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Sample records for risk factors insulin

  1. Effects of contraceptive steroids on cardiovascular risk factors in women with insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Petersen, K R; Skouby, S O; Sidelmann, Johannes Jakobsen

    1994-01-01

    OBJECTIVE: We evaluated established cardiovascular risk factors within lipoprotein metabolism, hemostasis, and endothelial function in women with insulin-dependent diabetes mellitus who were using oral contraceptives. STUDY DESIGN: Twenty-five women with uncomplicated insulin-dependent diabetes m...

  2. Serum insulin-like growth factors, insulin-like growth factor binding proteins, and breast cancer risk in postmenopausal women

    DEFF Research Database (Denmark)

    Grønbæk, Henning; Flyvbjerg, Allan; Mellemkjær, L.

    2004-01-01

    BACKGROUND: Studies have shown a positive association between serum insulin-like growth factor (IGF)-I and breast cancer risk in premenopausal but not postmenopausal women. IGF-II and estrogen receptor (ER) status has never been investigated. We examined the association between IGF-I, IGF-II, IGF...

  3. Serum insulin-like growth factors, insulin-like growth factor binding proteins, and breast cancer risk in postmenopausal women

    DEFF Research Database (Denmark)

    Grønbaek, Henning; Flyvbjerg, Allan; Mellemkjaer, Lene

    2004-01-01

    BACKGROUND: Studies have shown a positive association between serum insulin-like growth factor (IGF)-I and breast cancer risk in premenopausal but not postmenopausal women. IGF-II and estrogen receptor (ER) status has never been investigated. We examined the association between IGF-I, IGF-II, IGF......, or IGFBP-3 and risk of ER-negative breast cancer. CONCLUSION: Serum IGFBP-3 and IGF-II levels were positively associated with ER-positive breast cancer risk. This may suggest an important relationship among IGFs, IGFBPs, the ER system, and breast cancer development in postmenopausal women....

  4. Frequency and risk factors of severe hypoglycemia in insulin-treated type 2 diabetes

    DEFF Research Database (Denmark)

    Akram, Kamran; Pedersen-Bjergaard, Ulrik; Borch-Johnsen, Knut

    2006-01-01

    Intensive treatment regimens including early initiation of insulin treatment are important to prevent late complications in type 2 diabetes. The assumed risk of severe hypoglycemia (SH) is a major barrier to initiation of insulin treatment. To assess the relevance of this risk we evaluated...... the frequency of SH as reported in the literature. Using Medline and Embase search we identified 11 studies (5 retrospective and 6 prospective) including at least 50 patients with insulin-treated type 2 diabetes followed for at least 6 months in which frequency of SH was reported. The incidence of SH....... Only few studies looked into the impact of risk factors on the rate of SH. Impaired hypoglycemia awareness, high age, long duration of diabetes and insulin therapy increased the risk, while no association was found with HbA1c and insulin dose. The present knowledge of SH in insulin-treated type 2...

  5. 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.

  6. Frequency and risk factors of severe hypoglycaemia in insulin-treated Type 2 diabetes

    DEFF Research Database (Denmark)

    Akram, K; Pedersen-Bjergaard, U; Carstensen, B

    2006-01-01

    AIMS: The reported risk of severe hypoglycaemia in insulin-treated Type 2 diabetes is highly variable and few studies have evaluated the influence of risk factors. We assessed the incidence and the influence of potential risk factors for severe hypoglycaemia in a questionnaire survey in subjects...... with insulin-treated Type 2 diabetes receiving currently recommended multifactorial intervention. METHODS: Consecutive patients with insulin-treated Type 2 diabetes (n = 401) completed a questionnaire about occurrence of hypoglycaemia in the past, hypoglycaemia awareness and socio-demographic factors. A zero...... treatment and treatment with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor antagonists (ARBs) were associated with reduced risk. C-peptide concentration and HbA1c were not associated with the risk of severe hypoglycaemia. CONCLUSIONS: In this cohort of insulin-treated Type 2...

  7. Insulin sensitivity and clustering of coronary heart disease risk factors in young adults. The Northern Ireland Young Hearts Study

    DEFF Research Database (Denmark)

    Andersen, Lars Bo; Boreham, Colin A.G.; Young, Ian S.

    2006-01-01

    risk factor. Subjects with clustered risk were defined as those displaying four or more risk factors. Blood glucose and insulin were measured in the fasting state and 2 h after ingestion of a 75 g glucose load. Results. Fasting insulin and the homeostasis model assessment insulin resistance score (HOMA......) were strong, graded predictors of clustered risk. The odds ratio (OR) for having clustered risk was 10.8 (95% CI: 3.6-32.4) for the upper quartile of fasting insulin compared to the lowest quartile, and the corresponding OR for HOMA was 23.2 (95% CI: 5.3-101.6). Conclusion. HOMA score predicts...

  8. 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.

  9. Cardiometabolic risk factors and insulin resistance in obese children and adolescents: relation to puberty.

    Science.gov (United States)

    Tobisch, B; Blatniczky, L; Barkai, L

    2015-02-01

    The prevalence of obesity with concomitant increasing risk for having cardiometabolic diseases is rising in the childhood population. Insulin resistance has a key role in metabolic changes in these children. Insulin levels elevate as puberty commences in every individual. Children with increased risk for cardiometabolic diseases show significant differences in insulin levels even before the onset of puberty compared with those without risks. The pattern of appearance of dyslipidaemia also varies in children with risk factors even in the pre-pubertal group from those without risk. Children with metabolic syndrome display considerably pronounced changes in their metabolic parameters before the onset of puberty, which become more pronounced as puberty passes. Insulin resistance (IR) has a key role in the metabolic changes in obese children. In commencing puberty, the insulin levels elevate. It is not clear, however, how insulin levels develop if the metabolic syndrome appears. Metabolic changes were assessed in obese children before, during and after puberty to analyse the relationship between IR and puberty in subjects with and without metabolic syndrome. Three hundred thirty-four obese children (5-19 years) attended the study. The criteria of the International Diabetes Federation were used to assess the presence of cardiometabolic risks (CMRs). Subjects with increased CMR were compared with those without risk (nCMR). Pubertal staging, lipid levels, plasma glucose and insulin levels during oral glucose tolerance test were determined in each participant. IR was expressed by homeostasis model assessment (HOMA-IR) and the ratio of glucose and insulin areas under the curve (AUC-IR). Significantly higher AUC-IR were found in pre-pubertal CMR children compared with nCMR subjects (11.84 ± 1.03 vs. 8.00 ± 0.69; P puberty. HOMA-IR differs between CMR and nCMR only in post-puberty (6.03 ± 1.26 vs. 2.54 ± 0.23; P puberty. CMR is associated with increased

  10. Insulin resistance: an additional risk factor in the pathogenesis of cardiovascular disease in type 2 diabetes.

    Science.gov (United States)

    Patel, Tushar P; Rawal, Komal; Bagchi, Ashim K; Akolkar, Gauri; Bernardes, Nathalia; Dias, Danielle da Silva; Gupta, Sarita; Singal, Pawan K

    2016-01-01

    Sedentary life style and high calorie dietary habits are prominent leading cause of metabolic syndrome in modern world. Obesity plays a central role in occurrence of various diseases like hyperinsulinemia, hyperglycemia and hyperlipidemia, which lead to insulin resistance and metabolic derangements like cardiovascular diseases (CVDs) mediated by oxidative stress. The mortality rate due to CVDs is on the rise in developing countries. Insulin resistance (IR) leads to micro or macro angiopathy, peripheral arterial dysfunction, hampered blood flow, hypertension, as well as the cardiomyocyte and the endothelial cell dysfunctions, thus increasing risk factors for coronary artery blockage, stroke and heart failure suggesting that there is a strong association between IR and CVDs. The plausible linkages between these two pathophysiological conditions are altered levels of insulin signaling proteins such as IR-β, IRS-1, PI3K, Akt, Glut4 and PGC-1α that hamper insulin-mediated glucose uptake as well as other functions of insulin in the cardiomyocytes and the endothelial cells of the heart. Reduced AMPK, PFK-2 and elevated levels of NADP(H)-dependent oxidases produced by activated M1 macrophages of the adipose tissue and elevated levels of circulating angiotensin are also cause of CVD in diabetes mellitus condition. Insulin sensitizers, angiotensin blockers, superoxide scavengers are used as therapeutics in the amelioration of CVD. It evidently becomes important to unravel the mechanisms of the association between IR and CVDs in order to formulate novel efficient drugs to treat patients suffering from insulin resistance-mediated cardiovascular diseases. The possible associations between insulin resistance and cardiovascular diseases are reviewed here.

  11. Vitamin D deficiency and insulin resistance as risk factors for dyslipidemia in obese children.

    Science.gov (United States)

    Erol, Meltem; Bostan Gayret, Özlem; Hamilçıkan, Şahin; Can, Emrah; Yiğit, Özgu L

    2017-04-01

    Dyslipidemia is one of the major complications of obesity; vitamin D deficiency and insulin resistance are attending metabolic complications in dyslipidemic obese children. Objective. To determine if vitamin D deficiency and insulin resistance are risk factors for dyslipidemia in obese children. This study was conducted in the Department of Pediatrics at Bagcilar Training and Research Hospital in Istanbul, Turkey between 2014 and 2015. Obese patients whose age range was 8-14 were included in the study. The serum triglyceride, total cholesterol, low-density lipoprotein cholesterol, highdensity lipoprotein cholesterol, fasting glucose, insulin, alanine aminotransferase, vitamin D levels were measured; a liver ultrasonography was performed. Homeostatic model assessment (HOMA-IR), was used to calculate insulin resistance. 108 obese children were included; 39 (36.11%) had dyslipidemia. The average fasting blood glucose (88.74 ± 7.58 vs. 95.31 ± 6.82; p= 0.0001), insulin level (14.71 ± 12.44 vs. 24.39 ± 15.02; p= 0.0001) and alanine aminotransferase level (23.45 ± 11.18 vs. 30.4 ± 18.95; p= 0.018) were significantly higher in the children with dyslipidemia. In the dyslipidemic obese children, the average hepatosteatosis rate and HOMA-IR level were higher; 28 (71.9%) had hepatosteatosis, 37 (94.87%) had insulin resistance; the vitamin D levels were dyslipidemia. Obese children in our region exhibit low vitamin D and increased HOMA-IR levels, which are efficient risk factors of dyslipidemia.

  12. Insulin resistance possible risk factor for cognitive impairment in fibromialgic patients.

    Science.gov (United States)

    Fava, Antonietta; Plastino, Massimiliano; Cristiano, Dario; Spanò, Antonio; Cristofaro, Stefano; Opipari, Carlo; Chillà, Antonio; Casalinuovo, Fatima; Colica, Carmen; De Bartolo, Matteo; Pirritano, Domenico; Bosco, Domenico

    2013-12-01

    To evaluate glucose metabolism and/or insulin resistance (IR) in 96 patients with Fibromyalgia (FM), associated or not to cognitive impairment. We investigated glucose metabolism in 96 FM patients. Enrolled patients were divided into two groups: 48 patients with memory deficit (group A) and 48 without memory deficit (control group). We evaluated glucose and insulin levels after a 2 h-Oral-Glucose-Tolerance-Test (2 h-OGTT) and insulin resistance (IR) by the homeostasis model assessment formula (HOMA). Body Mass Index (BMI), waist-to-hip-ratio (WHR), anxiety level, fasting plasma insulin and Non-Steroidal Anti-Inflammatory agents use were higher in patients with FM with memory impairment; while age, sex, waist circumference, education level, fasting plasma glucose, glycate hemoglobin, triglycerides, blood lipid profile, C- Reactivity-Protein (CRP), blood pressure and smoking habits were similar in both groups. Following OGTT the prevalence of glucose metabolism abnormalities was significantly higher in group A. IR was present in 79% patients, of whom 23% had also impaired glucose tolerance, 4% newly diagnosed diabetes mellitus and 52% IR only. Obesity and overweight prevailed in group A. IR, but not BMI or WHR was associated to an increased risk of memory impairment (OR = 2,6; 95% CI: 1,22-3,7). The results of this study suggest that IR may represent a risk factor for memory impairment in fibromialgic patients.

  13. Interaction of insulin-like growth factor-I and insulin resistance-related genetic variants with lifestyle factors on postmenopausal breast cancer risk.

    Science.gov (United States)

    Jung, Su Yon; Ho, Gloria; Rohan, Thomas; Strickler, Howard; Bea, Jennifer; Papp, Jeanette; Sobel, Eric; Zhang, Zuo-Feng; Crandall, Carolyn

    2017-07-01

    Genetic variants and traits in metabolic signaling pathways may interact with obesity, physical activity, and exogenous estrogen (E), influencing postmenopausal breast cancer risk, but these inter-related pathways are incompletely understood. We used 75 single-nucleotide polymorphisms (SNPs) in genes related to insulin-like growth factor-I (IGF-I)/insulin resistance (IR) traits and signaling pathways, and data from 1003 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying via obesity and lifestyle modifiers, we assessed the role of IGF-I/IR traits (fasting IGF-I, IGF-binding protein 3, insulin, glucose, and homeostatic model assessment-insulin resistance) in breast cancer risk as a mediator or influencing factor. Seven SNPs in IGF-I and INS genes were associated with breast cancer risk. These associations differed between non-obese/active and obese/inactive women and between exogenous E non-users and users. The mediation effects of IGF-I/IR traits on the relationship between these SNPs and cancer differed between strata, but only roughly 35% of the cancer risk due to the SNPs was mediated by traits. Similarly, carriers of 20 SNPs in PIK3R1, AKT1/2, and MAPK1 genes (signaling pathways-genetic variants) had different associations with breast cancer between strata, and the proportion of the SNP-cancer relationship explained by traits varied 45-50% between the strata. Our findings suggest that IGF-I/IR genetic variants interact with obesity and lifestyle factors, altering cancer risk partially through pathways other than IGF-I/IR traits. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce breast cancer risk.

  14. Evaluation of Posttransplantation Diabetes Mellitus After Liver Transplantation: Assessment of Insulin Administration as a Risk Factor.

    Science.gov (United States)

    Linder, Kristin E; Baker, William L; Rochon, Caroline; May, Scott T; Sheiner, Patricia A; Martin, Spencer T

    2016-05-01

    Impaired glucose regulation posttransplantation can affect allograft survival and may lead to the development of posttransplant diabetes mellitus (PTDM). The primary purpose of this study is to assess the difference in insulin burden between liver transplant patients who develop PTDM and patients who do not. This was a single-center, retrospective study. Adult liver transplant recipients transplanted between January 1, 2005, and August 1, 2013, were included. PTDM was defined as: (1) use of an oral antihyperglycemic agent for ≥30 consecutive days after transplant, (2) use of insulin ≥30 consecutive days after transplant, or (3) hemoglobin A1C≥6.5 any time after transplant. Of the 114 patients included, 48 (42%) developed PTDM. The average 24-hour insulin requirement on the medical floors was 17.2 ± 14.5 units in the PTDM group and 11.3 ± 12.2 units in the PTDM-free group;P= 0.02. The average blood glucose level on the medical floor was 184.7 ± 31.5 mg/dL in the PTDM group and 169.3 ± 31.4 mg/dL in the PTDM-free group;P= 0.013. Multivariate analysis revealed that experiencing rejection was positively associated with the development of PTDM: adjusted odds ratio (AOR) = 3.237; 95% CI = 1.214-8.633. Basiliximab was negatively associated with the development of PTDM: AOR = 0.182; 95% CI = 0.040-0.836. Univariate analyses suggest that insulin burden is a positive risk factor for the development of PTDM; this association is lost in multivariate analyses. Rejection was a positive predictor, and use of basiliximab was a negative predictor for the development of PTDM. © The Author(s) 2016.

  15. Serum Insulin-Like Growth Factor 1 and the Risk of Ischemic Stroke: The Framingham Study.

    Science.gov (United States)

    Saber, Hamidreza; Himali, Jayandra J; Beiser, Alexa S; Shoamanesh, Ashkan; Pikula, Aleksandra; Roubenoff, Ronenn; Romero, Jose R; Kase, Carlos S; Vasan, Ramachandran S; Seshadri, Sudha

    2017-07-01

    Low insulin-like growth factor 1 (IGF-1) has been associated with increased risk of atherosclerosis and atrial fibrillation in cross-sectional studies. Yet, prospective data linking IGF-1 levels to the development of ischemic stroke remain inconclusive. We examined prospectively the association between serum IGF-1 levels and incident ischemic stroke. We measured serum IGF-1 levels in 757 elderly individuals (mean age 79±5, 62% women), free of prevalent stroke, from the Framingham original cohort participants at the 22nd examination cycle (1990-1994) and were followed up for the development of ischemic stroke. Cox models were used to relate IGF-1 levels to the risk for incident ischemic stroke, adjusted for potential confounders. During a mean follow-up of 10.2 years, 99 individuals developed ischemic stroke. After adjustment for age, sex, and potential confounders, higher IGF-1 levels were associated with a lower risk of incident ischemic stroke, with subjects in the lowest quintile of IGF-1 levels having a 2.3-fold higher risk of incident ischemic stroke (95% confidence interval, 1.09-5.06; P =0.03) as compared with those in the top quintile. We observed an effect modification by diabetes mellitus and waist-hip ratio for the association between IGF-1 and ischemic stroke ( P <0.1). In subgroup analyses, the effects were restricted to subjects with diabetics and those in top waist-hip ratio quartile, in whom each standard deviation increase in IGF-1 was associated with a 61% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P =0.007) and 41% (hazard ratio, 0.59; 95% confidence interval, 0.37-0.95; P =0.031) lower risk of incident ischemic stroke, respectively. IGF-1 levels were inversely associated with ischemic stroke, especially among persons with insulin resistance. © 2017 American Heart Association, Inc.

  16. Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Juul, Anders; Scheike, Thomas Harder; Davidsen, Michael

    2002-01-01

    Insulin-like growth factor I (IGF-I) has been suggested to be involved in the pathogenesis of atherosclerosis. We hypothesize that low IGF-I and high IGFBP-3 levels might be associated with increased risk of ischemic heart disease (IHD).......Insulin-like growth factor I (IGF-I) has been suggested to be involved in the pathogenesis of atherosclerosis. We hypothesize that low IGF-I and high IGFBP-3 levels might be associated with increased risk of ischemic heart disease (IHD)....

  17. 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.

  18. 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.

  19. Insulin-like growth factor-I, insulin-like growth factor binding protein-3 and the risk of fibrocystic breast conditions among Chinese women.

    Science.gov (United States)

    Chen, Chu; Doherty, Jennifer A; Lewis, S Kay; Ray, Roberta M; Gao, Dao Li; Stalsberg, Helge; Feng, Ziding; Thomas, David B

    2006-05-01

    We investigated whether circulating insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels are associated with the risk of fibrocystic breast conditions (FBC), in a case-control study nested within a randomized trial of breast self-examination conducted in Shanghai, China. Participants were enrolled during 1989-1991 and were followed over 10 years for the development of breast diseases. Controls (n = 897) were frequency-matched by age to cases (n = 451), who were diagnosed with FBC between 1995 and 2000. Circulating IGF-I and IGFBP-3 levels and their molar ratio were positively associated with risk of FBC. The odds ratios (ORs) and 95% confidence intervals (CI) for the upper fourth of the distribution compared to the lowest fourth for IGF-I, IGFBP3 and their molar ratio were 3.02 (2.02-4.52), 1.92 (1.37-2.71) and 2.26 (1.52-3.36), respectively. The strength of the association between IGF-I levels and FBC was attenuated after adjustment for IGFBP-3 and that for IGFBP-3 was largely eliminated after adjustment for IGF-I. Increasing levels of IGF-I were particularly associated with increasing risk of FBC with proliferative elements (ORs and 95% CIs for the 2nd, 3rd and upper fourth of the distribution of IGF-I: 3.13 (1.50-6.53), 4.57 (2.22-9.39) and 6.30 (3.08-12.89), compared with the lowest fourth. Our results suggest that elevated levels of IGF-I may contribute to the development of FBC. 2005 Wiley-Liss, Inc.

  20. Genetic variants and traits related to insulin-like growth factor-I and insulin resistance and their interaction with lifestyles on postmenopausal colorectal cancer risk.

    Directory of Open Access Journals (Sweden)

    Su Yon Jung

    Full Text Available Genetic variants and traits in metabolic signaling pathways may interact with lifestyle factors such as obesity, physical activity, and exogenous estrogen (E, influencing postmenopausal colorectal cancer (CRC risk, but these interrelated pathways are not fully understood. In this case-cohort study, we examined 33 single-nucleotide polymorphisms (SNPs in genes related to insulin-like growth factor-I (IGF-I/ insulin resistance (IR traits and signaling pathways, using data from 704 postmenopausal women in Women's Health Initiative Observation ancillary studies. Stratifying by the lifestyle modifiers, we assessed the effects of IGF-I/IR traits (fasting total and free IGF-I, IGF binding protein-3, insulin, glucose, and homeostatic model assessment-insulin resistance on CRC risk as a mediator or influencing factor. Six SNPs in the INS, IGF-I, and IGFBP3 genes were associated with CRC risk, and those associations differed between non-obese/active and obese/inactive women and between E nonusers and users. Roughly 30% of the cancer risk due to the SNP was mediated by IGF-I/IR traits. Likewise, carriers of 11 SNPs in the IRS1 and AKT1/2 genes (signaling pathway-related genetic variants had different associations with CRC risk between strata, and the proportion of the SNP-cancer association explained by traits varied from 30% to 50%. Our findings suggest that IGF-I/IR genetic variants interact with obesity, physical activity, and exogenous E, altering postmenopausal CRC risk, through IGF-I/IR traits, but also through different pathways. Unraveling gene-phenotype-lifestyle interactions will provide data on potential genetic targets in clinical trials for cancer prevention and intervention strategies to reduce CRC risk.

  1. Diabetes, insulin and cancer risk

    OpenAIRE

    Yang, Xi-Lin; Chan, Juliana CN

    2012-01-01

    There is a consensus that both type 1 and type 2 diabetes are associated with a spectrum of cancers but the underlying mechanisms are largely unknown. On the other hand, there are ongoing debates about the risk association of insulin use with cancer. We have briefly reviewed recent related research on exploration of risk factors for cancer and pharmacoepidemiological investigations into drug use in diabetes on the risk of cancer, as well as the current understanding of metabolic pathways impl...

  2. 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...

  3. Evidence for disturbed insulin and growth hormone signaling as potential risk factors in the development of schizophrenia.

    Science.gov (United States)

    van Beveren, N J M; Schwarz, E; Noll, R; Guest, P C; Meijer, C; de Haan, L; Bahn, S

    2014-08-26

    Molecular abnormalities in metabolic, hormonal and immune pathways are present in peripheral body fluids of a significant subgroup of schizophrenia patients. The authors have tested whether such disturbances also occur in psychiatrically ill and unaffected siblings of schizophrenia patients with the aim of identifying potential contributing factors to disease vulnerability. The subjects were recruited as part of the Genetic Risk and OUtcome of Psychosis (GROUP) study. The authors used multiplexed immunoassays to measure the levels of 184 molecules in serum from 112 schizophrenia patients, 133 siblings and 87 unrelated controls. Consistent with the findings of previous studies, serum from schizophrenia patients contained higher levels of insulin, C-peptide and proinsulin, decreased levels of growth hormone and altered concentrations of molecules involved in inflammation. In addition, significant differences were found in the levels of some of these proteins in siblings diagnosed with mood disorders (n=16) and in unaffected siblings (n=117). Most significantly, the insulin/growth hormone ratio was higher across all groups compared with the controls. Taken together, these findings suggest the presence of a molecular endophenotype involving disruption of insulin and growth factor signaling pathways as an increased risk factor for schizophrenia.

  4. 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.

  5. High cumulative insulin exposure: a risk factor of atherosclerosis in type 1 diabetes?

    NARCIS (Netherlands)

    Muis, Marian J.; Bots, Michiel L.; Bilo, Henk J. G.; Hoogma, Roel P. L. M.; Hoekstra, Joost B. L.; Grobbee, Diederick E.; Stolk, Ronald P.

    2005-01-01

    Background: Since insulin therapy might have an atherogenic effect, we studied the relationship between cumulative insulin dose and atherosclerosis in type 1 diabetes. We have focused on patients with type 1 diabetes instead of type 2 diabetes to minimise the effect of insulin resistance as a

  6. High cumulative insulin exposure : a risk factor of atherosclerosis in type 1 diabetes?

    NARCIS (Netherlands)

    Muis, MJ; Bots, ML; Bilo, HJG; Hoogma, RPLM; Hoekstra, JBL; Grobbee, DE; Stolk, RP

    Background: Since insulin therapy might have an atherogenic effect, we studied the relationship between cumulative insulin dose and atherosclerosis in type 1 diabetes. We have focused on patients with type 1 diabetes instead of type 2 diabetes to minimise the effect of insulin resistance as a

  7. Genetic variation in insulin-like growth factor 2 may play a role in ovarian cancer risk

    DEFF Research Database (Denmark)

    Pearce, Celeste Leigh; Doherty, Jennifer A; Van Den Berg, David J

    2011-01-01

    The insulin-like growth factor (IGF) signaling axis plays an important role in cancer biology. We hypothesized that genetic variation in this pathway may influence risk of ovarian cancer. A three-center study of non-Hispanic whites including 1880 control women, 1135 women with invasive epithelial...... disease, whereas five tSNPs in IGF2 were associated with risk of invasive epithelial ovarian cancer at Pcases and 5382 additional controls and were able to independently replicate our initial...... findings. In the combined set of studies, rs4320932 was associated with a 13% decreased risk of ovarian cancer per copy of the minor allele carried (95% confidence interval 0.81–0.93, P-trend=7.4 × 10-5). No heterogeneity of effect across study centers was observed (phet=0.25). IGF2 is emerging...

  8. Sedentary lifestyle and its relation to cardiovascular risk factors, insulin resistance and inflammatory profile.

    Science.gov (United States)

    León-Latre, Montserrat; Moreno-Franco, Belén; Andrés-Esteban, Eva M; Ledesma, Marta; Laclaustra, Martín; Alcalde, Víctor; Peñalvo, José L; Ordovás, José M; Casasnovas, José A

    2014-06-01

    To analyze the association between sitting time and biomarkers of insulin resistance and inflammation in a sample of healthy male workers. Cross-sectional study carried out in a sample of 929 volunteers belonging to the Aragon Workers' Health Study cohort. Sociodemographic, anthropometric, pharmacological and laboratory data were collected: lipids-total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoproteins A-1 and B-100, lipoprotein (a)-, insulin resistance-glucose, glycated hemoglobin, homeostasis model assessment of insulin resistance, insulin, and triglyceride/high-density lipoprotein cholesterol ratio-, and inflammatory profile-C-reactive protein and leukocytes. Information on sitting time and physical activity was assessed using a questionnaire. Sedentary behavior was analyzed in terms of prevalences and medians, according to tertiles, using a multivariate model (crude and adjusted linear regression) with biomarkers of inflammation and insulin resistance. The most sedentary individuals had higher body mass index, greater waist circumference, and higher systolic blood pressure, with a significant upward trend in each tertile. Likewise, they had a worse lipid profile with a higher C-reactive protein level, homeostasis model assessment of insulin resistance index, triglyceride/high-density lipoprotein cholesterol ratio, and insulin concentration. In the multivariate analysis, we observed a significant association between the latter parameters and sitting time in hours (log C-reactive protein [β = 0.07], log homeostasis model assessment of insulin resistance index [β = 0.05], triglyceride/high-density lipoprotein cholesterol ratio [β = 0.23], and insulin [β = 0.44]), which remained after adjustment for metabolic equivalents-h/week. Workers who spend more time sitting show a worse inflammatory and insulin resistance profile independently of the physical activity performed. Copyright © 2013

  9. Diabetes and pre-diabetes are associated with cardiovascular risk factors and carotid/femoral intima-media thickness independently of markers of insulin resistance and adiposity

    Directory of Open Access Journals (Sweden)

    Paccaud Fred

    2007-10-01

    Full Text Available Abstract Background Impaired glucose regulation (IGR is associated with detrimental cardiovascular outcomes such as cardiovascular disease risk factors (CVD risk factors or intima-media thickness (IMT. Our aim was to examine whether these associations are mediated by body mass index (BMI, waist circumference (waist or fasting serum insulin (insulin in a population in the African region. Methods Major CVD risk factors (systolic blood pressure, smoking, LDL-cholesterol, HDL-cholesterol, were measured in a random sample of adults aged 25–64 in the Seychelles (n = 1255, participation rate: 80.2%. According to the criteria of the American Diabetes Association, IGR was divided in four ordered categories: 1 normal fasting glucose (NFG, 2 impaired fasting glucose (IFG and normal glucose tolerance (IFG/NGT, 3 IFG and impaired glucose tolerance (IFG/IGT, and 4 diabetes mellitus (DM. Carotid and femoral IMT was assessed by ultrasound (n = 496. Results Age-adjusted levels of the major CVD risk factors worsened gradually across IGR categories (NFG Conclusion We found graded relationships between IGR categories and both major CVD risk factors and carotid/femoral IMT. These relationships were only partly accounted for by BMI, waist and insulin. This suggests that increased CVD-risk associated with IGR is also mediated by factors other than the considered markers of adiposity and insulin resistance. The results also imply that IGR and associated major CVD risk factors should be systematically screened and appropriately managed.

  10. 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.

  11. Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer.

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bonfrer, J.M.; Korse, C.M.; Doorn, J. van; Cats, A.; Depla, A.C.; Timmer, R.; Witteman, B.J.M.; Leeuwen, F.E. van; Veer, L.J. van 't; Rookus, M.A.; Kampman, E.

    2007-01-01

    BACKGROUND: Higher circulating insulin-like growth factor I (IGF-I) concentrations have been related to a greater risk of cancer. Lycopene intake is inversely associated with cancer risk, and experimental studies have shown that it may affect the IGF system, possibly through an effect on IGF-binding

  12. Lycopene supplementation elevates circulating insulin-like growth factor-binding protein-1 and-2 concentrations in persons at greater risk of colorectal cancer

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bonfrer, J.M.; Korse, C.M.; Doorn, J.; Cats, A.; Depla, A.C.; Timmer, R.; Witteman, B.J.M.; Leeuwen, van F.E.; van't Veer, L.J.; Rookus, M.A.; Kampman, E.

    2007-01-01

    Background: Higher circulating insulin-like growth factor I (IGF-I) concentrations have been related to a greater risk of cancer. Lycopene intake is inversely associated with cancer risk, and experimental studies have shown that it may affect the IGF system, possibly through an effect on IGF-binding

  13. Effects of Lycopene on the Insulin-Like Growth Factor (IGF) System in Premenopausal Breast Cancer Survivors and Women at High Familial Breast Cancer Risk

    NARCIS (Netherlands)

    Voskuil, Dorien W.; Vrieling, Alina; Korse, Catharina M.; Beijnen, Jos H.; Bonfrer, Johannes M. G.; van Doorn, Jaap; Kaas, Reinie; Oldenburg, Hester S. A.; Russell, Nicola S.; Rutgers, Emiel J. T.; Verhoef, Senno; van Leeuwen, Flora E.; van't Veer, Laura J.; Rookus, Matti A.

    2008-01-01

    Insulin-like growth factor-I (IGF-I) is an important growth factor associated with increased risk of premenopausal breast cancer. We conducted a randomized, placebo-controlled, double-blind, crossover trial to evaluate whether tomato-derived lycopene supplementation (30 mg/day for 2 mo) decreases

  14. Effects of lycopene on the insulin-like growth factor (IGF) system in premenopausal breast cancer survivors and women at high familial breast cancer risk

    NARCIS (Netherlands)

    Voskuil, Dorien W.; Vrieling, Alina; Korse, Catharina M.; Beijnen, Jos H.; Bonfrer, Johannes M. G.; van Doorn, Jaap; Kaas, Reinie; Oldenburg, Hester S. A.; Russell, Nicola S.; Rutgers, Emiel J. T.; Verhoef, Senno; van Leeuwen, Flora E.; van't Veer, Laura J.; Rookus, Matti A.

    2008-01-01

    Insulin-like growth factor-I (IGF-I) is an important growth factor associated with increased risk of premenopausal breast cancer. We conducted a randomized, placebo-controlled, double-blind, crossover trial to evaluate whether tomato-derived lycopene supplementation (30 mg/day for 2 mo) decreases

  15. Effects of Basal Insulin Analog and Metformin on Glycaemia Control and Weight as Risk Factors for Endothelial Dysfunction

    Directory of Open Access Journals (Sweden)

    Belma Aščić – Buturović

    2008-11-01

    Full Text Available Obese patients with type 2 diabetes and impaired glucose tolerance are at increased risk of development of cardiovascular diseases. Endothelial dysfunction may be a reason for development of atherosclerosis and cardiovascular diseases. Lifestyle modification, increased physical activity, weight reduction, energy restricted diet and good glycaemia control can be useful for the endothelial function improvement and may decrease the risk of cardiovascular diseases. The aim of this study was to evaluate the effects of basal insulin analog and metformin on glycaemia control and weight as risk factors of endothelial dysfunction. Total of 15 patients (9 male and 6 female with type 2 diabetes were studied. The patients were monitored over six months period. Glycated hemoglobin (HbA1c, fasting plasma glucose (FPG, postprandial plasma glucose (PPG, and body mass index (BMI were observed. Mean age of the subjects was 53,4 ± 6,27 years. Mean diabetes duration was 3,71 ± 1,89 years. At the end of the study mean body mass index decreased from 27,5 ± 1,45 kg/m2 to 25,7 ±1,22 kg/m2. In this study we included diabetic patients with fasting glycaemia over 7 mmol/ dm3, postmeal glycaemia over 7,8 mmol/dm3 and glycated hemoglobin over 7%. Prior to the study, the patients were treated with premix insulin divided in two daily doses and metformin after the lunch, which did not result in sufficient regulation of glycaemia. We started treatment with one daily insulin basal analog and three daily doses of metformin and monitored the above mentioned parameters. We advised patients to change their lifestyle, to practice energy restricted diet and to increase their daily physical activity. Insulin doses were titrated separately for each patient (0,7-1 IU/kg. Weight reduction was recorded after the study. Mean fasting glycaemia decreased from 8,6±0,49 mmol/dm3 to 7,04±0,19 mmol/dm3 (p < 0,05. Mean postmeal glycaemia decreased from 9,74 ± 0,79 mmol/dm3 to 7,6 ± 0

  16. Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

    NARCIS (Netherlands)

    Perez-Cornago, Aurora; Appleby, Paul N.; Tipper, Sarah; Key, Timothy J.; Allen, Naomi E.; Nieters, Alexandra; Vermeulen, Roel; Roulland, Sandrine; Casabonne, Delphine; Kaaks, Rudolf; Fortner, Renee T.; Boeing, Heiner; Trichopoulou, Antonia; La Vecchia, Carlo; Klinaki, Eleni; Hansen, Louise; Tjønneland, Anne; Bonnet, Fabrice; Fagherazzi, Guy; Boutron-Ruault, Marie Christine; Pala, Valeria; Masala, Giovanna; Sacerdote, Carlotta; Peeters, Petra H.; Bueno-de-Mesquita, H. Bas; Weiderpass, Elisabete; Dorronsoro, Miren; Quirós, J. Ramón; Barricarte, Aurelio; Gavrila, Diana; Agudo, Antonio; Borgquist, Signe; Rosendahl, Ann H.; Melin, Beatrice; Wareham, Nick; Khaw, Kay Tee; Gunter, Marc; Riboli, Elio; Vineis, Paolo; Travis, Ruth C.

    2017-01-01

    Insulin-like growth factor (IGF)-I has cancer promoting activities. However, the hypothesis that circulating IGF-I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF-I concentration was measured in pre-diagnostic plasma samples from a nested

  17. Daily chocolate consumption is inversely associated with insulin resistance and liver enzymes in the Observation of Cardiovascular Risk Factors in Luxembourg study.

    Science.gov (United States)

    Alkerwi, Ala'a; Sauvageot, Nicolas; Crichton, Georgina E; Elias, Merrill F; Stranges, Saverio

    2016-05-01

    This study examined the association of chocolate consumption with insulin resistance and serum liver enzymes in a national sample of adults in Luxembourg. A random sample of 1153 individuals, aged 18-69 years, was recruited to participate in the cross-sectional Observation of Cardiovascular Risk Factors in Luxembourg study. Chocolate consumption (g/d) was obtained from a semi-quantitative FFQ. Blood glucose and insulin levels were used for the homoeostasis model assessment of insulin resistance (HOMA-IR). Hepatic biomarkers such as serum γ-glutamyl-transpeptidase (γ-GT), serum aspartate transaminase and serum alanine transaminase (ALT) (mg/l) were assessed using standard laboratory assays. Chocolate consumers (81·8 %) were more likely to be younger, physically active, affluent people with higher education levels and fewer chronic co-morbidities. After excluding subjects taking antidiabetic medications, higher chocolate consumption was associated with lower HOMA-IR (β=-0·16, P=0·004), serum insulin levels (β=-0·16, P=0·003) and γ-GT (β=-0·12, P=0·009) and ALT (β=-0·09, P=0·004), after adjustment for age, sex, education, lifestyle and dietary confounding factors, including intakes of fruits and vegetables, alcohol, polyphenol-rich coffee and tea. This study reports an independent inverse relationship between daily chocolate consumption and levels of insulin, HOMA-IR and liver enzymes in adults, suggesting that chocolate consumption may improve liver enzymes and protect against insulin resistance, a well-established risk factor for cardiometabolic disorders. Further observational prospective research and well-designed randomised-controlled studies are needed to confirm this cross-sectional relationship and to comprehend the role and mechanisms that different types of chocolate may play in insulin resistance and cardiometabolic disorders.

  18. Cancer risk among insulin users

    DEFF Research Database (Denmark)

    But, Anna; De Bruin, Marie L.; Bazelier, Marloes T.

    2017-01-01

    Aims/hypothesis: The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies. Methods: National Health Registries from Denmark (1996–2010), Finland (1996–2011), Norway (2005......–2010) and Sweden (2007–2012) and the UK Clinical Practice Research Datalink database (1987–2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression...... models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (≤0.5, 0.5–1, 1–2, 2–3, 3–4, 4–5, 5–6 and >6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin. Results: A total of 21,390 cancer cases occurred during a mean...

  19. 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.

  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. Benefits of Nut Consumption on Insulin Resistance and Cardiovascular Risk Factors: Multiple Potential Mechanisms of Actions

    Directory of Open Access Journals (Sweden)

    Yoona Kim

    2017-11-01

    Full Text Available Epidemiological and clinical studies have indicated that nut consumption could be a healthy dietary strategy to prevent and treat type 2 diabetes (T2DM and related cardiovascular disease (CVD. The objective of this review is to examine the potential mechanisms of action of nuts addressing effects on glycemic control, weight management, energy balance, appetite, gut microbiota modification, lipid metabolism, oxidative stress, inflammation, endothelial function and blood pressure with a focus on data from both animal and human studies. The favourable effects of nuts could be explained by the unique nutrient composition and bioactive compounds in nuts. Unsaturated fatty acids (monounsaturated fatty acids and polyunsaturated fatty acids present in nuts may play a role in glucose control and appetite suppression. Fiber and polyphenols in nuts may also have an anti-diabetic effect by altering gut microbiota. Nuts lower serum cholesterol by reduced cholesterol absorption, inhibition of HMG-CoA reductase and increased bile acid production by stimulation of 7-α hydroxylase. Arginine and magnesium improve inflammation, oxidative stress, endothelial function and blood pressure. In conclusion, nuts contain compounds that favourably influence glucose homeostasis, weight control and vascular health. Further investigations are required to identify the most important mechanisms by which nuts decrease the risk of T2DM and CVD.

  2. Interactions among insulin resistance, inflammation factors, obesity-related gene polymorphisms, environmental risk factors, and diet in the development of gestational diabetes mellitus.

    Science.gov (United States)

    Feng, Yang; Jiang, Chen-Dong; Chang, Ai-Min; Shi, Ying; Gao, Junjun; Zhu, Linlin; Zhang, Zhan

    2018-03-08

    The aim of this study was to investigate the correlations and interactions between the polymorphisms of insulin resistance-related genes (ADIPOQ rs2241766), inflammation factors (TNF-α rs1800629, IL-6 rs1800795), obesity-related genes (GNB3 rs5443, ADRB rs1042714), and risk factors for gestational diabetes mellitus (GDM) such as diet structure in the development of GDM. This research was conducted among women who visited the third-affiliate hospital of Zhengzhou University for pregnancy checkups from 1 June 2014 to 30 December 2014. Based on the results of a 75-g glucose tolerance test (OGTT), 140 pregnant women with GDM were randomly selected as a part of the GDM group and140 healthy, pregnant women as part of the control group. Relevant clinical and laboratory data for the child and the mother including her pregnancy outcomes and the delivery mode were collected for the epidemiological survey. The results showed that risk factors for GDM are advanced age, the hepatitis B virus, family history of diabetes, high body mass index before pregnancy, and weight gain of ≥10 kg before 24-week gestation. We found that diet structures were severely unbalanced. The polymorphisms rs2241766 and rs5443 were found to potentially be associated with GDM; moreover, a positive interaction was demonstrated between rs2241766 and age, and a negative interaction was demonstrated with weight gain of ≥10 kg before 24-week gestation. Our findings demonstrate that both environmental risk factors and genetic background contribute to the development of GDM.

  3. [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.

  4. A predictive score for retinopathy of prematurity by using clinical risk factors and serum insulin-like growth factor-1 levels

    Directory of Open Access Journals (Sweden)

    Yeşim Coşkun

    2017-11-01

    Full Text Available AIM: To detect the impact of insulin-like growth factor-1 (IGF-1 and other risk factors for the early prediction of retinopathy of prematurity (ROP and to establish a scoring system for ROP prediction by using clinical criteria and serum IGF-1 levels. METHODS: The study was conducted with 127 preterm infants. IGF-1 levels in the 1st day of life, 1st, 2nd, 3rd and 4th week of life was analyzed. The score was established after logistic regression analysis, considering the impact of each variable on the occurrences of any stage ROP. A validation cohort containing 107 preterm infants was included in the study and the predictive ability of ROP score was calculated. RESULTS: Birth weights (BW, gestational weeks (GW and the prevalence of breast milk consumption were lower, respiratory distress syndrome (RDS, bronchopulmonary dysplasia (BPD and necrotizing enterocolitis (NEC were more frequent, the duration of mechanical ventilation and oxygen supplementation was longer in patients with ROP (P<0.05. Initial serum IGF-1 levels tended to be lower in newborns who developed ROP. Logistic regression analysis revealed that low BW (<1250 g, presence of intraventricular hemorrhage (IVH and formula feeding increased the risk of ROP. Afterwards, the scoring system was validated on 107 infants. The negative predictive values of a score less than 4 were 84.3%, 74.7% and 79.8% while positive predictive values were 76.3%, 65.5% and 71.6% respectively. CONCLUSION: In addition to BW <1250 g and IVH, formula consumption was detected as a risk factor for the development of ROP. Breastfeeding is important for prevention of ROP in preterm infants.

  5. Visceral adiposity, insulin resistance and cancer risk

    LENUS (Irish Health Repository)

    Donohoe, Claire L

    2011-06-22

    Abstract Background There is a well established link between obesity and cancer. Emerging research is characterising this relationship further and delineating the specific role of excess visceral adiposity, as opposed to simple obesity, in promoting tumorigenesis. This review summarises the evidence from an epidemiological and pathophysiological perspective. Methods Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. Results Numerous epidemiological studies consistently identify increased risk of developing carcinoma in the obese. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the paracrine effects of adipose tissue and systemic alterations associated with obesity. Systemic changes in the obese state include chronic inflammation and alterations in adipokines and sex steroids. Insulin and the insulin-like growth factor axis influence tumorigenesis and also have a complex relationship with adiposity. There is evidence to suggest that insulin and the IGF axis play an important role in mediating obesity associated malignancy. Conclusions There is much evidence to support a role for obesity in cancer progression, however further research is warranted to determine the specific effect of excess visceral adipose tissue on tumorigenesis. Investigation of the potential mechanisms underpinning the association, including the role of insulin and the IGF axis, will improve understanding of the obesity and cancer link and may uncover targets for intervention.

  6. Risk Factors

    Science.gov (United States)

    ... cells do not invade nearby tissues or spread. Risk Factors Key Points Factors That are Known to ... chemicals . Factors That are Known to Increase the Risk of Cancer Cigarette Smoking and Tobacco Use Tobacco ...

  7. Dissimilar association of conventional immune-reactive versus specific insulin with cardiovascular risk factors: a consequence of proinsulinaemia?

    NARCIS (Netherlands)

    Grootenhuis, P.A.; Mooy, J.M.; Kostense, P.J.; Popp-Snijders, C.; Bouter, L.M.; Heine, R.J.

    1998-01-01

    In this study involving 365 non-diabetic elderly Caucasians, we examined the relationship of immuno-specific insulin (ISI), total immuno-reactive insulin (IRI), proinsulin (PI) and proinsulin-insulin ratio (PI:ISI) to serum high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic

  8. Dissimilar association of conventional immuno-reactive versus specific insulin with cardiovascular risk factors : a consequence of proinsulinaemia?

