hormones (free T4 and TSH), leptin levels, and insulin resistance index (HOMA2-IR). The frequency of MetSyn (percentage +/- 95% confidence interval) according to several diagnostic criteria was as follows: National Cholesterol Education Panel (NCEP, original): 27.4% (22.1-32.7); modified NCEP: 31.8% (26.3-37.3); International Diabetes Federation: 40.9% (35.1-46.7); Latin American Diabetes Association: 27% (21.7-32.3), and Venezuelan criteria: 31.8% (26.3-37.3). The MetSyn was more frequent in males than in females with most diagnostic criteria. The estimated prevalence of type 2 diabetes mellitus was 2.9% either according to the patients' self reports or to fasting glucose level found to be above 126 mg/dL. Abnormal HOMA2-IR index, free T4 and TSH (above the 95th percentile) were detected in 4.5%, 4.4% and 5.1% of the sample, respectively. Free T4 and TSH levels below the 5th percentile were detected in 4.4% and 4.7% of subjects respectively. These values are presented for comparisons with forthcoming studies in specific clinical populations. While studies are being conducted about the different definitions of the MetSyn in Venezuela, we recommend analyzing and publishing local research data with all the available criteria so as to allow comparisons with the results already reported in the literature.

  20. Association between Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Components of Metabolic Syndrome in Young Chinese Men.

    Science.gov (United States)

    Ying, X; Song, Zh; Zhao, Ch; Jiang, Y

    2011-01-01

    To investigate the prevalence of metabolic syndrome (MetS) in young Chinese population and assess the association between HOMA-IR and different components of MetS in young Chinese men. Overall 5576 young Chinese subjects (age range [19-44 yr], 3636 men) were enrolled in, who visited our Health Care Center for a related health checkup from March to December 2008. The international diabetes federation (IDF) definition for MetS was used. The SPSS statistical package, version 11.5 was used for the statistical analysis. The prevalence of MetS was 21.81% in young men and 5.62% in young women. According to suffering from different numbers of MetS components, the male subjects were divided into four groups. Numbers of MetS components were more and HOMA-IR values were significantly higher. In this male population, the quartile of HOMA-IR was higher, values of triglyceride (TG), fasting plasma glucose (FBG), systolic blood pressure(SBP), diastolic blood pressure(DBP) and waist circumference (WC) were all significantly higher, as well as high density lipoprotein cholesterol (HDL-C) value was significantly lower (P= 0.000). In Spearman's correlation analysis, HOMA-IR was positively correlated with TG, FBG, SBP, DBP and WC, and negatively correlated with HDL-C (r= 0.460, 0.464, 0.362, 0.346, 0.586, -0.357, respectively, all P value= 0.000). The prevalence of MetS in these young Chinese men was obviously high. Insulin resistance played an important role in occurrence and development of MetS. Waist circumference was the best correlation with HOMA-IR among all components of MetS.

  1. The cutoff values of indirect indices for measuring insulin resistance for metabolic syndrome in Korean children and adolescents

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    Jun Woo Kim

    2016-09-01

    Full Text Available PurposeThe prevalence rates of metabolic syndrome (MetS and percentile distribution of insulin resistance (IR among Korean children and adolescents were investigated. The cutoff values of IR were calculated to identify high-risk MetS groups.MethodsData from 3,313 Korean subjects (1,756 boys and 1,557 girls, aged 10–18 years were included from the Korean National Health and Nutrition Examination Survey conducted during 2007–2010. Three different sets of criteria for MetS were used. Indirect measures of IR were homeostasis model assessment (HOMA-IR and triglyceride and glucose (TyG index. The cutoff values of the HOMA-IR and TyG index were obtained from the receiver operation characteristic curves.ResultsAccording to the MetS criteria of de Ferranti el al., Cook et al., and the International Diabetes Federation, the prevalence rates in males and females were 13.9% and 12.3%, 4.6% and 3.6%, and 1.4% and 1.8%, respectively. Uses these 3 criteria, the cutoff values of the HOMA-IR and TyG index were 2.94 and 8.41, 3.29 and 8.38, and 3.54 and 8.66, respectively. The cutoff values using each of the 3 criteria approximately corresponds to the 50th–75th, 75th, and 75th–90th percentiles of normal HOMA-IR and TyG index levels.ConclusionThis study describes the prevalence rates of MetS in Korean children and adolescents, an index of IR, and the cutoff values for MetS with the aim of detecting high-risk groups. The usefulness of these criteria needs to be verified by further evaluation.

  2. Carotid plaque age is a feature of plaque stability inversely related to levels of plasma insulin.

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    Sara Hägg

    Full Text Available BACKGROUND: The stability of atherosclerotic plaques determines the risk for rupture, which may lead to thrombus formation and potentially severe clinical complications such as myocardial infarction and stroke. Although the rate of plaque formation may be important for plaque stability, this process is not well understood. We took advantage of the atmospheric (14C-declination curve (a result of the atomic bomb tests in the 1950s and 1960s to determine the average biological age of carotid plaques. METHODOLOGY/PRINCIPAL FINDING: The cores of carotid plaques were dissected from 29 well-characterized, symptomatic patients with carotid stenosis and analyzed for (14C content by accelerator mass spectrometry. The average plaque age (i.e. formation time was 9.6±3.3 years. All but two plaques had formed within 5-15 years before surgery. Plaque age was not associated with the chronological ages of the patients but was inversely related to plasma insulin levels (p = 0.0014. Most plaques were echo-lucent rather than echo-rich (2.24±0.97, range 1-5. However, plaques in the lowest tercile of plaque age (most recently formed were characterized by further instability with a higher content of lipids and macrophages (67.8±12.4 vs. 50.4±6.2, p = 0.00005; 57.6±26.1 vs. 39.8±25.7, p<0.0005, respectively, less collagen (45.3±6.1 vs. 51.1±9.8, p<0.05, and fewer smooth muscle cells (130±31 vs. 141±21, p<0.05 than plaques in the highest tercile. Microarray analysis of plaques in the lowest tercile also showed increased activity of genes involved in immune responses and oxidative phosphorylation. CONCLUSIONS/SIGNIFICANCE: Our results show, for the first time, that plaque age, as judge by relative incorporation of (14C, can improve our understanding of carotid plaque stability and therefore risk for clinical complications. Our results also suggest that levels of plasma insulin might be involved in determining carotid plaque age.

  3. Cross-sectional analysis of the effects of age on the hormonal, metabolic, and ultrasonographic features and the prevalence of the different phenotypes of polycystic ovary syndrome.

    Science.gov (United States)

    Panidis, Dimitrios; Tziomalos, Konstantinos; Macut, Djuro; Delkos, Dimitrios; Betsas, George; Misichronis, Georgios; Katsikis, Ilias

    2012-02-01

    To assess the effects of age on the hormonal, metabolic, and ultrasonographic features of polycystic ovary syndrome (PCOS). Observational study. University department of obstetrics and gynecology. Patients with PCOS (n = 1,212) and healthy women (n = 254). None. Differences in the hormonal, metabolic, and ultrasonographic features of PCOS between age groups. A progressive decline in circulating androgens was observed with advancing age. Patients 21-30 years old had lower plasma glucose and insulin levels, lower area under the oral glucose tolerance test curve and lower homeostasis model assessment of insulin resistance index, and higher glucose/insulin and quantitative insulin sensitivity check index than patients 31-39 years old. The prevalence of PCOS phenotypes changed with age. More specifically, the distribution of the phenotypes did not differ substantially between patients ≤ 20 years old and patients 21-30 years old. However, a decline in the prevalence of phenotype 1 (characterized by anovulation, hyperandrogenemia, and polycystic ovaries) and an increase in the prevalence of phenotype 4 (characterized by anovulation and polycystic ovaries without hyperandrogenemia) were observed in patients 31-39 years old. In women with PCOS, hyperandrogenemia appears to diminish during reproductive life whereas insulin resistance worsens. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  4. Adipokines, insulin resistance, and adiposity as a predictors of metabolic syndrome in child survivors of lymphoma and acute lymphoblastic leukemia of a developing country.

    Science.gov (United States)

    Barbosa-Cortés, Lourdes; López-Alarcón, Mardia; Mejía-Aranguré, Juan Manuel; Klünder-Klünder, Miguel; Del Carmen Rodríguez-Zepeda, María; Rivera-Márquez, Hugo; de la Vega-Martínez, Alan; Martin-Trejo, Jorge; Shum-Luis, Juan; Solis-Labastida, Karina; López-Aguilar, Enrique; Matute-González, Guadalupe; Bernaldez-Rios, Roberto

    2017-02-13

    There is a growing body of evidence indicating that pediatric survivors of cancer are at a greater risk of developing metabolic syndrome. This study evaluated some probable predictors of metabolic syndrome (MS), such as leptin and adiponectin concentrations, the leptin/adiponectin ratio, insulin resistance, and adiposity, in a sample of child survivors of lymphoma and leukemia in Mexico City. Fifty two children (leukemia n = 26, lymphoma n = 26), who were within the first 5 years after cessation of therapy, were considered as eligible to participate in the study. Testing included fasting insulin, glucose, adipokines and lipids; body fat mass was measured by DXA. The MS components were analyzed according to tertiles of adipokines, insulin resistance, and adiposity. Comparisons between continuous variables were performed according to the data distribution. The MS components were analyzed according to tertiles of adipokines, insulin resistance, and adiposity. With the purpose of assessing the risk of a present MS diagnosis, odds ratios (OR) with a 95% confidence interval (95% IC) were obtained using logistic regression analysis according to the various metabolic markers. The median children age was 12.1 years, and the interval time from the completion of therapy to study enrollment was 4 years. Among the MS components, the prevalence of HDL-C low was most common (42%), followed by central obesity (29%). The HOMA-IR (OR 9.0, 95% CI 2.0; 41.1), body fat (OR 5.5, 95% CI 1.6; 19.3), leptin level (OR 5.7, 95% CI 1.6; 20.2) and leptin/adiponectin ratio (OR 9.4, 95% CI 2.0; 49.8) in the highest tertile, were predictive factors of developing MS; whereas the lowest tertile of adiponectin was associated with a protective effect but not significant. Biomarkers such as HOMA-IR, leptin and leptin/adiponectin are associated with each of the components of the MS and with a heightened risk of suffering MS among children survivors of cancer. Given the close relationship

  5. Glucokinase regulatory protein genetic variant interacts with omega-3 PUFA to influence insulin resistance and inflammation in metabolic syndrome.

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    Pablo Perez-Martinez

    Full Text Available Glucokinase Regulatory Protein (GCKR plays a central role regulating both hepatic triglyceride and glucose metabolism. Fatty acids are key metabolic regulators, which interact with genetic factors and influence glucose metabolism and other metabolic traits. Omega-3 polyunsaturated fatty acids (n-3 PUFA have been of considerable interest, due to their potential to reduce metabolic syndrome (MetS risk.To examine whether genetic variability at the GCKR gene locus was associated with the degree of insulin resistance, plasma concentrations of C-reactive protein (CRP and n-3 PUFA in MetS subjects.Homeostasis model assessment of insulin resistance (HOMA-IR, HOMA-B, plasma concentrations of C-peptide, CRP, fatty acid composition and the GCKR rs1260326-P446L polymorphism, were determined in a cross-sectional analysis of 379 subjects with MetS participating in the LIPGENE dietary cohort.Among subjects with n-3 PUFA levels below the population median, carriers of the common C/C genotype had higher plasma concentrations of fasting insulin (P = 0.019, C-peptide (P = 0.004, HOMA-IR (P = 0.008 and CRP (P = 0.032 as compared with subjects carrying the minor T-allele (Leu446. In contrast, homozygous C/C carriers with n-3 PUFA levels above the median showed lower plasma concentrations of fasting insulin, peptide C, HOMA-IR and CRP, as compared with individuals with the T-allele.We have demonstrated a significant interaction between the GCKR rs1260326-P446L polymorphism and plasma n-3 PUFA levels modulating insulin resistance and inflammatory markers in MetS subjects. Further studies are needed to confirm this gene-diet interaction in the general population and whether targeted dietary recommendations can prevent MetS in genetically susceptible individuals.ClinicalTrials.gov NCT00429195.

  6. Genetics and aging; the Werner syndrome as a segmental progeroid syndrome.

    Science.gov (United States)

    Martin, G M

    1985-01-01

    The maximum lifespan potential is a constitutional feature of speciation and must be subject to polygenic controls acting both in the domain of development and in the domain of the maintenance of macromolecular integrity. The enormous genetic heterogeneity that characterizes our own species, the complexities of numerous nature-nurture interactions, and the quantitative and qualitative variations of the senescent phenotype that are observed suggest that precise patterns of aging in each of us may be unique. Patterns of aging may also differ sharply among species (for example, semelparous vs. multiparous mammals). Some potential common denominators, however, allow one to identify progeroid syndromes in man that could lead to the elucidation of important pathways of gene action. (The suffix "-oid" means "like"; it does not mean identity.) Unimodal progeroid syndromes (eg., familial dementia of the Alzheimer type, an autosomal dominant) can help us understand the pathogenesis of a particular aspect of the senescent phenotype of man. Segmental progeroid syndromes (eg. the Werner syndrome, an autosomal recessive) may be relevant to multiple aspects of the senescent phenotype. Some results of research on the Werner syndrome may be interpreted as support for "peripheral" as opposed to "central" theories of aging; they are consistent with the view that gene action in the domain of development (adolescence, in this instance) can set the stage for patterns of aging in the adult; they point to the importance of mesenchymal cell populations in the pathogenesis of age-related disorders; finally, they underscore the role of chromosomal instability, especially in the pathogenesis of neoplasia.

  7. Effects of insulin resistance on white matter microstructure in middle-aged and older adults

    Science.gov (United States)

    Coutu, Jean-Philippe; Rosas, H. Diana; Salat, David H.

    2014-01-01

    Objective: To investigate the potential relationship between insulin resistance (IR) and white matter (WM) microstructure using diffusion tensor imaging in cognitively healthy middle-aged and older adults. Methods: Diffusion tensor imaging was acquired from 127 individuals (age range 41–86 years). IR was evaluated by the homeostasis model assessment of IR (HOMA-IR). Participants were divided into 2 groups based on HOMA-IR values: “high HOMA-IR” (≥2.5, n = 27) and “low HOMA-IR” (HOMA-IR group demonstrated decreased axial diffusivity broadly throughout the cerebral WM in areas such as the corpus callosum, corona radiata, cerebral peduncle, posterior thalamic radiation, and right superior longitudinal fasciculus, and WM underlying the frontal, parietal, and temporal lobes, as well as decreased fractional anisotropy in the body and genu of corpus callosum and parts of the superior and anterior corona radiata, compared with the low HOMA-IR group, independent of age, WM signal abnormality volume, and antihypertensive medication status. These regions additionally demonstrated linear associations between diffusion measures and HOMA-IR across all subjects, with higher HOMA-IR values being correlated with lower axial diffusivity. Conclusions: In generally healthy adults, greater IR is associated with alterations in WM tissue integrity. These cross-sectional findings suggest that IR contributes to WM microstructural alterations in middle-aged and older adults. PMID:24771537

  8. Is there an independent effect of polycystic ovary syndrome (PCOS) and menopause on the prevalence of subclinical atherosclerosis in middle aged women?

    OpenAIRE

    Evelyn O Talbott; Jeanne Zborowski; Judy Rager; Juley R Stragand

    2008-01-01

    Evelyn O Talbott, Jeanne Zborowski, Judy Rager, Juley R StragandDepartment of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USAAbstract: Polycystic ovary syndrome (PCOS), a common reproductive endocrine condition manifests at puberty, and is characterized by hyperandrogenism, chronic anovulation, and obesity. PCOS cases exhibit an adverse coronary heart disease (CHD) profile at an early age, including insulin resistance, dyslipidemia and increased c...

  9. Hair Coil Penile Tourniquet Syndrome in an Unusual Age

    Science.gov (United States)

    Zengin, Kursad; Ozdamar, Mustafa Yasar; Albayrak, Sebahattin; Tanik, Serhat; Atar, Muhittin; Bakirtas, Hasan; Imamoglu, Muhammed Abdurrahim; Gurdal, Mesut

    2015-01-01

    Penile tourniquet syndrome (PTS), a rare urologic emergency, may lead to undesirable results including necrosis and amputation of penis, if not diagnosed and treated appropriately. Sometimes these injuries may be accepted as a forensic case. Miscellaneous objects used for strangulation can be metallic or nonmetallic. Of all ages, the most vulnerable period is infancy. Telogen effluvium is the most common cause of PTS in infants who are 0–6 years old. In the literature, telogen effluvium as a reason of PTS was not found except for this age group. Therefore, we aimed to present a boy who is 8 years old diagnosed as PTS because of his mother's hair coil. PMID:25763288

  10. No association of the G972S polymorphism of the insulin receptor substrate-1 gene with polycystic ovary syndrome in lean PCOS women with biochemical hyperandrogenemia.

    Science.gov (United States)

    Marioli, Dimitra J; Koika, Vasiliki; Adonakis, George L; Saltamavros, Alexandros D; Karela, Anastasia; Armeni, Anastasia K; Tsapanos, Vasilios S; Decavalas, George O; Georgopoulos, Neoklis A

    2010-06-01

    The aim of the present study was to determine the prevalence and association of the G972S polymorphism of the insulin receptor substrate-1 gene (IRS-1 G972S SNP) with polycystic ovary syndrome (PCOS) and insulin resistance-related traits in a distinct phenotypic group of lean PCOS women with biochemical hyperandrogenemia, excluding obesity, which is considered to be an aggravating parameter of insulin resistance. The study included 162 women with PCOS and 122 regularly menstruating, ovulatory women as controls. Physical measurements included weight, height, fat-free mass, fat mass, systolic and diastolic blood pressure and resting heart rate. Biochemical parameters included the serum testosterone, free testosterone, androstenedione, total cholesterol, triglycerides, HDL and LDL cholesterol and glucose levels. Insulin resistance was assessed by determining fasting insulin levels, fasting glucose levels, the fasting glucose/insulin ratio, as well as the HOMA and QUICKI indexes. All DNA samples were genotyped by a PCR-restriction fragment length polymorphism (RLFP) assay. No association of the genotype frequencies of the G972S polymorphism in insulin receptor substrate-1 gene (IRS-1 G972S SNP) with PCOS phenotype and insulin resistance was detected. The G972S polymorphism of the IRS-1 gene should not be viewed as major contributor to the development of PCOS or as a causative variant for insulin resistance.

  11. Metabolic syndrome and related variables, insulin resistance, leptin levels, and PPAR-γ2 and leptin gene polymorphisms in a pedigree of subjects with bipolar disorder

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    Trino Baptista

    2015-06-01

    Full Text Available Objective:Evidence points to a high prevalence of metabolic dysfunction in bipolar disorder (BD, but few studies have evaluated the relatives of subjects with BD. We conducted a cross-sectional study in an extended family of patients with BD type I.Methods:The available relatives of the same family were interviewed (DSM-IV-R and assessed in fasting conditions for body mass index, constituent variables of the metabolic syndrome (MS, leptin levels, insulin resistance index, and single nucleotide polymorphisms (SNPs for the leptin receptor and promoter and PPAR-γ2 genes. The frequency of MS was compared with that recorded in the local general population.Results:Ninety-three relatives of three adults with BD were evaluated (30 aged 18 years. The frequency of MS was similar to that of the general population. Significantly higher frequencies of abnormal glucose, total and low density cholesterol (LDL-c levels (all p < 0.05, waist circumference (p = 0.057, and leptin and insulin resistance values (in adults only were observed in the family. Adults with the QQ genotype of the leptin receptor displayed higher LDL-c levels than carriers of the R allele.Conclusions:The associations among BD consanguinity, familial hypercholesterolemia, and leptin receptor SNPs reported herein should be replicated and extended in other pedigrees.

  12. Fasting Plasma Insulin at 5 Years of Age Predicted Subsequent Weight Increase in Early Childhood over a 5-Year Period—The Da Qing Children Cohort Study

    Science.gov (United States)

    Chen, Yan Yan; Wang, Jin Ping; Jiang, Ya Yun; Li, Hui; Hu, Ying Hua; Lee, Kok Onn; Li, Guang Wei

    2015-01-01

    Background The association between hyperinsulinemia and obesity is well known. However, it is uncertain especially in childhood obesity, if initial fasting hyperinsulinemia predicts obesity, or obesity leads to hyperinsulinemia through insulin resistance. Objective To investigate the predictive effect of fasting plasma insulin on subsequent weight change after a 5-year interval in childhood. Methods 424 Children from Da Qing city, China, were recruited at 5 years of age and followed up for 5 years. Blood pressure, anthropometric measurements, fasting plasma insulin, glucose and triglycerides were measured at baseline and 5 years later. Results Fasting plasma insulin at 5 years of age was significantly correlated with change of weight from 5 to 10 years (ΔWeight). Children in the lowest insulin quartile had ΔWeight of 13.08±0.73 kg compare to 18.39±0.86 in the highest insulin quartile (P<0.0001) in boys, and similarly 12.03±0.71 vs 15.80±0.60 kg (P<0.0001) in girls. Multivariate analysis showed that the predictive effect of insulin at 5 years of age on subsequent weight gain over 5 years remained statistically significant even after the adjustment for age, sex, birth weight, TV-viewing time and weight (or body mass index) at baseline. By contrast, the initial weight at 5 years of age did not predict subsequent changes in insulin level 5 years later. Children who had both higher fasting insulin and weight at 5 years of age showed much higher levels of systolic blood pressures, fasting plasma glucose, the homeostasis model assessment for insulin resistance (HOMA-IR) and triglycerides at 10 years of age. Conclusions Fasting plasma insulin at 5 years of age predicts weight gain and cardiovascular risk factors 5 year later in Chinese children of early childhood, but the absolute weight at 5 years of age did not predict subsequent change in fasting insulin. PMID:26047327

  13. Fasting Plasma Insulin at 5 Years of Age Predicted Subsequent Weight Increase in Early Childhood over a 5-Year Period-The Da Qing Children Cohort Study.

    Directory of Open Access Journals (Sweden)

    Yan Yan Chen

    Full Text Available The association between hyperinsulinemia and obesity is well known. However, it is uncertain especially in childhood obesity, if initial fasting hyperinsulinemia predicts obesity, or obesity leads to hyperinsulinemia through insulin resistance.To investigate the predictive effect of fasting plasma insulin on subsequent weight change after a 5-year interval in childhood.424 Children from Da Qing city, China, were recruited at 5 years of age and followed up for 5 years. Blood pressure, anthropometric measurements, fasting plasma insulin, glucose and triglycerides were measured at baseline and 5 years later.Fasting plasma insulin at 5 years of age was significantly correlated with change of weight from 5 to 10 years (ΔWeight. Children in the lowest insulin quartile had ΔWeight of 13.08±0.73 kg compare to 18.39±0.86 in the highest insulin quartile (P<0.0001 in boys, and similarly 12.03±0.71 vs 15.80±0.60 kg (P<0.0001 in girls. Multivariate analysis showed that the predictive effect of insulin at 5 years of age on subsequent weight gain over 5 years remained statistically significant even after the adjustment for age, sex, birth weight, TV-viewing time and weight (or body mass index at baseline. By contrast, the initial weight at 5 years of age did not predict subsequent changes in insulin level 5 years later. Children who had both higher fasting insulin and weight at 5 years of age showed much higher levels of systolic blood pressures, fasting plasma glucose, the homeostasis model assessment for insulin resistance (HOMA-IR and triglycerides at 10 years of age.Fasting plasma insulin at 5 years of age predicts weight gain and cardiovascular risk factors 5 year later in Chinese children of early childhood, but the absolute weight at 5 years of age did not predict subsequent change in fasting insulin.

  14. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These conditions ... agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  15. In vivo and in vitro attenuation of naloxone-precipitated experimental opioid withdrawal syndrome by insulin and selective KATP channel modulator.

    Science.gov (United States)

    Singh, Prabhat; Sharma, Bhupesh; Gupta, Surbhi; Sharma, B M

    2015-01-01

    Opiate exposure for longer duration develops state of dependence in humans and animals, which is revealed by signs and symptoms of withdrawal precipitated by opioid receptor antagonists. The sudden withdrawal of opioids produces a withdrawal syndrome in opioid-dependent subjects. Insulin and ATP-sensitive potassium (KATP) channel-mediated glucose homeostasis have been shown to modulate morphine withdrawal. Present study has been structured to investigate the role of insulin and pharmacological modulator of KATP channel (gliclazide) in experimental morphine withdrawal syndrome, both invivo and invitro. In this study, naloxone-precipitated morphine withdrawal syndrome in mice (invivo) as well as in rat ileum (invitro) were utilized to assess opioid withdrawal phenomenon. Morphine withdrawal syndromes like jumping and rearing frequency, forepaw licking, circling, fore paw tremor, wet dog shake, sneezing, overall morphine withdrawal severity (OMWS), serum glucose, brain malondialdehyde (MDA), glutathione (GSH), nitrite/nitrate, and calcium (Ca(+2)) were assessed. Naloxone has significantly increased morphine withdrawal syndrome, both invivo and invitro. Insulin and gliclazide have significantly attenuated, naloxone induced behavioral changes like jumping and rearing frequency, forepaw licking, wet dog shake, sneezing, straightening, circling, OMWS, and various biochemical impairments such as serum glucose, brain MDA, GSH, nitrite/nitrate, and Ca(+2) in morphine-dependent animals (invivo). In vitro, insulin and gliclazide have significantly reduced naloxone-induced contraction in morphine-withdrawn rat ileum preparation. Insulin and gliclazide (KATP channel blocker) have attenuated naloxone-precipitated morphine withdrawal syndrome, both invivo and invitro. Thus, insulin and KATP channel modulation may provide new avenues for research in morphine withdrawal.

  16. Age-Related Neurodegeneration and Memory Loss in Down Syndrome

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    Jason P. Lockrow

    2012-01-01

    Full Text Available Down syndrome (DS is a condition where a complete or segmental chromosome 21 trisomy causes variable intellectual disability, and progressive memory loss and neurodegeneration with age. Many research groups have examined development of the brain in DS individuals, but studies on age-related changes should also be considered, with the increased lifespan observed in DS. DS leads to pathological hallmarks of Alzheimer's disease (AD by 40 or 50 years of age. Progressive age-related memory deficits occurring in both AD and in DS have been connected to degeneration of several neuronal populations, but mechanisms are not fully elucidated. Inflammation and oxidative stress are early events in DS pathology, and focusing on these pathways may lead to development of successful intervention strategies for AD associated with DS. Here we discuss recent findings and potential treatment avenues regarding development of AD neuropathology and memory loss in DS.

  17. Lower dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome.

    Science.gov (United States)

    Malin, Steven K; Huang, Hazel; Mulya, Anny; Kashyap, Sangeeta R; Kirwan, John P

    2013-09-01

    Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin-stimulated glucose uptake and is linked to obesity and metabolic syndrome. However, the effect of exercise on plasma DPP-4 in adults with metabolic syndrome is unknown. Therefore, we determined the effect of exercise on DPP-4 and its role in explaining exercise-induced improvements in insulin sensitivity. Fourteen obese adults (67.9±1.2 years, BMI: 34.2±1.1kg/m(2)) with metabolic syndrome (ATP III criteria) underwent a 12-week supervised exercise intervention (60min/day for 5 days/week at ∼85% HRmax). Plasma DPP-4 was analyzed using an enzyme-linked immunosorbent assay. Insulin sensitivity was measured using the euglycemic-hyperinsulinemic clamp (40mU/m(2)/min) and estimated by HOMA-IR. Visceral fat (computerized tomography), 2-h glucose levels (75g oral glucose tolerance), and basal fat oxidation as well as aerobic fitness (indirect calorimetry) were also determined before and after exercise. The intervention reduced visceral fat, lowered blood pressure, glucose and lipids, and increased aerobic fitness (PExercise improved clamp-derived insulin sensitivity by 75% (PExercise training reduces plasma DPP-4, which may be linked to elevated insulin sensitivity and fat oxidation. Maintaining low plasma DPP-4 concentrations is a potential mechanism whereby exercise plus weight loss prevents/delays the onset of type 2 diabetes in adults with metabolic syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Association of Insulin Resistance With Cerebral Glucose Uptake in Late Middle-Aged Adults at Risk for Alzheimer Disease.

    Science.gov (United States)

    Willette, Auriel A; Bendlin, Barbara B; Starks, Erika J; Birdsill, Alex C; Johnson, Sterling C; Christian, Bradley T; Okonkwo, Ozioma C; La Rue, Asenath; Hermann, Bruce P; Koscik, Rebecca L; Jonaitis, Erin M; Sager, Mark A; Asthana, Sanjay

    2015-09-01

    Converging evidence suggests that Alzheimer disease (AD) involves insulin signaling impairment. Patients with AD and individuals at risk for AD show reduced glucose metabolism, as indexed by fludeoxyglucose F 18-labeled positron emission tomography (FDG-PET). To determine whether insulin resistance predicts AD-like global and regional glucose metabolism deficits in late middle-aged participants at risk for AD and to examine whether insulin resistance-predicted variation in regional glucose metabolism is associated with worse cognitive performance. This population-based, cross-sectional study included 150 cognitively normal, late middle-aged (mean [SD] age, 60.7 [5.8] years) adults from the Wisconsin Registry for Alzheimer's Prevention (WRAP) study, a general community sample enriched for AD parental history. Participants underwent cognitive testing, fasting blood draw, and FDG-PET at baseline. We used the homeostatic model assessment of peripheral insulin resistance (HOMA-IR). Regression analysis tested the statistical effect of HOMA-IR on global glucose metabolism. We used a voxelwise analysis to determine whether HOMA-IR predicted regional glucose metabolism. Finally, predicted variation in regional glucose metabolism was regressed against cognitive factors. Covariates included age, sex, body mass index, apolipoprotein E ε4 genotype, AD parental history status, and a reference region used to normalize regional uptake. Regional glucose uptake determined using FDG-PET and neuropsychological factors. Higher HOMA-IR was associated with lower global glucose metabolism (β = -0.29; P factor scores. Our results show that insulin resistance, a prevalent and increasingly common condition in developed countries, is associated with significantly lower regional cerebral glucose metabolism, which in turn may predict worse memory performance. Midlife may be a critical period for initiating treatments to lower peripheral insulin resistance to maintain neural metabolism

  19. Effect on Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator during Weight Loss in Obese Women with and without Polycystic Ovary Syndrome.

    Science.gov (United States)

    Cheang, Kai I; Sistrun, Sakita N; Morel, Kelley S; Nestler, John E

    2016-01-01

    Background. A deficiency of D-chiro-inositol-inositolphosphoglycan mediator (DCI-IPG) may contribute to insulin resistance in polycystic ovary syndrome (PCOS). Whether the relationship between impaired DCI-IPG release and insulin resistance is specific to PCOS rather than obesity is unknown. We assessed insulin-released DCI-IPG and its relationship to insulin sensitivity at baseline and after weight loss in obese women with and without PCOS. Methods. Obese PCOS ( n = 16) and normal ( n = 15) women underwent 8 weeks of a hypocaloric diet. The Matsuda index, area under the curve DCI-IPG (AUC DCI-IPG ), AUC insulin , and AUC DCI-IPG /AUC insulin were measured during a 2 hr OGTT at baseline and 8 weeks. Results. PCOS women had lower AUC DCI-IPG /AUC insulin at baseline and a significant relationship between AUC DCI-IPG /AUC insulin and Matsuda index ( p = 0.0003), which was not present in controls. Weight loss was similar between PCOS (-4.08 kg) and normal women (-4.29 kg, p = 0.6281). Weight loss in PCOS women did not change the relationship between AUC DCI-IPG /AUC insulin and Matsuda index ( p = 0.0100), and this relationship remained absent in control women. Conclusion. The association between AUC DCI-IPG /AUC insulin and insulin sensitivity was only found in PCOS but not in normal women, and this relationship was unaffected by weight loss. DCI and its messenger may contribute to insulin resistance in PCOS independent of obesity.

  20. Study the Effect of Zinc Supplementation on Lipid Profiles, Insulin Sensi-tivity and Biomarkers of Oxidative Stress in Women with Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Mehri Jamilian

    2016-11-01

    Full Text Available Abstract Background: We are aware of no study evaluating the effects of zinc supplementation on metabolic profiles of patients with polycystic ovary syndrome (PCOS. This study was conducted to evaluate the effects of zinc supplementation on glucose homeostasis parameters in PCOS women. Materials and Methods: This randomized, double-blind, placebo-controlled trial was conducted among 52 women diagnosed with PCOS and aged 18-40 years old. Participants were ran-domly divided into two groups to receive 220 mg zinc sulfate (containing 50 mg zinc supplements (n=26 or placebo (n=26 per day for 8 weeks. Fasting blood samples were taken at baseline and after 8 weeks of intervention to quantify glucose and insulin. Results: After 8 weeks of intervention, zinc-supplemented patients had reduced fasting plasma glucose (FPG (-4.3±9.6 vs. +0.5±6.0 mg/dL, p=0.03, serum insulin (-3.0 ± 2.9 vs . + 1.5 ± 8.4 µIU/ml, p=0.01, serum triglycerides levels (-15.6±40.3 vs. +14.5±25.3 mg/dL, p=0.002 and a significant increase in insulin sensitivity (+0.02±0.02 vs. -0.004±0.05, p=0.03 compared with the placebo. Conclusion: Taken together, 220 mg zinc sulfate supplementation per day for 8 weeks among PCOS women had beneficial effects on metabolic profiles.

  1. Definition of insulin resistance using the homeostasis model assessment (HOMA-IR) in IVF patients diagnosed with polycystic ovary syndrome (PCOS) according to the Rotterdam criteria.

    Science.gov (United States)

    Alebić, Miro Šimun; Bulum, Tomislav; Stojanović, Nataša; Duvnjak, Lea

    2014-11-01

    Polycystic ovary syndrome (PCOS) women are more insulin resistant than general population. Prevalence data on insulin resistance (IR) in PCOS vary depending on population characteristics and methodology used. The objectives of this study were to investigate whether IR in PCOS is exclusively associated with body mass and to assess the prevalence of IR in lean and overweight/obese PCOS. Study included 250 consecutive women who attended a Department of Human Reproduction diagnosed as having PCOS according to the Rotterdam criteria. Control group comprised 500 healthy women referred for male factor infertility evaluation during the same period as the PCOS women. PCOS women (n = 250) were more insulin resistant than controls (n = 500) even after adjustment for age and body mass index (BMI) (P = 0.03). Using logistic regression analysis, BMI ≥ 25 kg/m(2) (OR 6.0; 95 % CI 3.3-11.0), PCOS (OR 2.2; 95 % CI 1.4-3.5) and waist circumference ≥ 80 cm (OR 2.0; 95 % CI 1.1-3.8) were identified as independent determinants of IR (P IR was more prevalent in overweight/obese controls (n = 100) than in lean PCOS women (n = 150), 31 versus 9.3 %, but less prevalent than in overweight/obese PCOS (n = 100), 31 versus 57 %. The prevalence of IR between lean controls (5 %) and lean PCOS (9.3 %) did not significantly differ. Both PCOS-specific and obesity-related IR independently contribute to IR in PCOS. Using HOMA-IR cutoff value of 3.15 specific for Croatian women in our clinical setting, the assessed prevalence of IR in lean and overweight/obese PCOS women was 9.3 and 57 %, respectively.

  2. Low-dose metformin improves pregnancy rate in in vitro fertilization repeaters without polycystic ovary syndrome: prediction of effectiveness by multiple parameters related to insulin resistance.

    Science.gov (United States)

    Jinno, Masao; Kondou, Kenichi; Teruya, Koji

    2010-01-01

    Insulin resistance is associated with aging and stress, both common among patients repeatedly failing to conceive with in vitro fertilization (IVF repeaters). In the present study we examined whether low-dose metformin could improve the outcome in IVF repeaters without polycystic ovary syndrome (PCOS). Study I was a preliminary clinical trial aiming at defining indications for therapy; study II was a prospective randomized study. The studies involved a university hospital and a private infertility clinic. We studied 232 women without PCOS who had failed at least twice to conceive by previous IVF. Metformin (500 mg/ day) was administered for 8 to 12 weeks before and during ovarian stimulation (metformin IVF). In study I, IVF outcomes with metformin (n = 33) were compared to outcomes without metformin of previous IVF in the same subjects. A discriminant score (DS) was determined from nine parameters assessed before metformin administration to predict achievement of ongoing pregnancy by metformin IVF. In study II (n = 199), ongoing pregnancy rates were compared prospectively between groups with/without metformin and with DS above/below 0.6647. Study I. Ongoing pregnancy rate improved significantly with metformin compared with previous IVF, and pregnancy correlated significantly with a DS at an optimal threshold of 0.6647 (sensitivity, 0.90; specificity, 0.91). Study II. Ongoing pregnancy and implantation rates were significantly higher in women with a DS above 0.6647 who received metformin (56% and 33%) compared with those having a DS below 0.6647 with metformin (14% and 11%) and those having a DS above/below 0.6647 without metformin (20% and 7.1%/15% and 11%, respectively). Low-dose metformin improved pregnancy rate in IVF repeaters without PCOS, probably by decreasing insulin resistance. Indication can be determined from insulin-resistance-related multiple parameters assessed before metformin administration.

  3. INSULIN-LIKE GROWTH FACTOR (IGF-1 IN CNS AND CEREBROVASCULAR AGING

    Directory of Open Access Journals (Sweden)

    William E Sonntag

    2013-07-01

    Full Text Available Insulin-like growth factor-1 (IGF-1 is an important anabolic hormone that decreases with age. In the past two decades extensive research has determined that the reduction in IGF-1 is an important component of the age-related decline in cognitive function in multiple species including humans. Deficiency in circulating IGF-1 results in impairment in processing speed and deficiencies in both spatial and working memory. Replacement of IGF-1 or factors that increase IGF-1 to old animals and humans reverses many of these cognitive deficits. Despite the overwhelming evidence for IGF-1 as an important neurotrophic agent, the specific mechanisms through which IGF-1 acts have remained elusive. Recent evidence indicates that IGF-1 is both produced by and has important actions on the cerebrovasculature as well as neurons and glia. Nevertheless, the specific regulation and actions of brain- and vascular-derived IGF-1 is poorly understood. The diverse effects of IGF-1 discovered thus far reveal a complex endocrine and paracrine system essential for integrating many of the functions necessary for brain health. Identification of the mechanisms of IGF-1 actions will undoubtedly provide critical insight into regulation of brain function in general and the causes of cognitive decline with age.

  4. Attenuation of insulin-evoked responses in brain networks controlling appetite and reward in insulin resistance: the cerebral basis for impaired control of food intake in metabolic syndrome?

    Science.gov (United States)

    Anthony, Karen; Reed, Laurence J; Dunn, Joel T; Bingham, Emma; Hopkins, David; Marsden, Paul K; Amiel, Stephanie A

    2006-11-01

    The rising prevalence of obesity and type 2 diabetes is a global challenge. A possible mechanism linking insulin resistance and weight gain would be attenuation of insulin-evoked responses in brain areas relevant to eating in systemic insulin resistance. We measured brain glucose metabolism, using [(18)F]fluorodeoxyglucose positron emission tomography, in seven insulin-sensitive (homeostasis model assessment of insulin resistance [HOMA-IR] = 1.3) and seven insulin-resistant (HOMA-IR = 6.3) men, during suppression of endogenous insulin by somatostatin, with and without an insulin infusion that elevated insulin to 24.6 +/- 5.2 and 23.2 +/- 5.8 mU/l (P = 0.76), concentrations similar to fasting levels of the resistant subjects and approximately threefold above those of the insulin-sensitive subjects. Insulin-evoked change in global cerebral metabolic rate for glucose was reduced in insulin resistance (+7 vs. +17.4%, P = 0.033). Insulin was associated with increased metabolism in ventral striatum and prefrontal cortex and with decreased metabolism in right amygdala/hippocampus and cerebellar vermis (P reward. Diminishing the link be-tween control of food intake and energy balance may contribute to development of obesity in insulin resistance.

  5. Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome -- a randomized study (SYSDIET).

    Science.gov (United States)

    Uusitupa, M; Hermansen, K; Savolainen, M J; Schwab, U; Kolehmainen, M; Brader, L; Mortensen, L S; Cloetens, L; Johansson-Persson, A; Onning, G; Landin-Olsson, M; Herzig, K-H; Hukkanen, J; Rosqvist, F; Iggman, D; Paananen, J; Pulkki, K J; Siloaho, M; Dragsted, L; Barri, T; Overvad, K; Bach Knudsen, K E; Hedemann, M S; Arner, P; Dahlman, I; Borge, G I A; Baardseth, P; Ulven, S M; Gunnarsdottir, I; Jónsdóttir, S; Thorsdottir, I; Orešič, M; Poutanen, K S; Risérus, U; Akesson, B

    2013-07-01

    Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. We conducted a randomized dietary study lasting for 18-24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m(-2) , 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmol L(-1) 95% CI -0.35; -0.01, P = 0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37 ng L(-1) , P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, -0.23, -0.41; -0.05, P = 0.012) were associated with IL-1 Ra. Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  6. Increased insulin-like growth factor-1 in relation to cardiovascular function in polycystic ovary syndrome: friend or foe?

    Science.gov (United States)

    Desai, Namrata Ajaykumar; Patel, Snehal S

    2015-10-01

    The incidence of cardiovascular disease (CVD) in patients with polycystic ovary syndrome (PCOS) is very high and conventional risk factors only partially explain excessive risk of developing CVD in patients of PCOS. The pathophysiology of PCOS is very unique, and several hormonal and metabolic changes occur. Several observations suggest that serum IGF-1 levels decrease in insulin resistance, which results in IGF-1 deficiency. In patient of PCOS, close relationships have been demonstrated between insulin resistance and serum IGF-1 levels. Hyperinsulinemic insulin resistance results in a general augmentation of steroidogenesis and LH release in PCOS. The action of IGF-1 varies in different tissues possibly via autocrine or paracrine mechanisms. The increase or decrease in IGF-1 in different tissues results in differential outcomes. Several studies suggest that lowered circulating IGF-1 levels play important role in the initiation of the cardiac hypertrophic response which results in the risk of cardiovascular disease. While recent results suggests that individual with elevated IGF-1 is protected against cardiovascular disease. Thus IGF-1 shows versatile pleiotropic actions. This review provides a current perspective on increased level of IGF-1 in PCOS and also adds to the current controversy regarding the roles of IGF-1 in cardiovascular disease.

  7. Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age

    DEFF Research Database (Denmark)

    Akintola, Abimbola A; van den Berg, Annette; van Buchem, Mark A

    2015-01-01

    [fasted glucose and glucose area-under-the-curve (AUC)], insulin resistance [fasted insulin, AUCinsulin, and homeostatic model assessment of insulin resistance (HOMA-IR)], and pancreatic Beta cell secretory capacity (insulinogenic index). 3 Tesla MRI and Magnetization Transfer (MT) imaging MT-ratio (MTR......-height in gray and white matter was inversely associated with AUCinsulin, fasted insulin, HOMA-IR and insulinogenic-index (all p 65 years): in younger controls, significantly stronger inverse associations were observed between MTR peak-height and fasted glucose......, AUCglucose, fasted insulin, AUCinsulin and HOMA-IR in gray matter; and for AUCglucose, fasted insulin and HOMA-IR in white matter (all P-interaction

  8. Modern approach to basal-bolus therapy with glargine and glulisine insulin analoguesin various age groups

    Directory of Open Access Journals (Sweden)

    Natalya Nikitichna Volevodz

    2013-03-01

    Full Text Available DCCT (Diabetes Control and Complications Trial study established that intensified insulin therapy in multiple daily injections (MDI or continuous insulin infusion (CSII regimens substantially reduce both development and progression of complications in patients with type 1 diabetes mellitus (T1DM as compared to conventional insulin therapy. Insulin analogues possess better pharmacokinetic and pharmacodynamic characteristics than unmodified human insulin agents. These characteristics are beneficial for management of diabetes mellitus, allowing better glycemic outcomes with lower incidence of hypoglycemia.Current review discusses specifics of therapy with glargine (Lantus? and glulisine (Apidra? insulin analogues. Authors analyzed available to date results from corresponding clinical trials in children, adolescents and adults. Pharmacoeconomic aspects and matters of dosage of glargine and glulisine are further addressed.

  9. Induced Pluripotent Stem Cell-Derived Endothelial Cells in Insulin Resistance and Metabolic Syndrome.

    Science.gov (United States)

    Carcamo-Orive, Ivan; Huang, Ngan F; Quertermous, Thomas; Knowles, Joshua W

    2017-11-01

    Insulin resistance leads to a number of metabolic and cellular abnormalities including endothelial dysfunction that increase the risk of vascular disease. Although it has been particularly challenging to study the genetic determinants that predispose to abnormal function of the endothelium in insulin-resistant states, the possibility of deriving endothelial cells from induced pluripotent stem cells generated from individuals with detailed clinical phenotyping, including accurate measurements of insulin resistance accompanied by multilevel omic data (eg, genetic and genomic characterization), has opened new avenues to study this relationship. Unfortunately, several technical barriers have hampered these efforts. In the present review, we summarize the current status of induced pluripotent stem cell-derived endothelial cells for modeling endothelial dysfunction associated with insulin resistance and discuss the challenges to overcoming these limitations. © 2017 American Heart Association, Inc.

  10. The effect of exercise on insulin resistance in obese women with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Heba S Kareem

    2014-01-01

    Conclusion Regular aerobic exercises improve insulin resistance, abdominal fat distribution, and body weight in obese diabetic and nondiabetic women with polycystic ovary, and they are advised to perform regular aerobic exercises.

  11. Triiodothyronine : a link between the insulin resistance syndrome and blood pressure?

    NARCIS (Netherlands)

    Bakker, SJL; ter Maaten, JC; Popp-Snijders, C; Heine, RJ; Gans, ROB

    1999-01-01

    Objective Overall obesity is associated with elevated serum triiodothyronine concentrations and insulin resistance. Oral triiodothyronine is known to induce hypertension in laboratory rats, while triiodothyronine also increases the expression of genes encoding for enzymes involved in the synthesis

  12. Triiodothyronine: a link between the insulin resistance syndrome and blood pressure?

    NARCIS (Netherlands)

    Bakker, J.L.; ter Maaten, J.C; Popp-Snijders, C.; Heine, R.J.; Gans, R.O.B.

    1999-01-01

    Objective. Overall obesity is associated with elevated serum triiodothyronine concentrations and insulin resistance. Oral triiodothyronine is known to induce hypertension in laboratory rats, while triiodothyronine also increases the expression of genes encoding for enzymes involved in the synthesis

  13. Lifelong Physical Activity Prevents Aging-Associated Insulin Resistance in Human Skeletal Muscle Myotubes via Increased Glucose Transporter Expression

    DEFF Research Database (Denmark)

    Bunprajun, Tipwadee; Henriksen, Tora Ida; Scheele, Camilla

    2013-01-01

    , and significantly higher GLUT4 protein. It is likely that physical activity induces a number of stable adaptations, including increased GLUT4 expression that are retained in cells ex vivo and protect, or delay the onset of middle-aged-associated insulin resistance. Additionally, a sedentary lifestyle has an impact...

  14. NTproBNP in insulin-resistance mediated conditions: overweight/obesity, metabolic syndrome and diabetes. The population-based Casale Monferrato Study.