    NARCIS (Netherlands)

    Grootenhuis, P A; Mooy, J M; Kostense, P J; Popp-Snijders, C; Bouter, L M; Heine, R J

    In this study involving 365 non-diabetic elderly Caucasians, we examined the relationship of immuno-specific insulin (ISI), total immuno-reactive insulin (IRI), proinsulin (PI) and proinsulin-insulin ratio (PI:ISI) to serum high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic

  9. Glomerular filtration rate, cardiovascular risk factors and insulin resistance Filtrado glomerular, riesgo cardiovascular y resistencia a la insulina

    Directory of Open Access Journals (Sweden)

    Martín R. Salazar

    2009-10-01

    Full Text Available The aim of this paper was to study the estimated glomerular filtration rate (eGFR, its changes with age, and its association with systolic blood pressure (SBP and diastolic BP (DBP, indicators of obesity, dyslipemia, insulin resistance and inflammation on a random population sample. BP, weight, size and waist circumference (WC were recorded at home. Fasting morning blood samples were analysed. The eGFR was calculated with MDRD (eGFR-MDRD, Cockroft-Gault (eGFR-CG adjusted to 1.73 m² and reciprocal of serum creatinine (100/serum cretinine. A total of 1016 individuals, 722 females (41.97 ± 0.66 years old and 294 males (42.06 ± 0.99 years old, completed the laboratory tests. The mean of 100/Scr was 115.13 ± 0.60 (dl/mg, the mean eGFR-CG was 98.48 ± 0.82 ml/min/1.73 m²; the mean eGFR-MDRD was 85.15 ± 0.58 ml/min/1.73 m². The eGFR-MDRD decreased with age and with the number of risk factors in both sexes. The eGFR-MDRD El objetivo fue evaluar en una muestra poblacional aleatoria el filtrado glomerular estimado (FGe, sus cambios con la edad y su asociación con presión arterial sistólica (PAS y diastólica (PAD, indicadores de obesidad, dislipemia, resistencia a la insulina e inflamación. En cada domicilio fueron medidos presión arterial, peso y talla y perímetro de la cintura (PC. Se analizaron muestras de sangre en ayunas y fue calculado el FGe usando las fórmulas de MDRD (FGe-MDRD y Cockroft-Gault (FGe-CG ajustado a 1.73 m², y la inversa de la creatinina sérica (100/CrS. Completaron el protocolo de laboratorio 1016 sujetos, 722 mujeres (41.97 ± 0.66 años y 294 varones (42.06 ± 0.99 años. La media de 100/Crs fue 115.13 ± 0.60 (dl/mg, la del FGe-CG 98.48 ± 0.82 ml/min/1.73 m² y la del FGe-MDRD 85.15 ± 0.58 ml/min/1.73 m² (CI 95% 84.00-86.29. El FGe-MDRD disminuyó con la edad y con el número de factores de riesgo cardiovascular en ambos sexos. La prevalecencia ajustada de FGe-MDRD < 60 ml/min/1.73 m² fue 6.2 por 100

  10. Effects of childhood malnutrition on the increase of risk factors for obesity, non-insulin dependent diabetes mellitus and coronary heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Sawaya, A L [Centro de Recuperacao e Educacao Nutricional - CERN, Universidade Federal de Sao Paulo, Depto. de Fisiologia, Disc. de Fisiologia Endocrina, Sao Paulo, SP (Brazil); Roberts, S B [USDA Human Nutrition Research Center on Aging Tufts University, Boston, MA (United States)

    1999-07-01

    Studies in humans and animals have lent support to the theory that early undernutrition can promote later obesity, non-insulin dependent diabetes, and coronary heart diseases. The purpose of this study is therefore to investigate the effects of stunting, indicative of previous malnutrition on the increase risk factors for these diseases. The population studied will be 100 school age boys and girls (8-10 y) divided into two groups: stunted (-1.0 to -2.5 z score of height-for-age) but of normal weight-for-height ({+-} 0.5 z score of NCHS); and control having normal height-for-age and weight-for-height ({+-} 0.5 z score of NCHS). Differences in body composition, food intake, blood parameters (fasting glucose and insulin, glycosylated hemoglobin, glucagon, salivary cortisol, triglycerides, high density lipoprotein cholesterol, free-fat acids and IGF-1) and blood pressure will be evaluated. (author)

  11. Effects of childhood malnutrition on the increase of risk factors for obesity, non-insulin dependent diabetes mellitus and coronary heart disease

    International Nuclear Information System (INIS)

    Sawaya, A.L.; Roberts, S.B.

    1999-01-01

    Studies in humans and animals have lent support to the theory that early undernutrition can promote later obesity, non-insulin dependent diabetes, and coronary heart diseases. The purpose of this study is therefore to investigate the effects of stunting, indicative of previous malnutrition on the increase risk factors for these diseases. The population studied will be 100 school age boys and girls (8-10 y) divided into two groups: stunted (-1.0 to -2.5 z score of height-for-age) but of normal weight-for-height (± 0.5 z score of NCHS); and control having normal height-for-age and weight-for-height (± 0.5 z score of NCHS). Differences in body composition, food intake, blood parameters (fasting glucose and insulin, glycosylated hemoglobin, glucagon, salivary cortisol, triglycerides, high density lipoprotein cholesterol, free-fat acids and IGF-1) and blood pressure will be evaluated. (author)

  12. Failure to initiate early insulin therapy - A risk factor for diabetic retinopathy in insulin users with Type 2 diabetes mellitus: Sankara Nethralaya-Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS, Report number 35).

    Science.gov (United States)

    Gupta, Aditi; Delhiwala, Kushal S; Raman, Rajiv P G; Sharma, Tarun; Srinivasan, Sangeetha; Kulothungan, Vaitheeswaran

    2016-06-01

    Insulin users have been reported to have a higher incidence of diabetic retinopathy (DR). The aim was to elucidate the factors associated with DR among insulin users, especially association between duration, prior to initiating insulin for Type 2 diabetes mellitus (DM) and developing DR. Retrospective cross-sectional observational study included 1414 subjects having Type 2 DM. Insulin users were defined as subjects using insulin for glycemic control, and insulin nonusers as those either not using any antidiabetic treatment or using diet control or oral medications. The duration before initiating insulin after diagnosis was calculated by subtracting the duration of insulin usage from the duration of DM. DR was clinically graded using Klein's classification. SPSS (version 9.0) was used for statistical analysis. Insulin users had more incidence of DR (52.9% vs. 16.3%, P 1) and sight threatening DR (19.1% vs. 2.4%, P 1) in comparison to insulin nonusers. Among insulin users, longer duration of DM (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.00-1.25, P = 0.044) and abdominal obesity (OR 1.15, 95% CI 1.02-1.29, P = 0.021) was associated with DR. The presence of DR was significantly associated with longer duration (≥5 years) prior to initiating insulin therapy, overall (38.0% vs. 62.0%, P = 0.013), and in subjects with suboptimal glycemic control (32.5% vs. 67.5%, P = 0.022). The presence of DR is significantly associated with longer duration of diabetes (>5 years) and sub-optimal glycemic control (glycosylated hemoglobin insulin users, abdominal obesity was found to be a significant predictor of DR; DR is associated with longer duration prior to initiating insulin therapy in Type 2 DM subjects with suboptimal glycemic control.

  13. A three-year follow-up study on risk factors for obesity and non-insulin dependent diabetes mellitus in aging populations in China

    International Nuclear Information System (INIS)

    Ma Guansheng

    1999-01-01

    Obesity is being recognized as a major public health problem of global significance. The prevalence of obesity is increasing worldwide and also in China. Studies indicated that obesity is the major risk factor for several chronic degenerative diseases including cardiovascular disease, diabetes mellitus, and hypertension. However, the underlying mechanism of obesity development and its relation to non-insulin dependent diabetes mellitus (NIDDM) is not well understood. The major aim of the proposed research study is to investigate the effect of energy intake and expenditure on body composition and obesity development, and to identify obesity and NIDDM risk factors. This study will be conducted in 100 men and women aged 65 living in urban Beijing, China. 2-H and 18-O will be used for body composition and energy expenditure measurements, energy intake by a 3-day food weighted method, physical activity level by questionnaire, insulin determinations by radioimmunoassay (RIA). Demographic data of the subjects will also be collected. We anticipate that the results of this study would help us understand the underlying mechanism of obesity and the relation of obesity to NIDDM in Chinese aging population, so that effective strategies can be identified for prevention and management of obesity and NIDDM. (author)

  14. Impact of birth weight and early infant weight gain on insulin resistance and associated cardiovascular risk factors in adolescence

    DEFF Research Database (Denmark)

    Fabricius-Bjerre, Signe; Jensen, Rikke Beck; Færch, Kristine

    2011-01-01

    Low birth weight followed by accelerated weight gain during early childhood has been associated with adverse metabolic and cardiovascular outcomes later in life. The aim of this study was to examine the impact of early infant weight gain on glucose metabolism and cardiovascular risk factors...

  15. Insulin and insulin-like growth factor receptors and responses

    International Nuclear Information System (INIS)

    Roth, R.A.; Steele-Perkins, G.; Hari, J.; Stover, C.; Pierce, S.; Turner, J.; Edman, J.C.; Rutter, W.J.

    1988-01-01

    Insulin is a member of a family of structurally related hormones with diverse physiological functions. In humans, the best-characterized members of this family include insulin, insulin-like growth factor (IGF)-I, and IGF-II. Each of these three polypeptide hormones has its own distinct receptor. The structures of each of these receptors have now been deduced from analyses of isolated cDNA clones. To study further the responses mediated through these three different receptors, the authors have been studying cells expressing the proteins encoded by these three cDNAs. The isolated cDNAs have been transfected into Chinese hamster ovary (CHO) cells, and the resulting transfected cell lines have been characterized as to the ligand-binding activities and signal-transducing activities of the expressed proteins

  16. Effect of cigarette smoking on insulin resistance risk.

    Science.gov (United States)

    Haj Mouhamed, D; Ezzaher, A; Neffati, F; Douki, W; Gaha, L; Najjar, M F

    2016-02-01

    Smoking is one of the main risk factors for cardiovascular disease (CVD). The mechanism(s) of the effects of smoking on CVD are not clearly understood; however, a number of atherogenic characteristics, such as insulin resistance have been reported. We aim to investigate the effects of cigarette smoking on insulin resistance and to determine the correlation between this parameter with smoking status characteristics. This study was conducted on 138 non-smokers and 162 smokers aged respectively 35.6±16.0 and 38.5±21.9 years. All subjects are not diabetic. Fasting glucose was determined by enzymatic methods and insulin by chemiluminescence method. Insulin resistance (IR) was estimated using the Homeostasis Model of Assessment equation: HOMA-IR=[fasting insulin (mU/L)×fasting glucose (mmol/L)]/22.5. IR was defined as the upper quartile of HOMA-IR. Values above 2.5 were taken as abnormal and reflect insulin resistance. Compared to non-smokers, smokers had significantly higher levels of fasting glucose, fasting insulin and HOMA-IR index. These associations remained significant after adjustment for confounding factors (age, gender, BMI and alcohol consumption). A statistically significant association was noted between the smoking status parameters, including both the number of cigarettes smoked/day and the duration of smoking, and fasting insulin levels as well for HOMA-IR index. Among smokers, we noted a positive correlation between HOMA-IR index and both plasma thiocyanates and urinary cotinine. Our results show that smokers have a high risk to developing an insulin resistance and hyperinsulinemia, compared with a matched group of non-smokers, and may help to explain the high risk of cardiovascular diseases in smokers. Copyright © 2015. Published by Elsevier SAS.

  17. Do very small adipocytes in subcutaneous adipose tissue (a proposed risk factor for insulin insensitivity) have a fetal origin?

    DEFF Research Database (Denmark)

    Nielsen, Mette Olaf; Hou, Lei; Johnsen, Lærke

    2016-01-01

    Previous studies have shown that fetal life malnutrition affects preferences for fat deposition in the body thereby predisposing for visceral adipocity and associated disorders in glucose-insulin regulation. In this study, we aimed to test the hypotheses that late-gestation undernutrition 1) has...

  18. Plasma levels of lysine, tyrosine, and valine during pregnancy are independent risk factors of insulin resistance and gestational diabetes.

    Science.gov (United States)

    Park, Sunmin; Park, Jin Young; Lee, Ju Hong; Kim, Sung-Hoon

    2015-03-01

    This study compared plasma concentrations of amino acids in pregnant women with and without gestational diabetes mellitus (GDM) and identified the association between plasma amino acid levels and GDM, insulin resistance, and insulin secretion at 24-28 weeks of pregnancy. Circulating amino acid levels were evaluated using high-performance liquid chromatography at 24-28 weeks of pregnancy in 25 non-GDM and 64 GDM women after adjusting for covariates such as maternal age, body mass index (BMI) before pregnancy, BMI and gestational age at screening GDM, and daily caloric intake. Backward stepwise logistic regression analysis was used to identify the predictors of developing GDM, and homeostatic model assessments for insulin resistance (HOMA-IR) and β-cell function (HOMA-B). Circulating levels of amino acids except threonine and tyrosine were significantly higher in GDM women than non-GDM women. Along with the intakes of energy, protein, and fat from animal sources, the intakes of each amino acid were significantly higher in the GDM group without a direct correlation to plasma amino acid levels. The variation in GDM development was explained by maternal age, diastolic blood pressure, and plasma lysine levels (R(2)=0.691). Height, BMI before pregnancy, systolic blood pressure, and plasma tyrosine and valine levels accounted for the variation in HOMA-IR (R(2)=0.589). The 53.3% variation of HOMA-B was explained by maternal age, BMI at GDM screening, plasma insulin level at 1 h during the oral glucose tolerance test (OGTT), and plasma valine level. Circulating concentrations of lysine, tyrosine, and valine were independently and positively associated with GDM through modifying insulin resistance and secretion.

  19. Risk factors

    International Nuclear Information System (INIS)

    Dennery, M.; Dupont, M.A.

    2007-01-01

    This article deals with the development of risk management in the gas sector business: why a risk factor legal mention must precede any published financial information? Do gas companies have to face new risks? Is there specific risks bound to gas activities? Why companies want to master their risks? Is it mandatory or just a new habit? Do they expect a real benefit in return? These are the risk management questions that are analyzed in this article which is based on the public communication of 15 gas companies randomly selected over the world. The information comes from their annual reports or from documents available on their web sites. The intention of this document is not to be exhaustive or to make statistics but only to shade light on the risk factors of the gas sector. (J.S.)

  20. Insulin resistance, insulin response, and obesity as indicators of metabolic risk

    DEFF Research Database (Denmark)

    Ferrannini, Ele; Balkau, Beverley; Coppack, Simon W

    2007-01-01

    CONTEXT: Insulin resistance (IR) and obesity, especially abdominal obesity, are regarded as central pathophysiological features of a cluster of cardiovascular risk factors (CVRFs), but their relative roles remain undefined. Moreover, the differential impact of IR viz. insulin response has not been...... evaluated. OBJECTIVE: The objective of this study was to dissect out the impact of obesity, abdominal obesity, and IR/insulin response on CVRF. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at 21 research centers in Europe. SUBJECTS: The study included a cohort of 1308......-cholesterol, and lower high-density lipoprotein-cholesterol, and insulin response to higher heart rate, blood pressure and fasting glucose, and the same dyslipidemic profile as IR (P

  1. Bioavailable insulin-like growth factor-I as mediator of racial disparity in obesity-relevant breast and colorectal cancer risk among postmenopausal women.

    Science.gov (United States)

    Jung, Su Yon; Barrington, Wendy E; Lane, Dorothy S; Chen, Chu; Chlebowski, Rowan; Corbie-Smith, Giselle; Hou, Lifang; Zhang, Zuo-Feng; Paek, Min-So; Crandall, Carolyn J

    2017-03-01

    Bioavailable insulin-like growth factor-I (IGF-I) interacts with obesity and exogenous estrogen (E) in a racial disparity in obesity-related cancer risk, yet their interconnected pathways are not fully characterized. We investigated whether circulating bioavailable IGF-I acted as a mediator of the racial disparity in obesity-related cancers such as breast and colorectal (CR) cancers and how obesity and E use regulate this relationship. A total of 2,425 white and 164 African American (AA) postmenopausal women from the Women's Health Initiative Observational Study were followed from October 1, 1993 through August 29, 2014. To assess bioactive IGF-I as a mediator of race-cancer relationship, we used the Baron-Kenny method and quantitative estimation of the mediation effect. Compared with white women, AA women had higher IGF-I levels; their higher risk of CR cancer, after accounting for IGF-I, was no longer significant. IGF-I was associated with breast and CR cancers even after controlling for race. Among viscerally obese (waist/hip ratio >0.85) and overall nonobese women (body mass index obesity-related breast and CR cancer risk between postmenopausal AA and white women. Body fat distribution and E use may be part of the interconnected hormonal pathways related to racial difference in IGF-I levels and obesity-related cancer risk.

  2. An additional bolus of rapid-acting insulin to normalise postprandial cardiovascular risk factors following a high-carbohydrate high-fat meal in patients with type 1 diabetes: A randomised controlled trial.

    Science.gov (United States)

    Campbell, Matthew D; Walker, Mark; Ajjan, Ramzi A; Birch, Karen M; Gonzalez, Javier T; West, Daniel J

    2017-07-01

    To evaluate an additional rapid-acting insulin bolus on postprandial lipaemia, inflammation and pro-coagulation following high-carbohydrate high-fat feeding in people with type 1 diabetes. A total of 10 males with type 1 diabetes [HbA 1c 52.5 ± 5.9 mmol/mol (7.0% ± 0.5%)] underwent three conditions: (1) a low-fat (LF) meal with normal bolus insulin, (2), a high-fat (HF) meal with normal bolus insulin and (3) a high-fat meal with normal bolus insulin with an additional 30% insulin bolus administered 3-h post-meal (HFA). Meals had identical carbohydrate and protein content and bolus insulin dose determined by carbohydrate-counting. Blood was sampled periodically for 6-h post-meal and analysed for triglyceride, non-esterified-fatty acids, apolipoprotein B48, glucagon, tumour necrosis factor alpha, fibrinogen, human tissue factor activity and plasminogen activator inhibitor-1. Continuous glucose monitoring captured interstitial glucose responses. Triglyceride concentrations following LF remained similar to baseline, whereas triglyceride levels following HF were significantly greater throughout the 6-h observation period. The additional insulin bolus (HFA) normalised triglyceride similarly to low fat 3-6 h following the meal. HF was associated with late postprandial elevations in tumour necrosis factor alpha, whereas LF and HFA was not. Fibrinogen, plasminogen activator inhibitor-1 and tissue factor pathway levels were similar between conditions. Additional bolus insulin 3 h following a high-carbohydrate high-fat meal prevents late rises in postprandial triglycerides and tumour necrosis factor alpha, thus improving cardiovascular risk profile.

  3. Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study.

    NARCIS (Netherlands)

    Canzian, F; McKay, J D; Cleveland, R J; Dossus, Laure; Biessy, Carine; Rinaldi, Sabina; Landi, S; Boillot, C; Monnier, S; Chajès, V; Clavel-Chapelon, Françoise; Téhard, B; Chang-Claude, J; Linseisen, Jakob; Lahmann, Petra H; Pischon, Tobias; Trichopoulos, Dimitrios; Trichopoulou, Antonia; Zilis, D; Palli, Domenico; Tumino, Rosario; Vineis, Paolo; Berrino, Franco; Bueno-de-Mesquita, H Bas; Gils, C H van; Peeters, Petra H M; Pera, Guillem; Ardanaz, Eva; Chirlaque, María-Dolores; Quirós, José Ramón; Larrañaga, Nerea; Martínez-García, Carmen; Allen, Naomi E; Key, Timothy J; Bingham, Sheila A; Khaw, Kay-Tee; Slimani, N; Norat, Teresa; Riboli, Elio; Kaaks, Rudolf

    2006-01-01

    Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of

  4. Low serum insulin-like growth factor-I (IGF-I) level is associated with increased risk of vascular dementia.

    Science.gov (United States)

    Quinlan, Patrick; Horvath, Alexandra; Nordlund, Arto; Wallin, Anders; Svensson, Johan

    2017-12-01

    Insulin-like growth factor-I (IGF-I) is important for the adult brain, but little is known of the role of IGF-I in Alzheimeŕs disease (AD) or vascular dementia (VaD). A prospective study of 342 patients with subjective or objective mild cognitive impairment recruited at a single memory clinic. We determined whether serum IGF-I concentrations at baseline were associated with the risk of all-cause dementia, AD, or VaD. Patients developing mixed forms of AD and VaD were defined as suffering from VaD. The statistical analyses included Cox proportional hazards regression analysis. During the follow-up (mean 3.6 years), 95 (28%) of the patients developed all-cause dementia [AD, n=37 (11%) and VaD, n=42 (12%)]. Low as well as high serum IGF-I (quartile 1 or 4 vs. quartiles 2-3) did not associate with all-cause dementia [crude hazard ratio (HR) 1.30, 95% confidence interval (CI): 0.81-2.08 and crude HR 1.05, 95% CI: 0.63-1.75, respectively] or AD (crude HR 0.79, 95% CI: 0.35-1.79 and crude HR 0.94, 95% CI: 0.43-2.06, respectively]. In contrast, low serum IGF-I concentrations were associated with increased risk of VaD (quartile 1 vs. quartiles 2-3, crude HR 2.22, 95% CI: 1.13-4.36). The latter association remained significant also after adjustment for multiple covariates. In a memory clinic population, low serum IGF-I was a risk marker for subsequent VaD whereas low IGF-I did not associate with the risk of AD. High serum IGF-I was not related to the risk of conversion to dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Serum Insulin, Glucose, Indices of Insulin Resistance, and Risk of Lung Cancer.

    Science.gov (United States)

    Argirion, Ilona; Weinstein, Stephanie J; Männistö, Satu; Albanes, Demetrius; Mondul, Alison M

    2017-10-01

    Background: Although insulin may increase the risk of some cancers, few studies have examined fasting serum insulin and lung cancer risk. Methods: We examined serum insulin, glucose, and indices of insulin resistance [insulin:glucose molar ratio and homeostasis model assessment of insulin resistance (HOMA-IR)] and lung cancer risk using a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. A total of 196 cases and 395 subcohort members were included. Insulin and glucose were measured in fasting serum collected 5 to 12 years before diagnosis. Cox proportional hazards models were utilized to estimate the relative risk of lung cancer. Results: The average time between blood collection and lung cancer was 9.6 years. Fasting serum insulin levels were 8.7% higher in subcohort members than cases. After multivariable adjustment, men in the fourth quartile of insulin had a significantly higher risk of lung cancer than those in the first quartile [HR = 2.10; 95% confidence interval (CI), 1.12-3.94]. A similar relationship was seen with HOMA-IR (HR = 1.83; 95% CI, 0.99-3.38). Risk was not strongly associated with glucose or the insulin:glucose molar ratio ( P trend = 0.55 and P trend = 0.27, respectively). Conclusions: Higher fasting serum insulin concentrations, as well as the presence of insulin resistance, appear to be associated with an elevated risk of lung cancer development. Impact: Although insulin is hypothesized to increase risk of some cancers, insulin and lung cancer remain understudied. Higher insulin levels and insulin resistance were associated with increased lung cancer risk. Although smoking cessation is the best method of lung cancer prevention, other lifestyle changes that affect insulin concentrations and sensitivity may reduce lung cancer risk. Cancer Epidemiol Biomarkers Prev; 26(10); 1519-24. ©2017 AACR . ©2017 American Association for Cancer Research.

  6. Insulin Resistance and Risk of Cardiovascular Disease in Postmenopausal Women

    DEFF Research Database (Denmark)

    Schmiegelow, Michelle D; Hedlin, Haley; Stefanick, Marcia L

    2015-01-01

    BACKGROUND: Insulin resistance is associated with diabetes mellitus, but it is uncertain whether it improves cardiovascular disease (CVD) risk prediction beyond traditional cardiovascular risk factors. METHODS AND RESULTS: We identified 15,288 women from the Women's Health Initiative Biomarkers....../HDL-C, or impaired fasting glucose (serum glucose ≥110 mg/dL) to traditional risk factors in separate Cox multivariable analyses and assessed risk discrimination and reclassification. The study end point was major CVD events (nonfatal and fatal coronary heart disease and ischemic stroke) within 10 years, which...

  7. Factors influencing insulin secretion from encapsulated islets

    NARCIS (Netherlands)

    de Haan, BJ; Faas, MM; de Vos, P

    2003-01-01

    Adequate regulation of glucose levels by a microencapsulated pancreatic islet graft requires a minute-to-minute regulation of blood glucose. To design such a transplant, it is mandatory to have sufficient insight in factors influencing the kinetics of insulin secretion by encapsulated islets. The

  8. 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.

  9. Reduction in cardiovascular risk factors and insulin dose, but no beta-cell regeneration 1 year after Roux-en-Y gastric bypass in an obese patient with type 1 diabetes

    DEFF Research Database (Denmark)

    Dirksen, Carsten; Jacobsen, Siv H; Bojsen-Møller, Kirstine N

    2013-01-01

    Experience with Roux-en-Y gastric bypass in patients with type 1 diabetes is very limited, despite an increasing prevalence of obesity also in this population. We describe changes in anthropometric measures, insulin dose, HbA1c, blood pressure, lipid status, and metabolic response to a liquid mixed...... meal throughout the first year after RYGB in an obese patient with type 1 diabetes. No change in HbA1c was observed, but a 48% reduction in weight-adjusted insulin dose and improvements in cardiovascular risk factors was seen 1 year after surgery. Exaggerated secretions of anorexigenic gut hormones...

  10. Psycholosocial factors associated with psychological insulin resistance in primary care patients in Hong Kong

    Directory of Open Access Journals (Sweden)

    Kam Pui Lee

    2015-12-01

    Results: There was no relationship between the presence of depression and PIR. Furthermore, the prevalence of PIR was 47.2% in insulin-naive patients but only 8.7% in current insulin users. Tools such as the C-ITAS may help clinicians understand the etiology of PIR, which this study suggests is likely the result of multiple risk factors. Factors associated with a lower prevalence of PIR included current insulin use, a family history of insulin use, a high education level, male sex, and having received counseling from a physician about insulin within the previous 6 months.

  11. Effect of -55CT Polymorphism of UCP3 on Insulin Resistance and Cardiovascular Risk Factors after a High Protein/Low Carbohydrate versus a Standard Hypocaloric Diet.

    Science.gov (United States)

    de Luis, Daniel Antonio; Aller, Rocío; Izaola, Olatz; Romero, Enrique

    2016-01-01

    The C/C genotype of a polymorphism in the uncoupling protein3 (UCP3) promoter (-55C->T) (rs1800849) is associated with an increased body mass index. The aim of our study was to investigate the effect of polymorphism on the UCP3 promoter (-55C->T) on insulin resistance and cardiovascular risk factors secondary to a high protein/low carbohydrate vs. a standard hypocaloric diets (1,000 kcal/day). A population of 283 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 9-month period in which subjects received 1 of 2 diets (diet HP: high protein/low carbohydrate vs. diet S: standard diet). Weight improvement was higher in non-T carriers. With both diets and only in wild genotype (diet HP vs. diet S), total cholesterol (-9.7 ± 4.0 vs. -11.1 ± 2.0 mg/dl; p > 0.05) and low density lipoprotein (LDL) cholesterol (-8.3 ± 3.0 vs. -5.5 ± 2.7 mg/dl; p > 0.05) decreased. The improvement in these parameters was similar in subjects with diet HP than HS. With diet HP and only in wild genotype, glucose (-5.2 ± 2.2 mg/dl; p diet showed a better metabolic response than S diet in 55CC homozygous. © 2016 S. Karger AG, Basel.

  12. Serum insulin-like growth factor 1(IGF-I) and prostatic cancer risk a retrospective study

    International Nuclear Information System (INIS)

    Li Liren; Liu Jiumin; Lu Bailing

    2001-01-01

    Objective: To investigate the relationship between serum IGF-I levels and prostatic cancer. Methods: Serum IGF-I levels were determined by immunoradiometric assay (IRMA) in 30 cases of prostatic cancer, 30 cases of benign prostatic hyperplasia (BPH) and 30 healthy subjects as controls. Results: The mean levels of serum IGF-I in prostatic cancer (148 +- 49.6 μg/L) were significantly higher than those in BPH (91.0 +- 32.8 μg/L) and healthy subjects (105 +- 25.6 μg/L) (P 0.05). The IGF-I levels were not relates to BHP, but increased values of IGF-I were associated with increased risk of prostatic cancer. The odds ratio was 11.23 for patients of prostatic cancer compared with healthy subjects, (95 percent confidence interval 3.09 - 40.7). Conclusion: This finding suggests that high IGF-I may be associated with increase risk of prostate cancer in human

  13. An Audit of Clinical Practice in a Single Centre in Kuwait: Management of Children on Continuous Subcutaneous Insulin Infusion and Cardiovascular Risk Factors Screening.

    Science.gov (United States)

    Omar, Dina; Alsanae, Hala; Al Khawari, Mona; Abdulrasoul, Majedah; Rahme, Zahraa; Al Refaei, Faisal; Behbehani, Kazem; Shaltout, Azza

    2017-01-01

    To audit the current clinical practice of continuous subcutaneous insulin infusion (CSII) for the treatment of type 1 diabetes mellitus (T1D) in children and adolescents attending a single centre in Kuwait. A one year retrospective audit was performed in children and adolescents with T1D on CSII, who attended the paediatric diabetes clinic, Dasman Diabetes Institute during 2012. The primary outcome measure was glycaemic control as evidenced by glycated haemoglobin (HbA1c) level and the secondary outcome measures were the frequency of monitoring of the risk for microvascular complications and occurrence of acute complications and adverse events. 58 children and adolescents (mean age ± SD: 12.6 ± 4.1 years) were included. Mean HbA1c at baseline was 8.8% (72.7 mmol/mol) and 8.9% (73.8 mmol/mol) at the end of a 12 months observation period. Children with poor control (HbA1c >9.5% (80 mmol/mol) had a significant 1.4% reduction in HbA1c compared with the overall reduction of 0.1% (p=0.7). Rate of screening for cardiovascular risk factors and for long term complications were well documented. However, there was underreporting of acute complications such as severe hypoglycaemia and diabetic ketoacidosis. Only 1.7% of patients discontinued the pump. There was no significant change in HbA1c values at the end of 12 months follow up. However, HbA1c values in poorly controlled children improved. CSII requires care by skilled health professionals as well as education and selection of motivated parents and children.

  14. Expression of estrogen receptors in non-malignant mammary tissue modifies the association between insulin-like growth factor 1 and breast cancer risk.

    Science.gov (United States)

    Samoli, E; Lagiou, A; Zourna, P; Barbouni, A; Georgila, C; Tsikkinis, A; Vassilarou, D; Minaki, P; Sfikas, C; Spanos, E; Trichopoulos, D; Lagiou, P

    2015-04-01

    Several studies have reported that the insulin-like growth factor 1 (IGF-1) is positively associated with estrogen receptor-positive [ER(+)] breast cancer risk, whereas there is little or no association with respect to ER(-) breast cancer. All comparisons of ER(+) breast cancer cases, however, have been made versus healthy controls, for whom there is no information about the ER expression in their mammary gland. In the context of a case-control investigation conducted in Athens, Greece, we studied 102 women with incident ERα(+) breast cancer and compared their IGF-1 blood levels with those of 178 ERα(+) and 83 ERα(-) women with benign breast disease (BBD) who underwent biopsies in the context of their standard medical care. Data were analysed using multiple logistic regression and controlling for potential confounding variables. ERα(+) breast cancer patients had higher IGF-1 levels compared with women with BBD [odds ratio (OR) 1.36, 95% confidence interval (CI): 0.95-1.94, per 1 standard deviation (SD) increase in IGF-1 levels]. When ERα status of women with BBD was taken into account, the difference in IGF-1 levels between ERα(+) breast cancer patients and women with BBD was clearly driven by the comparison with BBD women who were ERα(+) (OR = 1.95, 95% CI: 1.31-2.89 per 1 SD increase in IGF-1 levels), whereas there was essentially no association with IGF-1 levels when ERα(+) breast cancer patients were compared with ERα(-) BBD women. These contrasts were particularly evident among post/peri-menopausal women. We found evidence in support of an interaction of IGF-1 with the expression of ERα in the non-malignant mammary tissue in the context of breast cancer pathogenesis. This is in line with previous evidence suggesting that IGF-1 increases the risk of ER(+) breast cancer. Published by Oxford University Press on behalf of the European Society for Medical Oncology 2014.

  15. Insulin resistance and risk of venous thromboembolism : results of a population-based cohort study

    NARCIS (Netherlands)

    Van Schouwenburg, I. M.; Mahmoodi, B. K.; Veeger, N. J. G. M.; Bakker, S. J. L.; Kluin-Nelemans, H. C.; Meijer, K.; Gansevoort, R. T.

    Background: Obesity is an established risk factor for venous thromboembolism (VTE), but it is uncertain how this is mediated. Insulin resistance has a central role in the pathophysiology of the metabolic effects of obesity. Objective: We aimed to investigate whether insulin resistance is a risk

  16. Risk factors for breast cancer and expression of insulin-like growth factor-2 (IGF-2 in women with breast cancer in Wuhan City, China.

    Directory of Open Access Journals (Sweden)

    Jun Qiu

    Full Text Available PURPOSE: The purpose of this study was to explore the risk factors for breast cancer and establish the expression rate of IGF-2 in female patients. METHODS: A case control study with 500 people in case group and 500 people in control group. A self-administered questionnaire was used to investigate risk factors for breast cancer. All cases were interviewed during a household survey. Immune-histochemical method was used to inspect the expression of IGF-2 in different tissues (benign breast lesions, breast cancer and tumor-adjacent tissue. RESULTS: Multivariate adjusted odds ratios and 95% confidence intervals were calculated using unconditional logistic regression. High body mass index (OR = 1.012,95%CI = 1.008-1.016, working attributes (OR = 1.004, 95%CI = 1.002 = 1.006, long menstrual period (OR = 1.007, 95%CI = 1.005-1.009, high parity OR = 1.003, 95%CI = 1.001-1.005 , frequent artificial abortion (OR = 1.004, 95%CI = 1.001-1.005, family history of cancer (OR = 1.003, 95%CI = 1.000-1.005, period of night shift (OR = 1.003, 95%CI = 1.001-1.006, live in high risk environment (OR = 1.005, 95%CI = 1.002-1.008, and family problems (OR = 1.010, 95%CI = 1.005-1.014 were associated with increased risk for breast cancer. In this study, good sleeping status, positive coping strategies, subjective support, and utility degree of social support were associated with reduced risk for breast cancer (OR = 0.998, 0.997, 0.985, 0.998 respectively; 95%CI = 0.996-1.000, 0.994-1.000, 0.980-0.989, 0.996-1.000, respectively. In benign breast lesions, breast cancer and tumor-adjacent tissue, IGF-2 was mainly expressed in the cytoplasm, but its expression rate was different (p<0.05. CONCLUSIONS: The incidence of breast cancer is a common result of multiple factors. IGF-2 is involved in the development of breast cancer, and its expression varies in different tissues (benign breast lesions

  17. Insulin-like growth factor I and risk of breast cancer by age and hormone receptor status-A prospective study within the EPIC cohort.

    Science.gov (United States)

    Kaaks, Rudolf; Johnson, Theron; Tikk, Kaja; Sookthai, Disorn; Tjønneland, Anne; Roswall, Nina; Overvad, Kim; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Dossus, Laure; Rinaldi, Sabina; Romieu, Isabelle; Boeing, Heiner; Schütze, Madlen; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Grioni, Sara; Tumino, Rosario; Sacerdote, Carlotta; Panico, Salvatore; Buckland, Genevieve; Argüelles, Marcial; Sánchez, María-José; Amiano, Pilar; Chirlaque, Maria-Dolores; Ardanaz, Eva; Bueno-de-Mesquita, H Bas; van Gils, Carla H; Peeters, Petra H; Andersson, Anne; Sund, Malin; Weiderpass, Elisabete; Gram, Inger Torhild; Lund, Eiliv; Khaw, Kay-Tee; Wareham, Nick; Key, Timothy J; Travis, Ruth C; Merritt, Melissa A; Gunter, Marc J; Riboli, Elio; Lukanova, Annekatrin

    2014-06-01

    Experimental evidence shows cross-talk in mammary cells between estrogen, insulin-like growth factor I (IGF-I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF-I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF-I levels may be related more to the risk of ER-positive than ER-negative breast cancer. Using a case-control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF-I levels with the risk of estrogen and progesterone receptor-positive and -negative breast tumors. IGF-I levels were positively associated with the risk of ER+ breast tumors overall (pre- and postmenopausal women combined, odds ratio (OR)Q4-Q1 = 1.41 [95% confidence interval (CI) 1.01-1.98] for the highest vs. lowest quartile; OR = 1.17 [95% CI 1.04-1.33] per 1-standard deviation (SD) increase in IGF-I, ptrend = 0.01) and among women who were diagnosed with breast cancer at 50 years or older (ORQ3-Q1 = 1.38 [95% CI 1.01-1.89]; OR = 1.19 [95% CI 1.04-1.36] per 1-SD increase in IGF-I, ptrend = 0.01) but not with receptor-positive disease diagnosed at an earlier age. No statistically significant associations were observed for ER- breast tumors overall and by age at diagnosis. Tests for heterogeneity by receptor status of the tumor were not statistically significant, except for women diagnosed with breast cancer at 50 years or older (phet = 0.03 for ER+/PR+ vs. ER-/PR- disease). Our data add to a global body of evidence indicating that higher circulating IGF-I levels may increase risk specifically of receptor-positive, but not receptor-negative, breast cancer diagnosed at 50 years or older. © 2013 UICC.

  18. 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.

  19. Insulin-like growth factor 1, liver enzymes, and insulin resistance in patients with PCOS and hirsutism

    OpenAIRE

    ÇAKIR, Evrim; TOPALOĞLU, Oya; BOZKURT, Nujen ÇOLAK; BAYRAKTAR, Başak KARBEK

    2015-01-01

    Hyperinsulinemia and insulin resistance are commonly seen in patients with hirsutism and polycystic ovary syndrome (PCOS), and are associated with cardiovascular disease risk. However, it is not yet known whether insulin-like growth factor I (IGF-I) and alanine transaminase (ALT) produced by the liver play roles in hyperinsulinemia and subclinical atherosclerotic process in patients with PCOS and idiopathic hirsutism (IH). Materials and methods: This was a prospective case-controlled study....

  20. Heart disease - risk factors

    Science.gov (United States)

    Heart disease - prevention; CVD - risk factors; Cardiovascular disease - risk factors; Coronary artery disease - risk factors; CAD - risk ... a certain health condition. Some risk factors for heart disease you cannot change, but some you can. ...

  1. Cardiovascular Risk Factors and Insulin Resistance after Two Hypocaloric Diets with Different Fat Distribution in Obese Subjects: Effect of the rs10767664 Gene Variant in Brain-Derived Neurotrophic Factor.

    Science.gov (United States)

    de Luis, Daniel Antonio; Romero, Enrique; Izaola, Olatz; Primo, David; Aller, Rocío

    2017-01-01

    The role of brain-derived neurotrophic factor (BDNF) variants on change in body weight and cardiovascular risk factors after weight loss remains unclear in obese patients. Our aim was to analyze the effects of the rs10767664 BDNF gene polymorphism on body weight, cardiovascular risk factors, and serum adipokine levels after a high monounsaturated fatty acids (MUFAs) hypocaloric diet (diet M) versus a high polyunsaturated fatty acids (PUFAs) hypocaloric diet (diet P). A Caucasian population of 361 obese patients was enrolled. Subjects who met the inclusion criteria were randomly allocated to one of two diets for a period of 3 months. Two hundred and sixteen subjects (59.8%) had the genotype AA (wild-type group), and 145 (40.2%) patients had the genotypes AT (122 patients, 33.8%) or TT (23 patients, 6.4%) (mutant-type group). After weight loss with diet P and diet M and in both genotype groups, body mass index, weight, fat mass, waist circumference, systolic blood pressure, serum leptin levels, low-density lipoprotein cholesterol, and total cholesterol decreased in a significant way. Secondary to weight loss with diet M and only in the wild-type group, insulin levels (-2.1 ± 2.0 vs. -0.7 ± 2.9 IU/L, p hypocaloric diet enriched with MUFAs. © 2018 S. Karger AG, Basel.

  2. 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.

    Science.gov (United States)

    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.

  3. Risk factors.

    Science.gov (United States)

    Robbins, Catherine J; Connors, K C; Sheehan, Timothy J; Vaughan, James S

    2005-06-01

    Minimize surprises on your financial statement by adopting a model for integrated risk management that: Examines interrelationships among operations, investments, and financing. Incorporates concepts of the capital asset pricing model to manage unexpected volatility

  4. Related Factors of Insulin Resistance in Korean Children: Adiposity and Maternal Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Kang-Sook Lee

    2011-12-01

    Full Text Available Increased adiposity and unhealthy lifestyle augment the risk for type 2 diabetes in children with familial predisposition. Insulin resistance (IR is an excellent clinical marker for identifying children at high risk for type 2 diabetes. This study was conducted to investigate parental, physiological, behavioral and socio-economic factors related to IR in Korean children. This study is a cross-sectional study using data from 111 children aged 7 years and their parents. Homeostasis model assessment of insulin resistance (HOMA-IR was calculated using fasting glucose and insulin level as a marker of IR. All children’s adiposity indices (r = 0.309–0.318, all P-value = 0.001 and maternal levels of fasting insulin (r = 0.285, P-value = 0.003 and HOMA-IR (r = 0.290, P-value = 0.002 were positively correlated with children’s HOMA-IR level. There was no statistical difference of children’s HOMA-IR level according to children’s lifestyle habits and socioeconomic status of families. An increase of 1 percentage point in body fat was related to 2.7% increase in children’s HOMA-IR (P-value < 0.001 and an increase of 1% of maternal level of HOMA-IR was related to 0.2% increase in children’s HOMA-IR (P-value = 0.002. This study shows that children’s adiposity and maternal IR are positively associated with children’s IR.

  5. Fasting insulin, insulin resistance and risk of hypertension in the general population: A meta-analysis.

    Science.gov (United States)

    Wang, Feng; Han, Lili; Hu, Dayi

    2017-01-01

    Studies on the association of fasting insulin concentrations or insulin resistance with subsequent risk of hypertension have yielded conflicting results. To quantitatively assess the association of fasting insulin concentrations or homeostasis model assessment insulin resistance (HOMA-IR) with incident hypertension in a general population by performing a meta-analysis. We searched the PubMed and Embase databases until August 31, 2016 for prospective observational studies investigating the elevated fasting insulin concentrations or HOMA-IR with subsequent risk of hypertension in the general population. Pooled risk ratio (RR) and 95% confidence interval (CI) of hypertension was calculated for the highest versus the lowest category of fasting insulin or HOMA-IR. Eleven studies involving 10,230 hypertension cases were identified from 55,059 participants. Meta-analysis showed that the pooled adjusted RR of hypertension was 1.54 (95% CI 1.34-1.76) for fasting insulin concentrations and 1.43 (95% CI 1.27-1.62) for HOMA-IR comparing the highest to the lowest category. Subgroup analysis results showed that the association of fasting insulin concentrations with subsequent risk of hypertension seemed more pronounced in women (RR 2.07; 95% CI 1.19-3.60) than in men (RR 1.48; 95% CI 1.17-1.88). This meta-analysis suggests that elevated fasting insulin concentrations or insulin resistance as estimated by homeostasis model assessment is independently associated with an exacerbated risk of hypertension in the general population. Early intervention of hyperinsulinemia or insulin resistance may help clinicians to identify the high risk of hypertensive population. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. [Factors associated with insulin resistence in rural populations].

    Science.gov (United States)

    Mendes, Larissa Loures; Gazzinelli, Andréa; Velásquez-Meléndez, Gustavo

    2009-04-01

    This study explores the relations of anthropometric, body composition assessments, biochemical and hemodynamic parameters with insulin resistance in two rural communities. Sample was composed by adults aged 18 or older, both sexes. Participants were excluded if pregnant and diabetic. Data collection included demographic lifestyle, hemodynamic, anthropometric and biochemical variables. From the 567 subjects, 50.4% were men and 49.6%, women. Most of the sample was non-white (75.7%), lived with partner (69.3%) and had low educational level. Overweight and obesity prevalences were 17.4% and 5.5%, respectively. Multivariate analysis found risk factors associated to insulin resistance for non-diabetic adults with low income and educational level: overweight, obesity, elevated waist-to-hip ratio, C-reactive protein and skin color.

  7. Premenopausal Levels of Circulating Insulin-Like Growth Factor I and the Risk of Post-Menopausal Breast Cancer: A Population-Based, Nested Case-Control Study

    National Research Council Canada - National Science Library

    Newschaffer, Craig

    2002-01-01

    High levels of circulating IGF-l may be a risk factor for breast cancer. Only one population-based epidemiologic study of IGF-l and breast cancer measured circulating IGF-l in serum drawn prior to diagnosis...

  8. Changing the insulin receptor to possess insulin-like growth factor I ligand specificity

    International Nuclear Information System (INIS)

    Andersen, A.S.; Kjeldsen, T.; Wiberg, F.C.; Christensen, P.M.; Rasmussen, J.S.; Norris, K.; Moeller, K.B.; Moeller, N.P.H.