    Science.gov (United States)

    Baldassarre, Stefano; Fragapani, Salvatore; Panero, Antonio; Fedele, Debora; Pinach, Silvia; Lucchiari, Manuela; Vitale, Anna Rita; Mengozzi, Giulio; Gruden, Gabriella; Bruno, Graziella

    2017-09-25

    NTproBNP and BNP levels are reduced in obese subjects, but population-based data comparing the pattern of this relationship in the full spectrum of insulin-resistance mediated conditions, overweight/obesity, metabolic syndrome and diabetes, are limited. The study-base were 3244 individuals aged 45-74 years, none of whom had heart failure, 1880 without diabetes and 1364 with diabetes, identified as part of two surveys of the population-based Casale Monferrato Study. All measurements were centralized. We examined with multiple linear regression and cubic regression splines the relationship between NTproBNP and BMI, independently of known risk factors and confounders. A logistic regression analysis was also performed to assess the effect of overweight/obesity (BMI ≥ 25 kg/m 2 ), diabetes and metabolic syndrome on NTproBNP values. Out of the overall cohort of 3244 people, overweight/obesity was observed in 1118 (59.4%) non-diabetic and 917 (67.2%) diabetic subjects, respectively. In logistic regression, compared to normal weight individuals, those with a BMI ≥ 25 kg/m 2 had a OR of 0.70 (95% CI 0.56-0.87) of having high NTproBNP values, independently of diabetes. As interaction between diabetes and NTproBNP was evident (p obesity or metabolic syndrome enhanced fourfold and over the OR of having high NTproBNP levels, while the presence of metabolic syndrome alone had a more modest effect (OR 1.54, 1.18-2.01) even after having excluded individuals with CVD. In the non-diabetic cohort, obesity/overweight and HOMA-IR ≥ 2.0 decreased to a similar extent the ORs of high NTproBNP [0.76 (0.60-0.95) and 0.74 (0.59-0.93)], but the association between overweight/obesity and NTproBNP was no longer significant after the inclusion into the model of HOMA-IR, whereas CRP > 3 mg/dl conferred a fully adjusted OR of 0.65 (0.49-0.86). NT-proBNP levels are lower in overweight/obesity, even in those with diabetes. Both insulin-resistance and chronic low-grade inflammation

  15. Association of oral contraceptive and metformin did not improve insulin resistance in women with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Margareth Chiharu Iwata

    2015-06-01

    Full Text Available Summary Objective: Objective: to compare clinical and laboratory parameters in women with polycystic ovary syndrome (PCOS using metformin or combined oral contraceptive (COC after 6 months. Methods: retrospective study analyzing records of patients with PCOS using the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS Society criteria. The groups were: I-COC (21 tablets, pause of 7 days; n=16; II-metformin (850mg 12/12h, n=16; III-COC plus metformin (n=9. Body mass index (BMI, acne (% of improvement, modified Ferriman-Gallway index and menstrual cycle index (MCI, luteinizing hormone (LH, follicle-stimulating hormone (FSH, total testosterone (TT, androstenedione (A and homeostasis model assessment: insulin resistance (HOMA-IR index were assessed Results: isolated use of COC compared to metformin was better regarding to acne, Ferriman index, MCI, LH, TT and A levels. On the other hand, metformin was better in the HOMA-IR index (4.44 and 1.67 respectively, p=0.0007. The association COC plus metformin, compared to metformin alone shows the maintenance of improvement of acne, Ferriman index, MCI, and testosterone levels. The HOMA-IR index remained lower in the metformin alone group (4.19 and 1.67, respectively; p=0,046. The comparison between COC plus metformin and COC alone, in turn, shows no difference in the improvement of acne, Ferriman index, MCI, LH, TT and A levels, indicating that the inclusion of metformin did not lead to additional benefits in these parameters. Still, the HOMA-IR index was similar in both groups (4.19 and 4.44 respectively; p=0.75, showing that the use of metformin associated with COC may not improve insulin resistance as much as it does if used alone. Conclusion: our data suggest that the combination of metformin and contraceptive does not improve insulin resistance as observed with metformin alone.

  16. Hypertension Is a Key Feature of the Metabolic Syndrome in Subjects Aging with HIV

    DEFF Research Database (Denmark)

    Martin-Iguacel, Raquel; Negredo, Eugènia; Peck, Robert

    2016-01-01

    to predispose to these metabolic complications and to the excess risk of CVD observed in the HIV population. The metabolic syndrome (MS) represents a clustering of RF for CVD that includes abdominal obesity, hypertension, dyslipidemia and insulin resistance. Hypertension is a prevalent feature of the MS in HIV...

  17. Enhanced Inflammation without Impairment of Insulin Signaling in the Visceral Adipose Tissue of 5α-Dihydrotestosterone-Induced Animal Model of Polycystic Ovary Syndrome.

    Science.gov (United States)

    Milutinović, Danijela Vojnović; Nikolić, Marina; Veličković, Nataša; Djordjevic, Ana; Bursać, Biljana; Nestorov, Jelena; Teofilović, Ana; Antić, Ivana Božić; Macut, Jelica Bjekić; Zidane, Abdulbaset Shirif; Matić, Gordana; Macut, Djuro

    2017-09-01

    Polycystic ovary syndrome is a heterogeneous endocrine and metabolic disorder associated with abdominal obesity, dyslipidemia and insulin resistance. Since abdominal obesity is characterized by low-grade inflammation, the aim of the study was to investigate whether visceral adipose tissue inflammation linked to abdominal obesity and dyslipidemia could lead to impaired insulin sensitivity in the animal model of polycystic ovary syndrome.Female Wistar rats were treated with nonaromatizable 5α-dihydrotestosterone pellets in order to induce reproductive and metabolic characteristics of polycystic ovary syndrome. Glucose, triglycerides, non-esterified fatty acids and insulin were determined in blood plasma. Visceral adipose tissue inflammation was evaluated by the nuclear factor kappa B intracellular distribution, macrophage migration inhibitory factor protein level, as well as TNFα, IL6 and IL1β mRNA levels. Insulin sensitivity was assessed by intraperitoneal glucose tolerance test and homeostasis model assessment index, and through analysis of insulin signaling pathway in the visceral adipose tissue.Dihydrotestosterone treatment led to increased body weight, abdominal obesity and elevated triglycerides and non-esterified fatty acids, which were accompanied by the activation of nuclear factor kappa B and increase in macrophage migration inhibitory factor, IL6 and IL1β levels in the visceral adipose tissue. In parallel, insulin sensitivity was affected in 5α-dihydrotestosterone-treated animals only at the systemic and not at the level of visceral adipose tissue.The results showed that abdominal obesity and dyslipidemia in the animal model of polycystic ovary syndrome were accompanied with low-grade inflammation in the visceral adipose tissue. However, these metabolic disturbances did not result in decreased tissue insulin sensitivity. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Effects of caloric intake timing on insulin resistance and hyperandrogenism in lean women with polycystic ovary syndrome.

    Science.gov (United States)

    Jakubowicz, Daniela; Barnea, Maayan; Wainstein, Julio; Froy, Oren

    2013-11-01

    In women with PCOS (polycystic ovary syndrome), hyperinsulinaemia stimulates ovarian cytochrome P450c17α activity that, in turn, stimulates ovarian androgen production. Our objective was to compare whether timed caloric intake differentially influences insulin resistance and hyperandrogenism in lean PCOS women. A total of 60 lean PCOS women [BMI (body mass index), 23.7±0.2 kg/m²] were randomized into two isocaloric (~1800 kcal; where 1 kcal≈4.184 J) maintenance diets with different meal timing distribution: a BF (breakfast diet) (980 kcal breakfast, 640 kcal lunch and 190 kcal dinner) or a D (dinner diet) group (190 kcal breakfast, 640 kcal lunch and 980 kcal dinner) for 90 days. In the BF group, a significant decrease was observed in both AUC(glucose) (glucose area under the curve) and AUC(insulin) (insulin area under the curve) by 7 and 54% respectively. In the BF group, free testosterone decreased by 50% and SHBG (sex hormone-binding globulin) increased by 105%. GnRH (gonadotropin-releasing hormone)-stimulated peak serum 17OHP (17α-hydroxyprogesterone) decreased by 39%. No change in these parameters was observed in the D group. In addition, women in the BF group had an increased ovulation rate. In lean PCOS women, a high caloric intake at breakfast with reduced intake at dinner results in improved insulin sensitivity indices and reduced cytochrome P450c17α activity, which ameliorates hyperandrogenism and improves ovulation rate. Meal timing and distribution should be considered as a therapeutic option for women with PCOS.

  19. Intrinsic factors rather than vitamin D deficiency are related to insulin resistance in lean women with polycystic ovary syndrome.

    Science.gov (United States)

    Sahin, S; Eroglu, M; Selcuk, S; Turkgeldi, L; Kozali, S; Davutoglu, S; Muhcu, M

    2014-10-01

    To investigate the correlation between insulin resistance (IR) and serum 25-OH-Vit D concentrations and hormonal parameters in lean women with polycystic ovary syndrome (PCOS). 50 lean women with PCOS and 40 body mass index (BMI) matched controls were compared in terms of fasting insulin and glucose, homeostatic model assessment insulin resistance (HOMA-IR), 25-OH-Vit D, high sensitivity C-reactive protein (hs-CRP), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, dehydroepiandrosterone sulfate (DHEA-S), total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides and Ferriman-Gallway (FG) scores. Correlation analyses were performed between HOMA-IR and metabolic and endocrine parameters. 30% of patients with PCOS demonstrated IR. Levels of 25-OH-Vit D, hsCRP, cholesterol, HDL, LDL, triglyceride and fasting glucose did not differ between the study and control groups. Fasting insulin, HOMA-IR, LH, total testosterone, and DHEA-S levels were higher in PCOS group. HOMA-IR was found to correlate with hs-CRP and total testosterone but not with 25-OH-Vit D levels in lean patients with PCOS. An association between 25-OH-Vit D levels and IR is not evident in lean women with PCOS. hs-CRP levels do not indicate to an increased risk of cardiovascular disease in this population of patients. Because a strong association between hyperinsulinemia and hyperandrogenism exists in lean women with PCOS, it is advisable for this population of patients to be screened for metabolic disturbances, especially in whom chronic anovulation and hyperandrogenism are observed together.

  20. Variations of insulin resistance and associated hormone levels in elderly and middle-aged male persons and their clinical significance

    International Nuclear Information System (INIS)

    Zhuo Liankun; Yan Daochun; Chen Xiumei; Liu Peng; Zhang Aihua

    2005-01-01

    To study the relationship between age and insulin resistance and the variation of associated hormones in elderly and middle-aged males, blood levels of LH, FSH, T, SHBG, TSH, INS were determined by RIA, FBG by GPO, IR by HOMA in 268 healthy male persons aged 41 to 60 years and in 80 normal control male persions of 35 to 40 years old. The results showed that levels of IR, LH, FSH, SHBG were increasing and T, TSH were decreasing along with the increase of age except for TSH. Therefore, analyzing these changes could evaluate the conditions of elderly and middle-aged males. (authors)

  1. Impact of the Triglyceride/High-Density Lipoprotein Cholesterol Ratio and the Hypertriglyceremic-Waist Phenotype to Predict the Metabolic Syndrome and Insulin Resistance.

    Science.gov (United States)

    von Bibra, Helene; Saha, Sarama; Hapfelmeier, Alexander; Müller, Gabriele; Schwarz, Peter E H

    2017-07-01

    Insulin resistance is the underlying mechanism for the metabolic syndrome and associated dyslipidaemia that theoretically implies a practical tool for identifying individuals at risk for cardiovascular disease and type-2-diabetes. Another screening tool is the hypertriglyceremic-waist phenotype (HTW). There is important impact of the ethnic background but a lack of studied European populations for the association of the triglyceride/high-density lipoprotein cholesterol (HDL-C) ratio and insulin resistance. This observational, retrospective study evaluated lipid ratios and the HTW for predicting the metabolic syndrome/insulin resistance in 1932 non-diabetic individuals from Germany in the fasting state and during a glucose tolerance test. The relations of triglyceride/HDL-C, total-cholesterol/HDL-C, and low-density lipoprotein cholesterol/HDL-C with 5 surrogate estimates of insulin resistance/sensitivity and metabolic syndrome were analysed by linear regression analysis and receiver operating characteristics (ROC) in participants with normal (n=1 333) or impaired fasting glucose (n=599), also for the impact of gender. Within the lipid ratios, triglyceride/HDL-C had the strongest associations with insulin resistance/sensitivity markers. In the prediction of metabolic syndrome, diagnostic accuracy was good for triglyceride/HDL-C (area under the ROC curve 0.817) with optimal cut-off points (in mg/dl units) of 2.8 for men (80% sensitivity, 71% specificity) and 1.9 for women (80% sensitivity, 75% specificity) and fair for HTW and HOMA-IR (area under the curve 0.773 and 0.761). These data suggest the triglyceride/HDL-C ratio as a physiologically relevant and practical index for predicting the concomitant presence of metabolic syndrome, insulin resistance and dyslipidaemia for therapeutic and preventive care in apparently healthy European populations. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Joselyn Rojas

    2014-01-01

    Full Text Available Introduction. Insulin allergy is a rare complication of insulin therapy, especially in type 1 diabetes mellitus (T1DM. Key manifestations are hypersensitivity-related symptoms and poor metabolic control. T1DM, as well as insulin allergy, may develop in the context of autoimmune polyendocrine syndrome (APS, further complicating management. Case Report. A 17-year-old male patient, diagnosed with T1DM, was treated with various insulin therapy schemes over several months, which resulted in recurrent anaphylactoid reactions and poor glycemic control, after which he was referred to our Endocrinology and Immunology Department. A prick test was carried out for all commercially available insulin presentations and another insulin scheme was designed but proved unsuccessful. A desensitization protocol was started with Glargine alongside administration of Prednisone, which successfully induced tolerance. Observation of skin lesions typical of vitiligo prompted laboratory workup for other autoimmune disorders, which returned positive for autoimmune gastritis/pernicious anemia. These findings are compatible with APS type 4. Discussion. To our knowledge, this is the first documented case of insulin allergy in type 4 APS, as well as this particular combination in APS. Etiopathogenic components shared by insulin allergy and APS beg for further research in immunogenetics to further comprehend pathophysiologic aspects of these diseases.

  3. The plasma nitric oxide and homocysteine levels and their association with insulin resistance in South Indian women with polycystic ovary syndrome

    OpenAIRE

    Kandasamy S.; Inmozhi Sivagamasundari R.; Bupathy A.; Sethupathy S.

    2016-01-01

    Background: Women with polycystic ovary syndrome (PCOS) exhibit features of the metabolic syndrome apart from low-grade chronic inflammation and endothelial dysfunction and may be at increased risk for cardiovascular disease (CVD). The Nitric oxide (NO) and Homocysteine (Hcy) are important plasma markers of endothelial dysfunction, an early marker of atherosclerosis. There are no Indian studies on NO and Hcy levels in women with PCOS and their association with Insulin Resistance (IR). Therefo...

  4. Determinants of insulin responsiveness in young women: Impact of polycystic ovarian syndrome, nitric oxide, and vitamin D.

    Science.gov (United States)

    Ngo, D T M; Chan, W P; Rajendran, S; Heresztyn, T; Amarasekera, A; Sverdlov, A L; O'Loughlin, P D; Morris, H A; Chirkov, Y Y; Norman, R J; Horowitz, J D

    2011-10-30

    Polycystic ovary syndrome (PCOS) is associated with incremental risk of atherosclerosis and possibly of cardiovascular events. Insulin resistance (IR) occurs frequently in PCOS subjects, which might be one of the mechanisms involved in engendering such risk. We sought to evaluate whether the impact of other factors potentially associated both with PCOS and with IR might differentially modulate degree of IR in women with and without PCOS. We measured body mass index (BMI), hs-CRP, plasma concentrations of asymmetric dimethylarginine (ADMA), vitamin D (25(OH)D3) levels and platelet responsiveness to nitric oxide donor sodium nitroprusside (NO responsiveness) in 47 young women (n=27 with PCOS and n=20 weight-matched controls) without metabolic syndrome, hypertension or overt cardiovascular disease. We performed univariate and multivariate regression analyses to establish correlates of the quantitative insulin-sensitivity check index (QUICKI), as a marker of IR. On univariate analysis, plasma 25(OH)D3 levels and low NO responsiveness tended to be direct correlates with QUICKI in the entire subject group. BMI, hs-CRP, and ADMA levels were significant inverse correlates of QUICKI in PCOS subjects, but not in subjects without PCOS. On multivariate analysis, NO responsiveness, and 25(OH)D3 levels, but not PCOS per se were significant correlates of QUICKI. In the entire cohort of young women, low NO responsiveness and vitamin D deficiency are associated with low QUICKI, while elevated ADMA, inflammatory activation and obesity are selectively associated with low QUICKI in PCOS subjects; this may contribute to the increased cardiovascular risk associated with this syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise

    DEFF Research Database (Denmark)

    Dela, Flemming; Mikines, K J; Larsen, J J

    1999-01-01

    Insulin and muscle contractions are major stimuli for glucose uptake in skeletal muscle and have in young healthy people been shown to be additive. We studied the effect of superimposed exercise during a maximal insulin stimulus on glucose uptake and clearance in trained (T) (1-legged bicycle tra...

  6. Short-term antidiabetic treatment with insulin or metformin has a similar impact on the components of metabolic syndrome in women with gestational diabetes mellitus requiring antidiabetic agents: results of a prospective, randomised study.

    Science.gov (United States)

    Zawiejska, A; Wender-Ozegowska, E; Grewling-Szmit, K; Brazert, M; Brazert, J

    2016-04-01

    Gestational diabetes mellitus (GDM) is associated with an increased prevalence of fetal and maternal complications primarily caused by maternal hyperglycemia, which results in abnormal fetal growth. Diet modification is a common first step in the treatment of GDM, followed by antidiabetic pharmacotherapy if this approach fails. Insulin therapy is generally accepted; however, oral hypoglycemic agents have been used in this population. In this prospective, randomised study, we compared maternal metabolic status after treatment with insulin or metformin. Pregnant women (gestational age: ≥ 20 weeks) with GDM requiring medical hypoglycemic treatment were randomly allocated to the Metformin (n = 35) or Insulin (n = 43) Groups. Maternal metabolic status - assessed by glycated hemoglobin (HBA1c) level, glycemic profile, insulin concentration, Homeostatic Model Assessment - Insulin Resistance index, and lipids - was recorded at booking and throughout pregnancy. The characteristics of the study group were: maternal age 33.5 ± 5.9 years, gestational age at baseline 28.5 ± 3.5 weeks, prepregnancy body mass index (BMI) 32.2 ± 3.5 kg/m(2), HbA1c at baseline 5.6 ± 0.6%, and average daily glycemia 5.9 ± 0.6 mmol/dl. Fasting glycemia at term was significantly lower in the Insulin Group but there were no significant differences in mean daily glycemia, HbA1c and BMI at term between the groups. Longitudinally, there was a small but significant increase in BMI and a significant increase in high-density lipoprotein-cholesterol in the Insulin Group and a significant increase in the atherogenic index of plasma (AIP) and a trend towards higher triglycerides in the Metformin Group. Both fasting and average daily glycemia were significantly reduced following treatment in both groups. No such change was evident for HbA1c. In a relative risk analysis, metformin treatment was associated with an insignificant elevated risk of HbA1c, triglycerides and lipid indices falling within the

  7. Prolonged Growth Hormone/Insulin/Insulin-like Growth Factor Nutrient Response Signaling Pathway as a Silent Killer of Stem Cells and a Culprit in Aging.

    Science.gov (United States)

    Ratajczak, Mariusz Z; Bartke, Andrzej; Darzynkiewicz, Zbigniew

    2017-08-01

    The dream of slowing down the aging process has always inspired mankind. Since stem cells are responsible for tissue and organ rejuvenation, it is logical that we should search for encoded mechanisms affecting life span in these cells. However, in adult life the hierarchy within the stem cell compartment is still not very well defined, and evidence has accumulated that adult tissues contain rare stem cells that possess a broad trans-germ layer differentiation potential. These most-primitive stem cells-those endowed with pluripotent or multipotent differentiation ability and that give rise to other cells more restricted in differentiation, known as tissue-committed stem cells (TCSCs) - are of particular interest. In this review we present the concept supported by accumulating evidence that a population of so-called very small embryonic-like stem cells (VSELs) residing in adult tissues positively impacts the overall survival of mammals, including humans. These unique cells are prevented in vertebrates from premature depletion by decreased sensitivity to growth hormone (GH), insulin (INS), and insulin-like growth factor (IGF) signaling, due to epigenetic changes in paternally imprinted genes that regulate their resistance to these factors. In this context, we can envision nutrient response GH/INS/IGF signaling pathway as a lethal factor for these most primitive stem cells and an important culprit in aging.

  8. The association between the metabolic syndrome and alanine amino transferase is mediated by insulin resistance via related metabolic intermediates (the Cohort on diabetes and atherosclerosis Maastricht (CODAM) study)

    NARCIS (Netherlands)

    Jacobs, M.; Greevenbroek, van M.M.J.; Kallen, van der C.J.H.; Ferreira, I.; Feskens, E.J.M.; Jansen, E.H.J.M.; Schalkwijk, C.G.; Stehouwer, C.D.A.

    2011-01-01

    The metabolic syndrome is associated with nonalcoholic fatty liver disease (NAFLD) as well as with insulin resistance, inflammatory adipokines, endothelial dysfunction, and higher plasma levels of nonesterified fatty acids (NEFA), all of which may also affect the development of NAFLD. Therefore, we

  9. Electrical vs manual acupuncture stimulation in a rat model of polycystic ovary syndrome: different effects on muscle and fat tissue insulin signaling.

    Directory of Open Access Journals (Sweden)

    Julia Johansson

    Full Text Available In rats with dihydrotestosterone (DHT-induced polycystic ovary syndrome (PCOS, repeated low-frequency electrical stimulation of acupuncture needles restores whole-body insulin sensitivity measured by euglycemic hyperinsulinemic clamp. We hypothesized that electrical stimulation causing muscle contractions and manual stimulation causing needle sensation have different effects on insulin sensitivity and related signaling pathways in skeletal muscle and adipose tissue, with electrical stimulation being more effective in DHT-induced PCOS rats. From age 70 days, rats received manual or low-frequency electrical stimulation of needles in abdominal and hind limb muscle five times/wk for 4-5 wks; controls were handled but untreated rats. Low-frequency electrical stimulation modified gene expression (decreased Tbc1d1 in soleus, increased Nr4a3 in mesenteric fat and protein expression (increased pAS160/AS160, Nr4a3 and decreased GLUT4 by western blot and increased GLUT4 expression by immunohistochemistry in soleus muscle; glucose clearance during oral glucose tolerance tests was unaffected. Manual stimulation led to faster glucose clearance and modified mainly gene expression in mesenteric adipose tissue (increased Nr4a3, Mapk3/Erk, Adcy3, Gsk3b, but not protein expression to the same extent; however, Nr4a3 was reduced in soleus muscle. The novel finding is that electrical and manual muscle stimulation affect glucose homeostasis in DHT-induced PCOS rats through different mechanisms. Repeated electrical stimulation regulated key functional molecular pathways important for insulin sensitivity in soleus muscle and mesenteric adipose tissue to a larger extent than manual stimulation. Manual stimulation improved whole-body glucose tolerance, an effect not observed after electrical stimulation, but did not affect molecular signaling pathways to the same extent as electrical stimulation. Although more functional signaling pathways related to insulin sensitivity

  10. Hair Coil Penile Tourniquet Syndrome in an Unusual Age

    Directory of Open Access Journals (Sweden)

    Kursad Zengin

    2015-01-01

    Full Text Available Penile tourniquet syndrome (PTS, a rare urologic emergency, may lead to undesirable results including necrosis and amputation of penis, if not diagnosed and treated appropriately. Sometimes these injuries may be accepted as a forensic case. Miscellaneous objects used for strangulation can be metallic or nonmetallic. Of all ages, the most vulnerable period is infancy. Telogen effluvium is the most common cause of PTS in infants who are 0–6 years old. In the literature, telogen effluvium as a reason of PTS was not found except for this age group. Therefore, we aimed to present a boy who is 8 years old diagnosed as PTS because of his mother’s hair coil.

  11. Small for Gestational Age and Magnesium: Intrauterine magnesium deficiency may induce metabolic syndrome in later life

    Directory of Open Access Journals (Sweden)

    Junji Takaya

    2015-12-01

    Full Text Available Magnesium deficiency during pregnancy as a result of insufficient or low intake of magnesium is common in developing and developed countries. Previous reports have shown that intracellular magnesium of cord blood platelets is lower among small for gestational age (SGA groups than that of appropriate for gestational age (AGA groups, suggesting that intrauterine magnesium deficiency may result in SGA. Additionally, the risk of adult-onset diseases such as insulin resistance syndrome is greater among children whose mothers were malnourished during pregnancy, and who consequently had a low birth weight. In a number of animal models, poor nutrition during pregnancy leads to offspring that exhibit pathophysiological changes similar to human diseases. The offspring of pregnant rats fed a magensium restricted diet have developed hypermethylation in the hepatic 11β-hydroxysteroid dehydrogenase-2 promoter. These findings indicate that maternal magnesium deficiencies during pregnancy influence regulation of non-imprinted genes by altering the epigenetic regulation of gene expression, thereby inducing different metabolic phenotypes. Magnesium deficiency during pregnancy may be responsible for not only maternal and fetal nutritional problems, but also lifelong consequences that affect the offspring throughout their life. Epidemiological, clinical, and basic research on the effects of magnesium deficiency now indicates underlying mechanisms, especially epigenetic processes.

  12. Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women

    Science.gov (United States)

    Baldani, Dinka Pavicic; Skrgatic, Lana; Ougouag, Roya

    2015-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events. PMID:26124830

  13. Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women

    Directory of Open Access Journals (Sweden)

    Dinka Pavicic Baldani

    2015-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events.

  14. Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women.

    Science.gov (United States)

    Baldani, Dinka Pavicic; Skrgatic, Lana; Ougouag, Roya

    2015-01-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events.

  15. Endothelial function in young women with polycystic ovary syndrome (PCOS): Implications of body mass index (BMI) and insulin resistance.

    Science.gov (United States)

    El-Kannishy, Ghada; Kamal, Shaheer; Mousa, Amany; Saleh, Omayma; Badrawy, Adel El; Farahaty, Reham El; Shokeir, Tarek

    2010-01-01

    Evidence regarding endothelial function in both obese and nonobese women with PCOS is contradictory. It is unknown whether obese women with PCOS carry an increased risk related to body mass index (BMI). To identify endothelial function and investigate its relationship to body mass index and insulin resistance in young women with PCOS. Twenty-two obese women with PCOS (BMI 35.2 ± 3.2) as well as fourteen lean women (BMI 22.8 ± 2.1)with PCOS were included in the study. Fasting serum insulin, blood glucose were estimated and HOMA and Quicki index were calculated. All patients were subjected to ultrasound recording of brachial artery diameter at rest and after reactive hyperemia (FMD) for assessment of endothelial function. Ten age matched healthy females with normal BMI were chosen as a control group. There were higher basal insulin levels with lower Quicki index and higher HOMA index in women with PCOS than normal group, but the differences were significant only between obese PCOS subgroup and control. On the other hand, FMD was significantly and equally decreased in both groups of women with PCOS, compared with control subjects (3.7 ± 3.2% in the nonobese subgroup and 3.5 ± 2.8% in the obese one vs. 10.6 ± 4.1% in control subjects, P, 0.001). FMD was not correlated with BMI nor insulin resistance indices. Endothelial dysfunction is already present in young women with PCOS. In this patient group, it cannot be attributed to insulin resistance or obesity. © 2010 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.

  16. Investigations on the role of insulin and scorpion antivenom in scorpion envenoming syndrome

    Directory of Open Access Journals (Sweden)

    K. Radha Krishna Murthy

    2003-01-01

    Full Text Available Acute myocardiopathy in alloxan treated experimental dogs and rabbits was induced by subcutaneous (SQ injection of scorpion venom from Mesobuthus tamulus concanesis, Pocock. Envenoming resulted in an initial transient hypertension (180-320 mm Hg. followed by hypotension. Simultaneous administration of venom and species-specific scorpion antivenom (SAV prevented hypertension and hypotension. Hypotension did not occur when SAV was given 60 min after envenoming. Blood glucose, triglycerides, cholesterol, amylase, insulin, glucagon, cortisol, hematocrit, mean corpuscular volume (MCV, mean corpuscular hemoglobin (MCH, mean corpuscular hemoglobin concentration (MCHC, platelet count, red blood cell (RBC count, hemoglobin (Hb, 2,3-diphosphoglycerate (2,3-DPG, and glutathione levels were increased 60 and 90 min after envenoming. Total white blood cell (WBC count was reduced 60 min and increased 90 min after envenoming. Simultaneous administration of venom and SAV did not alter Hb, MCHC, and packed cell volume (PCV levels, or ECG, and cardiovascular, biochemical, metabolic, and hormonal changes. Hematological parameters were reversed when SAV was given 30 and 60 min after envenoming. PCV, Hb, and MCHC values returned to normal 120 min after SAV. Alloxan-treated dogs showed increased blood glucose, cholesterol, glucagon, cortisol levels; reduced glycogen content of liver, cardiac and skeletal muscles; and reduced insulin levels and insulin/ glucagon ratio (I/G ratio. Envenoming in the alloxan pre-treated dogs further increased these levels and reduced tissue glycogen content, insulin levels, and I/G ratio. Administration of 4 U of insulin to alloxan pre-treated envenomed rabbits caused a biochemical and clinical improvement and increased glycogen content of all tissues in comparison with the values from those administered with SAV to alloxan pre-treated envenomed animals. SAV administration to envenomed alloxan pre-treated rabbits did not cause clinical or

  17. The survey of abnormal glucose tolerance and insulin resistace and incidence of diabetes type 2 in poly cystic ovary syndrome patients in Shiraz

    Directory of Open Access Journals (Sweden)

    marziye Akbarzadeh

    2009-03-01

    Full Text Available Background: Polycystic ovarian syndrome is one of the most commen hyper androgenic disorders affecting women, its prevalence being estimated at 5% – 10%. Our goal was to survey abnormal glucose tolerance, insulin resistance and incidence of diabetes type 2 in patients with polycystic ovary syndrome. Materials and methods: This investigation is a descriptive – analytic study which is done to survey abnormal glucose tolerance, insulin resistance and incidene of diabetes type 2 in polycystic ovary syndrome (PCOS. This study included 150 patients with the diagnosis of PCOS. These patients were chosen by target based sampling. Among the subjects, laboratory tests were performed for 125 patients. Questionnaire, fasting blood suger test, fasting insulin and glucose tolerance test by 75gr glucose, were used as data gathering tools. The results of the blood suger test were interpreted using the WHO 1999 criteria. Results: The results of oral and glucose tolerance test showed 14. 4 percent of the patients had impaired fasting glucose and 4 percent of the patients had diabetes type 2 (FBS>126mg/dl. Insulin resistance was seen in 9. 8 percent of the patients. 7. 2 percent of the patients had impaired blood suger after two hours (140-199 mg/dl and 0. 8 persent of patients had diabetes type 2 (200>mg/dl. Conclusion: level of fasting blood suger and insulin and ratio of fasting blood suger to fasting insulin were good markers for diagnosis of insulin resistance. American diabetic association recommended for the care of young women with PCOS, screening for impaired glucose tolerance and diabetes type2.

  18. A role for suppressed skeletal muscle thermogenesis in pathways from weight fluctuations to the insulin resistance syndrome.

    Science.gov (United States)

    Dulloo, A G

    2005-08-01

    lipogenesis and lipid oxidation - confers to the phase of weight recovery/catch-up growth its high sensitivity towards the development of insulin resistance and hyperinsulinaemia, and hence towards diseases that are clustered around the insulin resistance syndrome.

  19. Insulin resistance in human subjects having impaired glucose regulation

    International Nuclear Information System (INIS)

    Khan, S.H.; Khan, F.A.; Ijaz, A.

    2007-01-01

    To determine insulin resistance in human subjects having impaired glucose regulation (IGR) by Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). A total of 100 subjects with impaired glucose regulation were selected for evaluation of metabolic syndrome as per the criteria of National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III), along with 47 healthy age and gender-matched controls. Physical examination to determine blood pressure and waist circumference was carried out and so was sampling for plasma glucose, serum triglycerides, HDL-cholesterol and insulin. Insulin resistance was calculated by the HOMA-IR. Finally, subjects with and without metabolic syndrome were compared with controls (n=47), using one-way ANOVA for studying insulin resistance between groups, with Tukey's post-hoc comparison. The frequency of finding metabolic syndrome in cases of IGR remained 47%. The insulin resistance demonstrated stepwise worsening from control population (mean=1.54, 95 % CI: 1.77 - 2.37) to subjects suffering from only IGR (mean=2.07, 95 % CI: 1.77- 2.37) to metabolic syndrome (mean=2.67, 95 %, CI: 2.34 - 3.00) (p < 0.001). Patients with impaired glucose regulation may have significant insulin resistance. It is, thus, recommended that a vigorous search be made to measure insulin resistance in all cases diagnosed to have impaired glucose regulation. (author)

  20. Possible increase in insulin resistance and concealed glucose-coupled potassium-lowering mechanisms during acute coronary syndrome documented by covariance structure analysis.

    Science.gov (United States)

    Ito, Satoshi; Nagoshi, Tomohisa; Minai, Kosuke; Kashiwagi, Yusuke; Sekiyama, Hiroshi; Yoshii, Akira; Kimura, Haruka; Inoue, Yasunori; Ogawa, Kazuo; Tanaka, Toshikazu D; Ogawa, Takayuki; Kawai, Makoto; Yoshimura, Michihiro

    2017-01-01

    Although glucose-insulin-potassium (GIK) therapy ought to be beneficial for ischemic heart disease in general, variable outcomes in many clinical trials of GIK in acute coronary syndrome (ACS) had a controversial impact. This study was designed to examine whether "insulin resistance" is involved in ACS and to clarify other potential intrinsic compensatory mechanisms for GIK tolerance through highly statistical procedure. We compared the degree of insulin resistance during ACS attack and remission phase after treatment in individual patients (n = 104). During ACS, homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly increased (Pcovariance structure analysis with a strong impact (β: 0.398, P = 0.015). Intriguingly, a higher incidence of myocardial infarction relative to unstable angina pectoris, as well as a longer hospitalization period were observed in patients with larger ΔK, indicating that ΔK also reflects disease severity of ACS. Insulin resistance most likely increases during ACS; however, ΔK was positively correlated with plasma glucose level, which overwhelmed insulin resistance condition. The present study with covariance structure analysis suggests that there are potential endogenous glucose-coupled potassium lowering mechanisms, other than insulin, regulating glucose metabolism during ACS.

  1. Analysis of the relationship of leptin, high-sensitivity C-reactive protein, adiponectin, insulin, and uric acid to metabolic syndrome in lean, overweight, and obese young females.

    Science.gov (United States)

    Abdullah, Abdul Ridha; Hasan, Haydar A; Raigangar, Veena L

    2009-02-01

    Over the last decade there has been a steady rise in obesity and co-morbidity, but little is known about the rate of metabolic dysfunction among young adults in the United Arab Emirates. Various factors have been implicated as biomarkers of metabolic syndrome. The objective of this study was to analyze the relationships of leptin, C-reactive protein (CRP), adiponectin, insulin, and uric acid to the metabolic syndrome components in lean, overweight, and obese young females. This was a cross-sectional study of 69 apparently healthy young females, who were classified according to their body mass index (BMI) (kg/m(2)) into three groups: lean (25 and or=30). Estimated biomarkers were: leptin, insulin, adiponectin, high-sensitivity [hs]-CRP, uric acid, blood sugar, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and triglycerides (TG). Anthropometric measures, blood pressure, and homeostasis model assessment-insulin resistance (HOMA-IR) were also measured. Serum leptin, hs-CRP, insulin, and uric acid increased significantly (p syndrome components was found in lean subjects (leptin vs. waist circumference r = 0.48) as opposed to six in the obese group (hs-CRP vs. waist circumference and systolic blood pressure [SBP], r = 0.45 and r = -0.41, respectively; insulin vs. diastolic blood pressure [DBP], r = 0.47; adiponectin vs. blood sugar, r = -0.44; and uric acid vs. waist circumference and TG, r = 0.5 and r = 0.51, respectively). Estimation of the levels of studied biomarkers could be an important tool for early detection of metabolic syndrome before the appearance of its frank components. Uric acid seems to be the most reliable biomarker to identify obese subjects with metabolic syndrome.

  2. Clinical Presentation of Klinefelter's Syndrome: Differences According to Age

    Directory of Open Access Journals (Sweden)

    Néstor Pacenza

    2012-01-01

    Full Text Available The aim of the study was to establish the characteristics of presentation of 94 patients with Kinelfelter's syndrome (KS referred to the endocrinologist at different ages. The diagnosis of KS was more frequent in the age group between 11 and 20 years (46.8%. Most of the patients (83.7% showed the classic 47,XXY karyotype and 7.1% showed a 47,XXY/46,XY mosaicism. Half of the patients younger than 18 years presented mild neurodevelopmental disorders. The most frequent clinical findings were cryptorchidism in prepubertal patients, and small testes, cryptorchidism, and gynecomastia in pubertal patients. FSH, LH, AMH, and inhibin B levels were normal in prepubertal patients and became abnormal from midpuberty. Most adults were referred for small testes, infertility, and gynecomastia; 43.6% had sexual dysfunction. Testosterone levels were low in 45%. Mean stature was above the 50th percentile, and 62.5% had BMI ≥25.0 kg/m2. In conclusion, the diagnosis of Klinefelter syndrome seems to be made earlier nowadays probably because pediatricians are more aware that boys and adolescents with neuro-developmental disorders and cryptorchidism are at increased risk. The increasing use of prenatal diagnosis has also decreased the mean age at diagnosis and allowed to get insight into the evolution of previously undiagnosed cases, which probably represent the mildest forms. In adults average height and weight are slightly higher than those in the normal population. Bone mineral density is mildly affected, more at the spine than at the femoral neck level, in less than half of cases.

  3. Leisure Activity and Caregiver Involvement in Middle-Aged and Older Adults with Down Syndrome

    Science.gov (United States)

    Mihaila, Iulia; Hartley, Sigan L.; Handen, Benjamin L.; Bulova, Peter D.; Tumuluru, Rameshwari V.; Devenny, Darlynne A.; Johnson, Sterling C.; Lao, Patrick J.; Christian, Bradley, T.

    2017-01-01

    The present study examined leisure activity and its association with caregiver involvement (i.e., residence and time spent with primary caregiver) in 62 middle-aged and older adults with Down syndrome (aged 30-53 years). Findings indicated that middle-aged and older adults with Down syndrome frequently participated in social and passive leisure…

  4. [Influence of cryoglobulinemic syndrome and insulin resistance on the progression of liver cirrhosis in patients with chronic hepatitis C].

    Science.gov (United States)

    Kondratiuk, L O; Bezrodna, O V; Kuliesh, O V

    2014-01-01

    The article presents the results of analysis of the frequency of detection of cryoglobulinemic syndrome (CGS) and insulin resistance (IR) in patients with HCV-associated liver cirrhosis (LC) depending on its stage. There were also evaluated clinical and laboratory features of the disease. The study involved 72 patients with chronic hepatitis C who were divided into 3 main groups according to the presence of LC. The I group included 32 patients with chronic hepatitis C without LC. The II group consisted of 19 patients with compensated HCV-associated LC and III group included 21 patients with decompensated LC. It was shown that terminal stages of the LC (class B-C by Child-Pugh) are characterized by more frequent presence of IR and CGS with more severe clinical picture, which may be caused not only by the influence of the hepatitis C virus (HCV), but also by the progression of LC.

  5. Insulin-like growth factor-I treatment of children with Laron syndrome (primary growth hormone insensitivity).

    Science.gov (United States)

    Laron, Zvi

    2008-03-01

    Laron syndrome (LS, congenital primary GH insensitivity) is caused by deletions or mutations in the GH receptor gene, resulting in an inability to generate insulin-like growth factor-I (IGF-I). If untreated, the deficiency of IGF-I results in severe dwarfism, as well as skeletal and muscular underdevelopment. The only treatment is the daily administration of recombinant IGF-I. This review summarizes the present experience by several groups worldwide. The main conclusions are: A. The one or two injections regimen result in the same growth velocity; B. The growth velocity obtained with IGF-I administration is smaller than that observed with hGH in children with congenital isolated GH deficiency; C. Overdosage of IGF-I causes a series of adverse effects which can be avoided by carefully monitoring the serum IGF-I and GH levels.

  6. Pigment epithelium-derived factor, insulin sensitivity, and adiposity in polycystic ovary syndrome: impact of exercise training.

    Science.gov (United States)

    Joham, Anju E; Teede, Helena J; Hutchison, Samantha K; Stepto, Nigel K; Harrison, Cheryce L; Strauss, Boyd J; Paul, Eldho; Watt, Matthew J

    2012-12-01

    Pigment epithelium-derived factor (PEDF) is upregulated in obese rodents and is involved in the development of insulin resistance (IR). We aim to explore the relationships between PEDF, adiposity, insulin sensitivity, and cardiovascular risk factors in obese women with polycystic ovary syndrome (PCOS) and weight-matched controls and to examine the impact of endurance exercise training on PEDF. This prospective cohort intervention study was based at a tertiary medical center. Twenty obese PCOS women and 14 non-PCOS weight-matched women were studied at baseline. PEDF, cardiometabolic markers, detailed body composition, and euglycemic-hyperinsulinemic clamps were performed and measures were repeated in 10 PCOS and 8 non-PCOS women following 12 weeks of intensified aerobic exercise. Mean glucose infusion rate (GIR) was 31.7% lower (P = 0.02) in PCOS compared to controls (175.6 ± 96.3 and 257.2 ± 64.3 mg.m(-2).min(-1)) at baseline, yet both PEDF and BMI were similar between groups. PEDF negatively correlated to GIR (r = -0.41, P = 0.03) and high-density lipoprotein (HDL) (r = -0.46, P = 0.01), and positively to cardiovascular risk factors, systolic (r = 0.41, P = 0.02) and diastolic blood pressure (r = 0.47, P = 0.01) and triglycerides (r = 0.49, P = 0.004). The correlation with GIR was not significant after adjusting for fat mass (P = 0.07). Exercise training maintained BMI and increased GIR in both groups; however, plasma PEDF was unchanged. In summary, PEDF is not elevated in PCOS, is not associated with IR when adjusted for fat mass, and is not reduced by endurance exercise training despite improved insulin sensitivity. PEDF was associated with cardiovascular risk factors, suggesting PEDF may be a marker of cardiovascular risk status.

  7. The evolutionary benefit of insulin resistance

    NARCIS (Netherlands)

    Soeters, Maarten R.; Soeters, Peter B.

    2012-01-01

    Insulin resistance is perceived as deleterious, associated with conditions as the metabolic syndrome, type 2 diabetes mellitus and critical illness. However, insulin resistance is evolutionarily well preserved and its persistence suggests that it benefits survival. Insulin resistance is important in

  8. Aging With Down Syndrome: The Dual Diagnosis: Alzheimer's Disease and Down Syndrome.

    Science.gov (United States)

    Cipriani, Gabriele; Danti, Sabrina; Carlesi, Cecilia; Di Fiorino, Mario

    2018-06-01

    People with Down syndrome (DS) enjoy a longer life expectancy now than they ever have before and are therefore at greater risk of developing conditions associated with aging, including dementia. To explore the phenomenon of dementia in DS. Medline and Google Scholar searches were conducted for relevant articles, chapters, and books published until 2017. Search terms included Alzheimer's disease, cognitive impairment, dementia, DS, and trisomy 21. Publications found through this indexed search were reviewed for further references. Virtually, all subject aged 35 to 40 show key neuropathologic changes characteristic of Alzheimer's disease, but only a part of them show clinical signs of dementia, usually around the age of 50 years. Early signs of dementia in people with DS may be different from those experienced by the general population. Failure to recognize this can delay diagnosis and subsequent interventions.

  9. Increased serum chemerin concentrations in patients with polycystic ovary syndrome: Relationship between insulin resistance and ovarian volume.

    Science.gov (United States)

    Huang, Rong; Yue, Jiang; Sun, Yun; Zheng, Jun; Tao, Tao; Li, Shengxian; Liu, Wei

    2015-10-23

    Chemerin has been linked to adiposity, and insulin resistance (IR) which are the common characteristics of polycystic ovary syndrome (PCOS). Chemerin also shows inhibitory action on follicular steroidogenesis. We investigated the associations between chemerin and IR or polycystic ovary morphology in patients with PCOS. A total of 148 women with newly diagnosed PCOS using Rotterdam criteria and 88 healthy individuals were enrolled. The recruited patients with PCOS were further stratified by tertiles of serum chemerin concentrations as follows: Group 1 ( 30.27 ng/ml). Compared to controls, women with PCOS in each tertile had higher serum chemerin concentrations. By linear regression analysis, homeostasis model assessment-insulin resistance and ovarian volume showed significant associations with chemerin after adjusting for confounding factors (β = 0.257, P = 0.028; β = 0.276, P = 0.005, respectively). The odds ratios (ORs) for ovarian volume excess gradually increased across increasing tertiles of chemerin in the adjusted model [Group 1: reference; Group 2: OR 1.602; 95% confidence interval (CI): 1.170–2.194; Group 3: OR 1.857; 95% CI: 1.335-2.583]. Patients with PCOS showed increased serum chemerin concentrations as compared to healthy women. Individuals with higher chemerin tended to have higher risk for ovarian volume excess in patients with PCOS, regardless of adiposity.

  10. Depression and Dementia in Aging Adults with Down Syndrome: A Case Study Approach.

    Science.gov (United States)

    Sung, Hyunsook; And Others

    1997-01-01

    A case study of three adults (ages 46-47) with Down syndrome investigated the patterns of symptoms associated with depression and dementia. Characteristics that distinguish between dementia and depression in adults with Down syndrome are described. Periodic comprehensive assessment of adults with Down syndrome to detect functioning changes is…

  11. Small Molecule Kaempferol Promotes Insulin Sensitivity and Preserved Pancreatic β-Cell Mass in Middle-Aged Obese Diabetic Mice

    Science.gov (United States)

    Alkhalidy, Hana; Moore, William; Zhang, Yanling; Wang, Aihua; Ali, Mostafa; Suh, Kyung-Shin; Zhen, Wei; Cheng, Zhiyong; Jia, Zhenquan; Hulver, Matthew

    2015-01-01

    Insulin resistance and a progressive decline in functional β-cell mass are hallmarks of developing type 2 diabetes (T2D). Thus, searching for natural, low-cost compounds to target these two defects could be a promising strategy to prevent the pathogenesis of T2D. Here, we show that dietary intake of flavonol kaempferol (0.05% in the diet) significantly ameliorated hyperglycemia, hyperinsulinemia, and circulating lipid profile, which were associated with the improved peripheral insulin sensitivity in middle-aged obese mice fed a high-fat (HF) diet. Kaempferol treatment reversed HF diet impaired glucose transport-4 (Glut4) and AMP-dependent protein kinase (AMPK) expression in both muscle and adipose tissues from obese mice. In vitro, kaempferol increased lipolysis and prevented high fatty acid-impaired glucose uptake, glycogen synthesis, AMPK activity, and Glut4 expression in skeletal muscle cells. Using another mouse model of T2D generated by HF diet feeding and low doses of streptozotocin injection, we found that kaempferol treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in obese diabetic mice, which are associated with the improved islet β-cell mass. These results demonstrate that kaempferol may be a naturally occurring anti-diabetic agent by improving peripheral insulin sensitivity and protecting against pancreatic β-cell dysfunction. PMID:26064984

  12. Metformin improves glucose effectiveness, not insulin sensitivity: predicting treatment response in women with polycystic ovary syndrome in an open-label, interventional study.

    Science.gov (United States)

    Pau, Cindy T; Keefe, Candace; Duran, Jessica; Welt, Corrine K

    2014-05-01

    Although metformin is widely used to improve insulin resistance in women with polycystic ovary syndrome (PCOS), its mechanism of action is complex, with inconsistent effects on insulin sensitivity and variability in treatment response. The aim of the study was to delineate the effect of metformin on glucose and insulin parameters, determine additional treatment outcomes, and predict patients with PCOS who will respond to treatment. We conducted an open-label, interventional study at an academic medical center. Women with PCOS (n = 36) diagnosed by the National Institutes of Health criteria participated in the study. Subjects underwent fasting blood sampling, an IV glucose tolerance test, dual-energy x-ray absorptiometry scan, transvaginal ultrasound, and measurement of human chorionic gonadotropin-stimulated androgen levels before and after 12 weeks of treatment with metformin extended release 1500 mg/d. Interval visits were performed to monitor anthropometric measurements and menstrual cycle parameters. Changes in glucose and insulin parameters, androgen levels, anthropometric measurements, and ovulatory menstrual cycles were evaluated. Insulin sensitivity did not change despite weight loss. Glucose effectiveness (P = .002) and the acute insulin response to glucose (P = .002) increased, and basal glucose levels (P = .001) decreased after metformin treatment. T levels also decreased. Women with improved ovulatory function (61%) had lower baseline T levels and lower baseline and stimulated T and androstenedione levels after metformin treatment (all P effectiveness and insulin sensitivity, metformin does not improve insulin sensitivity in women with PCOS but does improve glucose effectiveness. The improvement in glucose effectiveness may be partially mediated by decreased glucose levels. T levels also decreased with metformin treatment. Ovulation during metformin treatment was associated with lower baseline T levels and greater T and androstenedione decreases during

  13. Sleep apnoea syndrome and 10-year cardiovascular risk in females with type 2 diabetes: relationship with insulin secretion and insulin resistance.