    1990-01-01

    To examine the role of the N-terminal part of the insulin-like growth factor I (IGF-I) receptor and insulin receptor in determining ligand specificity, the authors prepared an expression vector encoding a hybrid receptor where exon 1 (encoding the signal peptide and seven amino acids of the α-subunit), exon 2, and exon 3 of the insulin receptor were replaced with the corresponding IGF-I receptor cDNA (938 nucleotides). To allow direct quantitative comparison of the binding capabilities of this hybrid receptor with those of the human IGF-I receptor and the insulin receptor, all three receptors were expressed in baby hamster kidney (BHK) cells as soluble molecules and partially purified before characterization. The hybrid IGF-I/insulin receptor bound IGF-I with an affinity comparable to that of the wild-type IGF-I receptor. In contrast, the hybrid receptor no longer displayed high-affinity binding of insulin. These results directly demonstrate that it is possible to change the specificity of the insulin receptor to that of the IGF-I receptor and, furthermore, that the binding specificity for IGF-I is encoded within the nucleotide sequence from 135 to 938 of the IGF-I receptor cDNA. Since the hybrid receptor only bound insulin with low affinity, the insulin binding region is likely to be located within exons 2 and 3 of the insulin receptor

  9. Prognostic value of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 blood levels in breast cancer.

    NARCIS (Netherlands)

    Hartog, H.; Boezen, H.M.; Jong, M.M. de; Schaapveld, M.; Wesseling, J.; Graaf, W.T.A. van der

    2013-01-01

    High circulating insulin-like growth factor 1 (IGF-1) levels are firmly established as a risk factor for developing breast cancer, especially estrogen positive tumors. The effect of circulating IGF-1 on prognosis once a tumor is established is unknown. The authors explored the effect of IGF-1 blood

  10. Prognostic value of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 blood levels in breast cancer

    NARCIS (Netherlands)

    Hartog, H; Boezen, H M; de Jong, M M; Schaapveld, M; Wesseling, J; van der Graaf, W T A

    2013-01-01

    High circulating insulin-like growth factor 1 (IGF-1) levels are firmly established as a risk factor for developing breast cancer, especially estrogen positive tumors. The effect of circulating IGF-1 on prognosis once a tumor is established is unknown. The authors explored the effect of IGF-1 blood

  11. Insulin-like growth factor system in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Wilczak, N; de Keyser, J; Cianfarani, S; Clemmons, DR; Savage, MO

    2005-01-01

    Insulin-like growth factor-I (IGF-I) is a neurotrophic factor with insulin-like metabolic activities, and possesses potential clinical applications, particularly in neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS) is a chronic progressive devastating disorder of the central nervous

  12. The Insulin-like Growth Factor System in Cancer Prevention: Potential of Dietary intervention Strategies

    NARCIS (Netherlands)

    Voskuil, D.W.; Vrieling, A.; Veer, van 't L.J.; Kampman, E.; Rookus, M.A.

    2005-01-01

    The insulin-like growth factor (IGF) system is related to proliferation and tumor growth, and high levels of circulating IGF-I are thought to be a risk factor for several types of cancer. This review summarizes the epidemiologic evidence for an association between circulating IGF-I and cancer risk

  13. The insulin-like growth factor system in cancer prevention: potential of dietary intervention strategies.

    NARCIS (Netherlands)

    Voskuil, D.W.; Vrieling, A.; Veer, L.J. van 't; Kampman, E.; Rookus, M.A.

    2005-01-01

    The insulin-like growth factor (IGF) system is related to proliferation and tumor growth, and high levels of circulating IGF-I are thought to be a risk factor for several types of cancer. This review summarizes the epidemiologic evidence for an association between circulating IGF-I and cancer risk

  14. Potensi Terapeutik Fibroblast Growth Factor 21 terhadap Resistensi Insulin

    Directory of Open Access Journals (Sweden)

    Kurniasari Kurniasari

    2015-12-01

    Full Text Available Fibroblast growth factor 21 (FGF21 merupakan salah satu dari anggota FGF yang berperansebagai faktor endokrin. Hepar dan jaringan adiposa merupakan tempat kerja utama FGF21.Ekspresi FGF21 di hepar diatur oleh peroxisome proliferator activated receptor alpha (PPARαsedangkan di jaringan adiposa diatur oleh peroxisome proliferator activated receptor gamma(PPARγ. Kedua faktor transkripsi tersebut terlibat dalam metabolisme karbohidrat dan lipid. Padaresistensi insulin terdapat hiperglikemia, hiperinsulinemia, dan dislipidemia. Pemberian FGF21pada berbagai studi in vivo dan in vitro telah menunjukan potensi FGF21 dalam mengatasi kelainanakibat resistensi insulin sekaligus meningkatkan sensitivitas jaringan terhadap insulin. Kata kunci: FGF21, PPARγ, PPARα, resistensi insulin Fibroblast Growth Factor 21 (FGF21 Potension in InsulinResistance Treatment Abstract Fibroblast growth factor 21 (FGF21 is a member of FGF family that plays a role as endocrinefactor. Liver and adipose tissue are major target of FGF21. The expression of FGF21 in liveris regulated by peroxisome proliferator activated receptor alpha (PPARα, while peroxisomeproliferator activated receptor gamma (PPARγ regulate FGF21 expression in adipose tissue.Both transcription factors are involved in carbohydrate and lipid metabolism. Hyperglycemia,hyperinsulinemia, and dyslipidemia are observed in insulin resistance. Treatment with FGF21 inin vitro and in vivo study showed that FGF21 have the potential to overcome insulin resistance aswell as increasing tissue’s sensitivity towards insulin. Keywords: FGF21, PPARγ, PPARα, insulin resistance Normal 0 false false false IN X-NONE X-NONE

  15. C-reactive protein, insulin resistance and risk of cardiovascular disease: a population-based study

    DEFF Research Database (Denmark)

    Hansen, T.W.; Olsen, M.H.; Rasmussen, S.

    2008-01-01

    BACKGROUND: C-reactive protein (CRP), a marker of inflammation, and insulin resistance (IR), a metabolic disorder, are closely related. CRP and IR have both been identified as significant risk factors of cardiovascular disease (CVD) after adjustment for conventional CVD risk factors...

  16. FACTORS AFFECTING THE DEPOSITION OF AEROSOLIZED INSULIN

    Science.gov (United States)

    AbstractBackground The inhalation of insulin for absorption into the bloodstream via the lung seems to be a promising technique for the treatment of diabetes mellitus. A fundamental issue to be resolved in the development of such insulin aerosol delivery systems is their...

  17. Patient safety and minimizing risk with insulin administration - role of insulin degludec.

    Science.gov (United States)

    Aye, Myint M; Atkin, Stephen L

    2014-01-01

    Diabetes is a lifelong condition requiring ongoing medical care and patient self-management. Exogenous insulin therapy is essential in type 1 diabetes and becomes a necessity in patients with longstanding type 2 diabetes who fail to achieve optimal control with lifestyle modification, oral agents, and glucagon-like peptide 1-based therapy. One of the risks that hinders insulin use is hypoglycemia. Optimal insulin therapy should therefore minimize the risk of hypoglycemia while improving glycemic control. Insulin degludec (IDeg) is a novel basal insulin that, following subcutaneous injection, assembles into a depot of soluble multihexamer chains. These subsequently release IDeg monomers that are absorbed at a slow and steady rate into the circulation, with the terminal half-life of IDeg being ~25 hours. Thus, it requires only once-daily dosing unlike other basal insulin preparations that often require twice-daily dosing. Despite its long half-life, once-daily IDeg does not cause accumulation of insulin in the circulation after reaching steady state. IDeg once a day will produce a steady-state profile with a lower peak:trough ratio than other basal insulins. In clinical trials, this profile translates into a lower frequency of nocturnal hypoglycemia compared with insulin glargine, as well as an ability to allow some flexibility in dose timing without compromising efficacy and safety. Indeed, a study that tested the extremes of dosing intervals of 8 and 40 hours showed no detriment in either glycemic control or hypoglycemic frequency versus insulin glargine given at the same time each day. While extreme flexibility in dose timing is not recommended, these findings are reassuring. This may be particularly beneficial to elderly patients, patients with learning difficulties, or others who have to rely on health-care professionals for their daily insulin injections. Further studies are required to confirm whether this might benefit adherence to treatment, reduce long

  18. Insulin-like growth factor 1, liver enzymes, and insulin resistance in patients with PCOS and hirsutism.

    Science.gov (United States)

    Çakir, Evrim; Topaloğlu, Oya; Çolak Bozkurt, Nujen; Karbek Bayraktar, Başak; Güngüneş, Aşkın; Sayki Arslan, Müyesser; Öztürk Ünsal, İlknur; Tutal, Esra; Uçan, Bekir; Delıbaşi, Tuncay

    2014-01-01

    Hyperinsulinemia and insulin resistance are commonly seen in patients with hirsutism and polycystic ovary syndrome (PCOS), and are associated with cardiovascular disease risk. However, it is not yet known whether insulin-like growth factor I (IGF-I) and alanine transaminase (ALT) produced by the liver play roles in hyperinsulinemia and subclinical atherosclerotic process in patients with PCOS and idiopathic hirsutism (IH). This was a prospective case-controlled study. The study population consisted of 25 reproductive-age PCOS women, 33 women with IH, and 25 control subjects. Mean IGF-I levels and median ALT levels were higher in patients with IH and PCOS than controls, but these differences were not statistically significant. The participants who had a homeostasis model assessment insulin resistance index (HOMA-IR) greater than 2.7 had significantly higher IGF-1 and ALT levels. ALT levels were positively correlated with body mass index, FG, insulin and HOMA-IR. The study illustrated that IGF-1 and ALT levels were significantly higher in patients with increased insulin resistance. Due to short disease duration in younger participants, we did not observe any correlation between IGF-1 and hyperinsulinemia. These findings suggest that increased hepatic production of IGF-I and ALT might be an early indicator of insulin resistance in hirsutism.

  19. Risk Factors for Scleroderma

    Science.gov (United States)

    ... You are here: Home For Patients Risk Factors Risk Factors for Scleroderma The cause of scleroderma is ... what biological factors contribute to scleroderma pathogenesis. Genetic Risk Scleroderma does not tend to run in families ...

  20. Risk Factors and Prevention

    Science.gov (United States)

    ... Resources Risk Factors & Prevention Back to Patient Resources Risk Factors & Prevention Even people who look healthy and ... Blood Pressure , high cholesterol, diabetes, and thyroid disease. Risk Factors For Arrhythmias and Heart Disease The following ...

  1. 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.

  2. Environmental factors and dam characteristics associated with insulin sensitivity and insulin secretion in newborn Holstein calves

    International Nuclear Information System (INIS)

    Kamal, M.M.; Van Eetvelde, M.; Bogaert, H.; Hostens, M.; Vandaele, L.; Shamsuddin, M.; Opsomer, G.

    2015-01-01

    The objective of the present retrospective cohort study was to evaluate potential associations between environmental factors and dam characteristics, including level of milk production during gestation, and insulin traits in newborn Holstein calves

  3. Early-stage chronic kidney disease, insulin resistance, and osteoporosis as risk factors of sarcopenia in aged population: the fourth Korea National Health and Nutrition Examination Survey (KNHANES IV), 2008-2009.

    Science.gov (United States)

    Kim, J E; Lee, Y-H; Huh, J H; Kang, D R; Rhee, Y; Lim, S-K

    2014-09-01

    Sarcopenia means the progressive loss of skeletal muscle mass and strength with aging. In this study, we found that insulin resistance, chronic kidney disease stage 3, and osteoporosis at the femur neck were closely associated with sarcopenia in elderly men. These conditions modified to slow down the progression of sarcopenia. Sarcopenia is known to have multiple contributing factors; however, its modifiable risk factors have not yet been determined. The aim of this study was to identify the most influential and modifiable risk factors for sarcopenia in elderly. This was a population-based, cross-sectional study using data from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV), 2008-2009. This study included 940 men and 1,324 women aged 65 years and older who completed a body composition analysis using dual-energy X-ray absorptiometry. Sarcopenia was defined as an appendicular skeletal muscle mass divided by height(2) of less than 1 standard deviation below the sex-specific mean for a younger reference group. Using univariate analysis, age, body mass index (BMI), homeostasis model assessment for insulin resistance (HOMA-IR), limitations in daily activities, regular exercise, high-risk drinking, family income, osteoporosis, daily energy, and protein intake were associated with sarcopenia in men; age, BMI, limitations in daily activities, regular exercise, occupation, osteoporosis at the total hip, and daily energy intake were associated with sarcopenia in women. In the multivariate logistic regression analysis, HOMA-IR ≥2.5 (odds ratio [OR] for sarcopenia, 2.27; 95 % confidence interval [CI], 1.21-4.25), chronic kidney disease stage 3 (OR, 3.13; 95 % CI, 1.14-8.61), and osteoporosis at the femur neck (OR, 6.83; 95 % CI, 1.08-43.41) were identified as risk factors for sarcopenia in men. Insulin resistance, chronic kidney disease, and osteoporosis at the femur neck should be modified to prevent the acceleration of skeletal muscle

  4. Insulin Sensitivity and Mortality Risk Estimation in Patients with Type ...

    African Journals Online (AJOL)

    2016-07-15

    Jul 15, 2016 ... density lipoprotein cholesterol (LDL), triglycerides (TG), high‑density lipoprotein cholesterol (HDL), urinary albumin‑to‑creatinine ratio ... the mortality risk scores in patients with T2DM and its relationship with insulin resistance.

  5. Insulin glargine and cancer risk in patients with diabetes: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xulei Tang

    Full Text Available AIM: The role of insulin glargine as a risk factor for cancer is controversial in human studies. The aim of this meta-analysis was to evaluate the relationship between insulin glargine and cancer incidence. METHODS: All observational studies and randomized controlled trials evaluating the relationship of insulin glargine and cancer risk were identified in PubMed, Embase, Web of Science, Cochrane Library and the Chinese Biomedical Medical Literature Database, through March 2012. Odds ratios (ORs with corresponding 95% confidence interval (CI were calculated with a random-effects model. Confidence in the estimates of the obtained effects (quality of evidence was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: A total of 11 studies including 448,928 study subjects and 19,128 cancer patients were finally identified for the meta-analysis. Insulin glargine use was associated with a lower odds of cancer compared with non-glargine insulin use (OR 0.81, 95% CI 0.68 to 0.98, P = 0.03; very low-quality evidence. Glargine did not increase the odds of breast cancer (OR 0.99, 95% CI 0.68 to 1.46, P = 0.966; very low-quality evidence. Compared with non-glargine insulin, no significant association was found between insulin glargine and prostate cancer, pancreatic cancer and respiratory tract cancer. Insulin glargine use was associated with lower odds of other site-specific cancer. CONCLUSIONS: Results from the meta-analysis don't support the link between insulin glargine and an increased risk of cancer and the confidence in the estimates of the effects is very low. Further studies are needed to examine the relation between insulin glargine and cancer risk, especially breast cancer.

  6. Insulin Resistance and Cancer Risk: An Overview of the Pathogenetic Mechanisms

    Directory of Open Access Journals (Sweden)

    Biagio Arcidiacono

    2012-01-01

    Full Text Available Insulin resistance is common in individuals with obesity or type 2 diabetes (T2D, in which circulating insulin levels are frequently increased. Recent epidemiological and clinical evidence points to a link between insulin resistance and cancer. The mechanisms for this association are unknown, but hyperinsulinaemia (a hallmark of insulin resistance and the increase in bioavailable insulin-like growth factor I (IGF-I appear to have a role in tumor initiation and progression in insulin-resistant patients. Insulin and IGF-I inhibit the hepatic synthesis of sex-hormone binding globulin (SHBG, whereas both hormones stimulate the ovarian synthesis of sex steroids, whose effects, in breast epithelium and endometrium, can promote cellular proliferation and inhibit apoptosis. Furthermore, an increased risk of cancer among insulin-resistant patients can be due to overproduction of reactive oxygen species (ROS that can damage DNA contributing to mutagenesis and carcinogenesis. On the other hand, it is possible that the abundance of inflammatory cells in adipose tissue of obese and diabetic patients may promote systemic inflammation which can result in a protumorigenic environment. Here, we summarize recent progress on insulin resistance and cancer, focusing on various implicated mechanisms that have been described recently, and discuss how these mechanisms may contribute to cancer initiation and progression.

  7. Higher glucose, insulin and insulin resistance (HOMA-IR) in childhood predict adverse cardiovascular risk in early adulthood: the Pune Children's Study.

    Science.gov (United States)

    Yajnik, Chittaranjan S; Katre, Prachi A; Joshi, Suyog M; Kumaran, Kalyanaraman; Bhat, Dattatray S; Lubree, Himangi G; Memane, Nilam; Kinare, Arun S; Pandit, Anand N; Bhave, Sheila A; Bavdekar, Ashish; Fall, Caroline H D

    2015-07-01

    The Pune Children's Study aimed to test whether glucose and insulin measurements in childhood predict cardiovascular risk factors in young adulthood. We followed up 357 participants (75% follow-up) at 21 years of age who had undergone detailed measurements at 8 years of age (glucose, insulin, HOMA-IR and other indices). Oral glucose tolerance, anthropometry, plasma lipids, BP, carotid intima-media thickness (IMT) and arterial pulse wave velocity (PWV) were measured at 21 years. Higher fasting glucose, insulin and HOMA-IR at 8 years predicted higher glucose, insulin, HOMA-IR, BP, lipids and IMT at 21 years. A 1 SD change in 8 year variables was associated with a 0.10-0.27 SD change at 21 years independently of obesity/adiposity at 8 years of age. A greater rise in glucose-insulin variables between 8 and 21 years was associated with higher cardiovascular risk factors, including PWV. Participants whose HOMA-IR measurement remained in the highest quartile (n = 31) had a more adverse cardiovascular risk profile compared with those whose HOMA-IR measurement remained in the lowest quartile (n = 28). Prepubertal glucose-insulin metabolism is associated with adult cardiovascular risk and markers of atherosclerosis. Our results support interventions to improve glucose-insulin metabolism in childhood to reduce cardiovascular risk in later life.

  8. Fasting insulin has a stronger association with an adverse cardiometabolic risk profile than insulin resistance: the RISC study

    DEFF Research Database (Denmark)

    de Rooij, Susanne R; Dekker, Jacqueline M; Kozakova, Michaela

    2009-01-01

    OBJECTIVE: Fasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis. DESIGN AND METHODS: The Relationship between Insulin...... of the metabolic syndrome in 1177 participants. Carotid artery intima media thickness (IMT) was measured by ultrasound to assess preclinical atherosclerosis. RESULTS: Fasting insulin was correlated with all elements of the metabolic syndrome. Insulin sensitivity (M/I) was correlated with most elements. The odds...... ratio for the metabolic syndrome of those in the highest quartile of fasting insulin compared with those in the lower quartiles was 5.4 (95% confidence interval (CI) 2.8-10.3, adjusted for insulin sensitivity) in men and 5.1 (2.6-9.9) in women. The odds ratio for metabolic syndrome of those with insulin...

  9. Insulin-like growth factors: assay methods and their implications

    International Nuclear Information System (INIS)

    Guyda, H.J.; Posner, B.I.; Schiffrin, A.; Rappaport, R.; Postel-Vinay, M.C.; Corvol, M.T.

    1981-01-01

    The insulin-like growth factors (IGF's) are small molecular weight peptides (6-10 x 10 3 daltons) that circulate in blood plasma almost entirely bound to macromolecular carrier proteins. The growth-promoting and insulin-like activities of IGF's can be explained by the observed ability of these peptides to interact with the IGF receptor on the one hand and with the insulin receptor on the other. These observations have led to the establishment of radioreceptor assays (RRA's), competitive protein binding assays (CPBA's), and more recently radioimmunoassays (RIA's) for the IGF's that have different specificities. Because of their ease of performance and sensitivity, the radioligand assays have largely supplanted the biological assays originally utilized to identify and characterize these anabolic peptides. In this report the authors' studies are summarised which utilize a slightly acidic IGF which has been purified on the basis of its insulin-like activity in an insulin RRA and which was termed ILAs. They refer to purified insulin-like peptides that have the properties of a somatomedin by the generic term insulin-like growth factor (IGF). Somatomedin (SM) activity will be utilized to connote that activity in plasma or serum determined by bioassay. The competitive dose-response curves for IGF peptides in the insulin RRA as well as those in the ILAs RRA are presented. A combination of bioassays, RRA and RIA were employed to assess somatomedin activity and IGF peptide levels in a number of clinical circumstances. The correlations are discussed. (Auth.)

  10. Insulin and insulin-like growth factor-1 increased in preterm neonates following massage therapy.

    Science.gov (United States)

    Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria; Dieter, John N I; Kumar, Adarsh M; Schanberg, Saul; Kuhn, Cynthia

    2008-12-01

    To determine if massage therapy increased serum insulin and insulin-like growth factor-1 (IGF-1) in preterm neonates. Forty-two preterm neonates who averaged 34.6 weeks (M = 29.5 wk gestational age; M birth weight = 1237 g) and were in the "grower" (step-down) nursery were randomly assigned to a massage therapy group (body stroking and passive limb movements for three, 15-minute periods per day for 5 days) or a control group that received the standard nursery care without massage therapy. On Days 1 and 5, the serum collected by clinical heelsticks was also assayed for insulin and IGF-1, and weight gain and kilocalories consumed were recorded daily. Despite similar formula intake, the massaged preterm neonates showed greater increases during the 5-day period in (1) weight gain; (2) serum levels of insulin; and (3) IGF-1. Increased weight gain was significantly correlated with insulin and IGF-1. Previous data suggested that preterm infant weight gain following massage therapy related to increased vagal activity, which suggests decreased stress and gastric motility, which may contribute to more efficient food absorption. The data from this study suggest for the first time that weight gain was also related to increased serum insulin and IGF-1 levels following massage therapy. Preterm infants who received massage therapy not only showed greater weight gain but also a greater increase in serum insulin and IGF-1 levels, suggesting that massage therapy might be prescribed for all growing neonates.

  11. Application of insulin-like growth factor-I and insulin release test in diabetes mellitus

    International Nuclear Information System (INIS)

    Chen Dong; Ma Yongxiu; Duan Wenruo

    2003-01-01

    The purpose of this study was to determine the role of insulin-like growth factor-I (IGF-I) and insulin release test (IRT) in understanding the extent of damage to ability of reducing blood sugar in different types of diabetes mellitus (DM) and in selection of treatment plan and adjustment of using drugs. OGTT, IRT and determination of IGF-I level of 67 normal subjects and 217 DM patients were performed. The result was analyzed comparatively. The level of IGF-I was negatively correlated with the level of fasting blood sugar, and positively correlated with the level of fasting insulin. Our conclusions are: There are two ways of reducing blood sugar: one is by insulin, and the other is by IGF-I. IRT can reflect the former better, and IGF-I the latter. The combination of these two is of significant value in diagnosis and treatment of DM

  12. Cardiac Development and Transcription Factors: Insulin Signalling, Insulin Resistance, and Intrauterine Nutritional Programming of Cardiovascular Disease

    Science.gov (United States)

    Govindsamy, Annelene; Naidoo, Strinivasen

    2018-01-01

    Programming with an insult or stimulus during critical developmental life stages shapes metabolic disease through divergent mechanisms. Cardiovascular disease increasingly contributes to global morbidity and mortality, and the heart as an insulin-sensitive organ may become insulin resistant, which manifests as micro- and/or macrovascular complications due to diabetic complications. Cardiogenesis is a sequential process during which the heart develops into a mature organ and is regulated by several cardiac-specific transcription factors. Disrupted cardiac insulin signalling contributes to cardiac insulin resistance. Intrauterine under- or overnutrition alters offspring cardiac structure and function, notably cardiac hypertrophy, systolic and diastolic dysfunction, and hypertension that precede the onset of cardiovascular disease. Optimal intrauterine nutrition and oxygen saturation are required for normal cardiac development in offspring and the maintenance of their cardiovascular physiology. PMID:29484207

  13. Insulin like growth factor-1/insulin bypasses Pref-1/FA1-mediated inhibition of adipocyte differentiation

    DEFF Research Database (Denmark)

    Zhang, Hongbin; Nøhr, Jane; Jensen, Charlotte Harken

    2003-01-01

    that forced expression of the soluble form, FA1, or full-length Pref-1 did not inhibit adipocyte differentiation of 3T3-L1 cells when differentiation was induced by standard treatment with methylisobutylxanthine, dexamethasone, and high concentrations of insulin. However, forced expression of either form...... of Pref-1/FA1 in 3T3-L1 or 3T3-F442A cells inhibited adipocyte differentiation when insulin or insulin-like growth factor-1 (IGF-1) was omitted from the differentiation mixture. We demonstrate that the level of the mature form of the IGF-1 receptor is reduced and that IGF-1-dependent activation of p42/p44...... mitogen-activated protein kinases (MAPKs) is compromised in preadipocytes with forced expression of Pref-1. This is accompanied by suppression of clonal expansion and terminal differentiation. Accordingly, supplementation with insulin or IGF-1 rescued p42/p44 MAPK activation, clonal expansion...

  14. Sustainability of 8% weight loss, reduction of insulin resistance, and amelioration of atherogenic-metabolic risk factors over 4 years by metformin-diet in women with polycystic ovary syndrome.

    Science.gov (United States)

    Glueck, Charles J; Aregawi, Dawit; Agloria, Mahlia; Winiarska, Magdalena; Sieve, Luann; Wang, Ping

    2006-12-01

    In 74 women with polycystic ovary syndrome, treated for 4 years with metformin (MET) and diet, we prospectively assessed whether, and to what degree, weight loss, reduction of insulin resistance, and amelioration of coronary heart disease risk factors could be sustained. We hypothesized that response to MET-diet would not differ by pretreatment body mass index (BMI) classes or =25 to or =30 to or =40 (extremely obese). [table: see text] Metformin-diet was successful in producing stable approximately 8% weight reduction for all 4 years (trend P weight on MET-diet was significant (P or =40, > or =30 to or =25 to weight category (BMI, .1) in the 4 BMI categories. By stepwise regression, weight loss was a significant (P polycystic ovary syndrome effectively and safely reduces weight and LDL-C while raising HDL-C, and maintains these outcomes stable over 4 years.

  15. AZD5363 inhibits inflammatory synergy between interleukin-17 and insulin/insulin-like growth factor 1

    Directory of Open Access Journals (Sweden)

    Chong eChen

    2014-12-01

    Full Text Available In the United States, one third of population is affected by obesity and almost 29 million people are suffering from type 2 diabetes. Obese people have elevated serum levels of insulin, insulin-like growth factor 1 (IGF1 and interleukin-17 (IL-17. Insulin and IGF1 are known to enhance IL-17-induced expression of inflammatory cytokines and chemokines, which may contribute to the chronic inflammatory status observed in obese people. We have previously demonstrated that insulin/IGF1 signaling pathway crosstalks with IL-17-activated nuclear factor-kappa B (NF-κB pathway through inhibiting glycogen synthase kinase 3β (GSK3β activity. However, it is unclear whether GSK3α also plays a role and whether this crosstalk can be manipulated by AZD5363, a novel pan-Akt inhibitor that has been shown to increase GSK3 activity through reducing phosphorylation of GSK3α and GSK3β. In this study, we investigated IL-17-induced expression of C-X-C motif ligand 1 (Cxcl1, C-C motif ligand 20 (Ccl20 and interleukin-6 (Il-6 in wild-type, GSK3α-/-, and GSK3β-/- mouse embryonic fibroblast (MEF cells as well as in mouse prostate tissues by real-time quantitative PCR. We examined the proteins involved in the signaling pathways by Western blot analysis. We found that insulin and IGF1 enhanced IL-17- induced expression of Cxcl1, Ccl20 and Il-6, which was associated with increased phosphorylation of GSK3α and GSK3β in the presence of insulin and IGF1. AZD5363 inhibited the synergy between IL-17 and insulin/IGF1 through reducing phosphorylation of GSK3α and GSK3β by inhibiting Akt function. These findings imply that the cooperative crosstalk of IL-17 and insulin/IGF1 in initiating inflammatory responses may be alleviated by AZD5363.

  16. Macrophage-secreted factors induce adipocyte inflammation and insulin resistance

    International Nuclear Information System (INIS)

    Permana, Paska A.; Menge, Christopher; Reaven, Peter D.

    2006-01-01

    Macrophage infiltration into adipose tissue increases with obesity, a condition associated with low-grade inflammation and insulin resistance. We investigated the direct effects of macrophage-secreted factors on adipocyte inflammation and insulin resistance. 3T3-L1 adipocytes incubated with media conditioned by RAW264.7 macrophages (RAW-CM) showed dramatically increased transcription of several inflammation-related genes, greater nuclear factor kappa B (NF-κB) activity, and enhanced binding of U937 monocytes. All of these effects were prevented by co-incubation with pyrrolidinedithiocarbamate, an NF-κB inhibitor. Adipocytes incubated with RAW-CM also released more non-esterified fatty acids and this increased lipolysis was not suppressed by insulin. In addition, RAW-CM treatment decreased insulin-stimulated glucose uptake in adipocytes. Taken together, these results indicate that macrophage-secreted factors induce inflammatory responses and reduce insulin responsiveness in adipocytes. These effects of macrophage-secreted factors on adipocytes may contribute significantly to the systemic inflammation and insulin resistance associated with obesity

  17. Insulin and Insulin-like Growth Factor II Differentially Regulate Endocytic Sorting and Stability of Insulin Receptor Isoform A

    Czech Academy of Sciences Publication Activity Database

    Morcavallo, A.; Genua, M.; Palummo, A.; Kletvíková, Emília; Jiráček, Jiří; Brzozowski, A. M.; Lozzo, R. V.; Belfiore, A.; Morrione, A.

    2012-01-01

    Roč. 287, č. 14 (2012), s. 11422-11436 ISSN 0021-9258 Institutional research plan: CEZ:AV0Z40550506 Keywords : insulin * IGF -II * mitogenic response * IR-A Subject RIV: CE - Biochemistry Impact factor: 4.651, year: 2012

  18. Stroke - risk factors

    Science.gov (United States)

    ... oxygen. Brain cells can die, causing lasting damage. Risk factors are things that increase your chance of ... a disease or condition. This article discusses the risk factors for stroke and things you can do ...

  19. Renal protein synthesis in diabetes mellitus: effects of insulin and insulin-like growth factor I

    International Nuclear Information System (INIS)

    Barac-Nieto, M.; Lui, S.M.; Spitzer, A.

    1991-01-01

    Is increased synthesis of proteins responsible for the hypertrophy of kidney cells in diabetes mellitus? Does the lack of insulin, and/or the effect of insulin-like growth factor I (IGFI) on renal tubule protein synthesis play a role in diabetic renal hypertrophy? To answer these questions, we determined the rates of 3H-valine incorporation into tubule proteins and the valine-tRNA specific activity, in the presence or absence of insulin and/or IGFI, in proximal tubule suspension isolated from kidneys of streptozotocin diabetic and control rats. The rate of protein synthesis increased, while the stimulatory effects of insulin and IGFI on tubule protein synthesis were reduced, early (96 hours) after induction of experimental diabetes. Thus, hypertrophy of the kidneys in experimental diabetes mellitus is associated with increases in protein synthesis, rather than with decreases in protein degradation. Factor(s) other than the lack of insulin, or the effects of IGFI, must be responsible for the high rate of protein synthesis present in the hypertrophying tubules of diabetic rats

  20. 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...

  1. Extrinsic factors promoting insulin producing cell-differentiation and insulin expression enhancement-hope for diabetics.

    Science.gov (United States)

    Dave, Shruti

    2013-11-01

    Diabetes mellitus (DM) is considered to be an autoimmune disorder leading to destruction of beta-cells resulting in to a loss of blood sugar control. Attempts using many pharmacological compositions including exogenous insulin have failed to show tight control of glycemia and associated manifestations. Stem cells are considered a potential tool for the supply of insulin-producing cells (IPC) generation in vitro. Stem cell differentiation in to pancreatic lineages requires influence of both intrinsic and extrinsic factors. Application of islet growth factors is considered to be potential for enhancement of beta-cell replication, function and survival. Use of certain extrinsic factors is known to facilitate expression of transcription factors known to be important for beta-cell differentiation and production of insulin enabling IPC generation. Hierarchies of secreted signals and transcription factors have been identified by studies from several laboratories that guide cell differentiation in to IPC. This knowledge provides insights for in vitro IPC differentiation from stem cells. Current advancement in medical knowledge promises an insulin independency for DM patients. The review sheds light on few specific extrinsic factors which facilitate differentiation of stem cells in to IPC in vitro have been discussed; which can be proven as a potential therapeutic option for treatment of DM and associated diseases.

  2. Effects of childhood stunting on the increase of risk factors for obesity, non-insulin dependent diabetes mellitus and coronary heart disease

    International Nuclear Information System (INIS)

    Sawaya, A.L.; Bechere Fernandes, M.T.; Martins, P.A.

    2002-01-01

    Background: Previous studies by us and others have shown higher energy conservation mechanisms in marginally stunted Brazilian children such as, lower resting energy expenditure, lower fat oxidation, higher susceptibility to gain weight-for-height associated with a higher prevalence of stunted - obese subjects. Hypothesis: previous malnutrition as judged by height-for-age could be associated with alterations in fat patterning, circulating hormones such as insulin and IGF-1. In addition, previous malnutrition could be also associated with alterations in plasma lipid profiles, such as high triglycerides, low high-density lipoprotein cholesterol levels and hypertension. Sample and Methods: We recruited a population of 58 girls and boys with 11-14 years of age from the shantytown population in Sao Paulo, Brazil. Half of this population was of normal weight and height, and the other half was stunted. More than 300 children from to 11 years old were screened to participate in the study and were eligible if they had weight-for-height Z scores (WHZ) of -2 to +2 according to the IVCHS standards. Children recruited for the stunted group (n=28) had height-for-age (HAZ) ≤-1.5 Z score and those for the non-stunted group (n=30) had HAZ >1.50. In addition, the two groups were selectively recruited to assure group similarities in mean age and WH. General anthropometry, blood sampling for fasting insulin, glucose, glycosylated hemoglobin, triglycerides, high-density lipoprotein cholesterol, low-density cholesterol and IGF-1 were made as well as blood pressure. Results: Ninety two percent of the population had low values of IGF-1 indicating impaired growth. Stunted boys and girls had delayed pubertal stages. Lower fasting insulin levels and lower beta cell production according to HAM analysis in comparison to non-stunted children were found, after adjustment for differences in pubertal stages. In addition, a positive association was found between fasting insulin with age for the

  3. The correlations between insulin-like growth factor I, insulin and gestational diabetes mellitus

    International Nuclear Information System (INIS)

    Xu Yongle; Yang Weiwen; Pu Xiangke

    2006-01-01

    Objectives; To research the correlation between insulin-like growth factor I (IGF-I), insulin and gestational diabetes mellitus (GDM). Methods: Thirty cases of GDM are taken as the GDM group. Thirty cases of normal pregnant women were taken as the control group. The insulin in maternal serum of these two groups were measured at 31 ± 1 weeks gestational age by radioimmunity. The IGF-I in maternal serum at 31 ± 1 weeks gestational age and IGF-I in umbilical serum at term delivery were measured by ELISA. results: There was no significant difference in IGF-I level in maternal serum between the GDM group and the control group (P>0.05) and there was significant difference between these two groups maternal LnIRI, IGF-I in umbilical serum and weight of newborn baby (P<0.01). In the GDM group, the IGF-I in maternal serum positively correlated with the LnIRI (r=0.424, P<0.05) and IGF-I in umbilical serum positively correlated with the weight of new-born baby (r=0.434, P<0.05). Conclusion: GDM has serious insulin resistance. The IGF-I in maternal serum correlated with the IR in GDM. IGF-I in umbilical serum plays a role in the pathology and physiology process of fetal macrosomia. Abnormality of the axis of growth hormone-insulin-insulin-like growth factor caused by IGF-I might be through the way of insulin resistance, and GDM is resulted. (authors)

  4. Continuous insulin administration via complex central venous catheter infusion tubing is another risk factor for blood glucose imbalance. A retrospective study.

    Science.gov (United States)

    Maury, Eric; Vitry, Paola; Galbois, Arnauld; Ait-Oufella, Hafid; Baudel, Jean-Luc; Guidet, Bertrand; Offenstadt, Georges

    2012-06-14

    We assessed the potential impact of infusion tubing on blood glucose imbalance in ICU patients given intensive insulin therapy (IIT). We compared the incidence of blood glucose imbalance in patients equipped, in a nonrandomized fashion, with either conventional tubing or with a multiport infusion device. We retrospectively analyzed the nursing files of 35 patients given IIT through the distal line of a double-lumen central venous catheter. A total of 1389 hours of IIT were analyzed for occurrence of hypoglycemic events [defined as arterial blood glucose below 90 mg/dL requiring discontinuation of insulin]. Twenty-one hypoglycemic events were noted (density of incidence 15 for 1000 hours of ITT). In 17 of these 21 events (81%), medication had been administered during the previous hour through the line connected to the distal lumen of the catheter. Conventional tubing use was associated with a higher density of incidence of hypoglycemic events than multiport infusion device use (23 vs. 2 for 1,000 hours of IIT; rate ratio = 11.5; 95% confidence interval, 2.71-48.8; p tubing carrying other medications can lead to the delivery of significant amounts of unscheduled products. Hypoglycaemia observed during IIT could be related to this phenomenon. The use of a multiport infusion device with a limited dead volume could limit hypoglycemia in patients on IIT.

  5. Transcription factor 7-like 2 gene links increased in vivo insulin synthesis to type 2 diabetes

    NARCIS (Netherlands)

    S. Jainandunsing (Sjaam); Koole, H.R. (H. Rita); van Miert, J.N.I. (Joram N.I.); T. Rietveld (Trinet); J.L.D. Wattimena (Josias); E.J.G. Sijbrands (Eric); F.W.M. de Rooij (Felix)

    2018-01-01

    textabstractTranscription factor 7-like 2 (TCF7L2) is the main susceptibility gene for type 2 diabetes, primarily through impairing the insulin secretion by pancreatic β cells. However, the exact in vivo mechanisms remain poorly understood. We performed a family study and determined if the T risk

  6. Environmental factors and dam characteristics associated with insulin sensitivity and insulin secretion in newborn Holstein calves

    International Nuclear Information System (INIS)

    Kamal, M.M.; Van Eetvelde, M.; Bogaert, H.; Hostens, M.; Vandaele, L.; Shamsuddin, M.; Opsomer, G.

    2016-01-01

    Full text: The objective of the present retrospective cohort study was to evaluate potential associations between environmental factors and dam characteristics, including level of milk production during gestation, and insulin traits in newborn Holstein calves. Birth weight and gestational age of the calves at delivery were determined. On the next day, heart girth, wither height and diagonal length of both the calves and their dams were measured. Parity, body condition score and age at calving were recorded for all dams. For the cows, days open before last gestation, lactation length (LL), lenght of dry period (DP) and calving interval were also calculated. The magnitude and shape of the lactation curve both quantified using the MilkBot model based on monthly milk weights, were used to calculate the amount of milk produced during gestation. Using the same procedure, cumulative milk production from conception to drying off (MGEST) was calculated. A blood sample was collected from all calves (n=481; 169 born to heifers and 312 born to cows) at least 5 h after a milk meal on day 3 of life to measure basal glucose and insulin levels. In addition, an intravenous glucose-stimulated insulin secretion test was performed in a subset of the calves (n=316). After descriptive analysis, generalized linear mixed models were used to identify factors that were significantly associated with the major insulin traits (Insb, basal insulin level; QUICKI, quantitative insulin sensitivity check index; AIR, acute insulin response; DI, disposition index) of the newborn calves. The overall average birth weight of the calves was 42.7 ± 5.92 kg. The insulin traits were significantly associated with MGEST (P=0.076) and longer DP (P=0.034). The QUICKI was estimated to be lower in calves born to the cows having passed a higher MGEST (P=0.030) and longer DP (P=0.058). Moreover, the AIR (P=0.009) and DI (P=0.049) were estimated to be lower in male compared with female calves. Furthermore, the AIR

  7. Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins in the catabolic response to injury and infection.

    Science.gov (United States)

    Lang, Charles H; Frost, Robert A

    2002-05-01

    The erosion of lean body mass resulting from protracted critical illness remains a significant risk factor for increased morbidity and mortality in this patient population. Previous studies have documented the well known impairment in nitrogen balance results from both an increase in muscle protein degradation as well as a decreased rate of both myofibrillar and sacroplasmic protein synthesis. This protein imbalance may be caused by an increased presence or activity of various catabolic agents, such as tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 or glucocorticoids, or may be mediated via a decreased concentration or responsiveness to various anabolic hormones, such as growth hormone or insulin-like growth factor-I. This review focuses on recent developments pertaining to the importance of alterations in the growth hormone-insulin-like growth factor-I axis as a mechanism for the observed defects in muscle protein balance.

  8. [Insulin-like growth factor-binding protein-1: a new biochemical marker of nonalcoholic fatty liver disease?].

    Science.gov (United States)

    Graffigna, Mabel Nora; Belli, Susana H; de Larrañaga, Gabriela; Fainboim, Hugo; Estepo, Claudio; Peres, Silvia; García, Natalia; Levalle, Oscar

    2009-03-01

    to assess the presence of nonalcoholic fatty liver disease in patients with risk factors for this pathology (obesity, dyslipidemia, metabolic syndrome and diabetes type 2) and to determine the role of insulin, HOMA index, insulin-like growth factor-binding protein-1, sex hormone-binding globulin and plasminogen activator inhibitor type 1, as biochemical markers. Ninety-one patients with risk factors for nonalcoholic fatty liver disease were evaluated. Serum transaminases, insulin, sex hormone-binding globulin, insulin-like growth factor-binding protein-1 and plasminogen activator inhibitor type 1 were measured. The diagnosis of fatty liver was performed by ultrasonography and liver biopsies were performed to 31 subjects who had steatosis by ultrasonography and high alanine aminotransferase. Nonalcoholic fatty liver disease was present in 65 out of 91 patients (71,4%). Liver biopsy performed to 31 subjects confirmed nonalcoholic steatohepatitis. Twenty-five patients had different degrees of fibrosis. Those individuals with fatty liver had higher waist circumference, serum levels of triglycerides, insulin and HOMA index, and lower serum insulin-like growth factor-binding protein-1 concentration. The degree ofhepatic steatosis by ultrasonography was positively correlated to waist circumference, triglycerides, insulin and HOMA index (p<0,003; p<0,003; p<0,002 and p<0,001, respectively), and was negatively correlated to HDL-cholesterol and insulin-like growth factor-binding protein-1 (p<0,025 and p<0,018, respectively). We found a high prevalence of NAFLD in patients with risk factors, most of them overweight or obese. Although SHBG and PAI-1 have a closely relationship to insulin resistance, they did not show to be markers of NAFLD. Regardless of low IGFBP-1 levels associated with NAFLD, serum IGFBP-1 measure is less accessible than insulin and triglycerides levels, HOMA index and waist circumference. Moreover, it is not a better marker for NAFLD than the above

  9. Insulin and insulin-like growth factor receptors in the brain: physiological and pathological aspects.

    Science.gov (United States)

    Werner, Haim; LeRoith, Derek

    2014-12-01

    The involvement of insulin, the insulin-like growth factors (IGF1, IGF2) and their receptors in central nervous system development and function has been the focus of scientific interest for more than 30 years. The insulin-like peptides, both locally-produced proteins as well as those transported from the circulation into the brain via the blood-brain barrier, are involved in a myriad of biological activities. These actions include, among others, neuronal survival, neurogenes, angiogenesis, excitatory and inhibitory neurotransmission, regulation of food intake, and cognition. In recent years, a linkage between brain insulin/IGF1 and certain neuropathologies has been identified. Epidemiological studies have demonstrated a correlation between diabetes (mainly type 2) and Alzheimer׳s disease. In addition, an aberrant decline in IGF1 values was suggested to play a role in the development of Alzheimer׳s disease. The present review focuses on the expression and function of insulin, IGFs and their receptors in the brain in physiological and pathological conditions. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  10. Targeting Insulin and Insulin-Like Growth Factor Pathways in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Marie-Claude Beauchamp

    2010-01-01

    Full Text Available Ovarian cancer is the most lethal of all gynecological malignancies, due in part to the diagnosis at an advanced stage caused by the lack of specific signs and symptoms and the absence of reliable tests for screening and early detection. Most patients will respond initially to treatment but about 70% of them will suffer a recurrence. Therefore, new therapeutic modalities are urgently needed to overcome chemoresistance observed in ovarian cancer patients. Evidence accumulates suggesting that the insulin/insulin growth factor (IGF pathways could act as a good therapeutic target in several cancers, including ovarian cancer. In this paper, we will focus on the role of insulin/IGF in ovarian cancer tumorigenesis and treatment.

  11. Low cardiorespiratory fitness in people at risk for type 2 diabetes: early marker for insulin resistance

    Directory of Open Access Journals (Sweden)

    Leite Silmara AO

    2009-09-01

    Full Text Available Abstract Purpose There is a significant association between insulin resistance and low cardiorespiratory fitness in nondiabetic subjects. In a population with risk factors for type 2 diabetes (T2DM, before they are insulin resistant, we investigated low exercise capacity (VO2max as an early marker of impaired insulin sensitivity in order to determine earlier interventions to prevent development of insulin resistance syndrome (IRS and T2DM. Methods Cross-sectional analyses of data on 369 (78 men and 291 women people at risk for IRS and T2DM, aged 45.6 +/- 10 years (20-65 years old from the Community Diabetes Prevention Project in Minnesota were carried out. The cardiorespiratory fitness (VO2max by respiratory gas exchange and bicycle ergometer were measured in our at risk non insulin resistant population and compared with a control group living in the same geographic area. Both groups were equally sedentary, matched for age, gender and BMI. Results The most prevalent abnormality in the study population was markedly low VO2max when compared with general work site screening control group, (n = 177; 137F; 40 M, mean age 40 ± 11 years; BMI = 27.8 ± 6.1 kg/m2. Individuals at risk for IRS and T2DM had a VO2max (22 ± 6 ml/kg/min 15% lower than the control group VO2max (26 ± 9 ml/kg/min (p 2max was inversely correlated with HOMA-IR (r = -0.30, p Conclusions Decreased VO2max is correlated with impaired insulin sensitivity and was the most prevalent abnormality in a population at risk for IRS and T2DM but without overt disease. This raises the possibility that decreased VO2 max is among the earliest indicators of IRS and T2DM therefore, an important risk factor for disease progression.

  12. Depressive symptoms prior to and following insulin initiation in patients with type 2 diabetes mellitus: Prevalence, risk factors and effect on physician resource utilisation.

    Science.gov (United States)

    Dzida, Grzegorz; Karnieli, Eddy; Svendsen, Anne Louise; Sølje, Kristine Steensen; Hermanns, Norbert

    2015-10-01

    To study the frequency and intensity of depressive symptoms and associations with physician resource utilisation following insulin initiation in patients with type 2 diabetes mellitus. SOLVE was a 24-week observational study. In this sub-analysis of data from Poland, depressive symptoms were evaluated using the Patient Health Questionnaire (PHQ)-9. PHQ-9 was completed by 942 of 1169 patients (80.6%) at baseline, and 751 (64.2%) at both baseline and final (24-week) visit. PHQ-9 scores indicated depressive symptoms in 45.6% (n=430) at baseline, and 27.2% (n=223) at final visit. Mean PHQ-9 change was -2.38 [95% CI -2.73, -2.02], p1. Depressive symptoms at baseline (OR 6.32, p1), microvascular disease (OR 2.45, p=0.016), number of physician contacts (OR 1.16, p=0.009), and change in HbA1c (OR 0.60, p=0.025) were independently associated with moderate/severe depressive symptoms at final visit. Patients with more severe depressive symptoms spent more time training to self-inject (p=0.0016), self-adjust (p=0.0023) and manage other aspects of insulin delivery (p1). Patients with persistent depressive symptoms had more telephone contacts and dose changes at final visit than those without (both ptype 2 diabetes and associated with increased healthcare utilisation, reinforcing the need for holistic interdisciplinary management approaches. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  13. Characterization of the growth of murine fibroblasts that express human insulin receptors. II. Interaction of insulin with other growth factors

    International Nuclear Information System (INIS)

    Randazzo, P.A.; Jarett, L.

    1990-01-01

    The effects of insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin on DNA synthesis were studied in murine fibroblasts transfected with an expression vector containing human insulin receptor cDNA (NIH 3T3/HIR) and the parental NIH 3T3 cells. In NIH 3T3/HIR cells, individual growth factors in serum-free medium stimulated DNA synthesis with the following relative efficacies: insulin greater than or equal to 10% fetal calf serum greater than PDGF greater than IGF-1 much greater than EGF. In comparison, the relative efficacies of these factors in stimulating DNA synthesis by NIH 3T3 cells were 10% fetal calf serum greater than PDGF greater than EGF much greater than IGF-1 = insulin. In NIH 3T3/HIR cells, EGF was synergistic with 1-10 ng/ml insulin but not with 100 ng/ml insulin or more. Synergy of PDGF or IGF-1 with insulin was not detected. In the parental NIH 3T3 cells, insulin and IGF-1 were found to be synergistic with EGF (1 ng/ml), PDGF (100 ng/ml), and PDGF plus EGF. In NIH 3T3/HIR cells, the lack of interaction of insulin with other growth factors was also observed when the percentage of cells synthesizing DNA was examined. Despite insulin's inducing only 60% of NIH 3T3/HIR cells to incorporate thymidine, addition of PDGF, EGF, or PDGF plus EGF had no further effect. In contrast, combinations of growth factors resulted in 95% of the parental NIH 3T3 cells synthesizing DNA. The independence of insulin-stimulated DNA synthesis from other mitogens in the NIH 3T3/HIR cells is atypical for progression factor-stimulated DNA synthesis and is thought to be partly the result of insulin receptor expression in an inappropriate context or quantity

  14. Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors.

    Science.gov (United States)

    Bortvedt, Sarah F; Lund, P Kay

    2012-03-01

    To summarize the recent evidence that insulin-like growth factor 1 (IGF1) mediates growth effects of multiple trophic factors and discuss clinical relevance. Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogs in short bowel syndrome and Crohn's disease. This review highlights the evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn's disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that suppressor of cytokine signaling protein induction by GH or GLP2 in normal or inflamed intestine may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis, is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed. IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed.

  15. Development of real-time reverse transcription polymerase chain reaction assays to quantify insulin-like growth factor receptor and insulin receptor expression in equine tissue

    Directory of Open Access Journals (Sweden)

    Stephen B. Hughes

    2013-08-01

    Full Text Available The insulin-like growth factor system (insulin-like growth factor 1, insulin-like growth factor 2, insulin-like growth factor 1 receptor, insulin-like growth factor 2 receptor and six insulin-like growth factor-binding proteins and insulin are essential to muscle metabolism and most aspects of male and female reproduction. Insulin-like growth factor and insulin play important roles in the regulation of cell growth, differentiation and the maintenance of cell differentiation in mammals. In order to better understand the local factors that regulate equine physiology, such as muscle metabolism and reproduction (e.g., germ cell development and fertilisation, real-time reverse transcription polymerase chain reaction assays for quantification of equine insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid were developed. The assays were sensitive: 192 copies/µLand 891 copies/µL for insulin-like growth factor 1 receptor, messenger ribonucleic acid and insulin receptor respectively (95%limit of detection, and efficient: 1.01 for the insulin-like growth factor 1 receptor assay and 0.95 for the insulin receptor assay. The assays had a broad linear range of detection (seven logs for insulin-like growth factor 1 receptor and six logs for insulin receptor. This allowed for analysis of very small amounts of messenger ribonucleic acid. Low concentrations of both insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid were detected in endometrium, lung and spleen samples, whilst high concentrations were detected in heart, muscle and kidney samples, this was most likely due to the high level of glucose metabolism and glucose utilisation by these tissues. The assays developed for insulin-like growth factor 1 receptor and insulin receptor messenger ribonucleic acid expression have been shown to work on equine tissue and will contribute to the understanding of insulin and insulin-like growth factor 1

  16. Use of Insulin and Insulin Analogs and Risk of Cancer — Systematic Review and Meta-Analysis of Observational Studies

    Science.gov (United States)

    Karlstad, Øystein; Starup-Linde, Jacob; Vestergaard, Peter; Hjellvik, Vidar; T. Bazelier, Marloes; K. Schmidt, Marjanka; Andersen, Morten; Auvinen, Anssi; Haukka, Jari; Furu, Kari; de Vries, Frank; L. de Bruin, Marie

    2014-01-01

    Background: An association of insulin use and risk of cancer has been reported but evidence is conflicting and methodological issues have been identified. Objective: To summarize results regarding insulin use and cancer risk by a systematic review and meta-analysis of cohort and case-control studies examining risk of cancer associated with insulin use in patients with diabetes. Data Sources: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. Study Eligibility Criteria (PICOS): Population: diabetes patients. Exposure: Users of any exogenous insulin. Comparison: Diabetes patients with or without use of antidiabetic drugs. Outcome: Any incident cancer. Study Design: Cohort and case-control studies. Results: 42 eligible studies examined risk of any cancer and 27 site-specific cancers. Results of individual studies were heterogeneous. Meta-analyses were significant for: Insulin vs No Insulin: Increased risk for pancreas, liver, kidney, stomach and respiratory cancer, decreased risk for prostate cancer. Insulin vs Non-Insulin Antidiabetics: Increased risk for any, pancreatic and colorectal cancer. Glargine vs Non-Glargine Insulin: Increased risk for breast cancer, decreased risk for colon cancer. Limitations: Few studies available for most cancer sites and exposure contrasts, and few assess effect of dose and duration of exposure. Methodological issues in several studies. Availability of confounders. Conclusions: Insulin use was associated with risk of cancer at several sites. Cautious interpretation of results is warranted as methodological issues and limitations in several of the included studies have been identified. Choice of study design may have a profound effect on estimated cancer risk. PMID:24215311

  17. Insulin-like growth factor 2

    DEFF Research Database (Denmark)

    Valleh, Mehdi Vafaye; Hyttel, Poul; Rasmussen, Mikkel Aabech

    2014-01-01

    Intrinsic defects within the embryos, reflected by elevated cell death and low proliferative ability, are considered the most critical factors associated with bovine infertility. The identification of embryonic factors, which are responsible for successful embryo development, is thus critical...

  18. Metabolic syndrome as a risk factor for hypertension after preeclampsia

    NARCIS (Netherlands)

    Spaan, J.J.; Sep, S.J.; van Balen, V.L.; Spaanderman, M.E.A.; Peeters, L.L.

    2012-01-01

    OBJECTIVE: To identify metabolic and obstetric risk factors associated with hypertension after preeclampsia. METHODS: We analyzed demographic and clinical data from a postpartum screening (blood pressure, microalbuminuria and fasting plasma levels of glucose, insulin, and lipid profile) from 683

  19. Microbial translocation and cardiometabolic risk factors in HIV infection

    DEFF Research Database (Denmark)

    Trøseid, Marius; Manner, Ingjerd W; Pedersen, Karin K

    2014-01-01

    of microbial translocation are closely associated with several cardiovascular risk factors such as dyslipidemia, insulin resistance, hypertension, coagulation abnormalities, endothelial dysfunction, and carotid atherosclerosis. Future studies should investigate whether associations between microbial...

  20. Tobacco Smoke Exposure Impairs Brain Insulin/IGF Signaling: Potential Co-Factor Role in Neurodegeneration.

    Science.gov (United States)

    Deochand, Chetram; Tong, Ming; Agarwal, Amit R; Cadenas, Enrique; de la Monte, Suzanne M

    2016-01-01

    Human studies suggest tobacco smoking is a risk factor for cognitive impairment and neurodegeneration, including Alzheimer's disease (AD). However, experimental data linking tobacco smoke exposures to underlying mediators of neurodegeneration, including impairments in brain insulin and insulin-like growth factor (IGF) signaling in AD are lacking. This study tests the hypothesis that cigarette smoke (CS) exposures can impair brain insulin/IGF signaling and alter expression of AD-associated proteins. Adult male A/J mice were exposed to air for 8 weeks (A8), CS for 4 or 8 weeks (CS4, CS8), or CS8 followed by 2 weeks recovery (CS8+R). Gene expression was measured by qRT-PCR analysis and proteins were measured by multiplex bead-based or direct binding duplex ELISAs. CS exposure effects on insulin/IGF and insulin receptor substrate (IRS) proteins and phosphorylated proteins were striking compared with the mRNA. The main consequences of CS4 or CS8 exposures were to significantly reduce insulin R, IGF-1R, IRS-1, and tyrosine phosphorylated insulin R and IGF-1R proteins. Paradoxically, these effects were even greater in the CS8+R group. In addition, relative levels of S312-IRS-1, which inhibits downstream signaling, were increased in the CS4, CS8, and CS8+R groups. Correspondingly, CS and CS8+R exposures inhibited expression of proteins and phosphoproteins required for signaling through Akt, PRAS40, and/or p70S6K, increased AβPP-Aβ, and reduced ASPH protein, which is a target of insulin/IGF-1 signaling. Secondhand CS exposures caused molecular and biochemical abnormalities in brain that overlap with the findings in AD, and many of these effects were sustained or worsened despite short-term CS withdrawal.

  1. Association between Insulin Like Growth Factor-1 (IGF-1) gene ...

    African Journals Online (AJOL)

    The insulin-like growth factor-1 (IGF1) is a key regulator of muscle development and metabolism in birds and other vertebrate. Our objective was to determine the association between IGF1 gene polymorphism and carcass traits in FUNAAB Alpha chicken. Genomic DNA was extracted from the blood of 50 normal feathered ...

  2. Insulin-like growth factors and pancreas beta cells.

    NARCIS (Netherlands)

    Haeften, T.W. van; Twickler, M.

    2004-01-01

    Abstract Insulin-like growth factors (IGFs) have been implicated in normal growth, and especially foetal pancreas beta-cell development. As low birth weight has been implicated in the development of obesity and type 2 diabetes, much research has evolved into the importance of IGF and their

  3. Insulin-like growth factors and pancreas beta cells

    NARCIS (Netherlands)

    van Haeften, T. W.; Twickler, TB

    Insulin-like growth factors (IGFs) have been implicated in normal growth, and especially foetal pancreas beta-cell development. As low birth weight has been implicated in the development of obesity and type 2 diabetes, much research has evolved into the importance of IGF and their signalling

  4. Insulin-like growth factors and pancreas beta cells

    NARCIS (Netherlands)

    van Haeften, T. W.; Twickler, Th B.

    2004-01-01

    Abstract Insulin-like growth factors (IGFs) have been implicated in normal growth, and especially foetal pancreas beta-cell development. As low birth weight has been implicated in the development of obesity and type 2 diabetes, much research has evolved into the importance of IGF and their

  5. Pre-diagnosis insulin-like growth factor-I and risk of epithelial invasive ovarian cancer by histological subtypes : A collaborative re-analysis from the Ovarian Cancer Cohort Consortium

    NARCIS (Netherlands)

    Ose, Jennifer; Schock, Helena; Poole, Elizabeth M; Lehtinen, Matti; Visvanathan, Kala; Helzlsouer, Kathy; Buring, Julie E; Lee, I-Min; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Trichopoulou, Antonia; Mattiello, Amalia; Onland-Moret, N Charlotte; Weiderpass, Elisabete; Sánchez, María-José; Idahl, Annika; Travis, Ruth C; Rinaldi, Sabina; Merritt, Melissa A; Wentzensen, Nicolas; Tworoger, Shelley S; Kaaks, Rudolf; Fortner, Renée T

    PURPOSE: Biologic evidence suggests that the Insulin-like growth factor (IGF)-family may be involved in the etiology of epithelial invasive ovarian cancer (EOC). However, prospective studies investigating the role of IGF-I in ovarian carcinogenesis have yielded conflicting results. METHODS: We

  6. [Risk factors of schizophrenia].

    Science.gov (United States)

    Suvisaari, Jaana

    2010-01-01

    Schizophrenia is a multifactorial, neurodevelopmental disorder caused by a combination of genetic and environmental risk factors. Disturbances of brain development begin prenatally, while different environmental insults further affect postnatal brain maturation during childhood and adolescence. Genome-wide association studies (GWAS) have succeeded in identifying hundreds of new risk variants for common, multifactorial diseases. In schizophrenia research, GWAS have found several rare copy number variants that considerably increase the risk of schizophrenia, and have shown an association between schizophrenia and the major histocompatibility complex. Research on environmental risk factors in recent years has provided new information particularly on risk factors related to pregnancy and childhood rearing environment. Gene-environment interactions have become a central research topic. There is evidence that genetically susceptible children are more vulnerable to the effects of unstable childhood rearing environment and other environmental risk factors.

  7. 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

  8. Do very small adipocytes in subcutaneous adipose tissue (a proposed risk factor for insulin insensitivity have a fetal origin?

    Directory of Open Access Journals (Sweden)

    Mette Olaf Nielsen

    2016-08-01

    Conclusions: The present study showed that greater preponderance of very small adipocytes, increased collagen infiltration and reduced subcutaneous lipid accumulation ability, as well as altered perirenal fat preferences for accumulation of C14:0 can have a fetal origin. Disturbance of normal (subcutaneous adipose tissue development may play a key role in linking fetal malnutrition to disease risk later in life.

  9. Mechanical stretch augments insulin-induced vascular smooth muscle cell proliferation by insulin-like growth factor-1 receptor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Gang [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Hitomi, Hirofumi, E-mail: hitomi@kms.ac.jp [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Hosomi, Naohisa [Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa (Japan); Lei, Bai; Nakano, Daisuke [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Deguchi, Kazushi; Mori, Hirohito; Masaki, Tsutomu [Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa (Japan); Ma, Hong [Department of Anesthesiology, First Affiliated Hospital of China Medical University, Shenyang (China); Griendling, Kathy K. [Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA (United States); Nishiyama, Akira [Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa (Japan)

    2011-10-15

    Insulin resistance and hypertension have been implicated in the pathogenesis of cardiovascular disease; however, little is known about the roles of insulin and mechanical force in vascular smooth muscle cell (VSMC) remodeling. We investigated the contribution of mechanical stretch to insulin-induced VSMC proliferation. Thymidine incorporation was stimulated by insulin in stretched VSMCs, but not in un-stretched VSMCs. Insulin increased 2-deoxy-glucose incorporation in both stretched and un-stretched VSMCs. Mechanical stretch augmented insulin-induced extracellular signal-regulated kinase (ERK) and Akt phosphorylation. Inhibitors of epidermal growth factor (EGF) receptor tyrosine kinase and Src attenuated insulin-induced ERK and Akt phosphorylation, as well as thymidine incorporation, whereas 2-deoxy-glucose incorporation was not affected by these inhibitors. Moreover, stretch augmented insulin-like growth factor (IGF)-1 receptor expression, although it did not alter the expression of insulin receptor and insulin receptor substrate-1. Insulin-induced ERK and Akt activation, and thymidine incorporation were inhibited by siRNA for the IGF-1 receptor. Mechanical stretch augments insulin-induced VSMC proliferation via upregulation of IGF-1 receptor, and downstream Src/EGF receptor-mediated ERK and Akt activation. Similar to in vitro experiment, IGF-1 receptor expression was also augmented in hypertensive rats. These results provide a basis for clarifying the molecular mechanisms of vascular remodeling in hypertensive patients with hyperinsulinemia. -- Highlights: {yields} Mechanical stretch augments insulin-induced VSMC proliferation via IGF-1 receptor. {yields} Src/EGFR-mediated ERK and Akt phosphorylation are augmented in stretched VSMCs. {yields} Similar to in vitro experiment, IGF-1 receptor is increased in hypertensive rats. {yields} Results provide possible mechanisms of vascular remodeling in hypertension with DM.

  10. Optimal cut-off of homeostasis model assessment of insulin resistance (HOMA-IR) for the diagnosis of metabolic syndrome: third national surveillance of risk factors of non-communicable diseases in Iran (SuRFNCD-2007).

    Science.gov (United States)

    Esteghamati, Alireza; Ashraf, Haleh; Khalilzadeh, Omid; Zandieh, Ali; Nakhjavani, Manouchehr; Rashidi, Armin; Haghazali, Mehrdad; Asgari, Fereshteh

    2010-04-07

    We have recently determined the optimal cut-off of the homeostatic model assessment of insulin resistance for the diagnosis of insulin resistance (IR) and metabolic syndrome (MetS) in non-diabetic residents of Tehran, the capital of Iran. The aim of the present study is to establish the optimal cut-off at the national level in the Iranian population with and without diabetes. Data of the third National Surveillance of Risk Factors of Non-Communicable Diseases, available for 3,071 adult Iranian individuals aging 25-64 years were analyzed. MetS was defined according to the Adult Treatment Panel III (ATPIII) and International Diabetes Federation (IDF) criteria. HOMA-IR cut-offs from the 50th to the 95th percentile were calculated and sensitivity, specificity, and positive likelihood ratio for MetS diagnosis were determined. The receiver operating characteristic (ROC) curves of HOMA-IR for MetS diagnosis were depicted, and the optimal cut-offs were determined by two different methods: Youden index, and the shortest distance from the top left corner of the curve. The area under the curve (AUC) (95%CI) was 0.650 (0.631-0.670) for IDF-defined MetS and 0.683 (0.664-0.703) with the ATPIII definition. The optimal HOMA-IR cut-off for the diagnosis of IDF- and ATPIII-defined MetS in non-diabetic individuals was 1.775 (sensitivity: 57.3%, specificity: 65.3%, with ATPIII; sensitivity: 55.9%, specificity: 64.7%, with IDF). The optimal cut-offs in diabetic individuals were 3.875 (sensitivity: 49.7%, specificity: 69.6%) and 4.325 (sensitivity: 45.4%, specificity: 69.0%) for ATPIII- and IDF-defined MetS, respectively. We determined the optimal HOMA-IR cut-off points for the diagnosis of MetS in the Iranian population with and without diabetes.

  11. Risk factors for neoplasms

    International Nuclear Information System (INIS)

    Brachner, A.; Grosche, B.

    1991-06-01

    A broad survey is given of risk factors for neoplasms. The main carcinogenic substances (including also ionizing radiation and air pollution) are listed, and are correlated with the risk factors for various cancers most frequently explained and discussed in the literature. The study is intended to serve as a basis for a general assessment of the incidence of neoplasms in children, and of cancer mortality in the entire population of Bavaria in the years 1983-1989, or 1979-1988, respectively, with the principal idea of drawing up an environment-related health survey. The study therefore takes into account not only ionizing radiation as a main risk factor, but also other risk factors detectable within the ecologic context, as e.g. industrial installations and their effects, refuse incineration plants or waste dumps, or the social status. (orig./MG) [de

  12. Insulin-like growth factor-1 is a negative modulator of glucagon secretion

    OpenAIRE

    Mancuso, Elettra; Mannino, Gaia C.; Fatta, Concetta Di; Fuoco, Anastasia; Spiga, Rosangela; Andreozzi, Francesco; Sesti, Giorgio

    2017-01-01

    Glucagon secretion involves a combination of paracrine, autocrine, hormonal, and autonomic neural mechanisms. Type 2 diabetes often presents impaired glucagon suppression by insulin and glucose. Insulin-like growth factor-I (IGF-1) has elevated homology with insulin, and regulates pancreatic ?-cells insulin secretion. Insulin and IGF-1 receptors share considerable structure homology and function. We hypothesized the existence of a mechanism linking the inhibition of ?-cells glucagon secretion...

  13. 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.

  14. Insulin-Like Growth Factor-1 and Neuroinflammation

    OpenAIRE

    Labandeira-Garcia, Jose L.; Costa-Besada, Maria A.; Labandeira, Carmen M.; Villar-Cheda, Begoña; Rodríguez-Perez, Ana I.

    2017-01-01

    Insulin-like growth factor-1 (IGF-1) effects on aging and neurodegeneration is still controversial. However, it is widely admitted that IGF-1 is involved in the neuroinflammatory response. In peripheral tissues, several studies showed that IGF-1 inhibited the expression of inflammatory markers, although other studies concluded that IGF-1 has proinflammatory functions. Furthermore, proinflammatory cytokines such as TNF-α impaired IGF-1 signaling. In the brain, there are controversial results o...

  15. Effect of Insulin Infusion on insulin-like growth factor I (IGF-I) during Hemodialysis

    DEFF Research Database (Denmark)

    Reinhard, Mark; Frystyk, Jan; Bjerre, Mette

    2012-01-01

    Background: Hemodialysis (HD) is a catabolic procedure probably contributing to the high frequency of protein-energy wasting among patients on maintenance HD. The aim was to investigate the effect of insulin infusion on insulin-like growth factor I (IGF-I) during HD compared with a meal alone...... infusion and followed by the only meal allowed during the study. Results: Data are presented as mean±SD. From baseline to end of HD session we observed an overall increase in both serum bioactive IGF-I (from 0.83±0.27 to 1.01±0.34 µg/L, p... in the change between the groups (p=0.43). Conclusion: A meal at the beginning of a HD session leads to an increase in bioactive IGF-I thereby assumingly counteracting the catabolic effects of HD. However, according to changes in bioactive IGF-I neither glucose nor glucose-insulin infusion during HD appear...

  16. Reprodutibilidade de informações em estudo de fatores de risco para o diabetes mellitus insulino-dependente Reproducibility of information in a study of the risk factors for insulin-dependent diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Suely Godoy Agostinho Gimeno

    1997-10-01

    Full Text Available Examina-se, em uma subamostra de 38 casos e 38 controles de um estudo sobre os fatores de risco para o diabetes mellitus insulino-dependente, a reprodutibilidade de informações obtidas para as variáveis escolaridade da mãe e do pai, peso e comprimento da criança ao nascer, história de episódios graves de diarréia, tempo de aleitamento ao seio e idade da introdução de leite de vaca na alimentação infantil, selecionadas a partir do questionário padronizado utilizado em visita domiciliar. A repetição das perguntas foi feita por telefone. A concordância entre as respostas da primeira e segunda entrevista foi verificada mediante a utilização da estatística kappa (variáveis categóricas e do coeficiente de correlação intraclasse (variáveis quantitativas, para casos e controles separadamente. Os resultados levam a aceitar as informações como reprodutíveis.The reliability of information about mothers' and fathers' education, weight and height at birth, history of diarrhoea, duration of exclusive breast feeding and age of introduction of cows' milk products, selected from a structured questionnaire used in home interviewers was examined in a sample of 38 cases and 38 controls from a study related to the risk factors of insulin-dependent diabetes mellitus. The repetition of the questions was done by telephone. The agreement between the answers of both interviewers was verified using the kappa statistic (categorical variables and the intra-class correlation coefficient (quantitative variables. The results enable one to conclude that the information is reproducible.

  17. Cancer risk among insulin users: comparing analogues with human insulin in the CARING five-country cohort study.

    Science.gov (United States)

    But, Anna; De Bruin, Marie L; Bazelier, Marloes T; Hjellvik, Vidar; Andersen, Morten; Auvinen, Anssi; Starup-Linde, Jakob; Schmidt, Marjanka K; Furu, Kari; de Vries, Frank; Karlstad, Øystein; Ekström, Nils; Haukka, Jari

    2017-09-01

    The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies. National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (≤0.5, 0.5-1, 1-2, 2-3, 3-4, 4-5, 5-6 and >6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin. A total of 21,390 cancer cases occurred during a mean follow-up of 4.6 years. No trend with cumulative treatment time for insulin glargine relative to human insulin was observed in risk for any of the ten studied cancer types. Of the 136 associations tested in the main analysis, only a few increased and decreased risks were found: among women, a higher risk was observed for colorectal (RR 1.54, 95% CI 1.06, 2.25) and endometrial cancer (RR 1.78, 95% CI 1.07, 2.94) for ≤0.5 years of treatment and for malignant melanoma for 2-3 years (RR 1.92, 95% CI 1.02, 3.61) and 4-5 years (RR 3.55, 95% CI 1.68, 7.47]); among men, a lower risk was observed for pancreatic cancer for 2-3 years (RR 0.34, 95% CI 0.17, 0.66) and for liver cancer for 3-4 years (RR 0.36, 95% CI 0.14, 0.94) and >6 years (RR 0.22, 95% CI 0.05, 0.92). Comparisons of insulin detemir with human insulin also showed no consistent differences. The present multi-country study found no evidence of consistent differences in risk for ten cancers for insulin glargine or insulin detemir use compared with human insulin, at follow-up exceeding 5 years.

  18. Gender differences in factors influencing insulin resistance in elderly hyperlipemic non-diabetic subjects

    Directory of Open Access Journals (Sweden)

    Hrebícek Jirí

    2002-10-01

    Full Text Available Abstract Background The increase in the prevalence of insulin resistance-related metabolic syndrome, a disorder that greatly increases the risk of diabetes, heart attack and stroke, is alarming. One of the most frequent and early symptoms of metabolic syndrome is hypertriglyceridemia. We examined the gender differences between various metabolic factors related to insulin resistance in elderly non-diabetic men and postmenopausal women of comparable age suffering from hypertriglyceridemia, and compared them with healthy subjects of equal age. Results The indexes of insulin resistance HOMA IR and QUICKI were significantly higher in both hyperlipemic men and women than in controls; 95% confidence limits of hyperlipemic subjects did not overlap with controls. In both normolipemic and hyperlipemic men and women serum leptin correlated significantly with insulin resistance, while HDL-cholesterol correlated inversely with HOMA-IR only in women (both normo- and hyperlipemic, and serum tumor necrosis factor α (TNFα only in hyperlipemic women. According to results of multiple regression analysis with HOMA-IR as a dependent variable, leptin played a significant role in determining insulin resistance in both genders, but – aside from leptin – triglycerides, TNFα and decreased HDL-cholesterol were significant determinants in women, while body mass index and decreased HDL-cholesterol were significant determinants in men. The coefficient of determination (R2 of HOMA IR by above mentioned metabolic variables was in women above 60%, in men only about 40%. Conclusion The significant role of serum leptin in determination of insulin resistance in both elderly men and postmenopausal women of equal age was confirmed. However, the study also revealed significant gender differences : in women a strong influence of triglycerides, TNFα and decreased HDL-cholesterol, in men only a mild role of BMI and decreased HDL-cholesterol.

  19. Studies on binding and mitogenic effect of insulin and insulin-like growth factor I in glomerular mesangial cells

    International Nuclear Information System (INIS)

    Conti, F.G.; Striker, L.J.; Lesniak, M.A.; MacKay, K.; Roth, J.; Striker, G.E.

    1988-01-01

    The mesangial cells are actively involved in regulating glomerular hemodynamics. Their overlying endothelium is fenestrated; therefore, these cells are directly exposed to plasma substances, including hormones such as insulin and insulin-like growth factor I (IGF-I). These peptides may contribute to the mesangial sclerosis and cellular hyperplasia that characterize diabetic glomerulopathy. We report herein the characterization of the receptors and the mitogenic effects of IGF-I and insulin on mouse glomerular mesangial cells in culture. The IGF-I receptor was characterized on intact cells. The Kd of the IGF-I receptor was 1.47 X 10(-9) M, and the estimated number of sites was 64,000 receptors/cell. The binding was time, temperature, and pH dependent, and the receptor showed down-regulation after exposure to serum. The expression of the receptor did not change on cells at different densities. The specific binding for insulin was too low to allow characterization of the insulin receptor on intact cells. However, it was possible to identify the insulin receptor in a wheat germ agglutinin-purified preparation of solubilized mesangial cells. This receptor showed the characteristic features of the insulin receptor, including pH dependence of binding and a curvilinear Scatchard plot. The mitogenic effects of insulin and IGF-I on mesangial cells were measured by the incorporation of [3H]thymidine into DNA. IGF-I was more potent than insulin. The half-maximal response to IGF-I stimulation occurred at 1.3 X 10(-10) M, and a similar increase with insulin was observed at concentrations in the range of 10(-7) M, suggesting that this insulin action was mediated through the IGF-I receptor. These data show that the mouse microvascular smooth muscle cells of the glomerulus express a cell surface receptor for IGF-I in vitro and that this peptide is a potent mitogen for these mesangial cells

  20. Insulin-like growth factors and insulin-like growth factor binding proteins in mammary gland function

    International Nuclear Information System (INIS)

    Marshman, Emma; Streuli, Charles H

    2002-01-01

    Insulin-like growth factor (IGF)-mediated proliferation and survival are essential for normal development in the mammary gland during puberty and pregnancy. IGFs interact with IGF-binding proteins and regulate their function. The present review focuses on the role of IGFs and IGF-binding proteins in the mammary gland and describes how modulation of their actions occurs by association with hormones, other growth factors and the extracellular matrix. The review will also highlight the involvement of the IGF axis in breast cancer

  1. Relationships between plasma insulin-like growth factor-1 and insulin concentrations in multiparous dairy cows with cytological endometritis.

    Science.gov (United States)

    Valdmann, Merle; Kurykin, Jevgeni; Kaart, Tanel; Mällo, Gret-Kristel; Waldmann, Andres

    2018-04-21

    Cytological endometritis (CYTO) is a uterine inflammation characterised by the percentage of polymorphonuclear neutrophils in endometrial cytology. This observational study evaluated the association of blood plasma insulin-like growth factor-1 (IGF-1) and insulin concentrations at -2 weeks prepartum, +1 week and +3 weeks postpartum with the development of CYTO in 119 multiparous Holstein cows. Overall CYTO prevalence was 30.3 per cent. Multivariable logistic regression model revealed the odds of developing CYTO were 3.54 times (P=0.018) greater in cows with week -2 prepartum IGF-1 concentrations less than 74.6 ng/ml and 4.41 times (P=0.004) higher in cows with week +1 postpartum IGF-1 concentrations less than 13.2 ng/ml than the odds of this health outcome in cows with IGF-1 concentrations at least 74.6 and13.2 ng/ml, respectively. Additionally, cows with body condition score (BCS) up to 2.75 at week -2 prepartum and cows experiencing calving-related disorders and/or ill health had higher risk for CYTO compared with cows with BCS=3.50-3.75 (OR=6.8, P=0.049) and cows without health complications (OR=3.1, P=0.030). Insulin was not a significant predictor for CYTO in the model. Our findings provide further evidence that reduced dairy cow fertility associated with low plasma concentrations of IGF-1 is in part mediated through the inflammatory status of the uterus. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. 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 ...

  3. Iron and obesity status-associated insulin resistance influence circulating fibroblast-growth factor-23 concentrations.

    Directory of Open Access Journals (Sweden)

    José Manuel Fernández-Real

    Full Text Available Fibroblast growth factor 23 (FGF-23 is known to be produced by the bone and linked to metabolic risk. We aimed to explore circulating FGF-23 in association with fatness and insulin sensitivity, atherosclerosis and bone mineral density (BMD. Circulating intact FGF-23 (iFGF-23 and C-terminal (CtFGF-23 concentrations (ELISA were measured in 133 middle aged men from the general population in association with insulin sensitivity (Cohort 1; and in association with fat mass and bone mineral density (DEXA and atherosclerosis (intima media thickness, IMT in 78 subjects (52 women with a wide range of adiposity (Cohort 2. Circulating iFGF-23 was also measured before and after weight loss. In all subjects as a whole, serum intact and C-terminal concentrations were linearly and positively associated with BMI. In cohort 1, both serum iFGF-23 and CtFGF-23 concentrations increased with insulin resistance. Serum creatinine contributed to iFGF-23 variance, while serum ferritin and insulin sensitivity (but not BMI, age or serum creatinine contributed to 17% of CtFGF-23 variance. In cohort 2, CtFGF-23 levels were higher in women vs. men, and increased with BMI, fat mass, fasting and post-load serum glucose, insulin, HOMA-IR and PTH, being negatively associated with circulating vitamin D and ferritin levels. The associations of CtFGF-23 with bone density in the radius, lumbar spine and carotid IMT were no longer significant after controlling for BMI. Weight loss led to decreased iFGF-23 concentrations. In summary, the associations of circulating FGF-23 concentration with parameters of glucose metabolism, bone density and atherosclerosis are dependent on iron and obesity status-associated insulin resistance.

  4. Insulin-like growth factor-I and the liver

    DEFF Research Database (Denmark)

    Bonefeld, Karen; Møller, Søren

    2011-01-01

    Insulin-like growth factors (IGFs) play an essential role in growth and development, as well as in the overall cellular regulation and metabolism in the human body. In chronic liver disease, IGF levels are decreased, and the circulating levels correlate to the extent of hepatocellular dysfunction...... consequences in cirrhosis are only partly understood. Disruption of the growth hormone (GH)-IGF-I axis seems to be closely associated with the development of liver disease, and treatment with recombinant human IGF (rhIGF)-I has been shown to halt, and even reverse, the fibrotic degeneration. IGF-I in itself...

  5. Polycystic ovary syndrome: cardiovascular risk factors according to specific phenotypes.

    Science.gov (United States)

    Aziz, Mubeena; Sidelmann, Johannes J; Faber, Jens; Wissing, Marie-Louise M; Naver, Klara V; Mikkelsen, Anne-Lis; Nilas, Lisbeth; Skouby, Sven O

    2015-10-01

    Polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance. The objective of this cross-sectional study was to investigate the impact of insulin resistance and body mass index (BMI) on inflammatory and hemostatic variables associated with long-term risk of cardiovascular disease in women with PCOS. 149 premenopausal women with PCOS were recruited consecutively from April 2010 to February 2012 at three Danish University Hospitals. The study was conducted at the Department of Gynecology and Obstetrics, Herlev University Hospital, Denmark. PCOS was diagnosed in accordance with the Rotterdam criteria and the women were classified into four phenotypes according to BMI and insulin resistance measured by the homeostasis model assessment of insulin resistance index. Body composition was determined by dual-energy X-ray absorptiometry. Main outcome measures were the biomarkers C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor antigen. Normal weight insulin-resistant PCOS women were characterized by abdominal obesity and elevated levels of plasma PAI-1. Overweight/obese insulin-resistant PCOS women had increased levels of both PAI-1 and CRP. Of the three Rotterdam criteria, only hyperandrogenemia was significantly associated with the hemostatic risk marker of long-term cardiovascular disease risk. Surrogate risk markers for cardiovascular disease are elevated in women with PCOS, especially insulin-resistant and overweight/obese women. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  6. [Pathological gambling: risk factors].

    Science.gov (United States)

    Bouju, G; Grall-Bronnec, M; Landreat-Guillou, M; Venisse, J-L

    2011-09-01

    In France, consumption of gambling games increased by 148% between 1960 and 2005. In 2004, gamblers lost approximately 0.9% of household income, compared to 0.4% in 1960. This represents approximately 134 Euros per year and per head. In spite of this important increase, the level remains lower than the European average (1%). However, gambling practices may continue to escalate in France in the next few years, particularly with the recent announce of the legalisation of online games and sports betting. With the spread of legalised gambling, pathological gambling rates may increase in France in the next years, in response to more widely available and more attractive gambling opportunities. In this context, there is a need for better understanding of the risk factors that are implicated in the development and maintenance of pathological gambling. This paper briefly describes the major risk factors for pathological gambling by examining the recent published literature available during the first quarter of 2008. This documentary basis was collected by Inserm for the collective expert report procedure on Gambling (contexts and addictions). Seventy-two articles focusing on risk factors for pathological gambling were considered in this review. Only 47 of them were taken into account for analysis. The selection of these 47 publications was based on the guide on literature analysis established by the French National Agency for Accreditation and Assessment in Health (ANAES, 2000). Some publications from more recent literature have also been added, mostly about Internet gambling. We identify three major types of risk factors implicated in gambling problems: some of them are related to the subject (individual factors), others are related to the object of the addiction, here the gambling activity by itself (structural factors), and the last are related to environment (contextual or situational factors). Thus, the development and maintenance of pathological gambling seems to be

  7. Association between insulin resistance and risk of complications in children and adolescents with type 1 diabetes.

    Science.gov (United States)

    Krochik, Andrea G; Botto, Marianela; Bravo, Mónica; Hepner, Mirta; Frontroth, Juan P; Miranda, Miguel; Mazza, Carmen

    2015-01-01

    It has been hypothesized that insulin resistance may be involved in the development of type 1 diabetes complications and early diagnosis would be important for their prevention. Our aim was to study insulin resistance in our population of children with type 1 diabetes and to identify associated early risk factors for micro- and macrovascular complications. A descriptive, cross-sectional study was conducted including 150 children with type 1 diabetes. Anthropometric, bioelectric impedance, carotid Doppler ultrasonography, electromyography, and conduction velocity studies were performed. Baseline plasma glucose, lipid profile, uric acid, plasma thyrotropin, glycosylated hemoglobin A1C, and microalbuminuria were assessed. More insulin-resistant patients were defined as those having an estimated glucose disposal rate (eGDR) value below the first quartile. Clinically manifest microvascular complications were not found in any of the patients. More insulin-resistant patients had a greater sub scapular fold thickness, a higher incidence of obesity (12% vs. 1.7% p 0.007), higher fructosamine levels (496 vs. 403 p19, and a higher incidence of altered lipid metabolism (70% vs. 39% p 0.0007). In the subgroup of patients with lower eGDR there were more children with lipid disorders, obesity, and worse diabetic control, which, if not corrected, may lead to development of micro- and macrovascular complications. Copyright © 2014 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  8. Expression of insulin-like growth factor system components in colorectal tissue and its relation with serum IGF levels

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bosma, A.; Majoor, D.M.; Doorn, van J.; Cats, A.; Depla, A.; Timmer, R.; Witteman, B.J.M.; Wesseling, J.; Kampman, E.; van't Veer, L.J.

    2009-01-01

    Context: The insulin-like growth factor (IGF)-system has been implicated in colorectal tumor carcinogenesis. Although both tumor expression levels and serum concentrations of IGF-system components are related to colorectal cancer risk, it is unknown whether IGF levels in tissue and serum are

  9. Expression of insulin-like growth factor system components in colorectal tissue and its relation with serum IGF levels.

    NARCIS (Netherlands)

    Vrieling, A.; Voskuil, D.W.; Bosma, A.; Majoor, D.M.; Doorn, J. van; Cats, A.; Depla, A.C.; Timmer, R.; Witteman, B.J.; Wesseling, J.; Kampman, E.; Veer, L.J. van 't

    2009-01-01

    CONTEXT: The insulin-like growth factor (IGF)-system has been implicated in colorectal tumor carcinogenesis. Although both tumor expression levels and serum concentrations of IGF-system components are related to colorectal cancer risk, it is unknown whether IGF levels in tissue and serum are

  10. Insulin sensitivity and mortality risk estimation in patients with type 2 ...

    African Journals Online (AJOL)

    Background: There is at present the dearth of information on the possible contribution of insulin resistance to scores obtained from mortality risk estimation in patients with type 2 diabetes mellitus (T2DM). Aim: This study determined the mortality risk scores in patients with T2DM and its relationship with insulin resistance.

  11. Linking lifestyle factors and insulin resistance, based on fasting plasma insulin and HOMA-IR in middle-aged Japanese men: a cross-sectional study.

    Science.gov (United States)

    Otake, Toshie; Fukumoto, Jin; Abe, Masao; Takemura, Shigeki; Mihn, Pham Ngoc; Mizoue, Tetsuya; Kiyohara, Chikako

    2014-09-01

    Insulin resistance (IR) is regarded as one of the earliest features of many metabolic diseases, and major efforts are aimed at improving insulin function to confront this issue. The aim of this study was to investigate the relationship of body mass index (BMI), cigarette smoking, alcohol intake, physical activity, green tea and coffee consumption to IR. We performed a cross-sectional study of 1542 male self defense officials. IR was defined as the highest quartile of the fasting plasma insulin (≥ 50 pmol/L) or the homeostasis model assessment-estimated IR (HOMA-IR ≥ 1.81). An unconditional logistic model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between IR and influential factors. Stratified analysis by obesity status (BMI IR was significantly positively related to BMI and glucose tolerance, negatively related to alcohol use. Independent of obesity status, significant trends were observed between IR and alcohol use. Drinking 30 mL or more of ethanol per day reduced IR by less than 40%. Strong physical activity was associated with decreased risk of IR based on fasting plasma insulin only in the obese. Coffee consumption was inversely associated with the risk of IR based on HOMA-IR in the non-obese group. Higher coffee consumption may be protective against IR among only the non-obese. Further studies are warranted to examine the effect modification of the obesity status on the coffee-IR association.

  12. Diabetes but not insulin increases the risk of lung cancer: a Taiwanese population-based study.

    Directory of Open Access Journals (Sweden)

    Chin-Hsiao Tseng

    Full Text Available BACKGROUND: The trend of lung cancer incidence in Taiwan is unknown, and the association between type 2 diabetes/insulin use and lung cancer is rarely studied. METHODS: The trends of lung cancer incidence in 1979-2007 in the Taiwanese general population were calculated. A random sample of 1,000,000 subjects covered by the National Health Insurance in 2005 was recruited. A total of 494,002 men and 502,948 women and without lung cancer were followed for the annual cumulative incidence of lung cancer in 2005, with calculation of the risk ratios between diabetic and non-diabetic subjects. Logistic regression estimated the adjusted odds ratios for risk factors. RESULTS: The trends increased significantly in both sexes (P<0.0001. The sex-specific annual cumulative incidence increased with age in either the diabetic or non-diabetic subjects, but the risk ratios attenuated with age. In logistic regressions, diabetes was associated with a significantly higher risk, with odds ratios (95% confidence interval for diabetes duration <1, 1-3, 3-5 and ≥5 years versus non-diabetes of 2.189 (1.498-3.200, 1.420 (1.014-1.988, 1.545 (1.132-2.109, and 1.329 (1.063-1.660, respectively. Such an association was not related to a higher detection with chest X-ray examination. Insulin use and medications including oral anti-diabetic drugs, statin, fibrate, and anti-hypertensive agents were not significantly associated with lung cancer. Age, male sex, and chronic obstructive pulmonary disease were positively; but dyslipidemia, stroke and higher socioeconomic status were negatively associated with lung cancer. CONCLUSIONS: Diabetes is significantly associated with a higher risk of lung cancer, but insulin use does not increase the risk.

  13. Insulin resistance and hyperandrogenism drive steatosis and fibrosis risk in young females with PCOS.

    Science.gov (United States)

    Petta, Salvatore; Ciresi, Alessandro; Bianco, Jessica; Geraci, Vincenzo; Boemi, Roberta; Galvano, Luigi; Magliozzo, Franco; Merlino, Giovanni; Craxì, Antonio; Giordano, Carla

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) recognize obesity and insulin resistance (IR) as common pathogenic background. We assessed 1) whether PCOS is a risk factor for steatosis, and 2) the impact, in PCOS patients, of IR and hyperandrogenism on steatosis and fibrosis. We considered 202 consecutive Italian PCOS nondiabetic patients and 101 age-matched controls. PCOS was diagnosed applying the Rotterdam diagnostic criteria. Steatosis was diagnosed if hepatic steatosis index (HSI) >36, while fibrosis by using the FIB-4 score. As surrogate estimate of insulin sensitivity we considered the insulin sensitivity index (ISI). Free androgen index (FAI) was calculated as estimate of biochemical hyperandrogenism. In the entire population, steatosis was observed in 68.8% of patients with PCOS, compared to 33.3 of controls (pPCOS patients, steatosis was independently linked to WC (OR 1.04, 95% CI 1.01-1.08; P = 0.006) and ISI Matsuda (OR 0.69, 95% CI 0.53-0.88; P = 0.004), not to free androgen index (OR 1.10, 95% CI 0.96-1.26; P = 0.14). Notably, ISI Matsuda was confirmed as independently associated with steatosis in both obese (OR 0.42, 95% CI 0.23-0.77, P = 0.005) and nonobese (OR 0.69, 95% CI 0.53-0.91, P = 0.009), patients, while FAI (OR 1.45, 95% CI 1.12-1.87; P = 0.004) emerged as an independent risk factor only in nonobese PCOS. Similarly, higher FIB-4 was independently associated with higher FAI (p = 0.02) in nonobese and with lower ISI Matsuda (p = 0.04) in obese patients. We found that PCOS is an independent risk factor for steatosis, and that, IR and hyperandrogenism, this last especially in nonobese patients, are the key players of liver damage in PCOS.

  14. Use of insulin and insulin analogs and risk of cancer - systematic review and meta-analysis of observational studies

    DEFF Research Database (Denmark)

    Karlstad, Oystein; Linde, Jakob Starup; Vestergaard, Peter

    2013-01-01

    -control studies examining risk of cancer associated with insulin use in patients with diabetes. DATA SOURCES: Systematic literature search in 5 databases: PubMed, Embase, Web of Science, Scopus and Cochrane Library. STUDY ELIGIBILITY CRITERIA (PICOS): POPULATION: diabetes patients. EXPOSURE: Users of any...

  15. Increased abundance of insulin/insulin-like growth factor-I hybrid receptors in skeletal muscle of obese subjects is correlated with in vivo insulin sensitivity.