    Science.gov (United States)

    Hermans, Michel P; Ahn, Sylvie A; Mahadeb, Yovan P; Rousseau, Michel F

    2013-03-01

    Obstructive sleep apnoea syndrome (OSAS) is a risk factor for type 2 diabetes mellitus (T2DM) and promotes cardiovascular events, especially in men. The prevalence of sleep apnoea and its association with microvascular and macrovascular diseases and glycaemic control are poorly documented in T2DM women. A total of 305 T2DM women were sleep apnoea diagnosed through (hetero)anamnesis, Epworth's score, oximetry and polysomnography. Sleep apnoea[+] (n = 25) were compared with sleep apnoea[-] (n = 280) regarding cardiovascular risk factors, glucose homeostasis, micro/macrovascular complications and the United Kingdom Prospective Diabetes Study (UKPDS) 10-year risk. Mean (1 SD) age was 66 (12) years, diabetes duration 15 (9) years, sleep apnoea prevalence 8.2% and metabolic syndrome 86%. There were no differences in age, diabetes duration, education, smoking and blood pressure between groups. Sleep apnoea[+] had significantly higher values of body mass index, waist, relative/absolute fat, conicity, visceral fat (all p Women with sleep apnoea had higher UKPDS risk of CAD: 18 (11)% versus 12 (10)% (p = 0.0136). Prevalent micro/macrovascular complications were not different between groups. Sleep apnoea, a frequent comorbidity of T2DM women, is associated with central fat, atherogenic dyslipidaemia, inflammation, worsening β-cell function, poorer glycaemic control and coronary artery disease risk. Sleep apnoea may increase residual vascular risk for microvascular and macrovascular events in T2DM women. Copyright © 2013 John Wiley & Sons, Ltd.

  14. Insulin resistance in a large cohort of women with polycystic ovary syndrome: a comparison between euglycaemic-hyperinsulinaemic clamp and surrogate indexes.

    Science.gov (United States)

    Tosi, Flavia; Bonora, Enzo; Moghetti, Paolo

    2017-12-01

    Could surrogate indexes identify insulin resistant individuals among women with polycystic ovary syndrome (PCOS)? Surrogate indexes may be able to rule in, but not rule out, insulin resistance in women with PCOS. Insulin resistance is a typical finding of women with PCOS and most clinical information on this issue is based upon surrogate indexes of insulin resistance. However, data on the performance of these indexes in PCOS women are very limited. A retrospective analysis of 406 women referred to our outpatient clinic for hyperandrogenism and/or menstrual dysfunction and submitted to hyperinsulinemic euglycaemic clamp between 1998 and 2015. In total, 375 of these women had PCOS by the Rotterdam criteria and were included in the study. Six surrogate indexes of insulin sensitivity were calculated from glucose and insulin levels, either at fasting (homeostasis model assessment (HOMA), glucose/insulin (G/I) ratio and quantitative insulin sensitivity check index (QUICKI)) or after oral glucose load (Gutt, Stumvoll0-120 and Matsuda). Overall, insulin resistance, as identified by the M-clamp value, was found in 74.9% of these women. The percentage was 59.3% in normal-weight vs 77.5% in overweight and 93.9% in obese subjects. All surrogate indexes were highly correlated with the M-clamp values. However, their ability to identify insulin resistant individuals was limited, in terms of sensitivity and especially in normal-weight subjects. ROC analysis showed similar performances of these indexes (AUC values 0.782-0.817). Potential referral bias of PCOS patients may have caused overestimation of the prevalence of insulin resistance in these women. By using surrogate indexes many subjects with PCOS may be erroneously diagnosed as insulin sensitive, especially among normal-weight women. These indexes can be used to rule in, but not rule out, insulin resistance in PCOS. Academic grants to P. Moghetti from the University of Verona. All authors declare no conflict of interest. N

  15. High-molecular-weight adiponectin is selectively reduced in women with polycystic ovary syndrome independent of body mass index and severity of insulin resistance.

    LENUS (Irish Health Repository)

    O'Connor, A

    2010-03-01

    Context: High-molecular-weight (HMW) adiponectin contributes to insulin resistance (IR), which is closely associated with the pathophysiology of polycystic ovary syndrome (PCOS). Abnormalities in adipocyte function have been identified in PCOS and potentially contribute to lower adiponectin concentrations. Objective: Our objective was to determine which variables in plasma and adipose tissue influence HMW adiponectin in a well characterized cohort of women with PCOS. Design: This was a cross-sectional study. Settings and Participants: A teaching hospital. Women with PCOS (n = 98) and body mass index (BMI)-matched controls (n = 103) (including 68 age-, BMI-, and IR-matched pairs). Interventions: A standard 75-g oral glucose tolerance test was performed for each participant. Subcutaneous adipose tissue samples were taken by needle biopsy for a subset of PCOS women (n = 9) and controls (n = 8). Main Outcome Measures: Serum levels of HMW adiponectin and their relation to indices of insulin sensitivity, body composition, and circulating androgens as well as adipose tissue expression levels of ADIPOQ, TNFalpha, PPARgamma, and AR were assessed. Results: HMW adiponectin was significantly lower in women with PCOS compared with both BMI- and BMI- and IR-matched controls (P = 0.009 and P = 0.027, respectively). Although BMI and IR were the main predictors of HMW adiponectin, an interaction between waist to hip ratio and plasma testosterone contributed to its variance (P = 0.026). Adipose tissue gene expression analysis demonstrated that AR and TNFalpha (P = 0.008 and P = 0.035, respectively) but not ADIPOQ mRNA levels were increased in PCOS compared with controls. Conclusions: HMW adiponectin is selectively reduced in women with PCOS, independent of BMI and IR. Gene expression analysis suggests that posttranscriptional\\/translational modification contributes to reduced HMW adiponectin in PCOS.

  16. Dioscoreophyllum cumminsii (Stapf) Diels leaves halt high-fructose induced metabolic syndrome: Hyperglycemia, insulin resistance, inflammation and oxidative stress.

    Science.gov (United States)

    Ajiboye, T O; Aliyu, H; Tanimu, M A; Muhammad, R M; Ibitoye, O B

    2016-11-04

    Dioscoreophyllum cumminsii is widely used in the management and treatment of diabetes and obesity in Nigeria. This study evaluates the effect of aqueous leaf extract of D. cumminsii on high-fructose diet-induced metabolic syndrome. Seventy male rats were randomized into seven groups. All rats were fed with high-fructose diet for 9 weeks except groups A and C rats, which received control diet. In addition to the diet treatment, groups A and B rats received distilled water for 3 weeks starting from the seventh week of the experimental period. Rats in groups C-F orally received 400, 100, 200 and 400mg/kg body weight of aqueous leaf extract of D. cumminsii respectively, while group G received 300mg/kg bodyweight of metformin for 3 weeks starting from the seventh week. There was significant (phigh-fructose diet-mediated increase in body weight, body mass index, abdominal circumference, blood glucose, insulin, leptin and insulin resistance by aqueous leaf extract of D. cumminsii. Conversely, high-fructose diet-mediated decrease in adiponectin was reversed by the extract. Increased levels of cholesterol, triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index, cardiac index and coronary artery index were significantly lowered by the extract, while high-fructose diet mediated decrease in high-density lipoprotein cholesterol was increased by the extract. Tumour necrosis factor-α, interleukin-6 and interleukin-8 levels increased significantly in high-fructose diet-fed rats, which were significantly reversed by the extract. High-fructose mediated-decrease in superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose 6-phosphate dehydrogenase and glutathione reduced were significantly reversed by aqueous leaf extract of D. cumminsii. Conversely, elevated levels of malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl and fragmented DNA were significantly lowered by the

  17. Insulin Resistance

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech

    Insulin resistance (IR) is escalating with alarming pace and is no longer restricted to westernized countries. As a forerunner for some of the most serious threats to human health including metabolic syndrome, cardiovascular diseases, and type 2-diabetes, the need for new treatment modalities...... interventions. We further show that improving the inflammatory toning, using fish oil as fat source, protects mice against diet induced obesity and -inflammation while preserving insulin sensitivity, even in the absence of free fatty acid receptor 4. Conversely, HFD-induced intestinal dysbiosis is associated...

  18. Association between Follicular Fluid Leptin and Serum Insulin Levels in Nonoverweight Women with Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    G. Garruti

    2014-01-01

    Full Text Available Aims. We evaluated the links between leptin and visfatin levels and fertilization rates in nonoverweight (NOW women with PCOS (NOW-PCOS from Apulia undergoing in vitro fertilization/embryo transfer (IVF. Materials and Methodology. We recruited 16 NOW women with PCOS (NOW-PCOS and 10 normally ovulating NOW women (control-NOW. All women underwent IVF. Androgens, 17-β-estradiol (17β-E2, and insulin levels were measured in plasma and/or serum and leptin and visfatin levels were assayed in both serum and follicular fluid (FF-leptin, FF-visfatin. Results. In NOW-PCOS, both serum and FF-leptin were significantly lower than in control-NOW. In NOW-PCOS, significant correlations were found between BMI and serum leptin and insulinemia and FF-leptin. By contrast, in control-NOW, FF-leptin levels were not correlated with insulinemia. Serum visfatin levels were not significantly different in NOW-PCOS and control-NOW, but FF-visfatin levels were 1.6-fold higher, although not significantly, in NOW-PCOS than in control-NOW. Conclusions. Both serum leptin levels and FF-leptin are BMI- and insulin-related in Southern Italian NOW-PCOS from Apulia. In line with other reports showing that FF-leptin levels are predictive of fertilization rates, lower than normal FF-leptin levels in NOW-PCOS may explain their lower fertilization rate and this may be related to the level of insulin and/or insulin resistance.

  19. Quality control of insulin radioreceptor assay for human erythrocytes. Effect of ageing of mono-125I-Tyr-A14-insulin preparation

    International Nuclear Information System (INIS)

    Marttinen, A.; Pasternack, A.; Koivula, T.; Jokela, H.; Lehtinen, M.

    1984-01-01

    The quality control of insulin radioreceptor assay for human erythrocytes is based on the storage of erythrocyte preparations in Hepes buffer of pH 8.0, containing 10 g/l of albumin and 20 mmol/l of glucose. The change of erythrocytes into spherocytes and crenated cells reduces the apparent number of insulin receptors in a relatively constant way by less than 8% a week after 10 days of storage. At the same time the dissociation constants of the insulin-receptor complex increase rapidly. Thus the use of a preparation must be limited to controlling the determination of the insulin binding sites of erythrocytes, and not to the measurement of the affinities of the receptors. When mono- 125 I-Tyr-A14-insulin gets old, a slow decrease in the insulin binding sites can be measured, but the dissociation constants of the insulin receptor complex are not affected. (author)

  20. Quality control of insulin radioreceptor assay for human erythrocytes. Effect of ageing of mono-/sup 125/I-Tyr-A14-insulin preparation

    Energy Technology Data Exchange (ETDEWEB)

    Marttinen, A; Pasternack, A [Tampere Univ. (Finland). Dept. of Clinical Sciences; Koivula, T; Jokela, H; Lehtinen, M [Tampere Univ. Central Hospital (Finland). Dept. of Clinical Chemistry

    1984-09-01

    The quality control of insulin radioreceptor assay for human erythrocytes is based on the storage of erythrocyte preparations in Hepes buffer of pH 8.0, containing 10 g/l of albumin and 20 mmol/l of glucose. The change of erythrocytes into spherocytes and crenated cells reduces the apparent number of insulin receptors in a relatively constant way by less than 8% a week after 10 days of storage. At the same time the dissociation constants of the insulin-receptor complex increase rapidly. Thus the use of a preparation must be limited to controlling the determination of the insulin binding sites of erythrocytes, and not to the measurement of the affinities of the receptors. When mono-/sup 125/I-Tyr-A14-insulin gets old, a slow decrease in the insulin binding sites can be measured, but the dissociation constants of the insulin receptor complex are not affected.

  1. Dietary sardine protein lowers insulin resistance, leptin and TNF-α and beneficially affects adipose tissue oxidative stress in rats with fructose-induced metabolic syndrome.

    Science.gov (United States)

    Madani, Zohra; Louchami, Karim; Sener, Abdullah; Malaisse, Willy J; Ait Yahia, Dalila

    2012-02-01

    The present study aims at exploring the effects of sardine protein on insulin resistance, plasma lipid profile, as well as oxidative and inflammatory status in rats with fructose-induced metabolic syndrome. Rats were fed sardine protein (S) or casein (C) diets supplemented or not with high-fructose (HF) for 2 months. Rats fed the HF diets had greater body weight and adiposity and lower food intake as compared to control rats. Increased plasma glucose, insulin, HbA1C, triacylglycerols, free fatty acids and impaired glucose tolerance and insulin resistance was observed in HF-fed rats. Moreover, a decline in adipose tissues antioxidant status and a rise in lipid peroxidation and plasma TNF-α and fibrinogen were noted. Rats fed sardine protein diets exhibited lower food intake and fat mass than those fed casein diets. Sardine protein diets diminished plasma insulin and insulin resistance. Plasma triacylglycerol and free fatty acids were also lower, while those of α-tocopherol, taurine and calcium were enhanced as compared to casein diets. Moreover, S-HF diet significantly decreased plasma glucose and HbA1C. Sardine protein consumption lowered hydroperoxide levels in perirenal and brown adipose tissues. The S-HF diet, as compared to C-HF diet decreased epididymal hydroperoxides. Feeding sardine protein diets decreased brown adipose tissue carbonyls and increased glutathione peroxidase activity. Perirenal and epididymal superoxide dismutase and catalase activities and brown catalase activity were significantly greater in S-HF group than in C-HF group. Sardine protein diets also prevented hyperleptinemia and reduced inflammatory status in comparison with rats fed casein diets. Taken together, these results support the beneficial effect of sardine protein in fructose-induced metabolic syndrome on such variables as hyperglycemia, insulin resistance, hyperlipidemia and oxidative and inflammatory status, suggesting the possible use of sardine protein as a protective

  2. Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome - a randomized study (SYSDIET)

    DEFF Research Database (Denmark)

    Uusitupa, M; Hermansen, Kjeld; Savolainen, M J

    2013-01-01

    BACKGROUND: Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. METHODS: We conducted a randomized dietary...... by repeated 4-day food diaries and fatty acid composition of serum phospholipids. RESULTS: Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmol L-1 95% CI -0.35; -0...

  3. The influence of sodium propionate on blood glucose, insulin and cortisol concentrations in calves of different ages

    Directory of Open Access Journals (Sweden)

    Biljana Radojičić

    2016-01-01

    Full Text Available The process of gluconeogenesis in ruminants is under the direct influence of insulin and glucocorticoid hormones. The goal of this study was to determine the effects of added Na-propionate on the neuroendocrine regulation of blood glucose in calves at three specific physiological periods: on exclusive milk nutrition; on mixed milk and forage nutrition; and with established ruminant digestion. The influence of Na-propionate on blood glucose, insulin and cortisol concentrations was examined in the same 20 female Holstein calves at different stages of forestomach development (15 days, 2 months, and 4 months of age of calves. Group 1 of calves (n = 10 received Na-propionate intravenously; group 2 (n = 10 received Na-propionate mixed in milk. Blood sampling was performed 1 and 3 h after Na-propionate administration. After i.v. administration of Na-propionate, a significant increase (P < 0.05 in blood glucose concentration was observed 1 h after administration only in calves aged 2 and 4 months; blood insulin concentration was significantly higher (P < 0.01 1 and 3 h after i.v. administration in 2-month-old calves; and cortisol concentration increased (P < 0.01 1 h after administration in each selected calf in all testing periods. Orally administered Na-propionate led to a significant increase (P < 0.01 of insulin concentration 1 and 3 h after administration in 15-day-old calves, and 3 h after administration in 2-month-old calves. Based on these results it could be assumed that i.v. and p.o. administration of Na-propionate affects the neuroendocrine regulation of glycaemia in calves of different age.

  4. [Relationship of plasma ghrelin, IGF-1 and insulin with the growth and development of 2 -7 year-old children with small for gestational age at birth].

    Science.gov (United States)

    Cheng, Yaying; Song, Guangyao; Zhou, Lixia; Cai, Baoping; Zhao, Xiumian; Yin, Jianying

    2012-01-01

    To explore the relationship of Ghrelin, insulin-like growth factor-1 (IGF-1) and insulin with the growth and development of 2 -7 year-old children with small for gestational age (SGA) at birth. The levels of ghrelin, IGF-1, IGFBP-3, insulin and glucose were measured in the children with preterm SGA and term SGA and compared with the children with preterm appropriate for gestational age (AGA) and term AGA. The correlation of ghrelin with IGF-1, IGFBP-3 and insulin was analyzed. Plasma ghrelin in preterm SGA was higher than that in term SGA (P 0.05). Plasma ghrelin in preterm AGA and term SGA was higher than that in term AGA (P development of preterm and SGA children, regardless of the magnitude of their catch up growth. As a re-regulatory factor to insulin, ghrelin regulates the energy metabolism in a form of negative feedback.

  5. Long-term testosterone treatment during pregnancy does not alter insulin or glucose profile in a sheep model of polycystic ovary syndrome.

    Science.gov (United States)

    Recabarren, Monica; Carrasco, Albert; Sandoval, Daniel; Diaz, Felipe; Sir-Petermann, Teresa; Recabarren, Sergio E

    2017-09-07

    The administration of testosterone to pregnant sheep to resemble fetal programming of the polycystic ovary syndrome could alter other hormones/factors of maternal origin with known effects on fetal growth. Hence, we studied the weekly profile of insulin, progesterone and glucose during a treatment with testosterone propionate given biweekly from weeks 5 to 17 of pregnancy (term at 21 weeks) and checked the outcome of their fetuses at 17 weeks of gestation after C-section. Control dams were only exposed to the vehicle of the hormone. The testosterone administration did not cause any significant change in the maternal weekly profile of insulin, progesterone or glucose concentration, although the plasma levels of testosterone in the treated dams were inversely correlated to the levels of progesterone. Testosterone treatment also induced an inverse correlation between mean maternal insulin levels and fetal insulin levels; however, the fetal zoometric parameters, body weight, or insulin levels did not differ between exposed and not exposed fetuses. Therefore, treatment with testosterone during pregnancy does not cause significant impact on insulin levels in the mother, leading to less effect on the programming of fetal growth.

  6. Effects of age and insulin-like growth factor-1 on rat neurotrophin receptor expression after nerve injury.

    Science.gov (United States)

    Luo, T David; Alton, Timothy B; Apel, Peter J; Cai, Jiaozhong; Barnwell, Jonathan C; Sonntag, William E; Smith, Thomas L; Li, Zhongyu

    2016-10-01

    Neurotrophin receptors, such as p75(NTR) , direct neuronal response to injury. Insulin-like growth factor-1 receptor (IGF-1R) mediates the increase in p75(NTR) during aging. The aim of this study was to examine the effect of aging and insulin-like growth factor-1 (IGF-1) treatment on recovery after peripheral nerve injury. Young and aged rats underwent tibial nerve transection with either local saline or IGF-1 treatment. Neurotrophin receptor mRNA and protein expression were quantified. Aged rats expressed elevated baseline IGF-1R (34% higher, P = 0.01) and p75(NTR) (68% higher, P < 0.01) compared with young rats. Post-injury, aged animals expressed significantly higher p75(NTR) levels (68.5% above baseline at 4 weeks). IGF-1 treatment suppressed p75(NTR) gene expression at 4 weeks (17.2% above baseline, P = 0.002) post-injury. Local IGF-1 treatment reverses age-related declines in recovery after peripheral nerve injuries by suppressing p75(NTR) upregulation and pro-apoptotic complexes. IGF-1 may be considered a viable adjuvant therapy to current treatment modalities. Muscle Nerve 54: 769-775, 2016. © 2016 Wiley Periodicals, Inc.

  7. [Controlling effect of bushen huatan compound on the insulin signal conducting molecule inside ovaries in polycystic ovary syndrome model rats].

    Science.gov (United States)

    Liang, Chen; Cong, Jing; Chang, Hui

    2011-12-01

    To study the effects of Bushen Huatan Compound (BHC) on the glycolipid metabolism and the expressions of the insulin signal conducting molecules inside ovaries in polycystic ovary syndrome (PCOS) model rats. Female Wistar rats were subcutaneously injected with 2.5 mg/kg testosterone propionate (Their female offspring were randomly divided into the medication group and the model group, 10 in each.) or neutral tea oil of the same dose (Ten female offspring was taken as the control group.) on the 16th day of pregnancy, once daily, for 3 successive days. BHC was given to rats in the medication group by gastrogavage, while equal volume of distilled water was given to rats in the model group and the control group by gastrogavage, both once daily for 20 successive days. The body weight and ovary weight were weighed to calculate the ratio of wet fat weight/body weight. The blood glucose levels were detected at 0, 0.5, 1, and 2 h using oral glucose tolerance test (OGTT). The serum concentrations of high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), fasting blood glucose (FBG), and insulin were detected to calculate homeostasis model assessment of insulin resistance (HOMA-IR). The expressions of protein kinase B (AKT2), glycogen synthase kinase-3beta (GSK3beta), glucose transporter-4 (GLUT4), extracellular signal regulated kinase-1 (ERK1) protein, P-AKT2, P-GSK3beta, and P-ERK1 in ovaries were detected using Western blot. Compared with the control group, the ratio of wet fat weight/ body weight, the blood glucose levels at 0.5 and 2 h in OGTT, and HOMA-IR all obviously increased, and the HDL-C level obviously decreased in the model group (P < 0.05). Compared with the model group, the ratio of wet fat weight/body weight and the blood glucose levels at 2 h in OGTT obviously decreased, and the HDL-C level obviously increased in the medication group (P < 0.05). The expressions of AKT2, P-AKT2, GSK3beta, P-GSK3beta, GLUT4, and ERK1 in the ovary tissue were obviously

  8. Activation of α7 nicotinic acetylcholine receptor decreases on-site mortality in crush syndrome through insulin signaling-Na/K-ATPase pathway

    Directory of Open Access Journals (Sweden)

    Bo-Shi eFan

    2016-03-01

    Full Text Available On-site mortality in crush syndrome remains high due to lack of effective drugs based on definite diagnosis. Anisodamine is widely used in China for treatment of shock, and activation of α7 nicotinic acetylcholine receptor (α7nAChR mediates such antishock effect. The present work was designed to test whether activation of α7nAChR with anisodamine decreased mortality in crush syndrome shortly after decompression. Sprague-Dawley rats and C57BL/6 mice with crush syndrome were injected with anisodamine (20 mg/kg and 28 mg/kg respectively, i.p. 30 min before decompression. Survival time, serum potassium, insulin, and glucose levels were observed shortly after decompression. Involvement of α7nAChR was verified with methyllycaconitine (selective α7nAChR antagonist and PNU282987 (selective α7nAChR agonist, or in α7nAChR knockout mice. Effect of anisodamine was also appraised in C2C12 myotubes. Anisodamine reduced mortality and serum potassium and enhanced insulin sensitivity shortly after decompression in animals with crush syndrome, and PNU282987 exerted similar effects. Such effects were counteracted by methyllycaconitine or in α7nAChR knockout mice. Mortality and serum potassium in rats with hyperkalemia were also reduced by anisodamine. Phosphorylation of Na/K-ATPase was enhanced by anisodamine in C2C12 myotubes. Inhibition of tyrosine kinase on insulin receptor, phosphoinositide 3-kinase, mammalian target of rapamycin, signal transducer and activator of transcription 3, and Na/K-ATPase counteracted the effect of anisodamine on extracellular potassium. These findings demonstrated that activation of α7nAChR could decrease on-site mortality in crush syndrome, at least in part based on the decline of serum potassium through insulin signaling-Na/K-ATPase pathway.