    Science.gov (United States)

    Federici, M; Porzio, O; Lauro, D; Borboni, P; Giovannone, B; Zucaro, L; Hribal, M L; Sesti, G

    1998-08-01

    We reported that in noninsulin-dependent diabetes melitus (NIDDM) patients expression of insulin/insulin-like growth factor I (IGF-I) hybrid receptors is increased in insulin target tissues. Whether this is a defect associated with NIDDM or represents a generalized abnormality associated with insulin resistant states is still unsettled. To address this, we applied a microwell-based immunoassay to measure abundance of insulin receptors, type 1 IGF receptors, and hybrid receptors in muscle of eight normal and eight obese subjects. Maximal insulin binding to insulin receptors was lower in obese than in control subjects (B/T = 1.8 +/- 0.20 and 2.6 +/- 0.30; P < 0.03, respectively) and was negatively correlated with insulinemia (r = -0.60; P < 0.01). Maximal IGF-I binding to type 1 IGF receptors was higher in obese than in controls (B/T = 1.9 +/- 0.20 and 0.86 +/- 0.10; P < 0.0001, respectively) and was negatively correlated with plasma IGF-I levels (r = -0.69; P < 0.003). Hybrid receptor abundance was higher in obese than in normal subjects (B/T = 1.21 +/- 0.14 and 0.44 +/- 0.06; P < 0.0003, respectively) and was negatively correlated with insulin binding (r = -0.60; P < 0.01) and positively correlated with IGF-I binding (r = 0.92; P < 0.0001). Increased abundance of hybrids was correlated with insulinemia (r = 0.70; P < 0.002) and body mass index (r = 0.71; P < 0.0019), whereas it was negatively correlated with in vivo insulin sensitivity measured by ITT (r = -0.67; P < 0.016). These results indicate that downregulation of insulin receptors or upregulation of type 1 IGF receptors because of changes in plasma insulin and IGF-I levels may result in modifications in hybrid receptor abundance.

  16. Risk factors for cancer

    International Nuclear Information System (INIS)

    Lyman, G.H.

    1992-01-01

    It is no longer reasonable to divide cancers into those that are genetic in origin and those that are environmental in origin. With rare exception, carcinogenesis involves environmental factors that directly or indirectly exert a change in the cell's genome. Virtually all causes of cancer are multifactorial, sometimes involving an inherited predisposition to the carcinogenic effects of environmental factors, which include chemicals, ionizing radiation, and oncogenic virus. Carcinogenesis is a multistep process including induction, promotion, and progression. Initiation requires an irreversible change in the cellular genome, whereas promotion is commonly associated with prolonged and reversible exposure. Tumor progression results in genotypic and phenotypic changes associated with tumor growth, invasion, and metastasis. Most information on human cancer risk is based on epidemiologic studies involving both exposed and unexposed individuals. The quality of such studies depends on their ability to assess the strength of any association of exposure and disease and careful attention to any potential bias. Few cancers are inherited in a Mendelian fashion. Several preneoplastic conditions, however, are clearly inherited and several malignancies demonstrate weak familial patterns. Environmental factors may exert their effect on DNA in a random fashion, but certain consistent changes, including specific translocations of genetic information, are often found. Currently, there is great interest in the close proximity of certain oncogenes governing growth control to the consistent chromosomal changes observed. Such changes may represent a final common pathway of action for environmental carcinogens. Sufficient laboratory and epidemiologic evidence exists to establish a causal association of several chemical agents with cancer

  17. Temporal Relationship Between Hyperuricemia and Insulin Resistance and Its Impact on Future Risk of Hypertension.

    Science.gov (United States)

    Han, Tianshu; Lan, Li; Qu, Rongge; Xu, Qian; Jiang, Ruyue; Na, Lixin; Sun, Changhao

    2017-10-01

    Although hyperuricemia and insulin resistance significantly correlated, their temporal sequence and how the sequence influence on future risk of hypertension are largely unknown. This study assessed temporal relationship between uric acid and insulin resistance and its impact on future risk of hypertension by examining a longitudinal cohort including 8543 subjects aged 20 to 74 years from China, with an average follow-up of 5.3 years. Measurements of fasting uric acid, as well as fasting and 2-hour serum glucose and insulin, were obtained at baseline and follow-up. Indicators of hepatic and peripheral insulin resistance were calculated. Cross-lagged panel and mediation analysis were used to examine the temporal relationship between uric acid and insulin resistance and its impact on follow-up hypertension. After adjusting for covariates, the cross-lagged path coefficients ( β 1 values) from baseline uric acid to follow-up insulin resistance indices were significantly greater than path coefficients ( β 2 values) from baseline insulin resistance indices to follow-up uric acid ( β 1 =0.110 versus β 2 =0.017; P hypertensive group were significantly greater than that in the normotensive group ( P hypertension, and the mediation effect of peripheral insulin resistance was significantly greater than that of hepatic insulin resistance (31.3% versus 13.2%; P hypertension than hepatic insulin resistance does. © 2017 American Heart Association, Inc.

  18. Insulin resistance in type 1 diabetes: what is ?double diabetes? and what are the risks?

    OpenAIRE

    Cleland, S. J.; Fisher, B. M.; Colhoun, H. M.; Sattar, N.; Petrie, J. R.

    2013-01-01

    In this review, we explore the concept of ‘double diabetes’, a combination of type 1 diabetes with features of insulin resistance and type 2 diabetes. After considering whether double diabetes is a useful concept, we discuss potential mechanisms of increased insulin resistance in type 1 diabetes before examining the extent to which double diabetes might increase the risk of cardiovascular disease (CVD). We then go on to consider the proposal that weight gain from intensive insulin regimens ma...

  19. Human insulin-like growth factor II leader 2 mediates internal initiation of translation

    DEFF Research Database (Denmark)

    Pedersen, Susanne; Christiansen, Jan; Hansen, T.O.

    2002-01-01

    Insulin-like growth factor II (IGF-II) is a fetal growth factor, which belongs to the family of insulin-like peptides. During fetal life, the IGF-II gene generates three mRNAs with different 5' untranslated regions (UTRs), but identical coding regions and 3' UTRs. We have shown previously that IG...

  20. Insulin and the Lung

    DEFF Research Database (Denmark)

    Singh, Suchita; Prakash, Y S; Linneberg, Allan

    2013-01-01

    , molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung...... and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin...

  1. Risk Factor Assessment Branch (RFAB)

    Science.gov (United States)

    The Risk Factor Assessment Branch (RFAB) focuses on the development, evaluation, and dissemination of high-quality risk factor metrics, methods, tools, technologies, and resources for use across the cancer research continuum, and the assessment of cancer-related risk factors in the population.

  2. Risk Factors in Pemphigus

    Directory of Open Access Journals (Sweden)

    Gülşen Tükenmez Demirc

    2011-09-01

    Full Text Available Background and Design: There have been reports suggesting the involvement of environmental factors in the disease process of pemphigus. In this study, we aimed to find out the risk factors which could play role in the etiopathogenesis in our pemphigus patients.Material and method: A total of 42 patients (15 male and 27 female who were diagnosed as pemphigus with histopathological and direct immunoflurosence examinations in our clinic between the years 1998-2004, were interviewed for assessment of regarding with the subjects of the demographic properties, occupational groups, educational level, the number of pregnancies, stressfull life events, diet habits, smoking and alcohol consumption before the onset of the disease and the results were compared to 42 age and gender-matched controls with similar socioeconomic circumstances. Results: Working in agriculture and livestock, multi-parity, absence of smoking and stressfull life events were found to be statistically significant in pemphigus patients than in controls. Conclusion: Working in agriculture and livestock, multi-parity, absence of smoking and stressfull life events were assumed to play role in the etiopathogenesis and course of pemphigus.

  3. Insulin-like growth factor I and anthropometric parameters in a Danish population

    DEFF Research Database (Denmark)

    Friedrich, N; Jørgensen, Torben; Juul, A

    2012-01-01

    study was to analyse the associations between anthropometric measures and IGF-I levels in a population-based sample. From the Danish cross-sectional Health2006 study 3,328 subjects (1,835 women; 1,493 men) aged 19-72 years were included in the analyses. Serum IGF-I levels were determined...... consumption, smoking and physical activity. Our large cross-sectional study suggests that IGF-I may serve as the link between obesity and mortality although any causal relation cannot be inferred and longitudinal analyses are needed to clarify the causal relation.......During the last decade several studies indicated that low insulin-like growth factor (IGF) I levels are related to higher risk of cardiovascular disease and mortality. Obesity represents one further main cardiovascular risk factor which might also be related to IGF-I. The objective of the present...

  4. Induction of insulin and islet amyloid polypeptide production in pancreatic islet glucagonoma cells by insulin promoter factor 1

    DEFF Research Database (Denmark)

    Serup, P; Jensen, J; Andersen, F G

    1996-01-01

    Insulin promoter factor 1 (IPF1), a member of the homeodomain protein family, serves an early role in pancreas formation, as evidenced by the lack of pancreas formation in mice carrying a targeted disruption of the IPF1 gene [Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. (1994) Nature (London...

  5. C-reactive protein, insulin resistance and risk of cardiovascular disease: a population-based study

    DEFF Research Database (Denmark)

    Jeppesen, Jørgen; Hansen, Tine Willum; Olsen, Michael H

    2008-01-01

    were recorded at baseline. CRP was determined by a high-sensitivity assay, and IR was determined by the homoeostasis model assessment (HOMA-IR) method. RESULTS: Over a median follow-up of 9.4 years, the incidence of the prespecified CV event, defined as the composite event of CV death, nonfatal...... and HOMA-IR, the hazard ratio (95% confidence interval) of a CV event was 1.33 (1.14-1.55; PHOMA-IR level. CONCLUSION......BACKGROUND: C-reactive protein (CRP), a marker of inflammation, and insulin resistance (IR), a metabolic disorder, are closely related. CRP and IR have both been identified as significant risk factors of cardiovascular disease (CVD) after adjustment for conventional CVD risk factors...

  6. Perinatal risk factors for strabismus

    DEFF Research Database (Denmark)

    Torp-Pedersen, Tobias; Boyd, Heather A; Poulsen, Gry

    2010-01-01

    Little is known about the aetiological factors underlying strabismus. We undertook a large cohort study to investigate perinatal risk factors for strabismus, overall and by subtype.......Little is known about the aetiological factors underlying strabismus. We undertook a large cohort study to investigate perinatal risk factors for strabismus, overall and by subtype....

  7. Effect of Moderate Alcohol Consumption on Adiponectin, Tumor Necrosis Factor-α, and Insulin Sensitivity

    NARCIS (Netherlands)

    Sierksma, A.; Patel, H.; Ouchi, N.; Kihara, S.; Funahashi, T.; Heine, R.J.; Grobbee, D.E.; Kluft, C.; Hendriks, H.F.J.

    2004-01-01

    OBJECTIVE - Epidemiological studies suggest that moderate alcohol consumers have enhanced insulin sensitivity and a reduced risk of type 2 diabetes. Adiponectin, an adipocyte-derived plasma protein, has been found to be negatively associated with adiposity and positively associated with insulin

  8. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Reynisdottir, Inga

    2007-01-01

    We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified...... risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0...... was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion....

  9. Insulin-Like Growth Factor (IGF System in Liver Diseases

    Directory of Open Access Journals (Sweden)

    Agnieszka Adamek

    2018-04-01

    Full Text Available Hepatocyte differentiation, proliferation, and apoptosis are affected by growth factors produced in liver. Insulin-like growth factor 1 and 2 (IGF1 and IGF2 act in response to growth hormone (GH. Other IGF family components include at least six binding proteins (IGFBP1 to 6, manifested by both IGFs develop due to interaction through the type 1 receptor (IGF1R. The data based on animal models and/or in vitro studies suggest the role of IGF system components in cellular aspects of hepatocarcinogenesis (cell cycle progression, uncontrolled proliferation, cell survival, migration, inhibition of apoptosis, protein synthesis and cell growth, and show that systemic IGF1 administration can reduce fibrosis and ameliorate general liver function. In epidemiologic and clinicopathological studies on chronic liver disease (CLD, lowered serum levels, decreased tissue expression of IGF1, elevated production of IGF1R and variable IGF2 expression has been noted, from the start of preneoplastic alterations up to the developed hepatocellular carcinoma (HCC stage. These changes result in well-known clinical symptoms of IGF1 deficiency. This review summarized the current data of the complex role of IGF system components in the most common CLD (nonalcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma. Better recognition and understanding of this system can contribute to discovery of new and improved versions of current preventive and therapeutic actions in CLD.

  10. Insulin treatment and breast cancer risk; A systematic review of in vitro, animal and epidemiological evidence

    NARCIS (Netherlands)

    Bronsveld, Heleen K.; Ter Braak, Bas; Karlstad, Øystein; Vestergaard, Peter; Starup-Linde, Jakob; Bazelier, Marloes T.; de Bruin, Marieke; De Boer, Anthonius; Siezen, Christine L.E.; Van De Water, Bob; Van Der Laan, Jan Willem; Schmidt, Marjanka K.

    2015-01-01

    Background: In 2009, the concern has been raised that insulin analogues, especially insulin glargine, might increase risk of (breast) cancer. Many in vitro and epidemiological and some animal studies have been performed, but there is still no clarity on this issue. Objectives: The aim of this study

  11. Risk factors in school shootings.

    Science.gov (United States)

    Verlinden, S; Hersen, M; Thomas, J

    2000-01-01

    Nine incidents of multiple-victim homicide in American secondary schools are examined and common risk factors are identified. The literature dealing with individual, family, social, societal, and situational risk factors for youth violence and aggression is reviewed along with existing risk assessment methods. Checklists of risk factors for serious youth violence and school violence are used in reviewing each school shooting case. Commonalties among the cases and implications for psychologists practicing in clinical and school settings are discussed.

  12. Prognostic value of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 blood levels in breast cancer.

    Science.gov (United States)

    Hartog, H; Boezen, H M; de Jong, M M; Schaapveld, M; Wesseling, J; van der Graaf, W T A

    2013-12-01

    High circulating insulin-like growth factor 1 (IGF-1) levels are firmly established as a risk factor for developing breast cancer, especially estrogen positive tumors. The effect of circulating IGF-1 on prognosis once a tumor is established is unknown. The authors explored the effect of IGF-1 blood levels and of it's main binding protein, IGFBP-3, on overall survival and occurrence of second primary breast tumors in breast cancer patients, as well as reproductive and lifestyle factors that could modify this risk. Patients were accrued from six hospitals in the Netherlands between 1998 and 2003. Total IGF-1 and IGFBP-3 were measured in 582 plasma samples. No significant association between IGF-1 and IGFBP-3 plasma levels and overall survival was found. However, in a multivariate Cox regression model including standard prognostic variables high IGF-1 levels were related to worse overall survival in patients receiving endocrine therapy (HR = 1.37, 95% CI: 1.11, 1.69, P 0.004). These data at least indicate that higher IGF-1 levels, and as a consequence most likely IGF-1-induced signaling, are related to a less favorable overall survival in breast cancer patients treated with endocrine therapy. Interventions aimed at reducing circulating levels of IGF-1 in hormone receptor positive breast cancer may improve survival. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Cytokines and clustered cardiovascular risk factors in children

    DEFF Research Database (Denmark)

    Andersen, Lars Bo; Müller, Klaus; Eiberg, Stig

    2010-01-01

    pronounced in fat and unfit children based on the association with CRP levels. The association between fitness and fatness variables, insulin resistance, and clustered risk could be caused by other mechanisms related to these exposures. The role of IL-6 remains unclear.......The aim was to evaluate the possible role of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), C-reactive protein (CRP), low fitness, and fatness in the early development of clustering of cardiovascular disease (CVD) risk factors and insulin resistance. Subjects for this cross......-sectional study were obtained from 18 schools near Copenhagen, Denmark. Two hundred ten 9-year-old children were selected for cytokine analysis from 434 third-grade children with complete CVD risk profiles. The subgroup was selected according to the CVD risk factor profile (upper and lower quartile of a composite...

  14. Risks factoring business: accounting measurement

    Directory of Open Access Journals (Sweden)

    Z.V. Gutsaylyuk

    2015-06-01

    Full Text Available The paper carried out the identification of risk factors for the development of possible accounting software management. Studied theoretical and methodological aspects of the risk classification of factoring operations in the part of the risk assessment factors. It is proposed to consider the risks factors as the risk that is acceptable controlled by accounting instruments and the risks that can not be taken into account in the accounting records. To minimize the risk factor, accounting-driven tools, a method of self-insurance, which is a factor in the creation of provision for factoring transactions designed to cover unexpected expenses and losses. Provision for factoring factor will establish more stable conditions of financial activity and avoid the fluctuations of profit factor in relation to the writing off of losses on factoring operatsіyam.Developed proposals allow for further research to improve the organizational and methodological basis of accounting and analysis of information as a basis for providing risk management factor, particularly in terms of improving the evaluation questions such risks and their qualitative and quantitative analysis.

  15. Stroke Risk Factors and Symptoms

    Science.gov (United States)

    ... » [ pdf, 433 kb ] Order Materials » Stroke Risk Factors and Symptoms Risk Factors for a Stroke Stroke prevention is still ... it. Treatment can delay complications that increase the risk of stroke. Transient ischemic attacks (TIAs). Seek help. ...

  16. 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

  17. Insulin-like growth factor I: a biologic maturation indicator.

    Science.gov (United States)

    Ishaq, Ramy Abdul Rahman; Soliman, Sanaa Abou Zeid; Foda, Manal Yehya; Fayed, Mona Mohamed Salah

    2012-11-01

    Determination of the maturation level and the subsequent evaluation of growth potential during preadolescence and adolescence are important for optimal orthodontic treatment planning and timing. This study was undertaken to evaluate the applicability of insulin-like growth factor I (IGF-I) blood level as a maturation indicator by correlating it to the cervical vertebral maturation index. The study was conducted with 120 subjects, equally divided into 60 males (ages, 10-18 years) and 60 females (ages, 8-16 years). A lateral cephalometric radiograph and a blood sample were taken from each subject. For each subject, cervical vertebral maturation and IGF-I serum level were assessed. Mean values of IGF-I in each stage of cervical vertebral maturation were calculated, and the means in each stage were statistically compared with those of the other stages. The IGF-I mean value at each cervical vertebral maturation stage was statistically different from the mean values at the other stages. The highest mean values were observed in stage 4, followed by stage 5 in males and stage 3 in females. IGF-I serum level is a reliable maturation indicator that could be applied in orthodontic diagnosis. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  18. 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.

  19. Fracture Risk and Risk Factors for Osteoporosis.

    Science.gov (United States)

    Schürer, Christian; Wallaschofski, Henri; Nauck, Matthias; Völzke, Henry; Schober, Hans-Christof; Hannemann, Anke

    2015-05-25

    As the population ages, diseases of the elderly are becoming more common, including osteoporosis. Ways to assess the risk of fracture and the distribution and effects of known risk factors for osteoporosis will be important in planning for future healthcare needs, as well as in the development of preventive strategies. The study population included 6029 men and women aged 20-90 who underwent examination in the second follow-up wave of the Study of Health in Pomerania (SHIP-2) or in the basal SHIP-Trend Study. The risk of fracture was estimated on the basis of quantitative ultrasonography of the calcaneus. Prior fractures and risk factors for osteoporosis were ascertained in standardized interviews. 4.6% of the male subjects and 10.6% of the female subjects were judged to have an elevated risk of fracture. The corresponding percentages among subjects over age 65 were 8.8% for men and 28.2% for women. Even among subjects under age 55, risk factors for osteoporosis were associated with lower bone stiffness: the mean stiffness index was 103/98 (men/women) without risk factors, 99/96 with one risk factor, and 93/95 with more than one risk factor. Logistic regression analysis yielded an odds ratio of 1.89 (95% confidence interval: 1.44-2.50; p<0.01) for prevalent fractures among subjects aged 75 and older compared to subjects under age 55. The data indicate a high prevalence of osteoporosis from age 65 onward. These findings are consistent with those of other studies from Germany and across Europe. Younger men and women should already begin taking steps to counteract modifiable risk factors.

  20. Importance of radioimmunoassay of insulin secretion disorder as atherogenic factor

    Energy Technology Data Exchange (ETDEWEB)

    Knyazev, Yu A; Bespalova, V A; Vakhrusheva, L L; Kirbasova, N P; Severtseva, V V

    1984-11-01

    Using a radioimmunoassay a C-peptide levei was revealed in children, pregnant and lying-in women as well as in patients with insulin-dependent diabetes mellitus. After breakfast and insulin administration wich curative purposes the IRI concentration in children increased whereas the C-peptide level changed insignificantly. Changes of the insulin secretion were more noticeable in severe diabetes mejlitus with vascular complications and in disease decompensation. The atherogenic nature of the lipid metaboiism (an increase in the cholesterol, triglyceride and ..beta..-lipoprotein levels), changes in the liver and tendency to vascular involvement are results of insulin effect inadequacy. Such metabolic derangements in pregnant women create unfavorable conditions for the development of fetus and may lead to early atherogenic processes.

  1. Adipokines and Hepatic Insulin Resistance

    Science.gov (United States)

    Hassan, Waseem

    2013-01-01

    Obesity is a major risk factor for insulin resistance and type 2 diabetes. Adipose tissue is now considered to be an active endocrine organ that secretes various adipokines such as adiponectin, leptin, resistin, tumour necrosis factor-α, and interleukin-6. Recent studies have shown that these factors might provide a molecular link between increased adiposity and impaired insulin sensitivity. Since hepatic insulin resistance plays the key role in the whole body insulin resistance, clarification of the regulatory processes about hepatic insulin resistance by adipokines in rodents and human would seem essential in order to understand the mechanism of type 2 diabetes and for developing novel therapeutic strategies to treat it. PMID:23762871

  2. Utility of Childhood Glucose Homeostasis Variables in Predicting Adult Diabetes and Related Cardiometabolic Risk Factors

    OpenAIRE

    Nguyen, Quoc Manh; Srinivasan, Sathanur R.; Xu, Ji-Hua; Chen, Wei; Kieltyka, Lyn; Berenson, Gerald S.

    2009-01-01

    OBJECTIVE This study examines the usefulness of childhood glucose homeostasis variables (glucose, insulin, and insulin resistance index [homeostasis model assessment of insulin resistance {HOMA-IR}]) in predicting pre-diabetes and type 2 diabetes and related cardiometabolic risk factors in adulthood. RESEARCH DESIGN AND METHODS This retrospective cohort study consisted of normoglycemic (n = 1,058), pre-diabetic (n = 37), and type 2 diabetic (n = 25) adults aged 19–39 years who were followed o...

  3. Microbial Translocation in HIV Infection is Associated with Dyslipidemia, Insulin Resistance, and Risk of Myocardial Infarction

    DEFF Research Database (Denmark)

    Pedersen, Karin Kaereby; Pedersen, Maria; Trøseid, Marius

    2013-01-01

    Microbial translocation has been suggested to be a driver of immune activation and inflammation. We hypothesized that microbial translocation may be related to dyslipidemia, insulin resistance, and the risk of coronary heart disease in HIV-infected individuals.......Microbial translocation has been suggested to be a driver of immune activation and inflammation. We hypothesized that microbial translocation may be related to dyslipidemia, insulin resistance, and the risk of coronary heart disease in HIV-infected individuals....

  4. Circulating growth factors data associated with insulin secretagogue use in women with incident breast cancer

    Directory of Open Access Journals (Sweden)

    Zachary A.P. Wintrob

    2017-04-01

    Full Text Available Oral drugs stimulating insulin production may impact growth factor levels. The data presented shows the relationship between pre-existing insulin secretagogues use, growth factor profiles at the time of breast cancer diagnosis and subsequent cancer outcomes in women diagnosed with breast cancer and type 2 diabetes mellitus. A Pearson correlation analysis evaluating the relationship between growth factors stratified by diabetes pharmacotherapy and controls is also provided.

  5. Epidermal growth factor and insulin-like growth factor I upregulate the expression of the epidermal growth factor system in rat liver

    DEFF Research Database (Denmark)

    Bor, M V; Sørensen, B S; Vinter-Jensen, L

    2000-01-01

    BACKGROUND/AIM: Both epidermal growth factor and insulin-like growth factor I play a role in connection with the liver. In the present study, the possible interaction of these two growth factor systems was studied by investigating the effect of epidermal growth factor or insulin-like growth factor...... I treatment on the expression of the epidermal growth factor receptor, and its activating ligands, transforming growth factor-alpha and epidermal growth factor. METHODS: Fifty-five male rats received no treatment, human recombinant epidermal growth factor or human recombinant insulin-like growth.......8+/-1.6 fmol/mg protein epidermal growth factor and 144+/-22 fmol/mg protein transforming growth factor-alpha. Both epidermal growth factor and insulin-like growth factor I treatment increased the expression of mRNA for transforming growth factor-alpha and epidermal growth factor receptor, as well...

  6. Liver-derived systemic factors drive β-cell hyperplasia in insulin resistant states

    Energy Technology Data Exchange (ETDEWEB)

    El Ouaamari, Abdelfattah; Kawamori, Dan; Dirice, Ercument; Liew, Chong Wee; Shadrach, Jennifer L.; Hu, Jiang; Katsuta, Hitoshi; Hollister-Lock, Jennifer; Qian, Weijun; Wagers, Amy J.; Kulkarni, Rohit N.

    2013-02-21

    Integrative organ cross-talk regulates key aspects of energy homeostasis and its dysregulation may underlie metabolic disorders such as obesity and diabetes. To test the hypothesis that cross-talk between the liver and pancreatic islets modulates β-cell growth in response to insulin resistance, we used the Liver-specific Insulin Receptor Knockout (LIRKO) mouse, a unique model that exhibits dramatic islet hyperplasia. Using complementary in vivo parabiosis and transplantation assays, and in vitro islet culture approaches, we demonstrate that humoral, non-neural, non-cell autonomous factor(s) induce β-cell proliferation in LIRKO mice. Furthermore, we report that a hepatocyte-derived factor(s) stimulates mouse and human β-cell proliferation in ex vivo assays, independent of ambient glucose and insulin levels. These data implicate the liver as a critical source of β-cell growth factors in insulin resistant states.

  7. Risk factors for stress fractures.

    Science.gov (United States)

    Bennell, K; Matheson, G; Meeuwisse, W; Brukner, P

    1999-08-01

    Preventing stress fractures requires knowledge of the risk factors that predispose to this injury. The aetiology of stress fractures is multifactorial, but methodological limitations and expediency often lead to research study designs that evaluate individual risk factors. Intrinsic risk factors include mechanical factors such as bone density, skeletal alignment and body size and composition, physiological factors such as bone turnover rate, flexibility, and muscular strength and endurance, as well as hormonal and nutritional factors. Extrinsic risk factors include mechanical factors such as surface, footwear and external loading as well as physical training parameters. Psychological traits may also play a role in increasing stress fracture risk. Equally important to these types of analyses of individual risk factors is the integration of information to produce a composite picture of risk. The purpose of this paper is to critically appraise the existing literature by evaluating study design and quality, in order to provide a current synopsis of the known scientific information related to stress fracture risk factors. The literature is not fully complete with well conducted studies on this topic, but a great deal of information has accumulated over the past 20 years. Although stress fractures result from repeated loading, the exact contribution of training factors (volume, intensity, surface) has not been clearly established. From what we do know, menstrual disturbances, caloric restriction, lower bone density, muscle weakness and leg length differences are risk factors for stress fracture. Other time-honoured risk factors such as lower extremity alignment have not been shown to be causative even though anecdotal evidence indicates they are likely to play an important role in stress fracture pathogenesis.

  8. Managing Multiple Risk Factors

    National Research Council Canada - National Science Library

    Lollis, Charlie

    1998-01-01

    ...) contribute to the racial differences in cardiovascular risk and events among women. High levels of socioeconomic stress, higher dietary fat intake and sedentary lifestyle are more prevalent among black than white women...

  9. The regulation of reproductive neuroendocrine function by insulin and insulin-like growth factor-1 (IGF-1).

    Science.gov (United States)

    Wolfe, Andrew; Divall, Sara; Wu, Sheng

    2014-10-01

    The mammalian reproductive hormone axis regulates gonadal steroid hormone levels and gonadal function essential for reproduction. The neuroendocrine control of the axis integrates signals from a wide array of inputs. The regulatory pathways important for mediating these inputs have been the subject of numerous studies. One class of proteins that have been shown to mediate metabolic and growth signals to the CNS includes Insulin and IGF-1. These proteins are structurally related and can exert endocrine and growth factor like action via related receptor tyrosine kinases. The role that insulin and IGF-1 play in controlling the hypothalamus and pituitary and their role in regulating puberty and nutritional control of reproduction has been studied extensively. This review summarizes the in vitro and in vivo models that have been used to study these neuroendocrine structures and the influence of these growth factors on neuroendocrine control of reproduction. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Adenovirus E4-ORF1 Dysregulates Epidermal Growth Factor and Insulin/Insulin-Like Growth Factor Receptors To Mediate Constitutive Myc Expression

    OpenAIRE

    Kong, Kathleen; Kumar, Manish; Taruishi, Midori; Javier, Ronald T.

    2015-01-01

    The E4-ORF1 protein encoded by human adenovirus stimulates viral replication in human epithelial cells by binding and activating cellular phosphatidylinositol 3-kinase (PI3K) at the plasma membrane and cellular Myc in the nucleus. In this study, we showed that E4-ORF1 hijacks the tyrosine kinase activities of cellular epidermal growth factor receptor (EGFR) and insulin receptor (InsR)/insulin-like growth factor receptor 1 (IGF1R), as well as the lipid kinase activity of PI3K, to mediate const...

  11. Elevated C-peptide and insulin predict increased risk of colorectal adenomas in normal mucosa

    International Nuclear Information System (INIS)

    Vidal, Adriana C; Keku, Temitope O; Lund, Pauline Kay; Hoyo, Cathrine; Galanko, Joseph; Burcal, Lauren; Holston, Rachel; Massa, Berri; Omofoye, Oluwaseun; Sandler, Robert S

    2012-01-01

    Lower concentrations of the insulin–like growth factor binding protein-1 (IGFBP-1) and elevated concentrations of insulin or C-peptide have been associated with an increase in colorectal cancer risk (CRC). However few studies have evaluated IGFBP-1 and C-peptide in relation to adenomatous polyps, the only known precursor for CRC. Between November 2001 and December 2002, we examined associations between circulating concentrations of insulin, C-peptide, IGFBP-1 and apoptosis among 190 individuals with one or more adenomatous polyps and 488 with no adenomatous polyps using logistic regression models. Individuals with the highest concentrations of C-peptide were more likely to have adenomas (OR = 2.2, 95% CI 1.4-4.0) than those with the lowest concentrations; associations that appeared to be stronger in men (OR = 4.4, 95% CI 1.7-10.9) than women. Individuals with high insulin concentrations also had a higher risk of adenomas (OR = 3.5, 95% CI 1.7-7.4), whereas higher levels of IGFBP-1 were associated with a reduced risk of adenomas in men only (OR = 0.3, 95% CI 0.1-0.7). Overweight and obese individuals with higher C-peptide levels (>1 st Q) were at increased risk for lower apoptosis index (OR = 2.5, 95% CI 0.9-7.1), an association that remained strong in overweight and obese men (OR = 6.3, 95% CI 1.0-36.7). Higher levels of IGFBP-1 in overweight and obese individuals were associated with a reduced risk of low apoptosis (OR = 0.3, 95% CI 0.1-1.0). Associations between these peptides and the apoptosis index in overweight and obese individuals, suggest that the mechanism by which C-peptide could induce adenomas may include its anti-apoptotic properties. This study suggests that hyperinsulinemia and IGF hormones predict adenoma risk, and that outcomes associated with colorectal carcinogenesis maybe modified by gender

  12. Hidden Risk Factors for Women

    Science.gov (United States)

    ... A.S.T. Quiz Hidden Stroke Risk Factors for Women Updated:Nov 22,2016 Excerpted from "What Women Need To Know About The Hidden Risk Factors ... 2012) This year, more than 100,000 U.S. women under 65 will have a stroke. Stroke is ...

  13. Neuroprotective Effect of Insulin-like Growth Factor-II on 1- Methyl-4 ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research July 2015; 14 (7): 1191-1197 ... Abstract. Purpose: To evaluate the receptor-mediated neuroprotective effect of insulin-like growth factor-II (IGF- ... catecholamines, reduces levels of dopamine and.

  14. 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

  15. Autocrine growth induced by the insulin-related factor in the insulin-independent teratoma cell line 1246-3A

    International Nuclear Information System (INIS)

    Yamada, Yukio; Serrero, G.

    1988-01-01

    An insulin-independent teratoma-derived cell line, called 1246-3A, has been isolated from the adipogenic cell line 1246, which stringently requires insulin for proliferation. The 1246-3A cell line, which can proliferate in the absence of exogenous insulin, produces in its conditioned medium a growth factor similar to pancreatic insulin by its biological and immunological properties. This factor, called insulin-related factor (IRF), was purified and iodinated to study its binding to cell surface receptors. 125 I-labeled IRF binding to intact 1246-3A cells is lower than to 1246 cells. Cell surface binding can be restored by culturing the 1246-3A cells in the presence of an anti-porcine insulin monoclonal antibody of by acid prewash of the cells prior to performing the binding. Scatchard analysis of binding indicates that IRF secreted by the 1246-3A cells partially occupies high-affinity binding sites on the producer cells. Moreover, insulin monoclonal antibody inhibits the proliferation of the IRF-producing 1246-3A cells, suggesting that these cells are dependent on the secreted IRF for growth in culture. The authors conclude that the insulin-related factor secreted by the insulin-independent 1246-3A cells stimulates their proliferation in an autocrine fashion

  16. Elevated insulin and reduced insulin like growth factor binding protein-3/prostate specific antigen ratio with increase in prostate size in Benign Prostatic Hyperplasia.

    Science.gov (United States)

    Sreenivasulu, Karli; Nandeesha, Hanumanthappa; Dorairajan, Lalgudi Narayanan; Rajappa, Medha; Vinayagam, Vickneshwaran

    2017-06-01

    Insulin and insulin like growth factor-1 (IGF-1) have growth promoting effects, while insulin like growth factor binding protein-3 (IGFBP-3) has growth inhibitory effects. The present study was designed to assess the concentrations of insulin, IGF-1, IGFBP-3 and their association with prostate size in patients with BPH. Ninety 90 BPH cases and 90 controls were enrolled in the study. Insulin, IGF-1, IGFBP-3, PSA, testosterone and estradiol were estimated in both the groups. Insulin, IGF-1 and estradiol were increased and IGFBP-3/PSA was decreased in BPH cases when compared with controls. Insulin (r=0.64, p=0.001) and IGF-1 (r=0.22, p=0.03) were positively correlated and IGFBP-3/PSA (r=-0.316, p=0.002) were negatively correlated with prostate size in BPH. Multivariate analysis showed that insulin (p=0.001) and IGFBP-3/PSA (p=0.004) predicts the prostate size in patients with BPH. Insulin was increased and IGFBP-3/PSA was reduced in BPH patients with increased prostate size. At a cutoff concentration of 527.52, IGFBP-3/PSA ratio was found to differentiate benign growth of prostate from normal prostate with 96% sensitivity and 96% specificity. Insulin is elevated and IGFBP-3/PSA is reduced with increase prostate size in BPH cases. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Environmental risk factors and pressures

    International Nuclear Information System (INIS)

    Klinda, J.; Lieskovska, Z.

    1998-01-01

    In this chapter the physical risk factors (as radiation [air contamination, contamination of the environment components and food contamination], radon and its radioactive decay products, radioactive wastes, noise), chemical risk factors [chemical substances, xenobiotics in the food chain the ozone depletion], wastes (waste generation, waste management, municipal waste management, import, export and transit of waste) and natural an technological hazards (water quality deterioration as a result of various accidents and fire risk) in the Slovak Republic in 1997 are reviewed

  18. Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts

    International Nuclear Information System (INIS)

    DiCicco-Bloom, E.; Black, I.B.

    1988-01-01

    While neuronal mitosis is uniquely restricted to early development, the underlying regulation remains to be defined. The authors have now developed a dissociated, embryonic sympathetic neuron culture system that uses fully defined medium in which cells enter the mitotic cycle. The cultured cells expressed two neuronal traits, tyrosine hydroxylase and the neuron-specific 160-kDa neurofilament subunit protein, but were devoid of glial fibrillary acidic protein, a marker for non-myelin-forming Schwann cells in ganglia. Approximately one-third of the tyrosine hydroxylase-positive cells synthesized DNA in culture, specifically incorporating [ 3 H]thymidine into their nuclei. They used this system to define factors regulating the mitotic cycle in sympathetic neuroblasts. Members of the insulin family of growth factors, including insulin and insulin-like growth factors I and II, regulated DNA synthesis in the presumptive neuroblasts. Insulin more than doubled the proportion of tyrosine hydroxylase-positive cells entering the mitotic cycle, as indicated by autoradiography of [ 3 H]thymidine incorporation into nuclei. Scintillation spectrometry was an even more sensitive index of DNA synthesis. In contrast, the trophic protein nerve growth factor exhibited no mitogenic effect, suggesting that the mitogenic action of insulin growth factors is highly specific. The observations are discussed in the context of the detection of insulin growth factors and receptors in the developing brain

  19. Cardiovascular risk factors and dementia.

    Science.gov (United States)

    Fillit, Howard; Nash, David T; Rundek, Tatjana; Zuckerman, Andrea

    2008-06-01

    Dementias, such as Alzheimer's disease (AD) and vascular dementia, are disorders of aging populations and represent a significant economic burden. Evidence is accumulating to suggest that cardiovascular disease (CVD) risk factors may be instrumental in the development of dementia. The goal of this review was to discuss the relationship between specific CVD risk factors and dementia and how current treatment strategies for dementia should focus on reducing CVD risks. We conducted a review of the literature for the simultaneous presence of 2 major topics, cardiovascular risk factors and dementia (eg, AD). Special emphasis was placed on clinical outcome studies examining the effects of treatments of pharmacologically modifiable CVD risk factors on dementia and cognitive impairment. Lifestyle risk factors for CVD, such as obesity, lack of exercise, smoking, and certain psychosocial factors, have been associated with an increased risk of cognitive decline and dementia. Some evidence suggests that effectively managing these factors may prevent cognitive decline/dementia. Randomized, placebo-controlled trials of antihypertensive medications have found that such therapy may reduce the risk of cognitive decline, and limited data suggest a benefit for patients with AD. Some small open-label and randomized clinical trials of statins have observed positive effects on cognitive function; larger studies of statins in patients with AD are ongoing. Although more research is needed, current evidence indicates an association between CVD risk factors--such as hypertension, dyslipidemia, and diabetes mellitus--and cognitive decline/dementia. From a clinical perspective, these data further support the rationale for physicians to provide effective management of CVD risk factors and for patients to be compliant with such recommendations to possibly prevent cognitive decline/dementia.

  20. Insulin resistance and risk of incident cardiovascular events in adults without diabetes: meta-analysis.

    Directory of Open Access Journals (Sweden)

    Karin B Gast

    Full Text Available BACKGROUND: Glucose, insulin and Homeostasis Model Assessment Insulin Resistance (HOMA-IR are markers of insulin resistance. The objective of this study is to compare fasting glucose, fasting insulin concentrations and HOMA-IR in strength of association with incident cardiovascular disease. METHODS: We searched the PubMed, MEDLINE, EMBASE, Web of Science, ScienceDirect and Cochrane Library databases from inception to March, 2011, and screened reference lists. Cohort studies or nested case-control studies that investigated the association between fasting glucose, fasting insulin or HOMA-IR and incident cardiovascular disease, were eligible. Two investigators independently performed the article selection, data extraction and risk of bias assessment. Cardiovascular endpoints were coronary heart disease (CHD, stroke or combined cardiovascular disease. We used fixed and random-effect meta-analyses to calculate the pooled relative risk for CHD, stroke and combined cardiovascular disease, comparing high to low concentrations of glucose, insulin or HOMA-IR. Study heterogeneity was calculated with the I(2 statistic. To enable a comparison between cardiovascular disease risks for glucose, insulin and HOMA-IR, we calculated pooled relative risks per increase of one standard deviation. RESULTS: We included 65 studies (involving 516,325 participants in this meta-analysis. In a random-effect meta-analysis the pooled relative risk of CHD (95% CI; I(2 comparing high to low concentrations was 1.52 (1.31, 1.76; 62.4% for glucose, 1.12 (0.92, 1.37; 41.0% for insulin and 1.64 (1.35, 2.00; 0% for HOMA-IR. The pooled relative risk of CHD per one standard deviation increase was 1.21 (1.13, 1.30; 64.9% for glucose, 1.04 (0.96, 1.12; 43.0% for insulin and 1.46 (1.26, 1.69; 0.0% for HOMA-IR. CONCLUSIONS: The relative risk of cardiovascular disease was higher for an increase of one standard deviation in HOMA-IR compared to an increase of one standard deviation in fasting

  1. Treatment of dwarfism with recombinant human insulin-like growth factor-1.

    Science.gov (United States)

    Ranke, Michael B; Wölfle, Joachim; Schnabel, Dirk; Bettendorf, Markus

    2009-10-01

    The growth hormone-IGF (insulin-like growth factor) system plays a central role in hormonal growth regulation. Recombinant human (rh) growth hormone (GH) has been available since the late 1980s for replacement therapy in GH-deficient patients and for the stimulation of growth in patients with short stature of various causes. Growth promotion by GH occurs in part indirectly through the induction of IGF-1 synthesis. In primary disturbances of IGF-1 production, short stature can only be treated with recombinant human IGF-1 (rhIGF-1). rhIGF-1 was recently approved for this indication but can also be used to treat other conditions. Selective review of the literature on IGF-1 therapy, based on a PubMed search. In children with severe primary IGF-1 deficiency (a rare condition whose prevalence is less than 1:10,000), the prognosis for final height is very poor (ca. 130 cm), and IGF-1 therapy is the appropriate form of pathophysiologically based treatment. There is no alternative treatment at present. The subcutaneous administration of IGF-1 twice daily in doses of 80 to 120 microg/kg accelerates growth and increases final height by 12 to 15 cm, according to current data. There is, however, a risk of hypoglycemia, as IGF-1 has an insulin-like effect. As treatment with IGF-1 is complex, this new medication should only be prescribed, for the time being, by experienced pediatric endocrinologists and diabetologists.

  2. Insulin-like growth factor-1 signaling in renal cell carcinoma

    International Nuclear Information System (INIS)

    Tracz, Adam F.; Szczylik, Cezary; Porta, Camillo; Czarnecka, Anna M.

    2016-01-01

    Renal cell carcinoma (RCC) incidence is highest in highly developed countries and it is the seventh most common neoplasm diagnosed. RCC management include nephrectomy and targeted therapies. Type 1 insulin-like growth factor (IGF-1) pathway plays an important role in cell proliferation and apoptosis resistance. IGF-1 and insulin share overlapping downstream signaling pathways in normal and cancer cells. IGF-1 receptor (IGF1R) stimulation may promote malignant transformation promoting cell proliferation, dedifferentiation and inhibiting apoptosis. Clear cell renal cell carcinoma (ccRCC) patients with IGF1R overexpression have 70 % increased risk of death compared to patients who had tumors without IGF1R expression. IGF1R signaling deregulation may results in p53, WT, BRCA1, VHL loss of function. RCC cells with high expression of IGF1R are more resistant to chemotherapy than cells with low expression. Silencing of IGF1R increase the chemosensitivity of ccRCC cells and the effect is greater in VHL mutated cells. Understanding the role of IGF-1 signaling pathway in RCC may result in development of new targeted therapeutic interventions. First preclinical attempts with anti-IGF-1R monoclonal antibodies or fragment antigen-binding (Fab) fragments alone or in combination with an mTOR inhibitor were shown to inhibit in vitro growth and reduced the number of colonies formed by of RCC cells

  3. Cardiovascular risk factors in men

    DEFF Research Database (Denmark)

    Gyllenborg, J; Rasmussen, S L; Borch-Johnsen, Knut

    2001-01-01

    Males have higher risk of cardiovascular disease (CVD) than premenopausal females. Gonadal steroids are probably involved in the gender difference in CVD, but previous results have been conflicting. We investigated the associations between CVD risk factors and sex hormones in a cross-sectional de......Males have higher risk of cardiovascular disease (CVD) than premenopausal females. Gonadal steroids are probably involved in the gender difference in CVD, but previous results have been conflicting. We investigated the associations between CVD risk factors and sex hormones in a cross...

  4. Systemic administration of kainic acid induces selective time dependent decrease in [125I]insulin-like growth factor I, [125I]insulin-like growth factor II and [125I]insulin receptor binding sites in adult rat hippocampal formation

    International Nuclear Information System (INIS)

    Quirion, R.; Chabot, J.-G.; Dore, S.; Seto, D.; Kar, S.

    1997-01-01

    Administration of kainic acid evokes acute seizure in hippocampal pathways that results in a complex sequence of functional and structural alterations resembling human temporal lobe epilepsy. The structural alterations induced by kainic acid include selective loss of neurones in CA1-CA3 subfields and the hilar region of the dentate gyrus followed by sprouting and permanent reorganization of the synaptic connections of the mossy fibre pathways. Although the neuronal degeneration and process of reactive synaptogenesis have been extensively studied, at present little is known about means to prevent pathological conditions leading to kainate-induced cell death. In the present study, to address the role of insulin-like growth factors I and II, and insulin in neuronal survival as well as synaptic reorganization following kainate-induced seizure, the time course alterations of the corresponding receptors were evaluated. Additionally, using histological preparations, the temporal profile of neuronal degeneration and hypertrophy of resident astroglial cells were also studied. [ 125 I]Insulin-like growth factor I binding was found to be decreased transiently in almost all regions of the hippocampal formation at 12 h following treatment with kainic acid. The dentate hilar region however, exhibited protracted decreases in [ 125 I]insulin-like growth factor I receptor sites throughout (i.e. 30 days) the study. [ 125 I]Insulin-like growth factor II receptor binding sites in the hippocampal formation were found to be differentially altered following systemic administration of kainic acid. A significant decrease in [ 125 I]insulin-like growth factor II receptor sites was observed in CA1 subfield and the pyramidal cell layer of the Ammon's horn at all time points studied whereas the hilar region and the stratum radiatum did not exhibit alteration at any time. A kainate-induced decrease in [ 125 I]insulin receptor binding was noted at all time points in the molecular layer of the

  5. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel

    2014-01-01

    OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...... was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...

  6. Role of Transcription Factor Modifications in the Pathogenesis of Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Mi-Young Kim

    2012-01-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is characterized by fat accumulation in the liver not due to alcohol abuse. NAFLD is accompanied by variety of symptoms related to metabolic syndrome. Although the metabolic link between NAFLD and insulin resistance is not fully understood, it is clear that NAFLD is one of the main cause of insulin resistance. NAFLD is shown to affect the functions of other organs, including pancreas, adipose tissue, muscle and inflammatory systems. Currently efforts are being made to understand molecular mechanism of interrelationship between NAFLD and insulin resistance at the transcriptional level with specific focus on post-translational modification (PTM of transcription factors. PTM of transcription factors plays a key role in controlling numerous biological events, including cellular energy metabolism, cell-cycle progression, and organ development. Cell type- and tissue-specific reversible modifications include lysine acetylation, methylation, ubiquitination, and SUMOylation. Moreover, phosphorylation and O-GlcNAcylation on serine and threonine residues have been shown to affect protein stability, subcellular distribution, DNA-binding affinity, and transcriptional activity. PTMs of transcription factors involved in insulin-sensitive tissues confer specific adaptive mechanisms in response to internal or external stimuli. Our understanding of the interplay between these modifications and their effects on transcriptional regulation is growing. Here, we summarize the diverse roles of PTMs in insulin-sensitive tissues and their involvement in the pathogenesis of insulin resistance.

  7. Insulin Like Growth Factor System: How Does it Affect Neonatal Anthropometry?

    Directory of Open Access Journals (Sweden)

    Emine Kacar

    2016-09-01

    Full Text Available Aim: The present study aims to clarify the role of insulin like growth factor-1 (IGF-1, insulin like growth factor binding protein-3 (IGFBP-3, ghrelin, and insulin in fetal growth. Material and Method: Based on Turkish standards, 14 newborns were defined as small for gestational age (SGA, 33 newborns were described as appropriate for gestational age (AGA, and 13 newborns were identified as large for gestational age (LGA. IGF-1, IGFBP-3, ghrelin, and insulin levels were measured in umbilical cord and maternal serum. Results: The LGA group had significantly higher levels of IGF-1, IGFBP-3, ghrelin, and insulin in umbilical cord and maternal serum than the SGA group. Umbilical cord and maternal serum levels of IGF-1 and IGFBP-3 correlated significantly and positively with body weight, body length, head circumference, and abdominal circumference of the neonates. Discussion: Based on the findings of the present study, it may be postulated that insulin like growth factor system has a role in fetal growth.

  8. EAMJ Risk Factors 10.indd

    African Journals Online (AJOL)

    2010-02-02

    Feb 2, 2010 ... Several factors have been suggested as independent risk factors for their development. Identification of these ... with age, gender or haematological test. ... A meta-analysis of prospective studies on ..... The marked difference may be because monthly .... and dyslipidemia among patients taking first-line,.

  9. Common elements in interleukin 4 and insulin signaling pathways in factor-dependent hematopoietic cells.

    Science.gov (United States)

    Wang, L M; Keegan, A D; Li, W; Lienhard, G E; Pacini, S; Gutkind, J S; Myers, M G; Sun, X J; White, M F; Aaronson, S A

    1993-05-01

    Interleukin 4 (IL-4), insulin, and insulin-like growth factor I (IGF-I) efficiently induced DNA synthesis in the IL-3-dependent murine myeloid cell lines FDC-P1 and FDC-P2. Although these factors could not individually sustain long-term growth of these lines, a combination of IL-4 with either insulin or IGF-I did support continuous growth. The principal tyrosine-phosphorylated substrate observed in FDC cells stimulated with IL-4, previously designated 4PS, was of the same size (170 kDa) as the major substrate phosphorylated in response to insulin or IGF-I. These substrates had phosphopeptides of the same size when analyzed by digestion with Staphylococcus aureus V8 protease, and each tightly associated with the 85-kDa component of phosphatidylinositol 3-kinase after factor stimulation. IRS-1, the principal substrate phosphorylated in response to insulin or IGF-I stimulation in nonhematopoietic cells, is similar in size to 4PS. However, anti-IRS-1 antibodies failed to efficiently precipitate 4PS, and some phosphopeptides generated by V8 protease digestion of IRS-1 were distinct in size from the phosphopeptides of 4PS. Nevertheless, IL-4, insulin, and IGF-I were capable of stimulating tyrosine phosphorylation of IRS-1 in FDC cells that expressed this substrate as a result of transfection. These findings indicate that (i) IL-4, insulin, and IGF-I use signal transduction pathways in FDC lines that have at least one major feature in common, the rapid tyrosine phosphorylation of 4PS, and (ii) insulin and IGF-I stimulation of hematopoietic cell lines leads to the phosphorylation of a substrate that may be related to but is not identical to IRS-1.

  10. 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.

  11. 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.

  12. 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.

  13. Impact of insulin like growth factor-1 in development of coronary artery ectasia

    Directory of Open Access Journals (Sweden)

    Ibrahim Faruk Akturk

    2014-09-01

    Full Text Available Coronary artery ectasia (CAE is characterized by inappropriate dilatation of the coronary vasculature. The mechanisms of CAE are not well known. Insulin-like growth factor-1 (IGF-1 may make endothelial cells and smooth muscle cells more sensitive to the effects of growth hormone. In the present study, we hypothesized that IGF-1 may have an impact on the formation of ectasia and aneurysm in arterial system, and aimed to investigate the associations between the presence of CAE and serum IGF-1 levels in patients undergoing coronary angiography. The study included 2.980 subjects undergoing elective diagnostic coronary angiography. We selected 40 patients diagnosed with CAE as CAE group and 44 subjects with absolutely normal coronary arteries were assigned as normal control group. IGF-1 levels were measured in both groups of patients. Groups were similar in terms of age, sex and coronary artery disease risk factors. The serum IGF-1 levels were significantly higher in CAE patients with 109.64±54.64 ng/mL than in controls with 84.76±34.01 ng/mL (p=0.016. HDL levels were lower in ectasia group with 41.5±10.7 mg/dL than controls with 47.7±10.4 mg/dL (p=0.018. By means of logistic regression analysis, high IGF-1 and low HDL levels were found to be independent risk factors for the presence of CAE (p<0.02, p<0.016, respectively. The study revealed that there was a positive correlation between serum IGF-1 levels and presence of CAE, and high IGF-1 levels and low HDL levels were independent risk factors for the presence of CAE. Future studies are needed to confirm these results.

  14. Fasting insulin, insulin resistance, and risk of cardiovascular or all-cause mortality in non-diabetic adults: a meta-analysis.

    Science.gov (United States)

    Zhang, Xiaohong; Li, Jun; Zheng, Shuiping; Luo, Qiuyun; Zhou, Chunmei; Wang, Chaoyang

    2017-10-31

    Studies on elevated fasting insulin or insulin resistance (IR) and cardiovascular or all-cause mortality risk in non-diabetic individuals have yielded conflicting results. This meta-analysis aimed to evaluate the association of elevated fasting insulin levels or IR as defined by homeostasis model assessment of IR (HOMA-IR) with cardiovascular or all-cause mortality in non-diabetic adults. We searched for relevant studies in PubMed and Emabse databases until November 2016. Only prospective observational studies investigating the association of elevated fasting insulin levels or HOMA-IR with cardiovascular or all-cause mortality risk in non-diabetic adults were included. Risk ratio (RR) with its 95% confidence intervals (CIs) was pooled for the highest compared with the lowest category of fasting insulin levels or HOMA-IR. Seven articles involving 26976 non-diabetic adults were included. The pooled, adjusted RR of all-cause mortality comparing the highest with the lowest category was 1.13 (95% CI: 1.00-1.27; P =0.058) for fasting insulin levels and 1.34 (95% CI: 1.11-1.62; P =0.002) for HOMA-IR, respectively. When comparing the highest with the lowest category, the pooled adjusted RR of cardiovascular mortality was 2.11 (95% CI: 1.01-4.41; P =0.048) for HOMA-IR in two studies and 1.40 (95% CI: 0.49-3.96; P =0.526) for fasting insulin levels in one study. IR as measured by HOMA-IR but not fasting insulin appears to be independently associated with greater risk of cardiovascular or all-cause mortality in non-diabetic adults. However, the association of fasting insulin and HOMA-IR with cardiovascular mortality may be unreliable due to the small number of articles included. © 2017 The Author(s).

  15. Insulin-like growth factor II: complexity of biosynthesis and receptor binding

    DEFF Research Database (Denmark)

    Gammeltoft, S; Christiansen, Jan; Nielsen, F C

    1991-01-01

    Insulin-like growth factor II (IGF-II) belongs to the insulin family of peptides and acts as a growth factor in many fetal tissues and tumors. The gene expression of IGF-II is initiated at three different promoters which gives rise to multiple transcripts. In a human rhabdomyosarcoma cell line......, Man-6-P induces cellular responses. We have studied rat brain neuronal precursor cells where Man-6-P acted as a mitogen suggesting that phosphomannosylated proteins may act as growth factors via the Man-6-P/IGF-II receptor. In conclusion, the gene expression and mechanism of action of IGF-II is very...

  16. Relationship between increased serum tumor necrosis factor levels and insulin resistance in patients with essential hypertension

    International Nuclear Information System (INIS)

    Wang Weimin; Li Jinliang; Huang Yongqiang

    2010-01-01

    Objective: To investigate the relationship between serum tumor necrosis factor-α (TNF-α) levels and insulin resistance (IR) in patients with essential by pertension. Methods: Serum TNF-α and free insulin (fINS)levels were measured with RIA in 41 patients with essential hypertension and 38 controls. Insulin resistance was calculated with insulin resistance index (HOMA-IR). Results: The serum TNF-α levels were significantly higher in patients with essential hypertension than those in the controls (P<0.001). The HOMA-IR was also significantly higher in hypertension group than that in controls (P<0.001). Serum TNF-α levels was positively correlated with BMI, HOMA-IR and SBP both in hypertension group and control group (P<0.05). Conclusion: Serum TNF-α level was increased in hypertensive patients and positively correlated with obesity and IR. (authors)

  17. Brain pericyte-derived soluble factors enhance insulin sensitivity in GT1-7 hypothalamic neurons.

    Science.gov (United States)

    Takahashi, Hiroyuki; Takata, Fuyuko; Matsumoto, Junichi; Machida, Takashi; Yamauchi, Atsushi; Dohgu, Shinya; Kataoka, Yasufumi

    2015-02-20

    Insulin signaling in the hypothalamus plays an important role in food intake and glucose homeostasis. Hypothalamic neuronal functions are modulated by glial cells; these form an extensive network connecting the neurons and cerebral vasculature, known as the neurovascular unit (NVU). Brain pericytes are periendothelial accessory structures of the blood-brain barrier and integral members of the NVU. However, the interaction between pericytes and neurons is largely unexplored. Here, we investigate whether brain pericytes could affect hypothalamic neuronal insulin signaling. Our immunohistochemical observations demonstrated the existence of pericytes in the mouse hypothalamus, exhibiting immunoreactivity of platelet-derived growth factor receptor β (a pericyte marker), and laminin, a basal lamina marker. We then exposed a murine hypothalamic neuronal cell line, GT1-7, to conditioned medium obtained from primary cultures of rat brain pericytes. Pericyte-conditioned medium (PCM), but not astrocyte- or aortic smooth muscle cell-conditioned medium, increased the insulin-stimulated phosphorylation of Akt in GT1-7 cells in a concentration-dependent manner. PCM also enhanced insulin-stimulated tyrosine phosphorylation of insulin receptor β without changing its expression or localization in cytosolic or plasma membrane fractions. These results suggest that pericytes, rather than astrocytes, increase insulin sensitivity in hypothalamic neurons by releasing soluble factors under physiological conditions in the NVU. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Development of a bioassay system for investigating insulin resistance factors of pregnancy

    International Nuclear Information System (INIS)

    Hausman, D.B.; Singh, R.; Martin, R.J.

    1986-01-01

    To determine if late-term pregnant serum and/or placenta could induce insulin resistance in normal adipose cells, the authors have developed an insulin sensitive bioassay system. Cells isolated from epididymal fat pads of 250-275 g Sprague Dawley rats are preincubated for 3 hours at 37 0 in media 199 and serum or placental extract. The cells are washed free of serum and tested for metabolic activity in a 2 hour incubation which measures the conversion of U- 14 C-glucose to 14 CO 2 and to 14 C-triglyceride fatty acids under basal and insulin stimulated conditions. Maximal insulin responsiveness (350-450% basal for CO 2 and 1400-1700% basal for fatty acids) is achieved using Worthington Type II collagenase and a 45-60 minute digestion period for cell isolations and Krebs-Ringer bicarbonate buffer containing 0.5 mM glucose, 2% Armour bovine serum albumin (CRG-7), 1000 μU/ml insulin and 110,000 to 120,000 cells in the 2 hour incubations. Using this bioasssay system the authors have found that insulin responsiveness, in terms of glucose conversion to fatty acids, is unchanged when cells are preincubated with 5% control pig serum but reduced following preincubation with late pregnant (110 day) pig serum. In future experiments the authors hope to further characterize the factor(s) in pregnant serum responsible for inducing this metabolic effect

  19. Predictive Risk Factors in the Treatment of Gestational Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Lebriz Hale Aktun

    2015-01-01

    Full Text Available Objective This study aims to investigate predictive risk factors in the treatment of gestational diabetes mellitus (GDM. Patients and Methods A total of 256 pregnant women who underwent 75 g oral glucose tolerance test (OGTT during 24–28 weeks of pregnancy were included according to the World Health Organization criteria. Demographic characteristics of the patients, including age, parity, family history of diabetes, body weight before pregnancy, and body weight at the diagnosis of GDM, were recorded. Fasting insulin and hemoglobin A1c (HbA1c values at the time of diagnosis were evaluated. The patients were divided into two groups: those requiring insulin treatment (insulin group, n = 89 and those receiving diet therapy (diet group, n = 167 during pregnancy according to the American Diabetes Association recommendations. Results A total of 34.76% of the pregnant women with GDM required insulin treatment. The mean age of these patients was significantly higher compared to the diet group (34.9 ± 0.6 years vs. 31.9 ± 0.6 years; P = 0.004. Body mass index before pregnancy was also significantly higher in the insulin group than that in the diet group (32 ± 0.9 kg/m 2 vs. 29 ± 0.7 kg/m 2 ; P = 0.004. Fasting blood glucose (FBG during OGTT was 105.6 ± 2.1 mg/dL and 96.7 ± 1.1 mg/dL in the insulin group and diet group, respectively ( P < 0.001. There was no significant difference in fasting plasma glucose during OGTT between the groups ( P = 0.069, while plasma glucose at two hours was 161.1 ± 6.8 mg/dL in the insulin group and 145.1 ± 3.7 mg/dL in the diet group ( P = 0.027. At the time of diagnosis, HbA1c values were significantly higher in the insulin group compared to the diet group (5.3 ± 0.1 vs. 4.9 ± 0.1; P = 0.001. There was no significant difference in FBG and homeostasis model assessment-insulin resistance values between the groups ( P = 0.908, P = 0.073. Conclusion Our study results suggest that age, family history of diabetes, body

  20. Roles of oxidative stress, adiponectin, and nuclear hormone receptors in obesity-associated insulin resistance and cardiovascular risk.

    Science.gov (United States)

    Matsuda, Morihiro; Shimomura, Iichiro

    2014-08-01

    Obesity leads to the development of type 2 diabetes mellitus, which is a strong risk factor for cardiovascular disease. A better understanding of the molecular basis of obesity will lead to the establishment of effective prevention strategies for cardiovascular diseases. Adipocytes have been shown to generate a variety of endocrine factors termed adipokines/adipocytokines. Obesity-associated changes to these adipocytokines contribute to the development of cardiovascular diseases. Adiponectin, which is one of the most well-characterized adipocytokines, is produced exclusively by adipocytes and exerts insulin-sensitizing and anti-atherogenic effects. Obese subjects have lower levels of circulating adiponectin, and this is recognized as one of the factors involved in obesity-induced insulin resistance and atherosclerosis. Another pathophysiological feature of obesity may involve the low-grade chronic inflammation in adipose tissue. This inflammatory process increases oxidative stress in adipose tissue, which may affect remote organs, leading to the development of diabetes, hypertension, and atherosclerosis. Nuclear hormone receptors (NRs) regulate the transcription of the target genes in response to binding with their ligands, which include metabolic and nutritional substrates. Among the various NRs, peroxisome proliferator-activated receptor γ promotes the transcription of adiponectin and antioxidative enzymes, whereas mineralocorticoid receptor mediates the effects of aldosterone and glucocorticoid to induce oxidative stress in adipocytes. It is hypothesized that both play crucial roles in the pathophysiology of obesity-associated insulin resistance and cardiovascular diseases. Thus, reduced adiponectin and increased oxidative stress play pathological roles in obesity-associated insulin resistance to increase the cardiovascular disease risk, and various NRs may be involved in this pathogenesis.

  1. Vascular risk factors, cognitve decline, and dementia

    Directory of Open Access Journals (Sweden)

    E Duron

    2008-04-01

    Full Text Available E Duron, Olivier HanonBroca Hospital, Paris, FranceAbstract: Dementia is one of the most important neurological disorders in the elderly. Aging is associated with a large increase in the prevalence and incidence of degenerative (Alzheimer’s disease and vascular dementia, leading to a devastating loss of autonomy. In view of the increasing longevity of populations worldwide, prevention of dementia has turned into a major public health challenge. In the past decade, several vascular risk factors have been found to be associated with vascular dementia but also Alzheimer’s disease. Some longitudinal studies, have found significant associations between hypertension, diabetus mellitus, and metabolic syndrome, assessed at middle age, and dementia. Studies assessing the link between hypercholesterolemia, atrial fibrillation, smoking, and dementia have given more conflicting results. Furthermore, some studies have highlighted the possible protective effect of antihypertensive therapy on cognition and some trials are evaluating the effects of statins and treatments for insulin resistance. Vascular risk factors and their treatments are a promising avenue of research for prevention of dementia, and further long-term, placebo-controlled, randomized studies, need to be performed.Keywords: dementia, hypertension, diabetus mellitus, hypercholesterolemia, metabolic syndrome

  2. [Risk factors of necrotizing enterocolitis].

    Science.gov (United States)

    Tapia-Rombo, C A; Velasco-Lavín, M R; Nieto-Caldelas, A

    1993-09-01

    The purpose of the present study is to compare risk factors of necrotizing enterocolitis (NEC) between two group: group A, newborns with the disease and group B, newborns with other diseases different from NEC, in order to know if these risk factors are more frequent or not in the first group. We assessed the clinical records of all the patients hospitalized in the Neonatal Intensive Care Unit and Neonatology Service of the La Raza General Hospital between 1987 and 1991 with the diagnosis of NEC. They were compared with 65 clinical records chosen at random of patients hospitalized in the same Unit with other diagnosis at the same time, and who were discharged by improvement or deceased. In all of them were look for known risk factors for NEC generally accepted such as: prematurity, neonatal asphyxia, poliglobulia, cyanotic congenital heart disease, patent ductus arteriosus, respiratory distress syndrome, catheterization of umbilical vessels, early feeding of elevated formula increases, exchange exchange transfusion, hypoxic ischemic encephalopathy, infection, etc. Just 25 records of the possible 50 with the diagnosis of NEC full filled inclusion criteria. There were no statistically significant difference in weight, sex, mortality and known risk factors of NEC between both groups. Were concluded that NEC is a disease of unknown etiology that should be studied more thoroughly. The known risk factors must be avoided because the patient susceptibility probably play an important role.

  3. Effects of diet composition on weight loss, metabolic factors and biomarkers in a 1-year weight loss intervention in obese women examined by baseline insulin resistance status.

    Science.gov (United States)

    Rock, Cheryl L; Flatt, Shirley W; Pakiz, Bilge; Quintana, Elizabeth L; Heath, Dennis D; Rana, Brinda K; Natarajan, Loki

    2016-11-01

    Obesity is a risk factor for postmenopausal breast cancer incidence and premenopausal and postmenopausal breast cancer mortality, which may be explained by several metabolic and hormonal factors (sex hormones, insulin resistance, and inflammation) that are biologically related. Differential effects of dietary composition on weight loss and these metabolic factors may occur in insulin-sensitive vs. insulin-resistant obese women. To examine the effect of diet composition on weight loss and metabolic, hormonal and inflammatory factors in overweight/obese women stratified by insulin resistance status in a 1-year weight loss intervention. Nondiabetic women who were overweight/obese (n=245) were randomly assigned to a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut-rich (18% energy), higher fat (35% energy), lower carbohydrate (45% energy) diet. All groups lost weight at follow-up (Ploss of 9.2(1.1)% in lower fat, 6.5(0.9)% in lower carbohydrate, and 8.2(1.0)% in walnut-rich groups at 12months. The diet×time×insulin resistance status interaction was not statistically significant in the model for overall weight loss, although insulin sensitive women at 12months lost more weight in the lower fat vs. lower carbohydrate group (7.5kg vs. 4.3kg, P=0.06), and in the walnut-rich vs. lower carbohydrate group (8.1kg vs. 4.3kg, P=0.04). Sex hormone binding globulin increased within each group except in the lower carbohydrate group at 12months (Ploss depending on insulin resistance status. Prescribing walnuts is associated with weight loss comparable to a standard lower fat diet in a behavioral weight loss intervention. Weight loss itself may be the most critical factor for reducing the chronic inflammation associated with increased breast cancer risk and progression. Copyright © 2016. Published by Elsevier Inc.

  4. MicroRNA-99a inhibits insulin-induced proliferation, migration, dedifferentiation, and rapamycin resistance of vascular smooth muscle cells by inhibiting insulin-like growth factor-1 receptor and mammalian target of rapamycin

    International Nuclear Information System (INIS)

    Zhang, Zi-wei; Guo, Rui-wei; Lv, Jin-lin; Wang, Xian-mei; Ye, Jin-shan; Lu, Ni-hong; Liang, Xing; Yang, Li-xia

    2017-01-01

    Patients with type 2 diabetes mellitus (T2DM) are characterized by insulin resistance and are subsequently at high risk for atherosclerosis. Hyperinsulinemia has been associated with proliferation, migration, and dedifferentiation of vascular smooth muscle cells (VSMCs) during the pathogenesis of atherosclerosis. Moreover, insulin-like growth factor-1 receptor (IGF-1R) and mammalian target of rapamycin (mTOR) have been demonstrated to be the underlying signaling pathways. Recently, microRNA-99a (miR-99a) has been suggested to regulate the phenotypic changes of VSMCs in cancer cells. However, whether it is involved in insulin-induced changes of VSCMs has not been determined. In this study, we found that insulin induced proliferation, migration, and dedifferentiation of mouse VSMCs in a dose-dependent manner. Furthermore, the stimulating effects of high-dose insulin on proliferation, migration, and dedifferentiation of mouse VSMCs were found to be associated with the attenuation of the inhibitory effects of miR-99a on IGF-1R and mTOR signaling activities. Finally, we found that the inducing effect of high-dose insulin on proliferation, migration, and dedifferentiation of VSMCs was partially inhibited by an active mimic of miR-99a. Taken together, these results suggest that miR-99a plays a key regulatory role in the pathogenesis of insulin-induced proliferation, migration, and phenotype conversion of VSMCs at least partly via inhibition of IGF-1R and mTOR signaling. Our results provide evidence that miR-99a may be a novel target for the treatment of hyperinsulinemia-induced atherosclerosis. - Highlights: • Suggesting a new mechanism of insulin-triggered VSMC functions. • Providing a new therapeutic strategies that target atherosclerosis in T2DM patients. • Providing a new strategies that target in-stent restenosis in T2DM patients.

  5. Vitamin C deficiency aggravates tumor necrosis factor α-induced insulin resistance.

    Science.gov (United States)

    Qing, Zhou; Xiao-Hui, Wu; Xi-Mei, Wu; Chao-Chun, Zou

    2018-06-15

    Chronic low-grade inflammation plays a major role in the development of insulin resistance. The potential role and underlying mechanism of vitamin C, an antioxidant and anti-inflammatory agent, was investigated in tumor necrosis factor-α (TNF-α)-induced insulin resistance. Gulonolactone oxidase knockout (Gulo -/- ) mice genetically unable to synthesize vitamin C were used to induce insulin resistance by continuously pumping small doses of TNF-α for seven days, and human liver hepatocellular carcinoma cells (HepG2 cells) were used to induce insulin resistance by treatment with TNF-α. Vitamin C deficiency aggravated TNF-α-induced insulin resistance in Gulo -/- mice, resulting in worse glucose tolerance test (GTT) results, higher fasting plasma insulin level, and the inactivation of the protein kinase B (AKT)/glycogen synthase kinase-3β (GSK3β) pathway in the liver. Vitamin C deficiency also worsened liver lipid accumulation and inflammation in TNF-α-treated Gulo -/- mice. In HepG2 cells, vitamin C reversed the TNF-α-induced reduction of glucose uptake and glycogen synthesis, which were mediated by increasing GLUT2 levels and the activation of the insulin receptor substrate (IRS-1)/AKT/GSK3β pathway. Furthermore, vitamin C inhibited the TNF-α-induced activation of not only the mitogen-activated protein kinase (MAPKs), but also nuclear factor-kappa B (NF-κB) signaling. Taken together, vitamin C is essential for preventing and improving insulin resistance, and the supplementing with vitamin C may be an effective therapeutic intervention for metabolic disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Insulin Resistance of Puberty.

    Science.gov (United States)

    Kelsey, Megan M; Zeitler, Philip S

    2016-07-01

    Puberty is a time of considerable metabolic and hormonal change. Notably, puberty is associated with a marked decrease in insulin sensitivity, on par with that seen during pregnancy. In otherwise healthy youth, there is a nadir in insulin sensitivity in mid-puberty, and then it recovers at puberty completion. However, there is evidence that insulin resistance (IR) does not resolve in youth who are obese going into puberty and may result in increased cardiometabolic risk. Little is known about the underlying pathophysiology of IR in puberty, and how it might contribute to increased disease risk (e.g., type 2 diabetes). In this review, we have outlined what is known about the IR in puberty in terms of pattern, potential underlying mechanisms and other mediating factors. We also outline other potentially related metabolic changes that occur during puberty, and effects of underlying insulin resistant states (e.g., obesity) on pubertal changes in insulin sensitivity.

  7. Risk factor for febrile seizures

    Directory of Open Access Journals (Sweden)

    Odalović Dragica

    2014-01-01

    Full Text Available Febrile seizures are the most frequent neurological disorder in the childhood. According to American Academy of Pediatrics (AAP, they have been defined as seizures provoked by high temperature in children aged between 6 months and 5 years, without previous history of afebrile seizures, intracranial infections and other possible causes of seizures. Seizures can be typical and atypical, according to the characteristics. Pathogenesis of this disorder has not been clarified yet, and it is believed to be a combination of genetic factors, high body temperature and brain maturation. The risk factors for recurrence of febrile seizures are: age in which seizures appeared for the first time, epilepsy in the first degree relative, febrile seizures in the first degree relative, frequent diseases with fever and low body temperature on the beginning of seizures. The frequency of recurrent seizures The risk for occurrence of epilepsy in children with simple seizures is about 1-1.5%, which is slightly higher compared to general population, while it increases to 4-15% in patients with complex seizures. However, there is no evidence that therapy prevents occurrence of epilepsy. When the prevention of recurrent seizures is considered, it is necessary to separate simple from complex seizures. The aim of this paper was to analyze the most important risk factors for febrile seizures, and to evaluate their impact on occurrence of recurrent seizures. Our study included 125 children with febrile seizures, aged from 6 months to 5 years. The presence of febrile seizures and epilepsy in the first degree relative has been noted in 22% of children. Typical febrile seizures were observed in 76% of cases, and atypical in 24%. Most patients had only one seizure (73.6%. Children, who had seizure earlier in life, had more frequent recurrences. Both risk factors were present in 25% of patients, while 68% of patients had only one risk factor. For the children with febrile disease

  8. Converting Insulin-like Growth Factors 1 and 2 into High-Affinity Ligands for Insulin Receptor Isoform A by the Introduction of an Evolutionarily Divergent Mutation

    Czech Academy of Sciences Publication Activity Database

    Macháčková, Kateřina; Chrudinová, Martina; Radosavljević, Jelena; Potalitsyn, Pavlo; Křížková, Květoslava; Fábry, Milan; Selicharová, Irena; Collinsová, Michaela; Brzozowski, A. M.; Žáková, Lenka; Jiráček, Jiří

    2018-01-01

    Roč. 57, č. 16 (2018), s. 2373-2382 ISSN 0006-2960 R&D Projects: GA ČR GA15-19018S Institutional support: RVO:61388963 ; RVO:68378050 Keywords : insulin-like growth factor * insulin * receptor * analog Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 2.938, year: 2016 https://pubs.acs.org/doi/10.1021/acs.biochem.7b01260

  9. Involvement of insulin-like factor 3 (Insl3) in diethylstilbestrol-induced cryptorchidism

    NARCIS (Netherlands)

    J.M.A. Emmen (Judith); A. McLuskey; I.M. Adham; W. Engel; M. Verhoef-Post (Miriam); A.P.N. Themmen (Axel); J.A. Grootegoed (Anton); A.O. Brinkmann (Albert)

    2000-01-01

    textabstractRecently, it has been shown that targeted inactivation of the Insl3 gene in male mice results in cryptorchidism. The Insl3 gene encodes insulin-like factor 3 (Insl3), which is expressed in fetal Leydig cells. The testicular factor Insl3 appears to play an

  10. Insulin-like growth factor binding protein 3 in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Kirman, Irena; Whelan, Richard Larry; Jain, Suvinit

    2005-01-01

    Epithelial cell growth regulation has been reported to be altered in inflammatory bowel disease (IBD) patients. The cell growth regulatory factor, insulin-like growth factor binding protein 3 (IGFBP-3), may be partly responsible for this phenomenon. So far, IGFBP-3 levels have been assessed...

  11. Insulin-Like Growth Factor Binding Protein 4 Fragments Provide Incremental Prognostic Information on Cardiovascular Events in Patients With ST-Segment Elevation Myocardial Infarction

    DEFF Research Database (Denmark)

    Hjortebjerg, Rikke; Lindberg, Søren; Pedersen, Sune

    2017-01-01

    BACKGROUND: Fragments of insulin-like growth factor binding protein 4 (IGFBP-4) are potential new biomarkers for cardiac risk assessment. The fragments are generated on specific cleavage by pregnancy-associated plasma protein-A, which exerts proatherogenic activity. This study investigated the pr...

  12. The risk factor of thyroid

    International Nuclear Information System (INIS)

    Kusama, Tomoko

    1979-01-01

    For the purposes of radiation protection, the noteworthy risk of thyroid is carcinogenesis. The risk factor which ICRP presented in the publication-26 is 5 x 10 - 6 rem - 1 . This numerical value is based upon the estimated likelihood of inducing fatal thyroid cancer. On the other hand, the risk factor presented by the BEIR report is 4 x 10 - 6 yr - 1 . This value was decided after consideration of the risks of both fatal and non-fatal cancer of thyroid. The following features distinguished thyroid cancer from malignancy of other tissue from medical point of view. 1) A large difference between incidence and mortality in case of thyroid cancer is recognized, because the thyroid cancer could be successfully treated by surgical or radiological treatment. 2) The high prevalence of clinically silent tumor in thyroid gland has been reported. The incidence of thyroid cancer, therefore, is very dependent on methods of medical inspection. The prevalence of radiation induced thyroid cancer is modified by various factors such as age, sex, latency, dose and dose rate. The latent period is very important factors such as ave, sex, latency, dose and dose rate. The latent period is a very important factor in the estimation of accumulated total risk of thyroid malignancy. What is included in the risk caused by thyroid irradiation must be investigated. The risk of non-fatal cancer should be considered in the same way as that of fatal cancer. The dose-equivalent limit of thyroid in non-uniform irradiation caused by radioactive iodine is decided by the limit for non-stochastic effects. Therefore the further consideration of non-stochastic effects of thyroid is necessary. (author)

  13. Fibroblast growth factor 21 improves insulin sensitivity and synergizes with insulin in human adipose stem cell-derived (hASC adipocytes.

    Directory of Open Access Journals (Sweden)

    Darwin V Lee

    Full Text Available Fibroblast growth factor 21 (FGF21 has evolved as a major metabolic regulator, the pharmacological administration of which causes weight loss, insulin sensitivity and glucose control in rodents and humans. To understand the molecular mechanisms by which FGF21 exerts its metabolic effects, we developed a human in vitro model of adipocytes to examine crosstalk between FGF21 and insulin signaling. Human adipose stem cell-derived (hASC adipocytes were acutely treated with FGF21 alone, insulin alone, or in combination. Insulin signaling under these conditions was assessed by measuring tyrosine phosphorylation of insulin receptor (InsR, insulin receptor substrate-1 (IRS-1, and serine 473 phosphorylation of Akt, followed by a functional assay using 14C-2-deoxyglucose [14C]-2DG to measure glucose uptake in these cells. FGF21 alone caused a modest increase of glucose uptake, but treatment with FGF21 in combination with insulin had a synergistic effect on glucose uptake in these cells. The presence of FGF21 also effectively lowered the insulin concentration required to achieve the same level of glucose uptake compared to the absence of FGF21 by 10-fold. This acute effect of FGF21 on insulin signaling was not due to IR, IGF-1R, or IRS-1 activation. Moreover, we observed a substantial increase in basal S473-Akt phosphorylation by FGF21 alone, in contrast to the minimal shift in basal glucose uptake. Taken together, our data demonstrate that acute co-treatment of hASC-adipocytes with FGF21 and insulin can result in a synergistic improvement in glucose uptake. These effects were shown to occur at or downstream of Akt, or separate from the canonical insulin signaling pathway.

  14. Insulin Resistance in Alzheimer's Disease

    Science.gov (United States)

    Dineley, Kelly T; Jahrling, Jordan B; Denner, Larry

    2014-01-01

    Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD. PMID:25237037

  15. Human Leptospirosis and risk factors.

    Directory of Open Access Journals (Sweden)

    Yanelis Emilia Tabío Henry

    2010-09-01

    Full Text Available The human leptospirosis is a zoonosis of world distribution, were risk factors exist that have favored the wild and domestic animal propagation and so man. A descpitive investigation was made with the objective of determining the behavior of risk factors in outpatients by human leptospirosis in “Camilo Cienfuegos“ University General Hospital from Sncti Spíritus In the comprised time period betwen december 1 st and 3 st , 2008.The sample of this study was conformed by 54 risk persons that keep inclusion criteria. Some variables were used:age, sex, risk factors and number of ill persons, according to the month. Some patients of masculine sex prevailed (61,9%, group of ages between 15-29 and 45-59 years (27,7%, patients treated since october to december (53,7%, the direct and indirect contact with animals (46,2 %. The risk factors cassually associated to human leptospirosis turned to be: the masculine sex, the contac with animals, the occupational exposition and the inmersion on sources of sweet water.

  16. Relation of Cardiometabolic Risk Factors between Parents and Children.

    Science.gov (United States)

    Halvorsen, Tanya; Moran, Antoinette; Jacobs, David R; Steffen, Lyn M; Sinaiko, Alan R; Zhou, Xia; Steinberger, Julia

    2015-11-01

    To explore the relations of parent-child cardiometabolic risk factors and assess the influence of adiposity on these associations. Associations of adiposity, blood pressure (BP), lipids, fasting insulin and glucose, and a risk factor cluster score (CS) were evaluated in a cross-sectional study of 179 parents and their children (6-18 years, N = 255). Insulin resistance was assessed by euglycemic clamp in parents and children aged 10 years or older. Metabolic syndrome in parents was defined by National Cholesterol Education Program's Adult Treatment Panel III criteria. CSs of the risk factors were created based on age-specific z-scores. Analyses included Pearson correlation and linear regression, adjusted for parent and child age, sex, race, and body mass index (BMI), accounting for within-family correlation. We found positive parent-child correlations for measures of adiposity (BMI, BMI percentile, waist, subcutaneous fat, and visceral fat; r = 0.22-0.34, all P ≤ .003), systolic BP (r = 0.20, P = .002), total cholesterol (r = 0.39, P parent-child correlations, except systolic BP, remained significant. Although adiposity is strongly correlated between parents and children, many cardiometabolic risk factors correlate independent of parent and child BMI. Adverse parental cardiometabolic profiles may identify at-risk children independent of the child's adiposity status. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Insulin Secretion and Risk for Future Diabetes in Subjects with a Nonpositive Insulinogenic Index

    Directory of Open Access Journals (Sweden)

    Daisuke Aono

    2018-01-01

    Full Text Available Aim. To characterize subjects with a nonpositive insulinogenic index and longitudinally observe changes in their glucose tolerance. Subjects and Methods. A historical cohort study was conducted using data from the medical checkups of public school workers. Indices of insulin secretion and insulin sensitivity derived from oral glucose tolerance test (OGTT and the incidences of diabetes and impaired glucose tolerance (IGT were compared among subgroups of subjects with different insulinogenic index (change in insulin/change in glucose over the first 30 min on the OGTT. Results. Of the 1464 nondiabetic subjects at baseline, 72 (4.9% subjects had a nonpositive insulinogenic index: 42 of those subjects had a nonpositive glucose response (ΔGlu0–30 ≤ 0 and 30 had a nonpositive insulin response (ΔIns0–30 ≤ 0. Compared with subjects who had normal glucose tolerance (NGT with insulinogenic index ≥ 0.4, subjects with a nonpositive glucose response had a higher first-phase Stumvoll and lower incidences of diabetes and IGT based on a log-rank test (p<0.05, whereas subjects with a nonpositive insulin response had lower indices of insulin secretion and a higher incidence of diabetes (p<0.05. Conclusions. These results demonstrate that in the first 30 min on the OGTT, subjects with a nonpositive insulinogenic index due to a nonpositive glucose response (ΔGlu0–30 ≤ 0 had a lower risk for future diabetes and that subjects with nonpositive insulin response (ΔIns0–30 ≤ 0 had a higher risk for future one.

  18. Cardiovascular risk factors and events in women with androgen excess.

    Science.gov (United States)

    Macut, D; Antić, I B; Bjekić-Macut, J

    2015-03-01

    Androgen excess (AE) was approximated to be present in 7% of the adult population of women. Polycystic ovary syndrome (PCOS) is the most prevalent among them, followed by idiopathic hirsutism (IH), congenital adrenal hyperplasia (CAH), hyperandrogenic insulin-resistant acanthosis nigricans (HAIRAN) syndrome, and androgen-secreting neoplasms (ASNs). Increased cardiovascular risk was implicated in women with AE. Serum testosterone independently increases risk for cardiovascular disease (CVD), and correlates even with indices of subclinical atherosclerosis in various populations of postmenopausal women. Hyperandrogenism in PCOS is closely related to the aggravation of abdominal obesity, and together with insulin resistance forming the metabolic core for the development of CVD. However, phenotypic variability of PCOS generates significant influence on the cardiometabolic risks. Numerous risk factors in PCOS lead to 5-7 times higher risk for CVD and over 2-fold higher risk for coronary heart disease and stroke. However, issue on the cardiometabolic risk in postmenopausal women with hyperandrogenic history is still challenging. There is a significant overlapping in the CVD characteristics of women with PCOS and variants of CAH. Relevant clinical data on the prevalence and cardiometabolic risk and events in women with IH, HAIRAN syndrome or ASNs are scarce. The effects of various oral contraceptives (OCs) and antiandrogenic compounds on metabolic profile are varying, and could be related to the selected populations and different therapy regiments mainly conducted in women with PCOS. It is assumed relation of OCs containing antiandrogenic progestins to the increased risk of cardiovascular and thromboembolic events.

  19. Structural analogs of human insulin-like growth factor I with reduced affinity for serum binding proteins and the type 2 insulin-like growth factor receptor

    International Nuclear Information System (INIS)

    Bayne, M.L.; Applebaum, J.; Chicchi, G.G.; Hayes, N.S.; Green, B.G.; Cascieri, M.A.

    1988-01-01

    Four structural analogs of human insulin-like growth factor I (hIGF-I) have been prepared by site-directed mutagenesis of a synthetic IGF-I gene and subsequent expression and purification of the mutant protein from the conditioned media of transformed yeast. [Phe -1 , Val 1 , Asn 2 , Gln 3 , His 4 , Ser 8 , His 9 , Glu 12 , Tyr 15 , Leu 16 ]IGF-I (B-chain mutant), in which the first 16 amino acids of hIGF-I were replaced with the first 17 amino acids of the B-chain of insulin, has >1000-, 100-, and 2-fold reduced potency for human serum binding proteins, the rat liver type 2 IGF receptor, and the human placental type 1 IGF receptor, respectively. The B-chain mutant also has 4-fold increased affinity for the human placental insulin receptor. [Gln 3 , Ala 4 ] IGF-I has 4-fold reduced affinity for human serum binding proteins, but is equipotent to hIGF-I at the types 1 and 2 IGF and insulin receptors. [Tyr 15 , Leu 16 ] IGH-I has 4-fold reduced affinity for human serum binding proteins and 10-fold increased affinity for the insulin receptor. The peptide in which these four-point mutations are combined, [Gln 3 , Ala 4 , Tyr 15 ,Leu 16 ]IGF-I, has 600-fold reduced affinity for the serum binding proteins. All four of these mutants stimulate DNA synthesis in the rat vascular smooth muscle cell line A10 with potencies reflecting their potency at the type 1 IGF receptor. These studies identify some of the domains of hIGF-I which are responsible for maintaining high affinity binding with the serum binding protein and the type 2 IGF receptor. In addition, These peptides will be useful in defining the role of the type 2 IGF receptor and serum binding proteins in the physiological actions of hIGF-I

  20. Insulin-like growth factor family and combined antisense approach in therapy of lung carcinoma.

    OpenAIRE

    Pavelić, Jasminka; Pavelić, Ljubomir; Karadza, Jerolim; Krizanac, Simun; Unesić, Josip; Spaventi, Sime; Pavelić, Kresimir

    2002-01-01

    BACKGROUND: Perturbation in a level of any peptide from insulin-like growth factor (IGF) family (ligands, receptors, and binding proteins) seems to be implicated in lung cancer formation; IGF ligands and IGF-I receptor through their mitogenic and anti-apoptotic action, and the mannose 6-phosphate/insulin-like growth factor II receptor (M6-P/IGF-IIR) possibly as a tumor suppressor. MATERIALS AND METHODS: To determine the identity, role, and mutual relationship of IGFs in lung cancer growth and...

  1. Sexual harassment: identifying risk factors.

    Science.gov (United States)

    O'Hare, E A; O'Donohue, W

    1998-12-01

    A new model of the etiology of sexual harassment, the four-factor model, is presented and compared with several models of sexual harassment including the biological model, the organizational model, the sociocultural model, and the sex role spillover model. A number of risk factors associated with sexually harassing behavior are examined within the framework of the four-factor model of sexual harassment. These include characteristics of the work environment (e.g., sexist attitudes among co-workers, unprofessional work environment, skewed sex ratios in the workplace, knowledge of grievance procedures for sexual harassment incidents) as well as personal characteristics of the subject (e.g., physical attractiveness, job status, sex-role). Subjects were 266 university female faculty, staff, and students who completed the Sexual Experience Questionnaire to assess the experience of sexual harassment and a questionnaire designed to assess the risk factors stated above. Results indicated that the four-factor model is a better predictor of sexual harassment than the alternative models. The risk factors most strongly associated with sexual harassment were an unprofessional environment in the workplace, sexist atmosphere, and lack of knowledge about the organization's formal grievance procedures.

  2. Growth factors II: insuline-like growth binging proteins (GFBPs Factores de crecimiento II: factores insulinoides de crecimiento

    Directory of Open Access Journals (Sweden)

    Hilda Norha Jaramillo Londoño

    1996-03-01

    Full Text Available This review summarizes recent knowledge concerning Insulin.like growth factors I and II, with emphasis on their biochemical structure, concentrations, binding proteins, receptors, mechanisms of action, biological effects, and alterations of their concentrations in biological fluids. Se revisan los Factores Insulinoides de Crecimiento, también denominados ";Factores de Crecimiento Similares a la Insulina";, sobre los cuales se dispone de abundante información. Se sintetizan conocimientos recientes sobre dichos factores con énfasis en los siguientes aspectos: estructura bioquímica, concentraciones y sus cambios en los líquidos biológicos, proteínas fijadoras, receptores, mecanismos de acción y efectos biológicos.

  3. Tumor necrosis factor-alpha inhibits insulin's stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans

    DEFF Research Database (Denmark)

    Rask-Madsen, Christian; Domínguez, Helena; Ihlemann, Nikolaj

    2003-01-01

    BACKGROUND: Inflammatory mechanisms could be involved in the pathogenesis of both insulin resistance and atherosclerosis. Therefore, we aimed at examining whether the proinflammatory cytokine tumor necrosis factor (TNF)-alpha inhibits insulin-stimulated glucose uptake and insulin....../or TNF-alpha were coinfused. During infusion of insulin alone for 20 minutes, forearm glucose uptake increased by 220+/-44%. This increase was completely inhibited during coinfusion of TNF-alpha (started 10 min before insulin) with a more pronounced inhibition of glucose extraction than of blood flow....... Furthermore, TNF-alpha inhibited the ACh forearm blood flow response (Palpha...

  4. Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Pedersen, A T

    1997-01-01

    Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH-I...