  9. Clinical presentation of Attenuated Psychosis Syndrome in children and adolescents: Is there an age effect?

    Science.gov (United States)

    Ribolsi, Michele; Lin, Ashleigh; Wardenaar, Klaas J; Pontillo, Maria; Mazzone, Luigi; Vicari, Stefano; Armando, Marco

    2017-06-01

    There is limited research on clinical features related to age of presentation of the Attenuated Psychosis Syndrome in children and adolescents (CAD). Based on findings in CAD with psychosis, we hypothesized that an older age at presentation of Attenuated Psychosis Syndrome would be associated with less severe symptoms and better psychosocial functioning than presentation in childhood or younger adolescence. Ninety-four CAD (age 9-18) meeting Attenuated Psychosis Syndrome criteria participated in the study. The sample was divided and compared according to the age of presentation of Attenuated Psychosis Syndrome (9-14 vs 15-18 years). The predictive value of age of Attenuated Psychosis Syndrome presentation was investigated using receiver operating characteristic (ROC)-curve calculations. The two Attenuated Psychosis Syndrome groups were homogeneous in terms of gender distribution, IQ scores and comorbid diagnoses. Older Attenuated Psychosis Syndrome patients showed better functioning and lower depressive scores. ROC curves revealed that severity of functional impairment was best predicted using an age of presentation cut-off of 14.9 years for social functioning and 15.9 years for role functioning. This study partially confirmed our hypothesis; older age at presentation of Attenuated Psychosis Syndrome was associated with less functional impairment, but age was not associated with psychotic symptoms. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  10. Repetition Priming in Adults with Williams Syndrome: Age-Related Dissociation between Implicit and Explicit Memory

    Science.gov (United States)

    Krinsky-McHale, Sharon J.; Kittler, Phyllis; Brown, W. Ted; Jenkins, Edmund C.; Devenny, Darlynne A.

    2005-01-01

    We examined implicit and explicit memory in adults with Williams syndrome. An age-related dissociation was found; repetition priming (reflecting implicit memory) did not show change with age, but free recall (reflecting explicit memory) was markedly reduced. We also compared the performance of adults with Williams syndrome to adults with Down…

  11. Frequency and clinical, hormonal and ultrasonographic characteristics suggestive of polycystic ovarian syndrome in a group of females with metabolic syndrome

    International Nuclear Information System (INIS)

    Ovies Carballo, Gisel; Dominguez Alonso, Emma; Verdeja Varela, Olga L; Zamora Recinos, Hugo

    2008-01-01

    The polycystic ovarian syndrome is the most frequent endocrine affection in females at reproductive age. Nowadays, it is known that insulin resistance and consequent hyperinsulinism seem to be the basis of the disorders characterizing it. That's why, it is not erroneous to think that in females with metabolic syndrome, whose physiopathological bases are insulin resistance and hyperinsulinism, there may appear clinical, humoral and ultrasonographic elements of the polycystic ovarian syndrome

  12. Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome – a randomized study (SYSDIET)

    Science.gov (United States)

    Uusitupa, M; Hermansen, K; Savolainen, M J; Schwab, U; Kolehmainen, M; Brader, L; Mortensen, L S; Cloetens, L; Johansson-Persson, A; Önning, G; Landin-Olsson, M; Herzig, K-H; Hukkanen, J; Rosqvist, F; Iggman, D; Paananen, J; Pulkki, K J; Siloaho, M; Dragsted, L; Barri, T; Overvad, K; Bach Knudsen, K E; Hedemann, M S; Arner, P; Dahlman, I; Borge, G I A; Baardseth, P; Ulven, S M; Gunnarsdottir, I; Jónsdóttir, S; Thorsdottir, I; Orešič, M; Poutanen, K S; Risérus, U; Åkesson, B

    2013-01-01

    Background Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. Methods We conducted a randomized dietary study lasting for 18–24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m−2, 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. Results Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (−0.18, mmol L−1 95% CI −0.35; −0.01, P = 0.04), LDL to HDL cholesterol (−0.15, −0.28; −0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (−0.04, −0.07; −0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference −84, −133; −37 ng L−1, P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, −0.23, −0.41; −0.05, P = 0.012) were associated with IL-1 Ra. Conclusions Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation. PMID:23398528

  13. Insulin and the Brain

    Directory of Open Access Journals (Sweden)

    Grosu Cristina

    2017-12-01

    Full Text Available The brain represents an important site for the action of insulin. Besides the traditionally known importance in glucoregulation, insulin has significant neurotrophic properties and influences the brain activity: insulin influences eating behavior, regulates the storage of energy and several aspects concerning memory and knowledge. Insulin resistance and hyperinsulinism could be associated with brain aging, vascular and metabolic pathologies. Elucidating the pathways and metabolism of brain insulin could have a major impact on future targeted therapies.

  14. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance.

    Science.gov (United States)

    Højlund, Kurt

    2014-07-01

    Type 2 diabetes, obesity and polycystic ovary syndrome (PCOS) are common metabolic disorders which are observed with increasing prevalences, and which are caused by a complex interplay between genetic and environmental factors, including increased calorie intake and physical inactivity. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes and cardiovascular disease. In several studies, we have investigated insulin action on glucose and lipid metabolism, and at the molecular level, insulin signaling to glucose transport and glycogen synthesis in skeletal muscle from healthy individuals and in obesity, PCOS and type 2 diabetes. Moreover, we have described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance. Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin action on glucose uptake and glycogen synthesis is impaired. This suggests that the defects in glucose and lipid oxidation in the common metabolic disorders are secondary to other factors. In young women with PCOS, the degree of insulin resistance was similar to that seen in middle-aged patients with type 2 diabetes. This supports the hypothesis of an unique pathogenesis of insulin resistance in PCOS. Insulin in physiological concentrations stimulates glucose uptake in human skeletal

  15. Acute High-intensity Interval Exercise-induced Redox Signaling is Associated with Enhanced Insulin Sensitivity in Obese Middle-aged Men.

    Directory of Open Access Journals (Sweden)

    Lewan Parker

    2016-09-01

    Full Text Available Background. Obesity and ageing are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK, and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods. Participants completed a 2 hour hyperinsulinaemic-euglycaemic clamp at rest, and 60 minutes after HIIE (4x4 mins at 95% HRpeak; 2 min recovery periods, separated by 1-3 weeks. Results. Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SAPK phosphorylation (JNK, p38 MAPK and NF-κB and SOD activity (p<0.05. Conclusion. These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 hours after HIIE.

  16. Effect of metformin compared with hypocaloric diet on serum C-reactive protein level and insulin resistance in obese and overweight women with polycystic ovary syndrome.

    Science.gov (United States)

    Esfahanian, Fatemeh; Zamani, Mohammad Mahdi; Heshmat, Ramin; Moini nia, Fatemeh

    2013-04-01

    The aim of the present study was to investigate the efficacy of Metformin compared with a hypocaloric diet on C-reactive protein (CRP) level and markers of insulin resistance in obese and overweight women with polycystic ovary syndrome (PCOS). Forty women with body mass index ≥ 27 and PCOS were randomly allocated to receive either Metformin or hypocaloric diet and were assessed before and after a treatment period of 12 weeks. High-sensitivity CRP (hs-CRP) and markers of insulin resistance (IR), homeostasis model assessment-IR, quantitative insulin-sensitivity check index and fasting glucose to insulin ratio were evaluated in each patient. A total of 10 subjects did not complete the trial (three patients in the Metformin group and seven patients in the diet group) and a total of 30 subjects completed the trial (17 subjects in the Metformin group and 13 subjects in the diet group). Serum concentration of hs-CRP significantly decreased in both the Metformin (5.29 ± 2.50 vs 3.81 ± 1.99, P = 0.008) and diet groups (6.08 ± 2.14 vs 4.27 ± 1.60, P = 0.004). There were no significant differences in mean hs-CRP decrement between the two groups. Decrease in hs-CRP levels was significantly correlated with waist circumference in the diet group (r = 0.8, P hypocaloric diet with 5-10% weight reduction on markers of insulin resistance (homeostasis model assessment-IR, fasting glucose to insulin ratio, quantitative insulin-sensitivity check index) was better than Metformin therapy (P = 0.001). Although weight reduction has equal efficacy with Metformin in decreasing serum hs-CRP levels, it was significantly more effective in improving insulin resistance in obese and overweight PCOS women. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  17. Correlation analysis between bone density measured by quantitative CT and blood sugar level of aged patients with non-insulin-dependent diabetes mellitus

    International Nuclear Information System (INIS)

    Wang Guizhi; Liang Ping; Qiao Junhua; Liu Chunyan

    2008-01-01

    Objective: To approach the correlation between the bone density measured by quantitative CT and the blood sugar level of the aged patients with non-insulin-dependent diabetes mellitus, and observe the effects of the blood sugar level on the bone density. Methods: The lumbar bone densities and the blood sugar levels of 160 aged patients with non-insulin-dependent diabetes mellitus (hyperglycemia group 80 cases, euglycemia group 80 cases ) and the healthy aged people (80 cases) were detected by quantitative CT and serum biochemical detection; the correlation between the blood sugar level and the bone density and the osteoporosis occurrence status of aged people in various groups were analyzed. Results: The bone density in the non-insulin-dependent diabetes and hyperglycemia group was lower than those in normal (control) group and non-insulin-dependent diabetes and euglycemia group (P<0.05); the morbility of osteoporosis in the non-insulin-dependent diabetes and hyperglycemia group was higher than those in normal (control) group and non-insulin-dependent diabetes and euglycemia group (P<0.05); negative correlation was found between the bone density and the blood sugar level (aged male group: r=-0.7382, P=0.0013; aged female group: r=-0.8343, P=0.0007). Conclusion: The blood sugar level affects the bone density of the aged patients with non-insulin-dependent diabetes mellitus; the higher the blood sugar level, the lower the bone density. The non-insulin-dependent diabetes aged patients with hyperglycemia have the liability of osteoporosis. (authors)

  18. Stochastic simulations of normal aging and Werner's syndrome.

    KAUST Repository

    Qi, Qi

    2014-04-26

    Human cells typically consist of 23 pairs of chromosomes. Telomeres are repetitive sequences of DNA located at the ends of chromosomes. During cell replication, a number of basepairs are lost from the end of the chromosome and this shortening restricts the number of divisions that a cell can complete before it becomes senescent, or non-replicative. In this paper, we use Monte Carlo simulations to form a stochastic model of telomere shortening to investigate how telomere shortening affects normal aging. Using this model, we study various hypotheses for the way in which shortening occurs by comparing their impact on aging at the chromosome and cell levels. We consider different types of length-dependent loss and replication probabilities to describe these processes. After analyzing a simple model for a population of independent chromosomes, we simulate a population of cells in which each cell has 46 chromosomes and the shortest telomere governs the replicative potential of the cell. We generalize these simulations to Werner\\'s syndrome, a condition in which large sections of DNA are removed during cell division and, amongst other conditions, results in rapid aging. Since the mechanisms governing the loss of additional basepairs are not known, we use our model to simulate a variety of possible forms for the rate at which additional telomeres are lost per replication and several expressions for how the probability of cell division depends on telomere length. As well as the evolution of the mean telomere length, we consider the standard deviation and the shape of the distribution. We compare our results with a variety of data from the literature, covering both experimental data and previous models. We find good agreement for the evolution of telomere length when plotted against population doubling.

  19. [Association analysis of SNP-63 and indel-19 variant in the calpain-10 gene with polycystic ovary syndrome in women of reproductive age].

    Science.gov (United States)

    Flores-Martínez, Silvia Esperanza; Castro-Martínez, Anna Gabriela; López-Quintero, Andrés; García-Zapién, Alejandra Guadalupe; Torres-Rodríguez, Ruth Noemí; Sánchez-Corona, José

    2015-01-01

    Polycystic ovary syndrome is a complex and heterogeneous disease involving both reproductive and metabolic problems. It has been suggested a genetic predisposition in the etiology of this syndrome. The identification of calpain-10 gene (CAPN10) as the first candidate gene for type 2 diabetes mellitus, has focused the interest in investigating their possible relation with the polycystic ovary syndrome, because this syndrome is associated with hyperinsulinemia and insulin resistance, two metabolic abnormalities associated with type 2 diabetes mellitus. To investigate if there is association between the SNP-63 and the variant indel-19 of the CAPN10 gene and polycystic ovary syndrome in women of reproductive age. This study included 101 women (55 with polycystic ovary syndrome and 46 without polycystic ovary syndrome). The genetic variant indel-19 was identified by electrophoresis of the amplified fragments by PCR, and the SNP-63 by PCR-RFLP. The allele and genotype frequencies of the two variants do not differ significatly between women with polycystic ovary syndrome and control women group. The haplotype 21 (defined by the insertion allele of indel-19 variant and C allele of SNP-63) was found with higher frequency in both study groups, being more frequent in the polycystic ovary syndrome patients group, however, this difference was not statistically significant (p = 0.8353). The results suggest that SNP-63 and indel-19 variant of the CAPN10 gene do not represent a risk factor for polycystic ovary syndrome in our patients group. Copyright © 2015. Published by Masson Doyma México S.A.

  20. Refining basal insulin therapy: what have we learned in the age of analogues?

    NARCIS (Netherlands)

    DeVries, J. H.; Nattrass, M.; Pieber, T. R.

    2007-01-01

    BACKGROUND: The basal insulin analogues glargine and detemir have been subject to a series of trials comparing their clinical profiles to the conventional preparation, neutral protamine Hagedorn (NPH). Careful review of these trials provides opportunities to learn clinically useful lessons about

  1. Ontogeny of polycystic ovary syndrome and insulin resistance in utero and early childhood

    Science.gov (United States)

    Polycystic ovary syndrome (PCOS) is a prevalent hyperandrogenic infertility and cardiometabolic disorder that increases a woman's lifetime risk of type 2 diabetes mellitus. It is heritable and intensely familial. Progress toward a cure has been delayed by absence of an etiology. Evidence is mounting...

  2. Over-stimulation of insulin/IGF-1 signaling by western diet may promote diseases of civilization: lessons learnt from laron syndrome

    Directory of Open Access Journals (Sweden)

    Schmitz Gerd

    2011-06-01

    Full Text Available Abstract The insulin/insulin-like growth factor-1 (IGF-1 pathway drives an evolutionarily conserved network that regulates lifespan and longevity. Individuals with Laron syndrome who carry mutations in the growth hormone receptor (GHR gene that lead to severe congenital IGF-1 deficiency with decreased insulin/IGF-1 signaling (IIS exhibit reduced prevalence rates of acne, diabetes and cancer. Western diet with high intake of hyperglycemic carbohydrates and insulinotropic dairy over-stimulates IIS. The reduction of IIS in Laron subjects unmasks the potential role of persistent hyperactive IIS mediated by Western diet in the development of diseases of civilization and offers a rational perspective for dietary adjustments with less insulinotropic diets like the Paleolithic diet.

  3. Over-stimulation of insulin/IGF-1 signaling by western diet may promote diseases of civilization: lessons learnt from laron syndrome.

    Science.gov (United States)

    Melnik, Bodo C; John, Swen Malte; Schmitz, Gerd

    2011-06-24

    The insulin/insulin-like growth factor-1 (IGF-1) pathway drives an evolutionarily conserved network that regulates lifespan and longevity. Individuals with Laron syndrome who carry mutations in the growth hormone receptor (GHR) gene that lead to severe congenital IGF-1 deficiency with decreased insulin/IGF-1 signaling (IIS) exhibit reduced prevalence rates of acne, diabetes and cancer. Western diet with high intake of hyperglycemic carbohydrates and insulinotropic dairy over-stimulates IIS. The reduction of IIS in Laron subjects unmasks the potential role of persistent hyperactive IIS mediated by Western diet in the development of diseases of civilization and offers a rational perspective for dietary adjustments with less insulinotropic diets like the Paleolithic diet.

  4. Association of Insulin Resistance and Hematologic Parameters: Study of a Middle-aged and Elderly Chinese Population in Taiwan

    Directory of Open Access Journals (Sweden)

    Liang-Kung Chen

    2006-06-01

    Conclusion: Elevated WBC count but not RBC count was significantly associated with insulin resistance and glycemic metabolism. The relationship between platelet count and insulin resistance deserves further investigations.

  5. Metabolic syndrome and Chronic Obstructive Pulmonary Disease (COPD): The interplay among smoking, insulin resistance and vitamin D.

    Science.gov (United States)

    Piazzolla, Giuseppina; Castrovilli, Anna; Liotino, Vito; Vulpi, Maria Rosaria; Fanelli, Margherita; Mazzocca, Antonio; Candigliota, Mafalda; Berardi, Elsa; Resta, Onofrio; Sabbà, Carlo; Tortorella, Cosimo

    2017-01-01

    A close relationship between Metabolic Syndrome (MetS) and Chronic Obstructive Pulmonary Disease (COPD) has been described, but the exact nature of this link remains unclear. Current epidemiological data refer exclusively to the MetS prevalence among patients with COPD and data about the prevalence of COPD in MetS patients are still unavailable. To analyse and compare risk factors, clinical and metabolic characteristics, as well as the main respiratory function parameters, among patients affected by MetS, COPD or both diseases. We recruited 59 outpatients with MetS and 76 outpatients with COPD. After medical history collection, physical examination, blood sampling for routine analysis, spirometric evaluation, they were subdivided into MetS (n = 46), MetS+COPD (n = 60), COPD (n = 29). A MetS diagnosis was assigned to 62% of COPD patients recruited in the COPD Outpatients Clinic of the Pneumology Department, while the COPD prevalence in MetS patients enrolled in the Internal Medicine Metabolic Disorders Outpatients Clinic was 22%. More than 60% of subjects enrolled in each Department were unaware that they suffered from an additional disease. MetS+COPD patients exhibited significantly higher C-peptide levels. We also found a positive relation between C-peptide and pack-years in all subjects and a negative correlation between C-peptide and vitamin D only in current smokers. Finally, a negative association emerged between smoking and vitamin D. We have estimated, for the first time, the COPD prevalence in MetS and suggest a potential role of smoking in inducing insulin resistance. Moreover, a direct effect of smoking on vitamin D levels is proposed as a novel mechanism, which may account for both insulin resistance and COPD development.

  6. Effects of insulin-like growth factor-I deficiency and replacement therapy on the hematopoietic system in patients with Laron syndrome (primary growth hormone insensitivity).

    Science.gov (United States)

    Sivan, Bezalel; Lilos, Pearl; Laron, Zvi

    2003-01-01

    Primary insulin-like growth factor-I (IGF-I) deficiencies, such as in Laron syndrome (LS), are a unique model in man to study the consequences resulting from defects in growth hormone (GH) signal transmission. To assess retrospectively the effect of IGF-I deficiency and its therapy on the various cells of the hematopoietic system as reflected by peripheral blood counts. Two groups of patients were studied. The first group consisted of 11 untreated patients with LS, seven males and four females, who were followed from childhood into adult age. Average age at the time of data analysis was 45.4 +/- 9.6 years. The second group included ten children with LS, six males and four females, who received IGF-I replacement therapy for an average period of 6 years, ranging in age from 0.9-11 years. The mean age at initiation of therapy was 6.9 +/- 4.28 years. Only the seven children treated for 5 years or more were included in the analysis. Data on blood counts were collected from the patients' charts. Blood samples were drawn at baseline, weekly during the first month, once a month during the first year, and once every 3 months thereafter. Statistical analysis of the change over time was performed using repeated measures ANOVA. Children with LS had red cell indices in the lower normal range and an elevated monocyte count. A statistically significant rise in red blood cell (RBC) indices was seen in children during IGF-I therapy: RBC rose from 4.66 x 10(6)/ml to 4.93 x 10(6)/ml (p = 0.011); hemoglobin from 11.55 g/dl to 13.01 g/dl (p syndrome, confirms that IGF-I has a strong stimulatory effect on erythropoiesis. In addition, IGF-I therapy had a reducing effect on monocytes and platelets, an effect not previously described. The mechanism by which IGF-I mediates these effects needs further elucidation.

  7. Age and body mass index-dependent relationship between correction of iron deficiency anemia and insulin resistance in non-diabetic premenopausal women

    International Nuclear Information System (INIS)

    Ozdemir, A.; Sevnic, C.; Selamaet, U.; Kamaci, B.; Atalay, S.

    2007-01-01

    No prospective studies have evaluated the effects of correction of iron deficiency anemia on insulin resistance in non-diabetic premenopausal women with iron deficiency anemia. All patients were treated with oral iron preparations. Insulin resistance was calculated with the Homeostasis Model Assessment formula. All patients were dichotomized by the median for age and BMI to assess how the relationship between iron deficiency anemia and insulin resistance was affected by the age and BMI. Although the fasting glucose levels did not change meaningfully, statistically significant decreases were found in fasting insulin levels following anemia treatment both in the younger age ( = 40 years) and the high BMI (>-27Kg/m) subgroups. Post-treatment fasting insulin levels were positively correlated both with BMI (r=0.386, P=0.004) and post-treatment hemoglobin levels. (r=0.285, P=0.036). Regression analysis revealed that the factors affecting post-treatment insulin levels were BMI (P=0.001) and post-treatment hemoglobin levels (p=0.030). Our results show that following he correction of iron deficiency anemia, insulin levels and HOMA scores decrease in younger and lean non-diabetic premenopausal women. (author)

  8. Metabolic syndrome, leptin-insulin resistance and uric acid: a trinomial foe for Algerian city-dweller adolescents' health.

    Science.gov (United States)

    Bouhenni, Hamida; Daoudi, Hadjer; Djemai, Haidar; Rouabah, Abdelkader; Vitiello, Damien; Rouabah, Leila

    2018-03-28

    Background Adolescence is one of the critical periods where increased risk for long-term obesity-related complications is an important health concern. This highlights the need to perform early diagnostics based on precise biomarkers to decrease the risk of complications in adolescents with obesity. Objective To determine the relationships between serum levels of uric acid (UA), leptin and insulin with metabolic syndrome (MS) components in Algerian adolescents. Subjects Nondiabetic adolescents (n = 204). Methods Blood pressure (BP) and anthropometric measurements were performed using standardized techniques. Blood samples were taken for determination of glycemia, triglyceridemia, uricemia, cholesterolemia, leptinemia and insulinemia. Results The rate of MS among an excess weight group was 17.4% [95% confidence interval (CI)]. Serum levels of UA, leptin and insulin were significantly higher in the excess weight group compared to a normal weight group (279.4 ± 86.05 vs. 204.9 ± 50.34 μmol/L and 25.65 ± 14.01 vs. 4.09 ± 2.60 μg/L, p < 0.001; 24.58 ± 13.85 vs. 13.34 ± 6.41 μIU/L, p < 0.05). Serum levels of UA, leptin and insulin were significantly higher in adolescents with MS compared to those without MS (304.86 ± 111.41 vs. 224.72 ± 77.81 μmol/L, 30.26 ± 12.46 vs. 16.93 ± 14.97 μg/L and 30.91 ± 17.30 vs. 18.71 ± 10.14 μIU/L, p < 0.05, respectively). Significant correlations were found between UA and leptin with waist circumference (r = 0.50 and 0.76), diastolic blood pressure (r = 0.58 and 0.43), triglycerides (r = 0.42 and 0.35) and high-density lipoprotein-cholesterol (r = -0.36 and -0.35). Conclusion Serum levels of UA and leptin may be useful biomarkers for early diagnosis of the risk of MS in our Algerian adolescent population.