  5. Beneficial effect of pistachio consumption on glucose metabolism, insulin resistance, inflammation, and related metabolic risk markers: a randomized clinical trial.

    Science.gov (United States)

    Hernández-Alonso, Pablo; Salas-Salvadó, Jordi; Baldrich-Mora, Mònica; Juanola-Falgarona, Martí; Bulló, Mònica

    2014-11-01

    To examine whether a pistachio-rich diet reduces the prediabetes stage and improves its metabolic risk profile. Prediabetic subjects were recruited to participate in this Spanish randomized clinical trial between 20 September 2011 and 4 February 2013. In a crossover manner, 54 subjects consumed two diets, each for 4 months: a pistachio-supplemented diet (PD) and a control diet (CD). A 2-week washout period separated study periods. Diets were isocaloric and matched for protein, fiber, and saturated fatty acids. A total of 55% of the CD calories came from carbohydrates and 30% from fat, whereas for the PD, these percentages were 50 and 35%, respectively (including 57 g/day of pistachios). Fasting glucose, insulin, and HOMA of insulin resistance decreased significantly after the PD compared with the CD. Other cardiometabolic risk markers such as fibrinogen, oxidized LDL, and platelet factor 4 significantly decreased under the PD compared with the CD (P pistachio intervention (P pistachio consumption is emerging as a useful nutritional strategy for the prediabetic state. Data suggest that pistachios have a glucose- and insulin-lowering effect, promote a healthier metabolic profile, and reverse certain metabolic deleterious consequences of prediabetes. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  6. Risk factors for undescended testis.

    NARCIS (Netherlands)

    Brouwers, M.M.; Bruijne, L.M. de; Gier, R.P.E. de; Zielhuis, G.A.; Feitz, W.F.J.; Roeleveld, N.

    2012-01-01

    OBJECTIVE: To contribute to the understanding of the etiology of undescended testis (UDT), by exploring a wide range of potential risk factors in a case-referent study. PATIENTS AND METHODS: Cases and referents were recruited at five hospitals and included 200 boys with surgically corrected UDT and

  7. Seasonality of cardiovascular risk factors

    DEFF Research Database (Denmark)

    Marti-Soler, Helena; Gubelmann, Cédric; Aeschbacher, Stefanie

    2014-01-01

    OBJECTIVE: To assess the seasonality of cardiovascular risk factors (CVRF) in a large set of population-based studies. METHODS: Cross-sectional data from 24 population-based studies from 15 countries, with a total sample size of 237 979 subjects. CVRFs included Body Mass Index (BMI) and waist...

  8. Bone mineral density and insulin-like growth factor-1 in children with spastic cerebral palsy.

    Science.gov (United States)

    Nazif, H; Shatla, R; Elsayed, R; Tawfik, E; Osman, N; Korra, S; Ibrahim, A

    2017-04-01

    Children with cerebral palsy (CP) have significant decrease linear growth rate and low bone mineral density (BMD). This study is to evaluate BMD in children with CP and its relation to the levels of insulin-like growth factor-1 (IGF-1). This cross-sectional study was carried out on 58 children suffering from spastic CP with the age range 4-12 years compared to 19 controls. All assessed by dual energy x-ray absorptiometry (DXA) to measure BMD, serum level of IGF-1, and serum vitamin D. The patients were classified according to their GMFCS. Fractures were reported in seven (12.1%) of cases. Our study demonstrated that, IGF-1 level and BMD decrease in correlation with the severity of CP. IGF-1correlates positively with serum vitamin D, BMI, and BMD. CP children with severe GMFCS level or who use anticonvulsive drugs are at a high risk for low BMD and low levels of IGF-1. Both BMD and IGF-1 were significantly in low children with spastic CP; IGF-1 negatively correlates with the severity of osteopenia in children with spastic. Children with CP who are not independently ambulant or with severe GMFCS level or who use anticonvulsive drugs are at a high risk for developing low BMD.

  9. Extrinsic Factors Involved in the Differentiation of Stem Cells into Insulin-Producing Cells: An Overview

    Directory of Open Access Journals (Sweden)

    Rebecca S. Y. Wong

    2011-01-01

    Full Text Available Diabetes mellitus is a chronic disease with many debilitating complications. Treatment of diabetes mellitus mainly revolves around conventional oral hypoglycaemic agents and insulin replacement therapy. Recently, scientists have turned their attention to the generation of insulin-producing cells (IPCs from stem cells of various sources. To date, many types of stem cells of human and animal origins have been successfully turned into IPCs in vitro and have been shown to exert glucose-lowering effect in vivo. However, scientists are still faced with the challenge of producing a sufficient number of IPCs that can in turn produce sufficient insulin for clinical use. A careful choice of stem cells, methods, and extrinsic factors for induction may all be contributing factors to successful production of functional beta-islet like IPCs. It is also important that the mechanism of differentiation and mechanism by which IPCs correct hyperglycaemia are carefully studied before they are used in human subjects.

  10. Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans.

    Directory of Open Access Journals (Sweden)

    Barbora de Courten

    Full Text Available Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists.Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography, % body fat (bioimpedance, abdominal subcutaneous and visceral adiposity (magnetic resonance imaging, insulin sensitivity (euglycaemic hyperinsulinemic clamp, resting energy expenditure (REE, indirect calorimetry, free-living ambulatory physical activity (accelerometers and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04 and subcutaneous (r = 0.38, p = 0.02 but not visceral fat (r = 0.17, p = 0.33. Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008, REE (r = -0.58, p<0.001 and HDL-cholesterol levels (r = -0.34, p = 0.048. Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity.Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease.

  11. Vitamin D deficiency: a new risk factor for type 2 diabetes?.

    Science.gov (United States)

    Mezza, T; Muscogiuri, G; Sorice, G P; Prioletta, A; Salomone, E; Pontecorvi, A; Giaccari, A

    2012-01-01

    Recent compelling evidence suggests a role of vitamin D deficiency in the pathogenesis of insulin resistance and insulin secretion derangements, with a consequent possible interference with type 2 diabetes mellitus. The mechanism of this link is incompletely understood. In fact, vitamin D deficiency is usually detected in obesity in which insulin resistance is also a common finding. The coexistence of insulin resistance and vitamin D deficiency has generated several hypotheses. Some cross-sectional and prospective studies have suggested that vitamin D deficiency may play a role in worsening insulin resistance; others have identified obesity as a risk factor predisposing individuals to exhibit both vitamin D deficiency and insulin resistance. The available data from intervention studies are largely confounded, and inadequate considerations of seasonal effects on 25(OH)D concentrations are also a common design flaw in many studies. On the contrary, there is strong evidence that obesity might cause both vitamin D deficiency and insulin resistance, leaving open the possibility that vitamin D and diabetes are not related at all. Although it might seem premature to draw firm conclusions on the role of vitamin D supplementation in reducing insulin resistance and preventing type 2 diabetes, this manuscript will review the circumstances leading to vitamin D deficiency and how such a deficiency can eventually independently affect insulin sensitivity. Copyright © 2012 S. Karger AG, Basel.

  12. Risk factors for congenital hydrocephalus

    DEFF Research Database (Denmark)

    Munch, Tina Noergaard; Rasmussen, Marie-Louise Hee; Wohlfahrt, Jan

    2014-01-01

    . Furthermore, to identify the risk factors unique for isolated CHC as compared to syndromic CHC. METHODS: We established a cohort of all children born in Denmark between 1978 and 2008. Information on CHC and maternal medical diseases were obtained from the National Patient Discharge Register, maternal intake...... increased risk of isolated CHC compared to unexposed children (RR 2.52, 95% CI 1.47 to 4.29) (1.5/1000 born children). Risk factors also found for syndromic CHC were: Male gender, multiples and maternal diabetes. CONCLUSIONS: The higher risk for isolated CHC in first-born children as well as behavioural......-born children, we observed 1193 cases of isolated CHC (0.062/1000) born children. First-borns had an increased risk of isolated CHC compared to later-borns (1.32 95% CI 1.17 to 1.49) (0.72/1000 born children). First trimester exposure to maternal use of antidepressants was associated with a significantly...

  13. Cardiometabolic Risks in Polycystic Ovary Syndrome: Non-Traditional Risk Factors and the Impact of Obesity.

    Science.gov (United States)

    Chiu, Wei-Ling; Boyle, Jacqueline; Vincent, Amanda; Teede, Helena; Moran, Lisa J

    2017-01-01

    Polycystic ovary syndrome (PCOS) is a common and complex endocrinopathy with reproductive, metabolic, and psychological features and significantly increased cardiometabolic risks. PCOS is underpinned by inherent insulin resistance and hyperandrogenism. Obesity, more common in PCOS, plays an important role in the pathophysiology, exacerbating hyperinsulinaemia and hyperandrogenism, leading to recommended first-line lifestyle intervention. Significant traditional and non-traditional risk factors are implicated in PCOS in addition to obesity-exacerbated cardiometabolic risks and are explored in this review to promote the understanding of this common metabolic and reproductive condition. © 2016 S. Karger AG, Basel.

  14. Insulin-Insulin-like Growth Factors Hybrids as Molecular Probes of Hormone:Receptor Binding Specificity

    Czech Academy of Sciences Publication Activity Database

    Křížková, Květoslava; Chrudinová, Martina; Povalová, Anna; Selicharová, Irena; Collinsová, Michaela; Vaněk, Václav; Brzozowski, A. M.; Jiráček, Jiří; Žáková, Lenka

    2016-01-01

    Roč. 55, č. 21 (2016), s. 2903-2913 ISSN 0006-2960 R&D Projects: GA ČR GA15-19018S Institutional support: RVO:61388963 Keywords : alanine scanning mutagenesis * high-affinity binding * type 1 IGF receptor Subject RIV: CE - Biochemistry Impact factor: 2.938, year: 2016 http://pubs.acs.org/doi/pdf/10.1021/acs.biochem.6b00140

  15. [Risk factors associated to preclampsia].

    Science.gov (United States)

    López-Carbajal, Mario Joaquín; Manríquez-Moreno, María Esther; Gálvez-Camargo, Daniela; Ramírez-Jiménez, Evelia

    2012-01-01

    preeclampsia constitutes one of the main causes of maternal and perinatal morbidity and mortality. The aim was to identify the risk factors associated to the developmental of preeclampsia mild-moderate and severe, as well as the force of association of these factors in a hospital of second-level medical care. study of cases and controls, a relation 1:1, in women withdrawn of the Service of Gynecology and Obstetrics during 2004 to 2007. Pregnant women with more than 20 weeks gestation were included. In the cases group we included patients with diagnosis of preeclampsia mild-moderate or severe (corroborated clinical and laboratory). In the controls group that had a normal childbirth without pathology during the pregnancy. 42 cases and 42 controls. The average age was of 27 years. The associated risk factors were overweight, obesity, irregular prenatal control, short or long intergenesic period, history of caesarean or preeclampsia in previous pregnancies. the knowledge of the risk factors will allow the accomplishment of preventive measures and decrease the fetal and maternal morbidity and mortality due to preeclampsia.

  16. The transcription factor Prep1 controls hepatic insulin sensitivity and gluconeogenesis by targeting nuclear localization of FOXO1

    International Nuclear Information System (INIS)

    Kulebyakin, Konstantin; Penkov, Dmitry; Blasi, Francesco; Akopyan, Zhanna; Tkachuk, Vsevolod

    2016-01-01

    Liver plays a key role in controlling body carbohydrate homeostasis by switching between accumulation and production of glucose and this way maintaining constant level of glucose in blood. Increased blood glucose level triggers release of insulin from pancreatic β-cells. Insulin represses hepatic glucose production and increases glucose accumulation. Insulin resistance is the main cause of type 2 diabetes and hyperglycemia. Currently thiazolidinediones (TZDs) targeting transcriptional factor PPARγ are used as insulin sensitizers for treating patients with type 2 diabetes. However, TZDs are reported to be associated with cardiovascular and liver problems and stimulate obesity. Thus, it is necessary to search new approaches to improve insulin sensitivity. A promising candidate is transcriptional factor Prep1, as it was shown earlier it could affect insulin sensitivity in variety of insulin-sensitive tissues. The aim of the present study was to evaluate a possible involvement of transcriptional factor Prep1 in control of hepatic glucose accumulation and production. We created mice with liver-specific Prep1 knockout and discovered that hepatocytes derived from these mice are much more sensitive to insulin, comparing to their WT littermates. Incubation of these cells with 100 nM insulin results in almost complete inhibition of gluconeogenesis, while in WT cells this repression is only partial. However, Prep1 doesn't affect gluconeogenesis in the absence of insulin. Also, we observed that nuclear content of gluconeogenic transcription factor FOXO1 was greatly reduced in Prep1 knockout hepatocytes. These findings suggest that Prep1 may control hepatic insulin sensitivity by targeting FOXO1 nuclear stability. - Highlights: • A novel model of liver-specific Prep1 knockout is established. • Ablation of Prep1 in hepatocytes increases insulin sensitivity. • Prep1 controls hepatic insulin sensitivity by regulating localization of FOXO1. • Prep1 regulates

  17. Advanced Glycation End-Products affect transcription factors regulating insulin gene expression

    International Nuclear Information System (INIS)

    Puddu, A.; Storace, D.; Odetti, P.; Viviani, G.L.

    2010-01-01

    Advanced Glycation End-Products (AGEs) are generated by the covalent interaction of reducing sugars with proteins, lipids or nucleic acids. AGEs are implicated in diabetic complications and pancreatic β-cell dysfunction. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T15 to high concentrations of AGEs leads to a significant decrease of insulin secretion and content. Insulin gene transcription is positively regulated by the beta cell specific transcription factor PDX-1 (Pancreatic and Duodenal Homeobox-1). On the contrary, the forkhead transcription factor FoxO1 inhibits PDX-1 gene transcription. Activity of FoxO1 is regulated by post-translational modifications: phosphorylation deactivates FoxO1, and acetylation prevents FoxO1 ubiquitination. In this work we investigated whether AGEs affect expression and subcellular localization of PDX-1 and FoxO1. HIT-T15 cells were cultured for 5 days in presence of AGEs. Cells were then lysed and processed for subcellular fractionation. We determined intracellular insulin content, then we assessed the expression and subcellular localization of PDX-1, FoxO1, phosphoFoxO1 and acetylFoxO1. As expected intracellular insulin content was lower in HIT-T15 cells cultured with AGEs. The results showed that AGEs decreased expression and nuclear localization of PDX-1, reduced phosphorylation of FoxO1, and increased expression and acetylation of FoxO1. These results suggest that AGEs decrease insulin content unbalancing transcription factors regulating insulin gene expression.

  18. Role of the insulin-like growth factor 1 axis and visceral adiposity in oesophageal adenocarcinoma.

    LENUS (Irish Health Repository)

    Donohoe, C L

    2012-03-01

    Epidemiological studies have linked obesity with many cancers. The insulin-like growth factor (IGF) 1 axis may be an important mediator in obesity-associated cancer. This study examined the relationship between IGF-1 and its receptor (IGF-1R) in oesophageal adenocarcinoma, a cancer strongly linked to obesity.

  19. Insulin-like growth factors and leucine kinetics during exercise training in children with cystic fibrosis

    NARCIS (Netherlands)

    Gulmans, [No Value; van der Laag, J; Wattimena, D; van Doorn, J; Oostveen, D; Berger, R; van de Meer, K

    Background: Little is known about the metabolic effects of exercise training in children with cystic fibrosis. The hypothesis for the current study was that in patients with declining clinical status, exercise increases circulating insulin-like growth factors (IGFs) and improves protein kinetics.

  20. Neuroprotective Effect of Insulin-like Growth Factor-II on 1- Methyl-4 ...

    African Journals Online (AJOL)

    Purpose: To evaluate the receptor-mediated neuroprotective effect of insulin-like growth factor-II (IGFII) on 1-methyl-4-phenyl pyridinium (MPP) induced oxidative damage in adult cortical neuronal cultures. Methods: Adult rats were randomly divided into 5 groups. Cortical neurons were prepared from rats. The cells were ...

  1. Leptin, insulin like growth factor-1 and thyroid profile in a studied ...

    African Journals Online (AJOL)

    Background: Several mechanisms have been suggested for obesity in Down syndrome. Aim of the study: Assessment of serum levels of leptin, insulin like growth factor-I (IGF-I), thyroid stimulating hormone (TSH) and free thyroxin (FT4) in a prepubertal Egyptian sample of children with DS compared to their age and sex ...

  2. Detection of polymorphism of the insulin-like growth factor-I (IGF-I ...

    African Journals Online (AJOL)

    Molecular genetic selection on individual genes is a promising method to genetically improve economically important traits in chickens. The insulin-like growth factor-I (IGF-I) gene may play important roles in growth of multiple tissues, including muscle cells, cartilage and bone. In the present study, polymorphism of the ...

  3. Cell-Cell Adhesion and Insulin-Like Growth Factor I Receptor in Breast Cancer

    National Research Council Canada - National Science Library

    Bartucci, Monica

    2001-01-01

    .... Our goal was to study the role of the insulin-like growth factor I receptor (IGF-IR) in breast cancer. The IGF-IR is a multifunctional tyrosine kinase that has been recently implicated in breast tumor development and progression...

  4. Leptin, insulin like growth factor-1 and thyroid profile in a studied ...

    African Journals Online (AJOL)

    Howida Hosny El Gebali

    2014-02-26

    Feb 26, 2014 ... roid stimulating hormone (TSH) and free thyroxin (FT4) in a prepubertal Egyptian sample of chil- dren with DS ... serum levels of leptin, IGF-I (insulin like growth factor-I), ..... a deficit in receptor synthesis in DS. They also ...

  5. Diagnostic utility of leptin and insulin-like growth factor binding ...

    African Journals Online (AJOL)

    Serum levels of leptin, insulin growth factor binding protein-2 (IGFBP-2) and alpha fetoprotein (AFP) were measured. ... renewal in response to nutrients. IGF pathway is not only involved in cell growth in tissue culture, but it is also involved in ...

  6. Monoclonal antibodies directed to human insulin-like growth factor I (IGF I)

    International Nuclear Information System (INIS)

    Laubli, U.K.; Baier, W.; Celio, M.R.; Binz, H.; Humbel, R.E.

    1982-01-01

    Mouse hybridomas secreting antibodies to human insulin-like growth factor I (IGF I) were produced by fusion of spleen cells of hyperimmunised mice with FO mouse-myeloma cells. Eight clones producing antibodies against human IGF I have been isolated, two of which have been characterised. One was used in a radioimmunoassay, the other for immunopurification of IGF. (Auth.)

  7. Determination of free insulin-like growth factor-I in human serum

    DEFF Research Database (Denmark)

    Frystyk, J.; Skjærbæk, C.; Ivarsen, P.

    2001-01-01

    Two fundamentally different methods are currently used for the determination of free insulin-like growth factor-I (IGF-I): ultrafiltration by centrifugation (UF) and direct immunoradiometric assay (IRMA). The aim was to evaluate a commercial IRMA (DSL, Webster, TX, USA) and to compare it with UF....

  8. Endonucleolysis in the turnover of insulin-like growth factor II mRNA

    DEFF Research Database (Denmark)

    Nielsen, F C; Christiansen, Jan

    1992-01-01

    The overlapping transcription units constituting the rat insulin-like growth factor II (IGF-II) locus generate multiple mRNAs by using different promoters. Three promoters have been identified, giving rise to 4.6-, 3.8-, and 3.6-kilobase mRNAs. The latter, originating from promoter P3, is the most...

  9. Insulin-Like Growth Factor I Does Not Drive New Bone Formation in Experimental Arthritis

    NARCIS (Netherlands)

    van Tok, Melissa N.; Yeremenko, Nataliya G.; Teitsma, Christine A.; Kream, Barbara E.; Knaup, Véronique L.; Lories, Rik J.; Baeten, Dominique L.; van Duivenvoorde, Leonie M.

    2016-01-01

    Insulin like growth factor (IGF)-I can act on a variety of cells involved in cartilage and bone repair, yet IGF-I has not been studied extensively in the context of inflammatory arthritis. The objective of this study was to investigate whether IGF-I overexpression in the osteoblast lineage could

  10. Insulin-like growth factor-I in growth and metabolism

    DEFF Research Database (Denmark)

    Backeljauw, P; Bang, P; Dunger, D B

    2010-01-01

    Deficiency of insulin-like growth factor-I (IGF-I) results in growth failure. A variety of molecular defects have been found to underlie severe primary IGF-I deficiency (IGFD), in which serum IGF-I concentrations are substantially decreased and fail to respond to GH therapy. Identification of more...

  11. Diminished concentrations of insulin-like growth factor I in cystic fibrosis

    DEFF Research Database (Denmark)

    Laursen, Erik; Juul, A; Lanng, S

    1995-01-01

    Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data...

  12. The effect of dietary fiber and other factors on insulin response: role in obesity.

    Science.gov (United States)

    Ullrich, I H; Albrink, M J

    1985-07-01

    Epidemiologic evidence favors the hypothesis that obesity may result from the fiber-depleted diet of industrialized societies. Since hyperinsulinemia is a universal characteristic and perhaps causal of obesity, the possibility is considered that dietary factors causing excess insulin secretion might lead to obesity. Dietary glucose causes a slightly greater insulin rise than cooked starch containing an equal amount of carbohydrate, and high fiber starchy foods cause a much lesser insulin response than does glucose in solution. Doubling the dose of carbohydrate in a meal causes only a small increase in glucose response but a large increase in insulin response. Dietary fiber could act by displacing some of the carbohydrate that would normally be absorbable in the small intestine, or could translocate the carbohydrate to a point lower in the intestinal tract where less effect on insulin secretion would be observed. Evidence is presented that a higher fiber diet is associated with a higher concentration of fasting circulating free fatty acids, a lesser post-cibal decrease in circulating free fatty acids and triglycerides and less chronic increase in fasting triglycerides than a low fiber diet. These differences are associated with a lesser insulin response to high fiber meals. The extreme fluctuations between the fed and fasted states seen with low fiber diets are thus dampened by high fiber diets. The less complete inhibition of lipolysis during the fed state, and more intense lipolysis during fasting, suggested by the above data, might tend to prevent obesity. The mechanisms of the lesser insulin response to high rather than low fiber meals are not known, but the possibility that dietary fiber decreases the GIP response is considered.

  13. Serum insulin-like factor 3 levels during puberty in healthy boys and boys with Klinefelter syndrome

    DEFF Research Database (Denmark)

    Wikström, Anne M; Bay, Katrine; Hero, Matti

    2006-01-01

    Levels of the Leydig cell-specific hormone insulin-like factor 3 (INSL3) are incompletely characterized in boys during pubertal development.......Levels of the Leydig cell-specific hormone insulin-like factor 3 (INSL3) are incompletely characterized in boys during pubertal development....

  14. Effect of naloxone on plasma insulin, insulin-like growth factor I, and its binding protein 1 in patients with polycystic ovarian disease.

    Science.gov (United States)

    Laatikainen, T; Anttila, L; Suikkari, A M; Ruutiainen, K; Erkkola, R; Seppälä, M

    1990-09-01

    Insulin and insulin-like growth factors (IGFs) stimulate ovarian steroidogenesis, and hyperinsulinemia is often accompanied by hyperandrogenemia in women with polycystic ovarian disease (PCOD). Because opioid peptides are involved in the regulation of insulin secretion, we studied the effect of naloxone-induced opiate receptor blockade on the circulating levels of insulin, IGF-I, and IGF binding protein 1 (IGFBP-1) in 13 nonobese and 7 obese PCOD patients and in 6 healthy subjects. In obese PCOD patients, the mean basal insulin concentration was significantly higher and the IGFBP-1 concentration lower than in nonobese PCOD patients. Plasma IGF-I levels were elevated both in obese and nonobese PCOD patients. After an intravenous bolus of 10 mg naloxone, no significant changes were found in the circulating insulin or IGF-I levels, whereas IGFBP-1 levels decreased in nonobese PCOD patients and remained low in obese PCOD patients. No significant decrease was found in healthy subjects. These results suggest that, in addition to insulin, endogenous opioids are involved in the regulation of serum IGFBP-1 level.

  15. Risk factors for unstable blood glucose level: integrative review of the risk factors related to the nursing diagnosis

    Directory of Open Access Journals (Sweden)

    Andressa Magalhães Teixeira

    Full Text Available ABSTRACT Objective: to identify evidence in the literature on the possible risk factors for the risk of unstable blood glucose diagnosis in individuals with type 2 diabetes mellitus, and to compare them with the risk factors described by NANDA International. Method: an integrative literature review guided by the question: what are the risk factors for unstable blood glucose level in people with type 2 diabetes mellitus? Primary studies were included whose outcomes were variations in glycemic levels, published in English, Portuguese or Spanish, in PubMed or CINAHL between 2010 and 2015. Results: altered levels of glycated hemoglobin, body mass index>31 kg/m2, previous history of hypoglycemia, cognitive deficit/dementia, autonomic cardiovascular neuropathy, comorbidities and weight loss corresponded to risk factors described in NANDA International. Other risk factors identified were: advanced age, black skin color, longer length of diabetes diagnosis, daytime sleepiness, macroalbuminuria, genetic polymorphisms, insulin therapy, use of oral antidiabetics, and use of metoclopramide, inadequate physical activity and low fasting glycemia. Conclusions: risk factors for the diagnosis, risk for unstable blood glucose level, for persons with type 2 diabetes mellitus were identified, and 42% of them corresponded to those of NANDA International. These findings may contribute to the practice of clinical nurses in preventing the deleterious effects of glycemic variation.

  16. Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance

    Science.gov (United States)

    Hotamisligil, Gokhan S.; Shargill, Narinder S.; Spiegelman, Bruce M.

    1993-01-01

    Tumor necrosis factor-α (TNF-α) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-α messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-α protein was also elevated locally and systemically. Neutralization of TNF-α in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-α in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.

  17. 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.

  18. Disability as a risk factor?

    DEFF Research Database (Denmark)

    Bøttcher, Louise; Dammeyer, Jesper

    2013-01-01

    Empirical research has established that children with disabilities are more likely to develop psychopathology than children without disabilities. But too little is known about the association between disability and psychopathology. The aim of this article is to discuss developmental...... psychopathological models that conceptualize the connection between childhood disability and psychopathology. Empirical studies of psychopathology among children with a congenital hearing impairment and children with cerebral palsy will be reviewed, representing in-depth examples of association between disability...... and psychopathology. Both a congenital hearing impairment and cerebral palsy were found to be dominating risk factors for all types of psychopathology, but no relationship was identified between degree of disability and risk of psychopathology. The higher risk cannot be explained by biological impairments alone...

  19. Neurodevelopmental risk factors in schizophrenia

    Directory of Open Access Journals (Sweden)

    Lobato M.I.

    2001-01-01

    Full Text Available The authors review environmental and neurodevelopmental risk factors for schizophrenic disorders, with emphasis on minor physical anomalies, particularly craniofacial anomalies and dermatoglyphic variations. The high prevalence of these anomalies among schizophrenic subjects supports the neurodevelopmental theory of the etiology of schizophrenia, since they suggest either genetically or epigenetically controlled faulty embryonic development of structures of ectodermal origin like brain and skin. This may disturb neurodevelopment that in turn may cause these subjects to be at increased risk for the development of schizophrenia and related disorders. The precise confirmation of this theory, at least in some cases, will provide further understanding of these illnesses, allowing easy and inexpensive identification of subjects at risk and providing guidelines for the development of new pharmacological interventions for early treatment and even for primary prevention of the illness.

  20. Insulin-like growth factor-I (lGF-l): safety and efficacy.

    Science.gov (United States)

    Laron, Zvi

    2004-11-01

    Insulin-like growth factor I (IGF-I) is a peptide synthesized mainly in the liver by stimulation by pituitary growth hormone (GH). It circulates almost entirely bound to its binding proteins. It is the anabolic effector hormone of GH. It is the only treatment in states of GH resistance such as Laron syndrome and blocking antibodies to human GH. As it suppresses insulin and GH secretion it has been used in states of insulin resistance including Type II diabetes mellitus. IGF-I is administered by once or twice daily injections. Adverse effects are mostly caused by overdosage. The usual daily dose in children ranges from 100-200 microg/kg.

  1. Interaction of insulin-like growth factor I with porcine thyroid cells cultured in monolayer

    International Nuclear Information System (INIS)

    Saji, M.; Tsushima, T.; Isozaki, O.; Murakami, H.; Ohba, Y.; Sato, K.; Arai, M.; Mariko, A.; Shizume, K.

    1987-01-01

    The interaction of insulin-like growth factor I (IGF-I) with porcine thyroid cells cultured in monolayer was studied. Specific binding of [ 125 I]iodo-IGF-I to thyroid cells was a reversible process dependent on the time and temperature of incubation. A steady state was achieved in 18 h at 4 C and averaged 14.2 +/- 2% (mean +/- SD)/10(6) cells. Binding of [ 125 I]iodo-IGF-I was inhibited by unlabeled IGF-I; half-maximal inhibition occurred at concentrations of 2-5 ng/ml. Multiplication-stimulating activity (rat IGF-II) and pork insulin had relative potencies of 1:20 and 1:300 compared with IGF-I. Scatchard analysis of binding data revealed a single class of IGF-I receptors with a Ka of 4.3 X 10(10) M-1, 49,000 binding sites were estimated per cell. Affinity cross-linking and autoradiography demonstrated the presence of type I IGF receptors. Thyroid cells also had specific receptors for insulin, but specific binding of [ 125 I]iodoinsulin was much lower than that of [ 125 I]iodo-IGF-I. Preincubation of thyroid cells with IGF-I or insulin caused a concentration-dependent decrease in [ 125 I]iodo-IGF-I binding due to an apparent loss of receptors. Preincubation with epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, or TSH did not alter subsequent binding of [ 125 I]iodo-IGF-I. Low concentrations of IGF-I stimulated DNA synthesis and proliferation of thyroid cells and acted synergistically with epidermal growth factor. Multiplication-stimulating activity and insulin had relative potencies in stimulating DNA synthesis comparable to their abilities to inhibit the binding of [ 125 I]iodo-IGF-I to thyroid cells

  2. Síndrome metabólica em crianças obesas e fatores de risco para doenças cardiovasculares de acordo com a resistência à insulina (HOMA-IR Metabolic syndrome and risk factors for cardiovascular disease in obese children: the relationship with insulin resistance (HOMA-IR

    Directory of Open Access Journals (Sweden)

    Aparecido Pimentel Ferreira

    2007-02-01

    Full Text Available OBJETIVO: Verificar a prevalência da síndrome metabólica e identificar fatores de risco para desenvolvimento de doenças cardiovasculares de acordo com a resistência à insulina. MÉTODOS: Realizou-se um estudo transversal em 52 crianças obesas. A amostra foi randomizada após avaliação do índice de massa corporal [peso (kg/estatura (m²] de 1.550 escolares. A obesidade foi definida quando esse índice se encontrava acima do percentil 95 da classificação do Centers for Disease Control and Prevention. O sangue de jejum foi utilizado para mensurar a glicemia, lipoproteínas de alta densidade, triglicerídeos e insulina. A gordura corporal foi avaliada pela absortometria de raio X de dupla energia. A pressão arterial e a resistência à insulina foram mensuradas. A síndrome metabólica foi definida segundo o critério do National Cholesterol Education Program, com pontos de corte ajustados para a idade da amostra. RESULTADOS: A síndrome metabólica esteve presente em 17,3% das crianças avaliadas. A resistência à insulina diferiu significativamente entre o sexo feminino (3,8±2,2; IC95% 2,9-4,8 e o sexo masculino (2,6±1,3; IC95% 2,1-3,1; p = 0,016. Cerca de 44,2% da amostra apresentou pelo menos dois fatores de risco, e 15% apresentou hipertensão arterial. A hipertrigliceridemia foi encontrada em 50 e 70,8% dos meninos e meninas, respectivamente. Os níveis de lipoproteínas de alta densidade abaixo do desejável foram encontrados somente nas meninas. CONCLUSÕES: Crianças obesas apresentaram alta prevalência de síndrome metabólica. Apresentaram mais fatores de risco aquelas que obtiveram maiores níveis de resistência à insulina. Desta forma, são necessárias medidas intervencionistas com intuito de barrar o ganho de peso durante a infância.OBJECTIVE: To identify the prevalence of metabolic syndrome and risk factors for the development of cardiovascular diseases and to investigate their relationship with insulin resistance

  3. Suppressive Effects of Insulin on Tumor Necrosis Factor-Dependent Early Osteoarthritic Changes Associated With Obesity and Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Hamada, Daisuke; Maynard, Robert; Schott, Eric; Drinkwater, Christopher J; Ketz, John P; Kates, Stephen L; Jonason, Jennifer H; Hilton, Matthew J; Zuscik, Michael J; Mooney, Robert A

    2016-06-01

    Obesity is a state of chronic inflammation that is associated with insulin resistance and type 2 diabetes mellitus (DM), as well as an increased risk of osteoarthritis (OA). This study was undertaken to define the links between obesity-associated inflammation, insulin resistance, and OA, by testing the hypotheses that 1) tumor necrosis factor (TNF) is critical in mediating these pathologic changes in OA, and 2) insulin has direct effects on the synovial joint that are compromised by insulin resistance. The effects of TNF and insulin on catabolic gene expression were determined in fibroblast-like synoviocytes (FLS) isolated from human OA synovium. Synovial TNF expression and OA progression were examined in 2 mouse models, high-fat (HF) diet-fed obese mice with type 2 DM and TNF-knockout mice. Insulin resistance was investigated in synovium from patients with type 2 DM. Insulin receptors (IRs) were abundant in both mouse and human synovial membranes. Human OA FLS were insulin responsive, as indicated by the dose-dependent phosphorylation of IRs and Akt. In cultures of human OA FLS with exogenous TNF, the expression and release of MMP1, MMP13, and ADAMTS4 by FLS were markedly increased, whereas after treatment with insulin, these effects were selectively inhibited by >50%. The expression of TNF and its abundance in the synovium were elevated in samples from obese mice with type 2 DM. In TNF-knockout mice, increases in osteophyte formation and synovial hyperplasia associated with the HF diet were blunted. The synovium from OA patients with type 2 DM contained markedly more macrophages and showed elevated TNF levels as compared to the synovium from OA patients without diabetes. Moreover, insulin-dependent phosphorylation of IRs and Akt was blunted in cultures of OA FLS from patients with type 2 DM. TNF appears to be involved in mediating the advanced progression of OA seen in type 2 DM. While insulin plays a protective, antiinflammatory role in the synovium, insulin

  4. Effect of fat supplementation on leptin, insulin-like growth factor I, growth hormone, and insulin in cattle.

    Science.gov (United States)

    Becú-Villalobos, Damasia; García-Tornadú, Isabel; Shroeder, Guillermo; Salado, Eloy E; Gagliostro, Gerardo; Delavaud, Carole; Chilliard, Yves; Lacau-Mengido, Isabel M

    2007-07-01

    We investigated the effect of fat supplementation on plasma levels of hormones related to metabolism, with special attention to leptin, in cows in early lactation and in feedlot steers. In experiment 1, 34 lactating cows received no fat or else 0.5 or 1.0 kg of partially hydrogenated oil per day in addition to their basal diet from day 20 before the expected calving date to day 70 postpartum. In experiment 2, part of the corn in the basal concentrate was replaced with 0.7 kg of the same oil such that the diets were isocaloric; 18 cows received the fat-substituted diet and 18 a control diet from day 20 before the expected calving date to day 75 postpartum. In experiment 3, calcium salts of fatty acids were added to the basal diet of 14 feedlot steers for 80 d; another 14 steers received a control diet. The basal plasma levels of leptin were higher in the cows than in the steers. Dietary fat supplementation did not affect the leptin levels in the lactating cows but lowered the levels in the feedlot steers despite greater energy intake and body fatness (body weight) in the steers receiving the supplement than in those receiving the control diet. The levels of insulin-like growth factor I and insulin were decreased with dietary fat supplementation in the lactating cows but were unaffected in the steers, suggesting that responses to fat ingestion depend on the physiological state of the animal, including age and sex. Finally, no effects of supplementary fat on the level of growth hormone were demonstrated in any of the models.

  5. The association between serum brain-derived neurotrophic factor and a cluster of cardiovascular risk factors in adolescents

    DEFF Research Database (Denmark)

    Pedersen, Natascha Holbæk; Tarp, Jakob; Andersen, Lars Bo

    2017-01-01

    BACKGROUND AND OBJECTIVE: Cardiovascular disease and type 2 diabetes pose a global health burden. Therefore, clarifying the pathology of these risk factors is essential. Previous studies have found positive and negative associations between one or more cardiovascular risk factors and brain...... fitness (CRF), anthropometrics, pubertal status, blood pressure (BP), serum BDNF, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), blood glucose and insulin were measured. Information about alcohol consumption and socio-economic status was collected via questionnaires. Associations were...

  6. Perinatal risk factors including malformation

    International Nuclear Information System (INIS)

    Brachner, A.; Grosche, B.

    1991-10-01

    The study gives a survey of the factors most frequently mentioned in the literature as factors likely to adversely affect a pregnancy. One essential aspect is the discussion of those factors that can be counted among the causes of malformations, as among others, prenatal radiation exposure. The study prepared within the framework of the research project 'Radiobiological environmental monitoring in Bavaria' is intended to serve as a basis for a retrospective and prospective evaluation of infant mortality, perinatal conditions and occurrence of malformations in Bavaria, with the principal idea of drawing up an environment - related health survey. The study therefore, in addition to ionizing radiation also takes into account other detectable risks within the ecologic context, as e.g. industrial installations, refuse incineration plants or waste dumps, or urbanity. (orig./MG) [de

  7. Risk factors for tornado injuries.

    Science.gov (United States)

    Eidson, M; Lybarger, J A; Parsons, J E; MacCormack, J N; Freeman, J I

    1990-12-01

    Tornadoes in North and South Carolina on 28 March 1984 caused 252 people to be injured seriously enough to require hospitalization and 59 to be killed. To evaluate risk factors, we gathered information on 238 (94%) of those hospitalized and 46 (78%) of those killed. Those hospitalized or deceased had statistically significantly more deep cuts, concussions, unconsciousness and broken bones than those with them at the time of the tornado who were not hospitalized or killed. People living in mobile homes were more likely to be hospitalized or die than people occupying conventional houses. Other risk factors for hospitalization or death included advanced age (60+ years), no physical protection (not having been covered with a blanket or other object), having been struck by broken window glass or other falling objects, home lifted off its foundation, collapsed ceiling or floor, or walls blown away. More awareness of the tornado risk before it strikes and better adherence to tornado protection guidelines could reduce injuries and deaths in the future.

  8. CARING (CAncer Risk and INsulin analoGues)

    DEFF Research Database (Denmark)

    Linde, Jakob Starup; Karlstad, Oystein; Eriksen, Stine Aistrup

    2013-01-01

    =1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index......BACKGROUND: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se. OBJECTIVE: To examine the association between DM and cancers by a systematic review and meta-analysis according...... to the PRISMA guidelines. DATA SOURCES: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: "Diabetes mellitus", "Neoplasms", and "Risk of cancer". STUDY ELIGIBILITY CRITERIA: The included studies compared...

  9. Obesity-associated Breast Cancer: Analysis of risk factors.

    Science.gov (United States)

    Engin, Atilla

    2017-01-01

    Several studies show that a significantly stronger association is obvious between increased body mass index (BMI) and higher breast cancer incidence. Furthermore, obese women are at higher risk of all-cause and breast cancer specific mortality when compared to non-obese women with breast cancer. In this context, increased levels of estrogens due to excessive aromatization activity of the adipose tissue, overexpression of pro-inflammatory cytokines, insulin resistance, hyperactivation of insulin-like growth factors (IGFs) pathways, adipocyte-derived adipokines, hypercholesterolemia and excessive oxidative stress contribute to the development of breast cancer in obese women. While higher breast cancer risk with hormone replacement therapy is particularly evident among lean women, in postmenopausal women who are not taking exogenous hormones, general obesity is a significant predictor for breast cancer. Moreover, increased plasma cholesterol leads to accelerated tumor formation and exacerbates their aggressiveness. In contrast to postmenopausal women, premenopausal women with high BMI are inversely associated with breast cancer risk. Nevertheless, life-style of women for breast cancer risk is regulated by avoiding the overweight and a high-fat diet. Estrogen-plus-progestin hormone therapy users for more than 5 years have elevated risks of both invasive ductal and lobular breast cancer. Additionally, these cases are more commonly node-positive and have a higher cancer-related mortality. Collectively, in this chapter, the impacts of obesity-related estrogen, cholesterol, saturated fatty acid, leptin and adiponectin concentrations, aromatase activity, leptin and insulin resistance on breast cancer patients are evaluated. Obesity-related prognostic factors of breast cancer also are discussed at molecular basis.

  10. Insulin infusion reduces hepatocyte growth factor in lean humans

    DEFF Research Database (Denmark)

    de Courten, Barbora; de Courten, Maximilian; Dougherty, Sonia

    2013-01-01

    OBJECTIVE: Plasma Hepatocyte Growth Factor (HGF) is significantly elevated in obesity and may contribute to vascular disease, metabolic syndrome or cancer in obese individuals. The current studies were done to determine if hyperinsulinemia increases plasma HGF. MATERIALS/METHODS: Twenty-two parti...

  11. Insulin and insulin-like growth factor-I (IGF-I) receptor phosphorylation in µ-calpain knockout mice

    Science.gov (United States)

    Numerous cellular processes are controlled by insulin and IGF-I signaling pathways. Due to previous work in our laboratories, we hypothesized that insulin (IR) and type 1 IGF-I (IGF-IR) receptor signaling is decreased due to increased protein tyrosine phosphatase 1B (PTP1B) activity. C57BL/6J mice...

  12. 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.

  13. IGF-1 levels across the spectrum of normal to elevated in acromegaly: relationship to insulin sensitivity, markers of cardiovascular risk and body composition.

    Science.gov (United States)

    Reid, Tirissa J; Jin, Zhezhen; Shen, Wei; Reyes-Vidal, Carlos M; Fernandez, Jean Carlos; Bruce, Jeffrey N; Kostadinov, Jane; Post, Kalmon D; Freda, Pamela U

    2015-12-01

    Activity of acromegaly is gauged by levels of GH and IGF-1 and epidemiological studies demonstrate that their normalization reduces acromegaly's excess mortality rate. However, few data are available linking IGF-1 levels to features of the disease that may relate to cardiovascular (CV) risk. Therefore, we tested the hypothesis that serum IGF-1 levels relative to the upper normal limit relate to insulin sensitivity, serum CV risk markers and body composition in acromegaly. In this prospective, cross-sectional study conducted at a pituitary tumor referral center we studied 138 adult acromegaly patients, newly diagnosed and previously treated surgically, with fasting and post-oral glucose levels of endocrine and CV risk markers and body composition assessed by DXA. Active acromegaly is associated with lower insulin sensitivity, body fat and CRP levels than acromegaly in remission. %ULN IGF-1 strongly predicts insulin sensitivity, better than GH and this persists after adjustment for body fat and lean tissue mass. %ULN IGF-1 also relates inversely to CRP levels and fat mass, positively to lean tissue and skeletal muscle estimated (SM(E)) by DXA, but not to blood pressure, lipids, BMI or waist circumference. Gender interacts with the IGF-1-lean tissue mass relationship. Active acromegaly presents a unique combination of features associated with CV risk, reduced insulin sensitivity yet lower body fat and lower levels of some serum CV risk markers, a pattern that is reversed in remission. %ULN IGF-1 levels strongly predict these features. Given the known increased CV risk of active acromegaly, these findings suggest that of these factors insulin resistance is most strongly related to disease activity and potentially to the increased CV risk of active acromegaly.

  14. Repopulation of the atrophied thymus in diabetic rats by insulin-like growth factor I

    International Nuclear Information System (INIS)

    Binz, K.; Joller, P.; Froesch, P.; Binz, H.; Zapf, J.; Froesch, E.R.

    1990-01-01

    Atrophy of the thymus is one of the consequences of severe insulin deficiency. The authors describe here that the weight and the architecture of the thymus of diabetic rats is restored towards normal not only by insulin but also by insulin-like growth factor I (IGF-I) treatment. In contrast to insulin, this effect of IGF-I occurs despite persisting hyperglycemia and adrenal hyperplasia. They also investigated the in vivo effect of IGF-I on replication and differentiation of thymocytes from streptozotocin-induced diabetic rats. Thymocytes from diabetic rats incorporated less [ 3 H]thymidine than did thymocytes from healthy rats. Insulin, as well as IGF-I treatment of diabetic rats increased [ 3 H]thymidine incorporation by thymocytes. Flow cytometry of thymocytes labeled with monoclonal antibodies revealed a decreased expression of the Thy-1 antigen in diabetic rats compared with control rats. In addition, a major deficiency of thymocytes expressing simultaneously the W3/25 and the Ox8 antigens was observed. These changes were restored towards normal by insulin as well as by IGF-I treatment. The antibody response to a T cell-dependent antigen (bovine serum albumin) was comparable in normal and diabetic rats. They conclude that IGF-I has important effects on the thymocyte number and the presence of CD4 + /CD8 + immature cells in the thymus of diabetic rats despite persisting hyperglycemia. However, helper T-cell function for antibody production appears to be preserved even in the severely diabetic state

  15. Insulin-like growth factor-I and insulin-like growth factor binding proteins in the bovine mammary gland: Receptors, endogenous secretion, and appearance in milk

    International Nuclear Information System (INIS)

    Campbell, P.G.