  9. Androgen deficiency and dry eye syndrome in the aging male.

    Science.gov (United States)

    Azcarate, Patrick M; Venincasa, Vincent D; Feuer, William; Stanczyk, Frank; Schally, Andrew V; Galor, Anat

    2014-07-03

    To evaluate the relationship between androgen levels and subjective and objective measures of dry eye syndrome (DES). A total of 263 male patients from the Miami Veterans Affairs Medical Center eye clinic aged ≥50 were recruited for this prospective cross-sectional study. Patients completed Dry Eye Questionnaire 5, underwent tear film evaluation, and had serum androgen levels measured. The correlations between androgen levels, DES composite scores, DES symptoms, and global, lipid, and aqueous tear film parameters were evaluated. Two hundred sixty-three patients with a mean age of 69 (50-95) were examined. There was no linear association between composite DES scores (generated using latent class analysis) and androgen levels. However, eyes with high DES scores (0.95-1.0) had higher levels of sex hormone-binding globulin (P = 0.03) and lower levels of dehydroepiandrosterone sulfate (DHEAS) (P = 0.02), androstenedione (A) (P = 0.02), and androstane-3α,17β-diol glucuronide (P = 0.03) compared to eyes with intermediate (0.05-0.95) or low (0-0.05) scores. There were no strong correlations between tear film measures and androgen levels. Regarding global parameters, a weak inverse correlation was found between corneal staining and A (r = -0.17, P = 0.009). For lipid parameters, a weak correlation existed between tear breakup time (TBUT) and A (r = 0.15, P = 0.02). When considering aqueous and lipid deficiency independently, the association between TBUT and A existed only with aqueous tear deficiency (r = 0.66, P = 0.002). Regarding aqueous parameters, a weak correlation existed between Schirmer test and DHEAS (r = 0.13, P = 0.047) and A (r = 0.21, P = 0.001). There was a weak correlation between higher levels of androstenedione and healthier global, lipid, and aqueous tear film parameters. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  10. Study of the Effects of Monacolin K and Other Constituents of Red Yeast Rice on Obesity, Insulin-Resistance, Hyperlipidemia, and Nonalcoholic Steatohepatitis Using a Mouse Model of Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Makoto Fujimoto

    2012-01-01

    Full Text Available Purpose. Nonalcoholic fatty liver disease (NAFLD is a progressive and intractable disease associated with metabolic syndrome. Red yeast rice (RYR contains monacolin K, a potent inhibitor of HMG-CoA reductase, and its consumption decreases cholesterol and triglyceride levels. We examined the efficacy of RYR constituents using a novel metabolic syndrome-NAFLD mouse model (MSG mice. Methods. Two types of RYR grown under different culture conditions were used. 1P-DU contained only 0.002 g/100 g of monacolin K, whereas 3P-D1 contained 0.131 g/100 g. MSG mice were divided into three groups: control (C group fed standard food, RYR-C group fed standard food with 1% 1P-DU, and RYR-M group fed standard food with 1% 3P-D1. Mice were examined from 12 to 24 weeks of age. Results. Serum insulin, leptin, and liver damage as well as macrophage aggregation in visceral fat in RYR-C and RYR-M groups were lower than those in C group. The serum adiponectin levels in RYR-C group were significantly higher than those in RYR-M and C groups. Conclusions. RYR was effective against obesity-related inflammation, insulin resistance, and NAFLD in MSG mice irrespective of monacolin K levels. GABA and various peptides produced during fermentation were determined as the active constituents of RYR.

  11. Alternative splicing of exon 17 and a missense mutation in exon 20 of the insulin receptor gene in two brothers with a novel syndrome of insulin resistance (congenital fiber-type disproportion myopathy)

    DEFF Research Database (Denmark)

    Vorwerk, P; Christoffersen, C T; Müller, J

    1999-01-01

    to be compound heterozygotes for mutations in the IR gene. The maternal allele was alternatively spliced in exon 17 due to a point mutation in the -1 donor splice site of the exon. The abnormal skipping of exon 17 shifts the amino acid reading frame and leads to a truncated IR, missing the entire tyrosine kinase......The insulin receptor (IR) in two brothers with a rare syndrome of congenital muscle fiber type disproportion myopathy (CFTDM) associated with diabetes and severe insulin resistance was studied. By direct sequencing of Epstein-Barr virus-transformed lymphocytes both patients were found...... domain. In the correct spliced variant, the point mutation is silent and results in a normally translated IR. The paternal allele carries a missense mutation in the tyrosine kinase domain. All three cDNA variants were present in the lymphocytes of the patients. Purified IR from 293 cells overexpressing...

  12. Ovulation induction with myo-inositol alone and in combination with clomiphene citrate in polycystic ovarian syndrome patients with insulin resistance.

    Science.gov (United States)

    Kamenov, Zdravko; Kolarov, Georgi; Gateva, Antoaneta; Carlomagno, Gianfranco; Genazzani, Alessandro D

    2015-02-01

    Insulin resistance plays a key role in the pathogenesis of polycystic ovarian syndrome (PCOS). One of the methods for correcting insulin resistance is using myo-inositol. The aim of the present study is to evaluate the effectiveness of myo-inositol alone or in combination with clomiphene citrate for (1) induction of ovulation and (2) pregnancy rate in anovulatory women with PCOS and proven insulin resistance. This study included 50 anovulatory PCOS patients with insulin resistance. All of them received myo-inositolduring three spontaneous cycles. If patients remained anovulatory and/or no pregnancy was achieved, combination of myo-inositol and clomiphene citrate was used in the next three cycles. Ovulation and pregnancy rate, changes in body mass index (BMI) and homeostatic model assessment (HOMA) index and the rate of adverse events were assessed. After myo-inositol treatment, ovulation was present in 29 women (61.7%) and 18 (38.3%) were resistant. Of the ovulatory women, 11 became pregnant (37.9%). Of the 18 myo-inositol resistant patients after clomiphene treatment, 13 (72.2%) ovulated. Of the 13 ovulatory women, 6 (42.6%) became pregnant. During follow-up, a reduction of body mass index and HOMA index was also observed. Myo-inositol treatment ameliorates insulin resistance and body weight, and improves ovarian activity in PCOS patients.

  13. Reduced Insulin/IGF-1 Signaling Restores the Dynamic Properties of Key Stress Granule Proteins during Aging

    Directory of Open Access Journals (Sweden)

    Marie C. Lechler

    2017-01-01

    Full Text Available Summary: Low-complexity “prion-like” domains in key RNA-binding proteins (RBPs mediate the reversible assembly of RNA granules. Individual RBPs harboring these domains have been linked to specific neurodegenerative diseases. Although their aggregation in neurodegeneration has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. We show that a wide variety of RNA granule components, including stress granule proteins, become highly insoluble with age in C. elegans and that reduced insulin/insulin-like growth factor 1 (IGF-1 daf-2 receptor signaling efficiently prevents their aggregation. Importantly, stress-granule-related RBP aggregates are associated with reduced fitness. We show that heat shock transcription factor 1 (HSF-1 is a main regulator of stress-granule-related RBP aggregation in both young and aged animals. During aging, increasing DAF-16 activity restores dynamic stress-granule-related RBPs, partly by decreasing the buildup of other misfolded proteins that seed RBP aggregation. Longevity-associated mechanisms found to maintain dynamic RBPs during aging could be relevant for neurodegenerative diseases. : Lechler et al. show that RNA-binding proteins (RBPs including stress granule proteins are prone to aggregate with age in C. elegans. Aggregation of stress granule RBPs with “prion-like” domains is associated with reduced fitness. Their aggregation is prevented by longevity pathways and promoted by the aggregation of other misfolded proteins. Keywords: neurodegenerative diseases, Caenorhabditis elegans, protein aggregation, aging, RNA-binding proteins, stress granules, HSF-1, DAF-2, longevity

  14. Leisure Activity and Caregiver Involvement in Middle-Aged and Older Adults With Down Syndrome

    OpenAIRE

    Mihaila, Iulia; Hartley, Sigan L.; Handen, Benjamin L.; Bulova, Peter D.; Tumuluru, Rameshwari V.; Devenny, Darlynne A.; Johnson, Sterling C.; Lao, Patrick J.; Christian, Bradley T.

    2017-01-01

    The present study examined leisure activity and its association with caregiver involvement (i.e., residence and time spent with primary caregiver) in 62 middle-aged and older adults with Down syndrome (aged 30–53 years). Findings indicated that middle-aged and older adults with Down syndrome frequently participated in social and passive leisure activities, with low participation in physical and mentally stimulating leisure activities. Residence and time spent with primary caregiver were assoc...

  15. Estradiol to testosterone ratio in metabolic syndrome men aged started 40 years above

    Science.gov (United States)

    Kusuma, R.; Siregar, Y.; Mardianto

    2018-03-01

    Disruption of adipose tissue, an endocrine organ, could turn out into the so-called metabolic syndrome. Aging men with lowering testosterone were related to metabolic syndrome and excessive aromatase activity in adipose tissue would increase estradiol level. This study hypothesized that estradiol to testosterone ratio is increasedin aging, metabolic syndrome men. A total of 52 men were randomly recruited for this study. A blood samplewas drawn before 11.00 AM after 10 hoursof overnight fasting, then aliquot serum kept in -20°C pending the research. Subjects were divided evenly into the metabolic syndrome and nonmetabolicsyndrome group. The hormonal assaywas measured on the day of research. Then examined with student t-test. Estradiol level in metabolic syndrome group was increased, but insignificant differ to the other group. Testosterone level decreased and significantly different between groups. In conclusion, estradiol to testosterone ratio was increased in themetabolic syndrome group but insignificant.

  16. Fatty acid binding protein 3 (fabp3) is associated with insulin, lipids and cardiovascular phenotypes of the metabolic syndrome through epigenetic modifications in a Northern European family population.

    Science.gov (United States)

    Zhang, Yi; Kent, Jack W; Lee, Adam; Cerjak, Diana; Ali, Omar; Diasio, Robert; Olivier, Michael; Blangero, John; Carless, Melanie A; Kissebah, Ahmed H

    2013-03-19

    Fatty acid-binding proteins (FABPs) play regulatory roles at the nexus of lipid metabolism and signaling. Dyslipidemia in clinical manifestation frequently co-occurs with obesity, insulin resistance and hypertension in the Metabolic Syndrome (MetS). Animal studies have suggested FABPs play regulatory roles in expressing MetS phenotypes. In our family cohort of Northern European descent, transcript levels in peripheral white blood cells (PWBCs) of a key FABPs, FABP3, is correlated with the MetS leading components. However, evidence supporting the functions of FABPs in humans using genetic approaches has been scarce, suggesting FABPs may be under epigenetic regulation. The objective of this study was to test the hypothesis that CpG methylation status of a key regulator of lipid homeostasis, FABP3, is a quantitative trait associated with status of MetS phenotypes in humans. We used a mass-spec based quantitative method, EpiTYPER®, to profile a CpG island that extends from the promoter to the first exon of the FABP3 gene in our family-based cohort of Northern European descent (n=517). We then conducted statistical analysis of the quantitative relationship of CpG methylation and MetS measures following the variance-component association model. Heritability of each methylation and the effect of age and sex on CpG methylation were also assessed in our families. We find that methylation levels of individual CpG units and the regional average are heritable and significantly influenced by age and sex. Regional methylation was strongly associated with plasma total cholesterol (p=0.00028) and suggestively associated with LDL-cholesterol (p=0.00495). Methylation at individual units was significantly associated with insulin sensitivity, lipid particle sizing and diastolic blood pressure (pmetabolism (βWHR=-0.72; βLDL-c=-0.53) while positively correlated with plasma adiponectin (β=0.24). Further, we show that differential methylation of FABP3 affects binding activity with

  17. Daily insulin requirement of children and adolescents with type 1 diabetes: effect of age, gender, body mass index and mode of therapy.

    Science.gov (United States)

    Wiegand, Susanna; Raile, Klemens; Reinehr, Thomas; Hofer, Sabine; Näke, Andrea; Rabl, Wolfgang; Holl, Reinhard W

    2008-04-01

    The purpose of this study was to generate insulin dose (ID) percentiles for children and adolescents with type 1 diabetes mellitus (DM1) having the opportunity to assess this important parameter in relation to age and sex. Daily IDs per weight (ID/kg) were recorded in 22,177 patients with DM1 (3-25 years of age, DM1 duration of more than 2 years, 48% female) and ID percentiles (ID-Perc) were created statistically. The ID-Perc were compared between male and female, and between multiple insulin injection therapy (MIT) and continuous s.c. insulin infusion (CSII). A multivariate regression analysis was performed for ID in the third year of DM1 with ID/kg, body weight, age, gender, and insulin delivery regimen as variables. The 50th ID-Perc (P50) varied among 0.67 IU/kg (age 3 years), 0.93 IU/kg (13 years), and 0.70 IU/kg (23 years) increasing from early childhood to adolescence and decreasing toward adulthood. Highest P50 ID was found at 12 years in females (0.94 IU/kg) and at 14 years in males (0.92 IU/kg). Using ICT, the ID was significantly higher compared with CSII (P50: 0.94 IU/kg versus 0.79 IU/kg at 13 years). In multivariate regression analysis, ID was significantly (P>0.001) associated with age, gender, and insulin delivery regime. The ID-Perc were significantly different during various periods of childhood and were influenced by gender, body weight, and insulin injection regimes. Therefore, the presented data 1) provide evidence to interpret individual ID in children and adolescents with DM1 and 2) more specifically identify children with unusually high (insulin resistance and non-compliance) or low (MODY and persistent remission) insulin requirement.

  18. Impact of Single or Repeated Dose Intranasal Zinc-free Insulin in Young and Aged F344 Rats on Cognition, Signaling, and Brain Metabolism.

    Science.gov (United States)

    Anderson, Katie L; Frazier, Hilaree N; Maimaiti, Shaniya; Bakshi, Vikas V; Majeed, Zana R; Brewer, Lawrence D; Porter, Nada M; Lin, Ai-Ling; Thibault, Olivier

    2017-02-01

    Novel therapies have turned to delivering compounds to the brain using nasal sprays, bypassing the blood brain barrier, and enriching treatment options for brain aging and/or Alzheimer's disease. We conducted a series of in vivo experiments to test the impact of intranasal Apidra, a zinc-free insulin formulation, on the brain of young and aged F344 rats. Both single acute and repeated daily doses were compared to test the hypothesis that insulin could improve memory recall in aged memory-deficient animals. We quantified insulin signaling in different brain regions and at different times following delivery. We measured cerebral blood flow (CBF) using MRI and also characterized several brain metabolite levels using MR spectroscopy. We show that neither acute nor chronic Apidra improved memory or recall in young or aged animals. Within 2 hours of a single dose, increased insulin signaling was seen in ventral areas of the aged brains only. Although chronic Apidra was able to offset reduced CBF with aging, it also caused significant reductions in markers of neuronal integrity. Our data suggest that this zinc-free insulin formulation may actually hasten cognitive decline with age when used chronically. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Decline in cerebral glucose utilisation and cognitive function with aging in Down's syndrome.

    OpenAIRE

    Schapiro, M B; Haxby, J V; Grady, C L; Duara, R; Schlageter, N L; White, B; Moore, A; Sundaram, M; Larson, S M; Rapoport, S I

    1987-01-01

    The cerebral metabolic rate for glucose (CMRglc) was measured with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose in 14 healthy subjects with Down's syndrome, 19 to 33 years old, and in six healthy Down's syndrome subjects over 35 years, two of whom were demented. Dementia was diagnosed from a history of mental deterioration, disorientation and hallucinations. All Down's syndrome subjects were trisomy 21 karyotype. CMRglc also was examined in 15 healthy men aged 20-35 years ...

  20. Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

    International Nuclear Information System (INIS)

    Naidoo, C.

    1986-01-01

    Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, 125 I-insulin binding to the solubilized erythrocyte membrane receptor and 125 I-insulin binding to fibroblasts in culture

  1. Studies on insulin secretion and insulin resistance in non-insulin-dependent diabetes in young Indians

    Energy Technology Data Exchange (ETDEWEB)

    Naidoo, C

    1986-01-01

    Patients with Non-insulin-dependent diabetes mellitus (NIDDM) have defects in insulin secretion and insulin action. In the discrete genetic syndrome of NIDDY (non-insulin-dependent diabetes in the young), the situation is less clear and these aspects is the subject of this thesis. This study included Indian pasients with three generation transmission of NIDDM via one parent. The insulin and C-peptide responses to oral and intravenous glucose in patients with NIDDY were studied. The insulin and glucose responses to non-glucose secretogogues glucagon, tolbutamide and arginine, in NIDDY were also investigated. The following aspects with regard to insulin resistance in NIDDY were examined: glucose and free fatty acid response to intravenous insulin administration, insulin binding to circulating erythrocytes and monocytes, /sup 125/I-insulin binding to the solubilized erythrocyte membrane receptor and /sup 125/I-insulin binding to fibroblasts in culture.

  2. Associations between levels of insulin-like growth factor 1 and sinusoidal obstruction syndrome after allogeneic haematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Weischendorff, Sarah; Kielsen, Katrine; Sengeløv, H

    2017-01-01

    . We hypothesised that insulin-like growth factor-1 (IGF-1), a mediator of growth and proliferation of various tissues, may attenuate chemotherapy-induced tissue damage after HSCT. We prospectively measured plasma levels of IGF-1 and its binding protein 3 (IGFBP-3) in 41 patients undergoing...... myeloablative HSCT. IGF-1 and IGFBP-3 levels were inversely correlated with C-reactive protein and interleukin-6 levels post HSCT. In multivariate analyses, low levels of IGF-1 and IGFBP-3 before conditioning were associated with increased risk of developing sinusoidal obstruction syndrome (SOS; OR=5.00 per 1...... SDS decrease in IGF-1 (95% CI: 1.45-16.67), P=0.011 and OR=5.00 (1.37-20.00), P=0.015, respectively). Furthermore, low pre-transplant levels of IGF-1 and IGFBP-3 were associated with increased fluid retention during the first 21 days post transplant (OR=7.69 (95% CI: 1.59-33.33), P=0.012, and OR=2...

  3. Eating habits of preschool children and the risk of obesity, insulin resistance and metabolic syndrome in adults.

    Science.gov (United States)

    Kostecka, Małgorzata

    2014-01-01

    Background & Objective : Nutrient excess and nutrient deficiency in the diets of preschool children can lead to permanent modification of metabolic pathways and increased risk of diet-dependent diseases in adults. Children are most susceptible to the adverse consequences of bad eating habits.The objective of this study was to evaluate the eating habits and the diets of preschool children as risk factors for excessive weight, obesity, insulin resistance and the metabolic syndrome. Methods : The study was conducted on 350 randomly selected preschool children attending kindergartens in south-eastern Poland. Three-day dietary recalls were processed and evaluated in the Dieta 5 application. Results : The analyzed diets were characterized by low diversity and a high share of processed foods, such as pate, sausages, ketchup, mayonnaise, fried meat, French fries and fast-food. The dietary content of vegetables, raw fruit, dairy products and whole grain products was alarmingly low. Conclusions : Diets characterized by excessive energy value and nutritional deficiency can lead to health problems. In most cases, excessive weight gain in children can be blamed on parents and caretakers who are not aware of the health consequences of high-calorie foods rich in fats and sugar.

  4. Sensitive and specific markers for insulin resistance, hyperandrogenemia, and inappropriate gonadotrophin secretion in women with polycystic ovary syndrome: a case-control study from Bahrain

    Directory of Open Access Journals (Sweden)

    Al-Ayadhi MA

    2012-05-01

    Full Text Available Jamal Golbahar,1,2,* Maha Al-Ayadhi,2,* Negalla Mohan Das,2 Khalid Gumaa,2 1Department of Molecular Medicine, Al-Jawhara Centre for Genetic Diagnosis and Research, 2Department of Medical Biochemistry, College of Medicine and Medical Sciences, AGU, Manama, Bahrain *These authors contributed equally to this articleBackground: In women with polycystic ovary syndrome (PCOS, despite a high prevalence of insulin resistance, hyperandrogenemia, and disturbances in the secretion of gonadotrophin, the principal causes of biochemical abnormalities and the best endocrine markers for PCOS have not been fully identified.Subjects and methods: Serum levels of insulin, glucose, follicle-stimulating hormone (FSH, luteinizing hormone (LH, total testosterone, estrogen, sex hormone-binding capacity (SHBG, and other related indices such as homeostasis model assessment, insulin glucose ratios, LH/FSH ratios, and the free androgen index (FAI were determined and compared in women with PCOS (n = 50 and women without PCOS (n = 50.Results: In multivariate logistic regression analyses, among all insulin resistance indices, only hyperinsulinemia (odds ratio [OR] = 2.6; confidence interval [CI]: 1.3–5.2; P = 0.008 was significantly and independently associated with PCOS when adjusted for body mass index (BMI, hyperandrogenemia, and LH/FSH ratios. The LH/FSH ratio (OR = 5.4; CI: 1.2–23.0, P = 0.03 was the only marker among those indices for inappropriate gonadotrophin secretion that significantly and independently associated with PCOS when adjusted for BMI and hyperinsulinemia. Among those indices for hyperandrogenemia, FAI (OR = 1.1; CI: 1.0–2.7; P = 0.02 and SHBG (OR = 1.2; CI: 1.2–3.4; P = 0.03 were significantly and independently associated with PCOS when adjusted for BMI and hyperinsulinemia. In addition, receiver operating characteristic analysis showed that the best predictive markers for PCOS were insulin (area under the curve [AUC] = 0.944; CI: 0.887–0

  5. Insulin-like Growth Factor 1 (IGF-1) as a marker of cognitive decline in normal ageing: A review.

    Science.gov (United States)

    Frater, Julanne; Lie, David; Bartlett, Perry; McGrath, John J

    2018-03-01

    Insulin-like Growth Factor 1 (IGF-1) and its signaling pathway play a primary role in normal growth and ageing, however serum IGF-1 is known to reduce with advancing age. Recent findings suggest IGF-1 is essential for neurogenesis in the adult brain, and this reduction of IGF-1 with ageing may contribute to age-related cognitive decline. Experimental studies have shown manipulation of the GH/GF-1 axis can slow rates of cognitive decline in animals, making IGF-1 a potential biomarker of cognition, and/or its signaling pathway a possible therapeutic target to prevent or slow age-related cognitive decline. A systematic literature review and qualitative narrative summary of current evidence for IGF-1 as a biomarker of cognitive decline in the ageing brain was undertaken. Results indicate IGF-1 concentrations do not confer additional diagnostic information for those with cognitive decline, and routine clinical measurement of IGF-1 is not currently justified. In cases of established cognitive impairment, it remains unclear whether increasing circulating or brain IGF-1 may reverse or slow down the rate of further decline. Advances in neuroimaging, genetics, neuroscience and the availability of large well characterized biobanks will facilitate research exploring the role of IGF-1 in both normal ageing and age-related cognitive decline. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Prevalence of metabolic syndrome in adolescents aged 10-18 years in Jammu, J and K

    Directory of Open Access Journals (Sweden)

    Narinder Singh

    2013-01-01

    Full Text Available Objective: To estimate the prevalence of metabolic syndrome among adolescents attending school in the Jammu region, India. Materials and Methods: This is a cross-sectional study conducted between November 2009 and December 2010, among a total of 1160 school-going adolescents of both sexes aged 10-18 years. Relevant metabolic and anthropometric variables were analyzed and criteria suggested by National Cholesterol Education Program Adult Treatment Panel Third (NCEP-ATP III modified for age was used to define metabolic syndrome. Results: The overall prevalence of metabolic syndrome was 2.6%. Prevalence of metabolic syndrome was higher in males (3.84% than in females (1.6% and slightly higher in urban area (2.80% than in rural area (2.52%, whereas prevalence of metabolic syndrome among centrally obese subjects was as high as 33.33%. High density lipoprotein cholesterol was the most common and high blood pressure was the least common constituent of metabolic syndrome. Metabolic syndrome was most prevalent in 16-18 years age group (4.79%. Conclusion : This study demonstrates that metabolic syndrome phenotype exists in substantial number (up to 3% of adolescent population in the Jammu region, India, and particularly 33% of obese adolescents are at risk to develop metabolic syndrome. These findings pose a serious threat to the current and future health of these young people.

  7. Lipid Accumulation Product (LAP) and Visceral Adiposity Index (VAI) as Markers of Insulin Resistance and Metabolic Associated Disturbances in Young Argentine Women with Polycystic Ovary Syndrome.

    Science.gov (United States)

    Abruzzese, Giselle A; Cerrrone, Gloria E; Gamez, Juan M; Graffigna, Mabel N; Belli, Susana; Lioy, Gustavo; Mormandi, Eduardo; Otero, Patricia; Levalle, Oscar A; Motta, Alicia B

    2017-01-01

    Polycystic ovary syndrome (PCOS) is an endocrine disorder. PCOS women are at high risk of developing insulin resistance (IR) and cardiovascular disorders since young age. We aimed to study the reliability of lipid accumulation product (LAP) and visceral adiposity index (VAI) as markers of metabolic disturbances (MD) associated with IR in young reproductive aged PCOS patients. We also evaluated the association between LAP and VAI and the presence of hyperandrogenism. In a cross-sectional study, 110 PCOS patients and 88 control women (18-35 years old) were recruited. PCOS patients were divided into 2 groups, as hyperandrogenic and non-hyperandrogenic considering the signs of hyperandrogenism (clinical or biochemical). Anthropometric measurements were taken and blood samples collected. Metabolic and anthropometric characteristics and their association with IR and associated MD were evaluated and LAP and VAI were calculated. LAP and VAI were compared with TC/HDL-c and TG/HDL-c to define the best markers of MD in this population. Independently of the phenotype, young PCOS patients showed high IR and dyslipidemia. Both LAP and VAI showed to be more effective markers to assess MD and IR in these young women than TG/HDL-c or TC/HDL-c [cut-off values: LAP: 18.24 (sensitivity: 81.43% specificity: 73.49%), positive predictive value (PPV): 75.0%, negative predictive value (NPV): 77.27%, VAI: 2.19 (sensitivity: 81.16% specificity: 72.15% PPV: 74.65% NPV: 72.22%)]. LAP and VAI are representative markers to assess MD associated with IR in young PCOS patients. All PCOS patients, independently of their androgenic condition, showed high metabolic risk. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Association of age at menarche with metabolic syndrome and its components in rural Bangladeshi women

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    Akter Shamima

    2012-11-01

    Full Text Available Abstract Background Early age at menarche is associated with increased risk of metabolic syndrome in both China and the West. However, little is known about the impact of age at menarche and metabolic syndrome in South Asian women, including those from low-income country, where age at menarche is also falling. The aim of the present study was to investigate whether age at menarche is inversely associated with metabolic syndrome in Bangladeshi women, who are mostly poor and have limited access to and or poor health care facilities. Methods This community-based cross-sectional study was performed using 1423 women aged between 15–75 years from rural Bangladesh in 2009 and 2010. Metabolic syndrome was defined according to standard NCEP-ATP III criteria. Logistic regression was used to estimate the association between age at menarche and metabolic syndrome, with adjustment of potential confounding variables, including age, education, marital status, tobacco users, use of contraceptives and number of pregnancies. Results Early onset of menarche (13 years was found to be associated with a higher prevalence of metabolic syndrome (odds ratio=1.55; 95 % confidence interval =1.05-2.30. Age at onset of menarche was also inversely associated with prevalence of high triglycerides (P for trend P for trend = 0.01, but positively associated with prevalence of high fasting blood glucose (P for trend =0.02. However, no significant association was found between age at menarche, high blood pressure and elevated waist circumference. Conclusion Early onset of menarche might promote or trigger development of metabolic syndrome. Thus, knowledge of the history of age at onset of menarche may be critical in identifying women at risk of developing metabolic syndrome and those likely to benefit the most from early interventions.

  9. Age and Pattern of Intellectual Decline among Down Syndrome and Other Mentally Retarded Adults.

    Science.gov (United States)

    Gibson, David; And Others

    1988-01-01

    A study of 18 Down Syndrome and 18 other mentally retarded adults found evidence of a significant erosion of Wechsler Intelligence Scale for Children scores from the third to fourth decades of life. The Block Design subtest was especially vulnerable to performance decline with age in the Down Syndrome adults. (Author/JDD)

  10. Decline in cerebral glucose utilisation and cognitive function with aging in Down's syndrome.

    Science.gov (United States)

    Schapiro, M B; Haxby, J V; Grady, C L; Duara, R; Schlageter, N L; White, B; Moore, A; Sundaram, M; Larson, S M; Rapoport, S I

    1987-01-01

    The cerebral metabolic rate for glucose (CMRglc) was measured with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose in 14 healthy subjects with Down's syndrome, 19 to 33 years old, and in six healthy Down's syndrome subjects over 35 years, two of whom were demented. Dementia was diagnosed from a history of mental deterioration, disorientation and hallucinations. All Down's syndrome subjects were trisomy 21 karyotype. CMRglc also was examined in 15 healthy men aged 20-35 years and in 20 healthy men aged 45-64 years. All subjects were at rest with eyes covered and ears plugged. Mean hemispheric CMRglc in the older Down's syndrome subjects was significantly less, by 23%, than in the young Down's syndrome group; statistically significant decreases in regional metabolism (rCMRglc) also were present in all lobar regions. Comparison of the younger control group with the older control group showed no difference in CMRglc or any rCMRglc (p greater than 0.05). Assessment of language, visuospatial ability, attention and memory showed significant reductions in test scores of the old as compared with the young Down's syndrome subjects. These results show that significant age differences in CMRglc and rCMRglc occur in Down's syndrome but not in healthy controls, and that, although only some older Down's syndrome subjects are demented, significant age reductions in neuropsychologic variables occur in all of them. PMID:2956363

  11. Decline in cerebral glucose utilisation and cognitive function with aging in Down's syndrome.

    Science.gov (United States)

    Schapiro, M B; Haxby, J V; Grady, C L; Duara, R; Schlageter, N L; White, B; Moore, A; Sundaram, M; Larson, S M; Rapoport, S I

    1987-06-01

    The cerebral metabolic rate for glucose (CMRglc) was measured with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose in 14 healthy subjects with Down's syndrome, 19 to 33 years old, and in six healthy Down's syndrome subjects over 35 years, two of whom were demented. Dementia was diagnosed from a history of mental deterioration, disorientation and hallucinations. All Down's syndrome subjects were trisomy 21 karyotype. CMRglc also was examined in 15 healthy men aged 20-35 years and in 20 healthy men aged 45-64 years. All subjects were at rest with eyes covered and ears plugged. Mean hemispheric CMRglc in the older Down's syndrome subjects was significantly less, by 23%, than in the young Down's syndrome group; statistically significant decreases in regional metabolism (rCMRglc) also were present in all lobar regions. Comparison of the younger control group with the older control group showed no difference in CMRglc or any rCMRglc (p greater than 0.05). Assessment of language, visuospatial ability, attention and memory showed significant reductions in test scores of the old as compared with the young Down's syndrome subjects. These results show that significant age differences in CMRglc and rCMRglc occur in Down's syndrome but not in healthy controls, and that, although only some older Down's syndrome subjects are demented, significant age reductions in neuropsychologic variables occur in all of them.

  12. Developmental Trajectories of Structural and Pragmatic Language Skills in School-Aged Children with Williams Syndrome

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    Van Den Heuvel, E.; Manders, E.; Swillen, A.; Zink, I.

    2016-01-01

    Background: This study aimed to compare developmental courses of structural and pragmatic language skills in school-aged children with Williams syndrome (WS) and children with idiopathic intellectual disability (IID). Comparison of these language trajectories could highlight syndrome-specific developmental features. Method: Twelve monolingual…

  13. Regulatory landscape of AGE-RAGE-oxidative stress axis and its modulation by PPARγ activation in high fructose diet-induced metabolic syndrome.

    Science.gov (United States)

    Cannizzaro, Luca; Rossoni, Giuseppe; Savi, Federica; Altomare, Alessandra; Marinello, Cristina; Saethang, Thammakorn; Carini, Marina; Payne, D Michael; Pisitkun, Trairak; Aldini, Giancarlo; Leelahavanichkul, Asada

    2017-01-01

    The AGE-RAGE-oxidative stress (AROS) axis is involved in the onset and progression of metabolic syndrome induced by a high-fructose diet (HFD). PPARγ activation is known to modulate metabolic syndrome; however a systems-level investigation looking at the protective effects of PPARγ activation as related to the AROS axis has not been performed. The aim of this work is to simultaneously characterize multiple molecular parameters within the AROS axis, using samples taken from different body fluids and tissues of a rat model of HFD-induced metabolic syndrome, in the presence or absence of a PPARγ agonist, Rosiglitazone (RGZ). Rats were fed with 60% HFD for the first half of the treatment duration (21 days) then continued with either HFD alone or HFD plus RGZ for the second half. Rats receiving HFD alone showed metabolic syndrome manifestations including hypertension, dyslipidemia, increased glucose levels and insulin resistance, as well as abnormal kidney and inflammatory parameters. Systolic blood pressure, plasma triglyceride and glucose levels, plasma creatinine, and albuminuria were significantly improved in the presence of RGZ. The following molecular parameters of the AROS axis were significantly upregulated in our rat model: carboxymethyl lysine (CML) in urine and liver; carboxyethyl lysine (CEL) in urine; advanced glycation end products (AGEs) in plasma; receptor for advanced glycation end products (RAGE) in liver and kidney; advanced oxidation protein products (AOPP) in plasma; and 4-hydroxynonenal (HNE) in plasma, liver, and kidney. Conversely, with RGZ administration, the upregulation of AOPP and AGEs in plasma, CML and CEL in urine, RAGE in liver as well as HNE in plasma and liver was significantly counteracted/prevented. Our data demonstrate (i) the systems-level regulatory landscape of HFD-induced metabolic syndrome involving multiple molecular parameters, including HNE, AGEs and their receptor RAGE, and (ii) attenuation of metabolic syndrome by

  14. Insulin resistance and associated factors: a cross-sectional study of bank employees.

    Science.gov (United States)

    Salaroli, Luciane Bresciani; Cattafesta, Monica; Molina, Maria Del Carmen Bisi; Zandonade, Eliana; Bissoli, Nazaré Souza

    2017-04-01

    Insulin resistance is characterized by the failure of target cells to respond to normal levels of circulating insulin, and this condition is related to cardiovascular disease. This study sought to evaluate the prevalence of insulin resistance and its association with markers of metabolic abnormalities and metabolic syndrome in bank employees. A cross-sectional study was performed on 498 working men and women aged ≥20 years old. The Homeostasis Model Assessment (HOMA-IR) was used to determine the presence of insulin resistance based on cut-off values of ≤2.71 for normal insulin levels and >2.71 for insulin resistance, as established for the adult Brazilian population. It was observed that the 52 (10.4%) overweight individuals with insulin resistance were 4.97 times (95%CI 1.31-18.83) more likely to have high HOMA-IR values than the normal-weight participants; among those who were obese, the likelihood increased to 17.87 (95%CI 4.36-73.21). Individuals with large waist circumferences were 3.27 times (95%CI 1.03-10.38) more likely to develop insulin resistance than those who were within normal parameters. The HOMA-IR values differed between subjects with and without metabolic syndrome, with values of 2.83±2.5 and 1.10±0.81 (p=0.001), respectively. The levels of insulin, ultrasensitive C-reactive protein and uric acid were also associated with insulin resistance. The prevalence of insulin resistance among bank employees is high, and insulin resistance is associated with and serves as a marker of metabolic syndrome. Cardiovascular disease and metabolic syndrome-associated metabolic abnormalities were observed, and insulin resistance may be a risk factor in this group of professionals.

  15. A cross-sectional study to assess any possible linkage of C/T polymorphism in CYP17A1 gene with insulin resistance in non-obese women with polycystic ovarian syndrome

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    Ushasi Banerjee

    2016-01-01

    Full Text Available Background & objectives: Insulin resistance (IR is a major confounding factor in polycystic ovarian syndrome (PCOS irrespective of obesity. Its exact mechanism remains elusive till now. C/T polymorphism in the -34 promoter region of the CYP17 gene is inconsistently attributed to elucidate the mechanism of IR and its link to hyperandrogenemia in obese PCOS patients. In the present study we aimed to evaluate any association of this polymorphism with IR in non-obese women with PCOS. Methods: Polymorphism study was performed by restriction fragment length polymorphism (RFLP analysis of the Msp A1 digest of the PCR product of the target gene in 75 PCOS cases against 73 age and BMI matched control women. Serum testosterone, BMI and HOMA-IR (homeostatic model of assessment-insulin resistance were analyzed by standard techniques. A realistic cut-off value for the HOMA-IR was obtained through receiver operating characteristic (ROC curve for exploring any possible link between IR and T/C polymorphism in the case group. Results: Significant increases in serum testosterone and HOMA-IR values were observed among the case group (P<0.001 without any significant elevation in BMI and FBG compared to controls. Cut-off value for IR in the PCOS patients was 1.40 against a maximum sensitivity of 0.83 and a minimum false positivity of 0.13. The analysis revealed an inconclusive link between the C/T polymorphic distribution and insulin resistant case subjects. Interpretation & conclusions: The results showed that CYP17A1 gene was not conclusively linked to either IR or its associated increased androgen secretion in non-obese women with PCOS. We propose that an increased sensitivity of insulin on the ovarian cells may be the predominant reason for the clinical effects and symptoms of androgen excess observed in non-obese PCOS patients in our region.

  16. Insulin resistance is associated with lower arterial blood flow and reduced cortical perfusion in cognitively asymptomatic middle-aged adults

    Science.gov (United States)

    Hoscheidt, Siobhan M; Kellawan, J Mikhail; Berman, Sara E; Rivera-Rivera, Leonardo A; Krause, Rachel A; Oh, Jennifer M; Beeri, Michal S; Rowley, Howard A; Wieben, Oliver; Carlsson, Cynthia M; Asthana, Sanjay; Johnson, Sterling C; Schrage, William G

    2016-01-01

    Insulin resistance (IR) is associated with poor cerebrovascular health and increased risk for dementia. Little is known about the unique effect of IR on both micro- and macrovascular flow particularly in midlife when interventions against dementia may be most effective. We examined the effect of IR as indexed by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) on cerebral blood flow in macro- and microvessels utilizing magnetic resonance imaging (MRI) among cognitively asymptomatic middle-aged individuals. We hypothesized that higher HOMA-IR would be associated with reduced flow in macrovessels and lower cortical perfusion. One hundred and twenty cognitively asymptomatic middle-aged adults (57 ± 5 yrs) underwent fasting blood draw, phase contrast-vastly undersampled isotropic projection reconstruction (PC VIPR) MRI, and arterial spin labeling (ASL) perfusion. Higher HOMA-IR was associated with lower arterial blood flow, particularly within the internal carotid arteries (ICAs), and lower cerebral perfusion in several brain regions including frontal and temporal lobe regions. Higher blood flow in bilateral ICAs predicted greater cortical perfusion in individuals with lower HOMA-IR, a relationship not observed among those with higher HOMA-IR. Findings provide novel evidence for an uncoupling of macrovascular blood flow and microvascular perfusion among individuals with higher IR in midlife. PMID:27488909

  17. Serum 25(OHD is inversely associated with metabolic syndrome risk profile among urban middle-aged Chinese population

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    Yin Xiao

    2012-09-01

    Full Text Available Abstract Background Vitamin D deficiency is associated with a variety of chronic metabolic diseases. Limited evidence regarding vitamin D deficiency exists within the Chinese population. The present study aims to examine the association between serum vitamin D concentrations and cardiometabolic risk factors in the young and middle-aged, urban Chinese population Methods The cross-sectional relationships between serum 25-hydroxyvitamin D [25(OHD] concentrations and indices of adiposity and cardiometabolic risk factors (e.g., body mass index, waist circumference, fasting plasma glucose, etc. were evaluated in 601 non-diabetic adults. Result Vitamin D deficiency or insufficiency was present in 66% of the tested population, and serum 25(OHD levels were lower in patients who were overweight/obese or suffered metabolic syndrome when compared to individuals of healthy weight without metabolic syndrome (24.08 ± 8.08 vs 31.70 ± 11.77 ng/ml, 21.52 ± 6.9 vs 31.74 ± 10.21 ng/ml respectively. 25(OHD was inversely associated with waist circumference, fasting glucose, fasting insulin, triglycerides and LDL-cholesterol, and it was positively associated with HDL-cholesterol in a multivariable-adjusted regression model. Conclusion Vitamin D deficiency is common in the young and middle-aged, urban Chinese population, with high prevalence in overweight/obese individuals and patients with metabolic syndrome. Low vitamin D concentration was associated with indices of adiposity and cardiometabolic risk factors. Further studies are warranted to elucidate the cause-effect relation between vitamin D status, obesity and related metabolic disorders. Trial registration Current Controlled Trials (ISRCTN21527585

  18. Insulinaemia and insulin resistance in Caucasian general paediatric population aged 2 to 10 years: Associated risk factors.

    Science.gov (United States)

    Alías-Hernández, Irene; Galera-Martínez, Rafael; García-García, Emilio; Muñoz-Vico, Francisco Javier; Vázquez Lopez, María Ángeles; Olvera-Porcel, María Carmen; Bonillo Perales, Antonio

    2018-02-01

    The aim of this study is to determine values of insulinaemia, homeostasis model assessment (HOMA) index and quantitative insulin sensitivity check index (QUICKI) among a population of prepubertal Caucasian children, to analyse factors associated with insulin resistance (IR), and to study its association with cardiovascular risk factors. Population-based study conducted on a randomly selected sample of prepubescent Caucasian subjects aged 2.00 to 9.99 years old. Anthropometric measurements, blood pressure, and fasting blood samples were obtained, including fasting glucose, triglycerides, High Density Lipoprotein (HDL)-cholesterol, and insulin. In addition, QUICKI and HOMA indices were calculated. Generalised additive models for location, scale and shape (GAMLSS) was used to calculate centiles curves and multivariate logistic regression analysis to assess factors associated with IR. A total of 654 subjects were included. Mean values obtained for insulinaemia, HOMA index, and QUICKI were 3.74 μIU/mL, 0.73, and 0.44, respectively, in the overall population and 3.32 μIU/mL, 0.64 and 0.46, respectively, in normal weight subjects. The main factor associated with IR was abdominal obesity (odds ratio [OR] 3.38 [95% CI 1.44-7.94] in the subgroup aged 2.00-5.99 years and OR 9.14 [3.42-24.41] for those aged 6.00-9.99 years). An increased risk of hyperglycaemia (P = 0.043), hypertriglyceridaemia (P < .001), and HDL < p10 (P = 0.021) was described among children aged 2.00 to 5.99 years with IR, and among those aged 6.00 to 9.99 years, IR was associated with an increased risk of hypertriglyceridaemia (P < .001). Abdominal obesity was the main factor associated with IR. Metabolic changes associated with IR seem to be present from early stages of life, which highlights the importance of the prevention, early diagnosis and treatment of obesity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. [Behaviour problems of children with Down syndrome in preschool-age - Results from the Heidelberg Down syndrome study].

    Science.gov (United States)

    Sarimski, Klaus

    2018-05-01

    We report on the frequency and the correlations of behaviour problems among children with Down syndrome in preschool-age. As part of a longitudinal study 48 mothers of children with Down syndrome completed the German version of the “Strengths and Difficulties Questionnaire” (SDQ-D) and the Parenting Stress Inventory (PSI). The mothers were asked to fill out the questionnaires when the children had a mean age of five years. The results were compared to norms from children with typical development. Thirty per cent of the children with Down syndrome were rated as abnormal. Specifically, mean scores indicating problems with children of the same age and hyperactivity were elevated. A regression analysis predicting the total problem score of the SDQ-D revealed maternal educational level, optimistic attitude, and subjective parental stress at the age of one year and the degree of behavioural abnormalities at the age of three years as significant influential factors. Early intervention for Down syndrome children should include supporting parenting competence and coping skills in order to prevent behaviour problems.

  20. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome

    NARCIS (Netherlands)

    Hirschtritt, M.E.; Lee, P.C.; Pauls, D.L.; Dion, Y.; Grados, M.A.; Illmann, C.; King, R.A.; Sandor, P.; McMahon, W.M.; Lyon, G.J.; Cath, D.C.; Kurlan, R.; Robertson, M.M.; Osiecki, L.; Scharf, J.M.; Mathews, C.A.; Posthuma, D.; Singer, H.S.; Yu, D.; Cox, N.J.; Freimer, N.B.; Budman, C.L.; Chouinard, S.; Rouleau, G.; Barr, C.L.

    2015-01-01

    Importance: Tourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, fewstudies have fully characterized these comorbidities. Furthermore, most studies have included relatively fewparticipants (< 200), and none has examined the ages of highest risk for each

  1. Lifetime Prevalence, Age of Risk, and Genetic Relationships of Comorbid Psychiatric Disorders in Tourette Syndrome

    NARCIS (Netherlands)

    Hirschtritt, Matthew E; Lee, Paul C; Pauls, David L; Dion, Yves; Grados, Marco A; Illmann, Cornelia; King, Robert A; Sandor, Paul; McMahon, William M; Lyon, Gholson J; Cath, Danielle C; Kurlan, Roger; Robertson, Mary M; Osiecki, Lisa; Scharf, Jeremiah M; Mathews, Carol A

    IMPORTANCE: Tourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, few studies have fully characterized these comorbidities. Furthermore, most studies have included relatively few participants (<200), and none has examined the ages of highest risk for each

  2. Patients with old age or proximal tumors benefit from metabolic syndrome in early stage gastric cancer.

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    Xiao-li Wei

    Full Text Available BACKGROUND: Metabolic syndrome and/or its components have been demonstrated to be risk factors for several cancers. They are also found to influence survival in breast, colon and prostate cancer, but the prognostic value of metabolic syndrome in gastric cancer has not been investigated. METHODS: Clinical data and pre-treatment information of metabolic syndrome of 587 patients diagnosed with early stage gastric cancer were retrospectively collected. The associations of metabolic syndrome and/or its components with clinical characteristics and overall survival in early stage gastric cancer were analyzed. RESULTS: Metabolic syndrome was identified to be associated with a higher tumor cell differentiation (P=0.036. Metabolic syndrome was also demonstrated to be a significant and independent predictor for better survival in patients aged >50 years old (P=0.009 in multivariate analysis or patients with proximal gastric cancer (P=0.047 in multivariate analysis. No association was found between single metabolic syndrome component and overall survival in early stage gastric cancer. In addition, patients with hypertension might have a trend of better survival through a good control of blood pressure (P=0.052 in univariate analysis. CONCLUSIONS: Metabolic syndrome was associated with a better tumor cell differentiation in patients with early stage gastric cancer. Moreover, metabolic syndrome was a significant and independent predictor for better survival in patients with old age or proximal tumors.

  3. Effect on Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator during Weight Loss in Obese Women with and without Polycystic Ovary Syndrome

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    Kai I. Cheang

    2016-01-01

    Full Text Available Background. A deficiency of D-chiro-inositol-inositolphosphoglycan mediator (DCI-IPG may contribute to insulin resistance in polycystic ovary syndrome (PCOS. Whether the relationship between impaired DCI-IPG release and insulin resistance is specific to PCOS rather than obesity is unknown. We assessed insulin-released DCI-IPG and its relationship to insulin sensitivity at baseline and after weight loss in obese women with and without PCOS. Methods. Obese PCOS (n=16 and normal (n=15 women underwent 8 weeks of a hypocaloric diet. The Matsuda index, area under the curve DCI-IPG (AUCDCI-IPG, AUCinsulin, and AUCDCI-IPG/AUCinsulin were measured during a 2 hr OGTT at baseline and 8 weeks. Results. PCOS women had lower AUCDCI-IPG/AUCinsulin at baseline and a significant relationship between AUCDCI-IPG/AUCinsulin and Matsuda index (p=0.0003, which was not present in controls. Weight loss was similar between PCOS (−4.08 kg and normal women (−4.29 kg, p=0.6281. Weight loss in PCOS women did not change the relationship between AUCDCI-IPG/AUCinsulin and Matsuda index (p=0.0100, and this relationship remained absent in control women. Conclusion. The association between AUCDCI-IPG/AUCinsulin and insulin sensitivity was only found in PCOS but not in normal women, and this relationship was unaffected by weight loss. DCI and its messenger may contribute to insulin resistance in PCOS independent of obesity.

  4. Associations of Vitamin D with Inter- and Intra-Muscular Adipose Tissue and Insulin Resistance in Women with and without Polycystic Ovary Syndrome

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    David Scott

    2016-11-01

    Full Text Available Low vitamin D and insulin resistance are common in polycystic ovary syndrome (PCOS and associated with higher inter- and intra-muscular adipose tissue (IMAT. We investigated associations between vitamin D, IMAT and insulin resistance in a cross-sectional study of 40 women with PCOS and 30 women without PCOS, and pre- and post-exercise in a 12-week intervention in 16 overweight participants (10 with PCOS and six without PCOS. A non-classical body mass index (BMI threshold was used to differentiate lean and overweight women (BMI ≥ 27 kg/m2. Measurements included plasma 25-hydroxyvitamin D (25OHD, insulin resistance (glucose infusion rate (GIR; mg/m2/min, fasting glucose and insulin, and glycated haemoglobin, visceral fat, mid-thigh IMAT (computed tomography and total body fat (dual-energy X-ray absorptiometry. Women with both PCOS and low 25OHD levels had the lowest GIR (all p < 0.05. Higher IMAT was associated with lower 25OHD (B = −3.95; 95% CI −6.86, −1.05 and GIR (B = −21.3; 95% CI −37.16, −5.44 in women with PCOS. Overweight women with pre-exercise 25OHD ≥30 nmol/L had significant increases in GIR, and decreases in total and visceral fat (all p < 0.044, but no associations were observed when stratified by PCOS status. Women with PCOS and low 25OHD levels have increased insulin resistance which may be partly explained by higher IMAT. Higher pre-training 25OHD levels may enhance exercise-induced changes in body composition and insulin resistance in overweight women.

  5. Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II

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    Luz Ibarra-Lara

    2016-12-01

    Full Text Available Renin-angiotensin system (RAS activation