    1988-01-01

    This is the first study to characterize both insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) in bovine milk, to characterize the IGF-I receptor in the dry and lactating mammary gland, and to report de novo synthesis and secretion of IGF-I and IGFBP from normal mammary tissue. Immunoreactive IGF-I was principally associated with 45 kDa IGFBP in milk. Multiparous cows had a higher IGF-I concentration of 307 ng/ml than primiparous cows at 147 ng/ml. IGF-I concentration on day 56 of lactation was 34 ng/ml for combined parity groups. At parturition, IGF-I mass in blood and milk pools was 1.4 and 1.2 mg, respectively. Binding of 125 I-IGF-I was specific for IGF-I with anIC 50 of 2.2 ng which was a 10- and 1273-fold greater affinity than IGF-II and insulin, respectively. Association constants, as determined by Scatchard analysis, were similar for both pregnant and lactating cows at 3.5 and 4.0 L/nM, respectively. In addition, estimated mean receptor concentration was 0.25 and 0.23 pM/mg protein for pregnant and lactating cows, respectively. In a survey of mammary microscomes prepared from 48 cows, 125 I-IGF-I binding declined with progressing lactation and a similar trend was observed during pregnancy

  16. Risk factor management: antiatherogenic therapies.

    Science.gov (United States)

    Gielen, Stephan; Sandri, Marcus; Schuler, Gerhard; Teupser, Daniel

    2009-08-01

    Despite the advances in interventional techniques, the management of stable atherosclerosis remains the domain of optimal guideline-oriented therapy. Recent studies on the effects of aggressive lipid lowering on atheroma volume changes using intravascular ultrasound indicate that it is possible to achieve atherosclerosis regression by reaching low-density lipoprotein (LDL) levels less than 75 mg/dl. The pleiotropic anti-inflammatory effects of statins contribute to the reduction of cardiovascular (CV) event observed with aggressive lipid lowering. As a second important strategy to prevent disease progression, lifestyle changes with regular physical exercise are capable of halting the atherosclerotic process and reducing angina symptoms and CV events. Optimal medical therapy, a healthy lifestyle with regular physical exercise, and coronary interventions are not mutually exclusive treatment strategies. Over the last few decades, both have proved to be effective in significantly reducing the CV mortality in the Western world. However, risk factor modification contributed to at least half the effect in the reduction of CV mortality. This figure provides an estimate of what could be achieved if we were to take risk factor modification more seriously - especially in the acute care setting. The knowledge is there: today we have a better understanding on how to stop progression and even induce regression of atherosclerosis. Much research still needs to be done and will be done. In the meantime, however, our primary focus should lie in implementing what is already known. In addition, it is essential not just to treat CV risk factors, but also to treat them to achieve the target values as set by the guidelines of European Society of Cardiology.

  17. Risk factors of teenage pregnancy

    OpenAIRE

    Maria Siettou; Maria Saridi

    2011-01-01

    Teenage pregnancy is a worldwide medical and social issue, associated with many physical, psychological and social consequences and can result in birth, miscarriage or abortion. Aim: The aim of the present study is to find those risk factors that contribute to teenage pregnancy. Results: In U.S.A., according to data from Unicef, the birth rate among teenagers touches the 52.1% and it is four times higher, than the corresponding rate recorded in the countries of Western Europe. The United King...

  18. Activity of insulin growth factors and shrimp neurosecretory organ extracts on a lepidopteran cell line.

    Science.gov (United States)

    Hatt, P J; Liebon, C; Morinière, M; Oberlander, H; Porcheron, P

    1997-01-01

    Ecdysteroids, or molting hormones, have been proven to be key differentiation regulators for epidermal cells in the postembryonic development of arthropods. Regulators of cell proliferation, however, remain largely unknown. To date, no diffusible insect peptidic growth factors have been characterized. Molecules structurally related to insulin have been discovered in insects, as in other eucaryotes. We developed in vitro tests for the preliminary characterization of potential growth factors in arthropods by adapting the procedures designed to detect such factors in vertebrates to an insect cell line (IAL-PID2) established from imaginal discs of the Indian meal moth. We verified the ability of these tests to measure the proliferation of IAL-PID2 cells. We tested mammalian insulin and insulin-like growth factors (IGF-I, IGF-II). Following an arrest of cell proliferation by serum deprivation, IGF-I and IGF-II caused partial resumption of the cell cycle, evidenced by DNA synthesis. In contrast, the addition of 20-hydroxyecdysone arrested the proliferation of the IAL-PID2 cells. The cell line was then used in a test for functional characterization of potential growth factors originating from the penaeid shrimp, Penaeus vannamei. Crude extracts of neurosecretory and nervous tissues, eyestalks, and ventral neural chain compensated for serum deprivation and stimulated completion of mitosis. Arch.

  19. Expression of human choline kinase in NIH 3T3 fibroblasts increases the mitogenic potential of insulin and insulin-like growth factor I.

    Science.gov (United States)

    Chung, T; Huang, J S; Mukherjee, J J; Crilly, K S; Kiss, Z

    2000-05-01

    In mammalian cells, growth factors, oncogenes, and carcinogens stimulate phosphocholine (PCho) synthesis by choline kinase (CK), suggesting that PCho may regulate cell growth. To validate the role of PCho in mitogenesis, we determined the effects of insulin, insulin-like growth factor I (IGF-I), and other growth factors on DNA synthesis in NIH 3T3 fibroblast sublines highly expressing human choline kinase (CK) without increasing phosphatidylcholine synthesis. In serum-starved CK expressor cells, insulin and IGF-I stimulated DNA synthesis, p70 S6 kinase (p70 S6K) activity, phosphatidylinositol 3-kinase (PI3K) activity, and activating phosphorylation of p42/p44 mitogen-activated protein kinases (MAPK) to greater extents than in the corresponding vector control cells. Furthermore, the CK inhibitor hemicholinium-3 (HC-3) inhibited insulin- and IGF-I-induced DNA synthesis in the CK overexpressors, but not in the vector control cells. The results indicate that high cellular levels of PCho potentiate insulin- and IGF-I-induced DNA synthesis by MAPK- and p70 S6K-regulated mechanisms.

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

    Science.gov (United States)

    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.

  1. Risk Factors in Derivatives Markets

    Directory of Open Access Journals (Sweden)

    Raimonda Martinkutė-Kaulienė

    2015-02-01

    Full Text Available The objective of the article is to analyse and present the classification of risks actual to derivative securities. The analysis is based on classical and modern literature findings and analysis of newest statistical data. The analysis led to the conclusion, that the main risks typical for derivatives contracts and their traders are market risk, liquidity risk, credit and counterparty risk, legal risk and transactions risk. Pricing risk and systemic risk is also quite important. The analysis showed that market risk is the most important kind of risk that in many situations influences the level of remaining risks.

  2. Association between Myeloperoxidase Levels and Risk of Insulin Resistance in Egyptian Obese Women

    Science.gov (United States)

    Zaki, Moushira; Basha, Walaa; Reyad, Hanaa; Mohamed, Ramy; Hassan, Naglaa; Kholousi, Shams

    2018-01-01

    BACKGROUND: Myeloperoxidase (MPO) is an enzyme involved in the pathogenesis of several diseases. AIM: The current study aimed to investigate serum MPO levels in obese Egyptian women and assess its relation with insulin resistance (IR) and other biochemical risk parameters. METHODS: The study included 80 obese women and 50 age-and-sex-matched healthy controls. Insulin resistance (IR) was evaluated by the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). Serum MPO, fasting glucose, insulin and blood lipids and anthropometry were measured. Obese cases were divided into three groups based on MPO tertiles. ROC analysis was performed to obtain the optimal cut-off values of MPO to predicate IR in obese women. RESULTS: The mean serum MPO was significantly higher in obese cases than controls. Cases in the highest MPO tertile had higher HOMA-IR, blood lipids and pressure levels compared with those in the lower tertile. The cutoff point of MPO was > 87.8 (ng/mL) and area under curves was 0.82 (p < 0.01) for diagnosis of IR. MPO levels were higher in obese Egyptian women than healthy controls. CONCLUSION: Elevation of MPO was associated with abnormal metabolic parameters. MPO might be used as an earlier biomarker for IR and metabolic disturbance in obese women. PMID:29731928

  3. The transcription factor Prep1 controls hepatic insulin sensitivity and gluconeogenesis by targeting nuclear localization of FOXO1.

    Science.gov (United States)

    Kulebyakin, Konstantin; Penkov, Dmitry; Blasi, Francesco; Akopyan, Zhanna; Tkachuk, Vsevolod

    2016-12-02

    Liver plays a key role in controlling body carbohydrate homeostasis by switching between accumulation and production of glucose and this way maintaining constant level of glucose in blood. Increased blood glucose level triggers release of insulin from pancreatic β-cells. Insulin represses hepatic glucose production and increases glucose accumulation. Insulin resistance is the main cause of type 2 diabetes and hyperglycemia. Currently thiazolidinediones (TZDs) targeting transcriptional factor PPARγ are used as insulin sensitizers for treating patients with type 2 diabetes. However, TZDs are reported to be associated with cardiovascular and liver problems and stimulate obesity. Thus, it is necessary to search new approaches to improve insulin sensitivity. A promising candidate is transcriptional factor Prep1, as it was shown earlier it could affect insulin sensitivity in variety of insulin-sensitive tissues. The aim of the present study was to evaluate a possible involvement of transcriptional factor Prep1 in control of hepatic glucose accumulation and production. We created mice with liver-specific Prep1 knockout and discovered that hepatocytes derived from these mice are much more sensitive to insulin, comparing to their WT littermates. Incubation of these cells with 100 nM insulin results in almost complete inhibition of gluconeogenesis, while in WT cells this repression is only partial. However, Prep1 doesn't affect gluconeogenesis in the absence of insulin. Also, we observed that nuclear content of gluconeogenic transcription factor FOXO1 was greatly reduced in Prep1 knockout hepatocytes. These findings suggest that Prep1 may control hepatic insulin sensitivity by targeting FOXO1 nuclear stability. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Different Effects of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-2 on Myogenic Differentiation of Human Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Doaa Aboalola

    2017-01-01

    Full Text Available Insulin-like growth factors (IGFs are critical components of the stem cell niche, as they regulate proliferation and differentiation of stem cells into different lineages, including skeletal muscle. We have previously reported that insulin-like growth factor binding protein-6 (IGFBP-6, which has high affinity for IGF-2, alters the differentiation process of placental mesenchymal stem cells (PMSCs into skeletal muscle. In this study, we determined the roles of IGF-1 and IGF-2 and their interactions with IGFBP-6. We showed that IGF-1 increased IGFBP-6 levels within 24 hours but decreased after 3 days, while IGF-2 maintained higher levels of IGFBP-6 throughout myogenesis. IGF-1 increased IGFBP-6 in the early phase as a requirement for muscle commitment. In contrast, IGF-2 enhanced muscle differentiation as shown by the expression of muscle differentiation markers MyoD, MyoG, and MHC. IGF-1 and IGF-2 had different effects on muscle differentiation with IGF-1 promoting early commitment to muscle and IGF-2 promoting complete muscle differentiation. We also showed that PMSCs acquired increasing capacity to synthesize IGF-2 during muscle differentiation, and the capacity increased as the differentiation progressed suggesting an autocrine and/or paracrine effect. Additionally, we demonstrated that IGFBP-6 could enhance the muscle differentiation process in the absence of IGF-2.

  5. Fibroblast growth factor regulates insulin-like growth factor-binding protein production by vascular smooth muscle cells.

    Science.gov (United States)

    Ververis, J; Ku, L; Delafontaine, P

    1994-02-01

    Insulin-like growth factor I is an important mitogen for vascular smooth muscle cells, and its effects are regulated by several binding proteins. Western ligand blotting of conditioned medium from rat aortic smooth muscle cells detected a 24 kDa binding protein and a 28 kDa glycosylated variant of this protein, consistent with insulin-like growth factor binding protein-4 by size. Low amounts of a glycosylated 38 to 42 kDa doublet (consistent with binding protein-3) and a 31 kDa non-glycosylated protein also were present. Basic fibroblast growth factor markedly increased secretion of the 24 kDa binding protein and its 28 kDa glycosylated variant. This effect was dose- and time-dependent and was inhibited by co-incubation with cycloheximide. Crosslinking of [125I]-insulin-like growth factor I to cell monolayers revealed no surface-associated binding proteins, either basally or after agonist treatment. Induction of binding protein production by fibroblast growth factor at sites of vascular injury may be important in vascular proliferative responses in vivo.

  6. 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.

  7. Vitamin D and cardiometabolic risk factors and diseases.

    Science.gov (United States)

    Mousa, A; Naderpoor, N; Teede, H J; De Courten, M P J; Scragg, R; De Courten, B

    2015-09-01

    Obesity, type 2 diabetes, and cardiovascular disease (CVD) are the most common preventable causes of morbidity and mortality worldwide. Insulin resistance, which is a shared feature in these conditions, is also strongly linked to the development of polycystic ovary syndrome (PCOS), which is the most common endocrine disease in women of reproductive age and a major cause of infertility. Vitamin D deficiency has reached epidemic proportions worldwide, primarily due to the shift to sedentary, indoor lifestyles and sun avoidance behaviours to protect against skin cancer. In recent years, vitamin D deficiency has been implicated in the aetiology of type 2 diabetes, PCOS and CVD, and has been shown to be associated with their risk factors including obesity, insulin resistance, hypertension, as well as chronic low-grade inflammation. Treating vitamin D deficiency may offer a feasible and cost-effective means of reducing cardiometabolic risk factors at a population level in order to prevent the development of type 2 diabetes and CVD. However, not all intervention studies show that vitamin D supplementation alleviates these risk factors. Importantly, there is significant heterogeneity in existing studies with regards to doses and drug regimens used, populations studied (i.e. vitamin D deficient or sufficient), and the lengths of supplementation, and only few studies have directly examined the effect of vitamin D on insulin secretion and resistance with the use of clamp methods. Therefore, there is a need for well-designed large scale trials to clarify the role of vitamin D supplementation in the prevention of type 2 diabetes, PCOS, and CVD.

  8. New risk factors for atherosclerosis and patient risk assessment

    NARCIS (Netherlands)

    Fruchart, Jean-Charles; Nierman, Melchior C.; Stroes, Erik S. G.; Kastelein, John J. P.; Duriez, Patrick

    2004-01-01

    Advances in our understanding of the ways in which the traditional cardiovascular risk factors, including standard lipid (eg, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) and nonlipid (eg, hypertension) risk factors, interact to initiate

  9. Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors

    Science.gov (United States)

    Ahmed, Muhammad S.; Rainer, Carolyn; Nielsen, Sebastian R.; Quaranta, Valeria; Weyer-Czernilofsky, Ulrike; Engle, Danielle D.; Perez-Mancera, Pedro A.; Coupland, Sarah E.; Taktak, Azzam; Bogenrieder, Thomas; Tuveson, David A.; Campbell, Fiona; Schmid, Michael C.; Mielgo, Ainhoa

    2017-01-01

    Tumor-associated macrophages (TAM) and myofibroblasts are key drivers in cancer that are associated with drug resistance in many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM and fibroblasts contribute to chemoresistance is unclear. In this study, we found that TAM and myofibroblasts directly support chemoresistance of pancreatic cancer cells by secreting insulin-like growth factors (IGF) 1 and 2, which activate insulin/IGF receptors on pancreatic cancer cells. Immunohistochemical analysis of biopsies from patients with pancreatic cancer revealed that 72% of the patients expressed activated insulin/IGF receptors on tumor cells, and this positively correlates with increased CD163+ TAM infiltration. In vivo, we found that TAM and myofibroblasts were the main sources of IGF production, and pharmacologic blockade of IGF sensitized pancreatic tumors to gemcitabine. These findings suggest that inhibition of IGF in combination with chemotherapy could benefit patients with PDAC, and that insulin/IGF1R activation may be used as a biomarker to identify patients for such therapeutic intervention. PMID:27742686

  10. A high ratio of insulin-like growth factor II/insulin-like growth factor binding protein 2 messenger RNA as a marker for anaplasia in meningiomas.

    Science.gov (United States)

    Nordqvist, A C; Peyrard, M; Pettersson, H; Mathiesen, T; Collins, V P; Dumanski, J P; Schalling, M

    1997-07-01

    Insulin-like growth factors (IGFs) I and II have been implicated as autocrine or paracrine growth promoters. These growth factors bind to specific receptors, and the response is modulated by interaction with IGF-binding proteins (IGFBPs). We observed a strong correlation between anaplastic/atypical histopathology and a high IGF-II/IGFBP-2 mRNA ratio in a set of 68 sporadic meningiomas. A strong correlation was also found between clinical outcome and IGF-II/IGFBP-2 ratio, whereas previously used histochemical markers were less correlated to outcome. We suggest that a high IGF-II/IGFBP-2 mRNA ratio may be a sign of biologically aggressive behavior in meningiomas that can influence treatment strategies. We propose that low IGFBP-2 levels in combination with increased levels of IGF-II would result in more free IGF-II and consequently greater stimulation of proliferation.

  11. Changes in serum concentrations of growth hormone, insulin, insulin-like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle

    DEFF Research Database (Denmark)

    Juul, A; Scheike, Thomas Harder; Pedersen, A T

    1997-01-01

    Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH......-IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women (aged 18-40 years). Blood sampling and urinary collection was performed every morning at 0800 h for 32 consecutive days. Every second day the subjects were fasted overnight before blood sampling. Follicle stimulating hormone, luteinizing...... hormone (LH), oestradiol, progesterone, IGF-I, IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and GH were determined in all samples, whereas insulin and IGFBP-1 were determined in fasted samples only. Serum IGF-I concentrations showed some fluctuation during the menstrual cycle...

  12. Skin Cancer: Biology, Risk Factors & Treatment

    Science.gov (United States)

    ... turn Javascript on. Feature: Skin Cancer Skin Cancer: Biology, Risk Factors & Treatment Past Issues / Summer 2013 Table ... Articles Skin Cancer Can Strike Anyone / Skin Cancer: Biology, Risk Factors & Treatment / Timely Healthcare Checkup Catches Melanoma ...

  13. 459 Preventing Cardiovascular Disease Risk Factors through ...

    African Journals Online (AJOL)

    FIRST LADY

    2011-01-18

    Jan 18, 2011 ... injury. Risk factors may be considered as characteristic indicators ... by examining the cardiovascular risk factors that are related to various forms .... Cross country race, Handball, Jogging, Rope jumping, Running Soccer,.

  14. Risk factors identified for certain lymphoma subtypes

    Science.gov (United States)

    In a large international collaborative analysis of risk factors for non-Hodgkin lymphoma (NHL), scientists were able to quantify risk associated with medical history, lifestyle factors, family history of blood or lymph-borne cancers, and occupation for 11

  15. Insulin-like growth factor-I, physical activity, and control of cellular anabolism.

    Science.gov (United States)

    Nindl, Bradley C

    2010-01-01

    The underlying mechanisms responsible for mediating the beneficial outcomes of exercise undoubtedly are many, but the insulin-like growth factor-I (IGF-I) system is emerging as an important and central hormonal axis that plays a significant role concerning cellular anabolism. This introductory article summarizes the intent and the content for papers presented as part of a 2008 American College of Sports Medicine national symposium entitled "Insulin-like Growth Factor-I, Physical Activity, and Control of Cellular Anabolism." The individual authors and their papers are as follows: Jan Frystyk authoring "The relationship between exercise and the growth hormone/insulin-like growth factor-I axis," Greg Adams authoring "IGF-I signaling in skeletal muscle and the potential for cytokine interactions," and Brad Nindl authoring "Insulin-like growth factor-I as a biomarker of health, fitness, and training status." These papers focus on 1) different assay methodologies for IGF-I within the paradigm of exercise studies, 2) research demonstrating that intracellular signaling components associated with several proinflammatory cytokines have the potential to interact with anabolic signaling processes in skeletal muscle, and 3) an overview of IGF-I as a biomarker related to exercise training, muscle and bone remodeling, body composition, cognition, and cancer. When summed in total, the contribution that these papers will make will undoubtedly involve bringing attention to the vast regulatory complexity of the IGF-I system and will hopefully convince the reader that the IGF-I system warrants further detailed scientific inquiry to resolve many unanswered questions and paradoxical experimental findings. The IGF-I system remains one of the most intriguing and captivating marvels of human physiology that seems central in mediating numerous adaptations from physical activity.

  16. Insulin-like growth factor-1 levels in children with Beta-thalassemia minor

    OpenAIRE

    Mehran Karimi; Hamdollah Karamifar; Nargrs Sobhani

    2008-01-01

    Objective: Growth retardation in children with b-thalassemia major is multifactorial. Some etiologies described for this condition are hemochromatosis, disturbed growth hormone (GH) / insulin growth factor-1 (IGF-1) axis, undernutrition and hypermetabolism. It has also been proven that growth retardation is present in b-thalassemia major children despite regular transfusion and chelation. Our aim was to evaluate the level of IGF-1 in b-thalassemia minor subjects and compare it with that in he...

  17. Insulin-like Growth Factor Receptor Inhibitors: Baby or the Bathwater?

    OpenAIRE

    Yee, Douglas

    2012-01-01

    The success of targeted therapies for cancer is undisputed; strong preclinical evidence has resulted in the approval of several new agents for cancer treatment. The type I insulin-like growth factor receptor (IGF1R) appeared to be one of these promising new targets. Substantial population and preclinical data have all pointed toward this pathway as an important regulator of tumor cell biology. Although early results from clinical trials that targeted the IGF1R showed some evidence of response...

  18. Women's Heart Disease: Heart Disease Risk Factors

    Science.gov (United States)

    ... this page please turn JavaScript on. Feature: Women's Heart Disease Heart Disease Risk Factors Past Issues / Winter 2014 Table ... or habits may raise your risk for coronary heart disease (CHD). These conditions are known as risk ...

  19. Risk factors for venous thromboembolism during pregnancy

    DEFF Research Database (Denmark)

    Jensen, Thomas Bo; Gerds, Thomas Alexander; Grøn, Randi

    2013-01-01

    Pregnant women are at an increased risk of venous thromboembolism (VTE). Risk factors for VTE among pregnant women are not sufficiently investigated.......Pregnant women are at an increased risk of venous thromboembolism (VTE). Risk factors for VTE among pregnant women are not sufficiently investigated....

  20. Chronic periodontitis with multiple risk factor syndrome: a case report.

    Science.gov (United States)

    Shimoe, Masayuki; Yamamoto, Tadashi; Iwamoto, Yoshihiro; Shiomi, Nobuyuki; Maeda, Hiroshi; Nishimura, Fusanori; Takashiba, Shogo

    2011-07-01

    Multiple risk factor syndrome is a clustering of cardiovascular risk factors, such as diabetes, dyslipidemia, hypertension, and obesity associated epidemiologically with insulin resistance. This report describes the clinical course of a patient suffering from severe periodontitis with multiple risk factor syndrome, and discusses the association between periodontal infection and systemic health. The patient had a history of type 2 diabetes, dyslipidemia, and hypertension for over 10 years. At baseline, her hemoglobin A1 c was 8.1%. However, she had no diabetic complications except periodontitis. The IgG antibody titers against Porphyromonas gingivalis FDC 381 and SU63 were elevated above the mean of healthy subjects +2 standard deviations. Intensive periodontal treatment, including periodontal surgery, was performed to reduce periodontal infection and bacteremia. Her systemic and periodontal conditions were evaluated longitudinally for 10 years. Following periodontal treatment, antibody titers against Porphyromonas gingivalis and hemoglobin A1c values were significantly improved. The other clinical data and medication for her systemic condition also remained stable during supportive periodontal therapy. However, she developed myocardial infarction, and showed continuous deterioration of hemoglobin A1 c level and periodontitis. The long-term clustering of risk factors, such as diabetes, dyslipidemia, hypertension, and periodontitis, are associated with the development of myocardial infarction. Treatment of systemic conditions in combination with comprehensive periodontal treatment is important in management of patients with multiple risk factor syndrome.

  1. Fasting plasma insulin and the default mode network in women at risk for Alzheimer's disease.

    Science.gov (United States)

    Kenna, Heather; Hoeft, Fumiko; Kelley, Ryan; Wroolie, Tonita; DeMuth, Bevin; Reiss, Allan; Rasgon, Natalie

    2013-03-01

    Brain imaging studies in Alzheimer's disease research have demonstrated structural and functional perturbations in the hippocampus and default mode network (DMN). Additional evidence suggests risk for pathological brain aging in association with insulin resistance (IR). This study piloted investigation of associations of IR with DMN-hippocampal functional connectivity among postmenopausal women at risk for Alzheimer's disease. Twenty middle-aged women underwent resting state functional magnetic resonance imaging. Subjects were dichotomized relative to fasting plasma insulin levels (i.e., > 8 μIU/mL [n = 10] and < 8 μIU/mL [n = 10]), and functional connectivity analysis contrasted their respective blood oxygen level-dependent signal correlation between DMN and hippocampal regions. Higher-insulin women had significantly reduced positive associations between the medial prefrontal cortex and bilateral parahippocampal regions extending to the right hippocampus, and conversely, between the left and right hippocampus and medial prefrontal cortex. Neuropsychological data (all within normal ranges) also showed significant differences with respect to executive functioning and global intelligence. The results provide further evidence of deleterious effects of IR on the hippocampus and cognition. Further imaging studies of the IR-related perturbations in DMN-hippocampal functional connectivity are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Molecular Risk Factors for Schizophrenia.

    Science.gov (United States)

    Modai, Shira; Shomron, Noam

    2016-03-01

    Schizophrenia (SZ) is a complex and strongly heritable mental disorder, which is also associated with developmental-environmental triggers. As opposed to most diagnosable diseases (yet similar to other mental disorders), SZ diagnosis is commonly based on psychiatric evaluations. Recently, large-scale genetic and epigenetic approaches have been applied to SZ research with the goal of potentially improving diagnosis. Increased computational analyses and applied statistical algorithms may shed some light on the complex genetic and epigenetic pathways contributing to SZ pathogenesis. This review discusses the latest advances in molecular risk factors and diagnostics for SZ. Approaches such as these may lead to a more accurate definition of SZ and assist in creating extended and reliable clinical diagnoses with the potential for personalized treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Early Stress History Alters Serum Insulin-Like Growth Factor-1 and Impairs Muscle Mitochondrial Function in Adult Male Rats.

    Science.gov (United States)

    Ghosh, S; Banerjee, K K; Vaidya, V A; Kolthur-Seetharam, U

    2016-09-01

    Early-life adversity is associated with an enhanced risk for adult psychopathology. Psychiatric disorders such as depression exhibit comorbidity for metabolic dysfunction, including obesity and diabetes. However, it is poorly understood whether, besides altering anxiety and depression-like behaviour, early stress also evokes dysregulation of metabolic pathways and enhances vulnerability for metabolic disorders. We used the rodent model of the early stress of maternal separation (ES) to examine the effects of early stress on serum metabolites, insulin-like growth factor (IGF)-1 signalling, and muscle mitochondrial content. Adult ES animals exhibited dyslipidaemia, decreased serum IGF1 levels, increased expression of liver IGF binding proteins, and a decline in the expression of specific metabolic genes in the liver and muscle, including Pck1, Lpl, Pdk4 and Hmox1. These changes occurred in the absence of alterations in body weight, food intake, glucose tolerance, insulin tolerance or insulin levels. ES animals also exhibited a decline in markers of muscle mitochondrial content, such as mitochondrial DNA levels and expression of TFAM (transcription factor A, mitochondrial). Furthermore, the expression of several genes involved in mitochondrial function, such as Ppargc1a, Nrf1, Tfam, Cat, Sesn3 and Ucp3, was reduced in skeletal muscle. Adult-onset chronic unpredictable stress resulted in overlapping and distinct consequences from ES, including increased circulating triglyceride levels, and a decline in the expression of specific metabolic genes in the liver and muscle, with no change in the expression of genes involved in muscle mitochondrial function. Taken together, our results indicate that a history of early adversity can evoke persistent changes in circulating IGF-1 and muscle mitochondrial function and content, which could serve to enhance predisposition for metabolic dysfunction in adulthood. © 2016 British Society for Neuroendocrinology.

  4. Development of receptors for insulin and insulin-like growth factor-I in head and brain of chick embryos: Autoradiographic localization

    International Nuclear Information System (INIS)

    Bassas, L.; Girbau, M.; Lesniak, M.A.; Roth, J.; de Pablo, F.

    1989-01-01

    In whole brain of chick embryos insulin receptors are highest at the end of embryonic development, while insulin-like growth factor-I (IGF-I) receptors dominate in the early stages. These studies provided evidence for developmental regulation of both types of receptors, but they did not provide information on possible differences between brain regions at each developmental stage or within one region at different embryonic ages. We have now localized the specific binding of [125I]insulin and [125I]IGF-I in sections of head and brain using autoradiography and computer-assisted densitometric analysis. Embryos have been studied from the latter part of organogenesis (days 6 and 12) through late development (day 18, i.e. 3 days before hatching), and the binding patterns have been compared with those in the adult brain. At all ages the binding of both ligands was to discrete anatomical regions. Interestingly, while in late embryos and adult brain the patterns of [125I]insulin and [125I] IGF-I binding were quite distinct, in young embryos both ligands showed very similar localization of binding. In young embryos the retina and lateral wall of the growing encephalic vesicles had the highest binding of both [125I]insulin and [125I]IGF-I. In older embryos, as in the adult brain, insulin binding was high in the paleostriatum augmentatum and molecular layer of the cerebellum, while IGF-I binding was prominent in the hippocampus and neostriatum. The mapping of receptors in a vertebrate embryo model from early prenatal development until adulthood predicts great overlap in any possible function of insulin and IGF-I in brain development, while it anticipates differential localized actions of the peptides in the mature brain

  5. Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion

    DEFF Research Database (Denmark)

    Lyssenko, Valeriya; Nagorny, Cecilia L F; Erdos, Michael R

    2009-01-01

    Genome-wide association studies have shown that variation in MTNR1B (melatonin receptor 1B) is associated with insulin and glucose concentrations. Here we show that the risk genotype of this SNP predicts future type 2 diabetes (T2D) in two large prospective studies. Specifically, the risk genotype...... was associated with impairment of early insulin response to both oral and intravenous glucose and with faster deterioration of insulin secretion over time. We also show that the MTNR1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in beta cells in islets....... Nondiabetic individuals carrying the risk allele and individuals with T2D showed increased expression of the receptor in islets. Insulin release from clonal beta cells in response to glucose was inhibited in the presence of melatonin. These data suggest that the circulating hormone melatonin, which...

  6. A pilot study of factors associated with glycaemic control in adults with Type 1 diabetes mellitus on insulin pump therapy.

    Science.gov (United States)

    Wen, W; Frampton, R; Wright, K; Fattore, S; Shadbolt, B; Perampalam, S

    2016-02-01

    To identify the knowledge and management factors associated with glycaemic control among adults with Type 1 diabetes mellitus treated with insulin pump therapy. A cross-sectional study of adults with Type 1 diabetes mellitus on insulin pump therapy for at least 12 months (n = 50, 18-70 years old) was undertaken between December 2013 and May 2014. A new questionnaire was developed to evaluate participants' knowledge and management related to insulin pump therapy, and were correlated with insulin pump data, HbA1c and frequency of hypoglycaemia. Participants who changed their insulin pump settings when indicated had significantly better glycaemic control than those who did not (P = 0.04). Multivariate logistic regression analysis found that better overall insulin pump therapy management was a significant predictor of better glycaemic control (odds ratio 4.45, 95% confidence interval 1.61-12.3; P = 0.004) after adjusting for potential confounders including age, gender, duration of diabetes and insulin pump therapy. However, overall insulin pump therapy knowledge was not a significant predictor of glycaemic control (P = 0.058). There was no significant association between frequency of hypoglycaemia and insulin pump therapy knowledge or management. We identified some key knowledge and management factors associated with glycaemic control in adults with Type 1 diabetes mellitus on insulin pump therapy using a newly designed questionnaire. The pilot study assessed the clinical utility of this evaluation tool, which may facilitate provision of targeted education to insulin pump therapy users to achieve optimal glycaemic control. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  7. Regulation of the pituitary tumor transforming gene by insulin-like-growth factor-I and insulin differs between malignant and non-neoplastic astrocytes

    International Nuclear Information System (INIS)

    Chamaon, Kathrin; Kirches, Elmar; Kanakis, Dimitrios; Braeuninger, Stefan; Dietzmann, Knut; Mawrin, Christian

    2005-01-01

    The reasons for overexpression of the oncogene pituitary tumor transforming gene (PTTG) in tumors are still not fully understood. A possible influence of the insulin-like growth factor I (Igf-I) may be of interest, since enhanced Igf-I signalling was reported in various human tumors. We examined the influence of Igf-I and insulin on PTTG expression in human astrocytoma cells in comparison to proliferating non-neoplastic rat embryonal astrocytes. PTTG mRNA expression and protein levels were increased in malignant astrocytes treated with Igf-I or insulin, whereas in rat embryonic astrocytes PTTG expression and protein levels increased only when cells were exposed to Igf-I. Enhanced transcription did not occur after treatment with inhibitors of phosphoinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK), blocking the two basic signalling pathways of Igf-I and insulin. In addition to this transcriptional regulation, both kinases directly bind to PTTG, suggesting a second regulatory route by phosphorylation. However, the interaction of endogenous PTTG with MAPK and PI3K, as well as PTTG phosphorylation were independent from Igf-I or insulin. The latter results were also found in human testis, which contains high PTTG levels as well as in nonneoplastic astrocytes. This suggest, that PI3K and MAPK signalling is involved in PTTG regulation not only in malignant astrocytomas but also in non-tumorous cells

  8. The serum concentration of tumor necrosis factor alpha is not an index of growth-hormone- or obesity-induced insulin resistance.

    Science.gov (United States)

    Pincelli, A I; Brunani, A; Scacchi, M; Dubini, A; Borsotti, R; Tibaldi, A; Pasqualinotto, L; Maestri, E; Cavagnini, F

    2001-01-01

    The tumor necrosis factor alpha (TNF-alpha) might play a central role in insulin resistance, a frequent correlate of obesity likely contributing to some obesity-associated complications. Adult growth hormone (GH) deficiency syndrome (GHDA) shares with obesity excessive fat mass, hyperlipidemia, increased cardiovascular risk, and insulin resistance. On the other hand, GH has been shown to induce transient deterioration of glucose metabolism and insulin resistance when administered in normal humans and in GHDA patients. No information is presently available on the relationship between serum TNF-alpha levels and insulin sensitivity in GHDA. We compared the serum TNF-alpha levels found in 10 GHDA patients before and after a 6-month recombinant human GH therapy (Genotropin), in an insulin resistance prone population of 16 obese (OB) patients and in 38 normal-weight healthy blood donors (controls). The insulin sensitivity was assessed by a euglycemic-hyperinsulinemic glucose clamp in all the GHDA patients and in 10 OB and in 6 control subjects. The serum TNF-alpha levels were not significantly different in OB patients (42.2 +/- 12.81 pg/ml), in GHDA patients at baseline (71.3 +/- 23.97 pg/ml), and in controls (55.3 +/- 14.28 pg/ml). A slight decrease of TNF-alpha values was noted in GHDA patients after 6 months of recombinant human GH treatment (44.5 +/- 20.19 pg/ml; NS vs. baseline). The insulin sensitivity (M) was significantly reduced in OB patients (2.4 +/- 0.30 mg/kg/min) as compared with control subjects (7.5 +/- 0.39 mg/kg/min) and in GHDA patients both at baseline (6.6 +/- 0.6 mg/kg/min) and after recombinant human GH therapy (5.6 +/- 0.7 mg/kg/min). The insulin sensitivity in the GHDA patients, similar to that of controls at baseline, worsened after recombinant human GH treatment (p < 0.05 vs. baseline; p = 0.05 vs. controls). Linear regression analysis showed no correlation between TNF-alpha and M values (see text) in all patient groups. These data indicate

  9. Dexras1 links glucocorticoids to insulin-like growth factor-1 signaling in adipogenesis

    Science.gov (United States)

    Kim, Hyo Jung; Cha, Jiyoung Y.; Seok, Jo Woon; Choi, Yoonjeong; Yoon, Bo Kyung; Choi, Hyeonjin; Yu, Jung Hwan; Song, Su Jin; Kim, Ara; Lee, Hyemin; Kim, Daeun; Han, Ji Yoon; Kim, Jae-woo

    2016-01-01

    Glucocorticoids are associated with obesity, but the underlying mechanism by which they function remains poorly understood. Previously, we showed that small G protein Dexras1 is expressed by glucocorticoids and leads to adipocyte differentiation. In this study, we explored the mechanism by which Dexras1 mediates adipogenesis and show a link to the insulin-like growth factor-1 (IGF-1) signaling pathway. Without Dexras1, the activation of MAPK and subsequent phosphorylation of CCAAT/enhancer binding protein β (C/EBPβ) is abolished, thereby inhibiting mitotic clonal expansion and further adipocyte differentiation. Dexras1 translocates to the plasma membrane upon insulin or IGF-1 treatment, for which the unique C-terminal domain (amino acids 223–276) is essential. Dexras1-dependent MAPK activation is selectively involved in the IGF-1 signaling, because another Ras protein, H-ras localized to the plasma membrane independently of insulin treatment. Moreover, neither epidermal growth factor nor other cell types shows Dexras1-dependent MAPK activation, indicating the importance of Dexras1 in IGF-1 signaling in adipogenesis. Dexras1 interacts with Shc and Raf, indicating that Dexras1-induced activation of MAPK is largely dependent on the Shc-Grb2-Raf complex. These results suggest that Dexras1 is a critical mediator of the IGF-1 signal to activate MAPK, linking glucocorticoid signaling to IGF-1 signaling in adipogenesis. PMID:27345868

  10. Polysomnographic sleep, growth hormone insulin-like growth factor-I axis, leptin, and weight loss

    DEFF Research Database (Denmark)

    Rasmussen, Michael; Wildschiødtz, Gordon; Juul, Anders

    2008-01-01

    compared with nonobese subjects After diet-induced weight loss the differences in GH, free IGF-I, and leptin were no longer present between previously obese and nonobese subjects, whereas a significant difference in sleep duration and total IGF-I levels persisted. Rapid eye movement (REM) sleep, non-REM......Short sleep appears to be strongly associated with obesity and altered metabolic function, and sleep and growth hormone (GH) secretion seems interlinked. In obesity, both the GH-insulin-like-growth-factor-I (GH-IGF-I) axis and sleep have been reported to be abnormal, however, no studies have...... investigated sleep in relation to the GH-IGF-I axis and weight loss in obese subjects. In this study polygraphic sleep recordings, 24-h GH release, 24-h leptin levels, free-IGF-I, total-IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), cortisol and insulin sensitivity were determined in six...

  11. Mactosylceramide Prevents Glial Cell Overgrowth by Inhibiting Insulin and Fibroblast Growth Factor Receptor Signaling

    DEFF Research Database (Denmark)

    Gerdøe-Kristensen, Stine; Lund, Viktor K; Wandall, Hans H

    2017-01-01

    , in which the mannosyltransferase Egghead controls conversion of glucosylceramide (GlcCer) to mactosylceramide (MacCer). Lack of elongated GSL in egghead (egh) mutants causes overgrowth of subperineurial glia (SPG), largely due to aberrant activation of phosphatidylinositol 3-kinase (PI3K). However, to what...... of the Drosophila Insulin Receptor (InR) and the FGFR homolog Heartless (Htl) in wild type SPG, and is suppressed by inhibiting Htl and InR activity in egh. Knockdown of GlcCer synthase in the SPG fails to suppress glial overgrowth in egh nerves, and slightly promotes overgrowth in wild type, suggesting that RTK...... hyperactivation is caused by absence of MacCer and not by GlcCer accumulation. We conclude that an early product in GSL biosynthesis, MacCer, prevents inappropriate activation of Insulin and Fibroblast Growth Factor Receptors in Drosophila glia. This article is protected by copyright. All rights reserved....

  12. Insulin-like growth factor (IGF-I and IGF binding proteins axis in diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Min Sun Kim

    2015-06-01

    Full Text Available Increasing evidence suggests an important role of the insulin-like growth factor (IGF-IGF binding protein (IGFBP axis in the maintenance of normal glucose and lipid metabolism. Significant changes occur in the local IGF-I-IGFBPs environment in response to the diabetic milieu. A significant reduction of serum IGF-I levels was observed in patients with type 1 diabetes mellitus (T1DM. Inversely, considerably increased serum levels of IGF-I and IGFBP-3 levels were detected in individuals with glucose intolerance including T2DM. Recently, several prospective studies indicated that baseline levels of IGF-I and IGFBPs are associated with the development of diabetes. These findings suggest that disturbances in insulin and IGF-I-IGFBP axis can affect the development of glucose intolerance including diabetes.

  13. Skin Tags and Acanthosis Nigricans in Patients with Hepatitis C Infection in Relation to Insulin Resistance and Insulin Like Growth Factor-1 Levels

    Science.gov (United States)

    El Safoury, Omar Soliman; Shaker, Olfat G; Fawzy, May Mohsen

    2012-01-01

    Background: Skin tags (ST) are papillomas commonly found in the neck, axillae of middle-aged and elderly people Aim: Insulin and insulin-like growth factor (IGF-1) levels are affected by hepatitis C virus (HCV) infection and both of them may be implicated in the etiopathogenesis of ST and acanthosis nigricans (AN) through their proliferative and differentiating properties. So, the aim of this work was to evaluate the impact of HCV infection on ST and AN through the estimation of insulin resistance and IGF-1. Materials and Methods: Participants were arranged into four groups: (ST +ve / HCV +ve) 23 subjects, (ST+ / HCV -ve) 19 subjects, (HCV -ve / ST-ve) 20 subjects and (ST-ve /HCV +ve) 22 subjects. Age, ST size, color, number, AN, fasting glucose, fasting insulin, insulin resistance, IGF-1, HCV-antibodies (Ab) were recorded. Results: The mean number of ST in Group 1 was half the number of ST in Group 2 (11.0±9.3 / 22.3±14.0) (P=0.005). The difference in insulin resistance between the same groups was non-significant (13.1±10.6 / 9.0±5.5) (P=0.441) while the difference in IGF-1 was statistically significant (218.6±46.2 /285.4±32.8) (P=0.002). The multivariate logistic regression for the variables revealed that insulin resistance is the only factor affecting the occurrence of ST (OR=1.096, P=0.023). Multivariate regression analysis for the variables showed that HCV was borderline but not a significant factor affecting the number of ST (Beta=-0.409, P=0.053). The number of patients with AN was doubled in Group 2 in comparison to Group 1 but this was non significant 3(13%) / 6(32%) (P=0.2800). Conclusion: HCV is associated with a significant decrease in the ST number and in the serum level of IGF-1 together with an obvious decrease in the occurrence of AN. Our results may point to the entrant effect of insulin resistance and IGF-1 in ST and AN development. The current study suggests the evaluation of IGF-1-lowering agents in the control of ST and AN especially in

  14. Influence of insulin therapy on circulating ghrelin and insulin-like ghrelinowth factor-1(IGF-1) levels in children with type-1 diabetes mellitus

    International Nuclear Information System (INIS)

    Moawad, A.T.; Nassar, E.M.; Mostafa, A.M.; Mohammed, S.K.

    2009-01-01

    Diabetes mellitus type 1 (IDDM)is a chronic disease associated with alterations in the growth hormone/insulin -like growth factor (GH-IGF) system and ghrelin level which may lead to changes in metabolic control. This study aimed to evaluate the circulating levels of the gut-derived peptides (ghrelin and insulin-like growth factors (IGF s ) in children with IDDM and to link these two peptides with the glucose level in diabetic children at diagnoses and after insulin therapy. Design and methods: the studied group consisted of 30 newly diagnosed diabetic children (17 females and 13 males) diagnosed in paediatric diabetes unit, children's hospital, Ain shams university. Their age ranged from (6.2-11.8) years with mean of 10.10± 1.74 years. Twenty non diabetic healthy children matching in age and sex served as controls. Serum ghrelin was determined by enzyme linked immuno absorbanet assay (ELISA), while IGF-1 and insulin-like growth factors binding proteins -1 and 3 (IGFBP s ) were assessed by radioimmunoassay(RIA). Results: body mass index (BMI) in patients was significantly decreased in the diabetic group as compared to the healthy group at diagnosis. After insulin therapy BMI was significantly increase as compared to its value at diagnosis (p< 0.05) such increase was not significant on comparing to controls. Regarding blood glucose level there was very highly significant decrease in the level of HBAI (glycolated HB) in diabetic patients after insulin therapy (p<0.0001) than at diagnosis . The mean ghrelin level was highly significantly decreased in diabetic children at diagnosis and after insulin therapy as compared to controls (p<0.0001). No differences were found in the mean ghrelin levels in diabetic children at diagnosis or after insulin therapy.conclusions : the decrease in mean gherlin levels in this study at diagnosis and after therapy could reflect an attempt by the body to decrease the glucose level and thus may prevent hyperglycemia in diabetic patients

  15. The Relationship Between Socioeconomic Status and CV Risk Factors

    Science.gov (United States)

    Quispe, Renato; Benziger, Catherine P.; Bazo-Alvarez, Juan Carlos; Howe, Laura D.; Checkley, William; Gilman, Robert H.; Smeeth, Liam; Bernabé-Ortiz, Antonio; Miranda, J. Jaime; Bernabé-Ortiz, Antonio; Casas, Juan P.; Smith, George Davey; Ebrahim, Shah; García, Héctor H.; Gilman, Robert H.; Huicho, Luis; Málaga, Germán; Miranda, J. Jaime; Montori, Víctor M.; Smeeth, Liam; Checkley, William; Diette, Gregory B.; Gilman, Robert H.; Huicho, Luis; León-Velarde, Fabiola; Rivera, María; Wise, Robert A.; Checkley, William; García, Héctor H.; Gilman, Robert H.; Miranda, J. Jaime; Sacksteder, Katherine

    2016-01-01

    Background Variations in the distribution of cardiovascular disease and risk factors by socioeconomic status (SES) have been described in affluent societies, yet a better understanding of these patterns is needed for most low- and middle-income countries. Objective This study sought to describe the relationship between cardiovascular risk factors and SES using monthly family income, educational attainment, and assets index, in 4 Peruvian sites. Methods Baseline data from an age- and sex-stratified random sample of participants, ages ≥35 years, from 4 Peruvian sites (CRONICAS Cohort Study, 2010) were used. The SES indicators considered were monthly family income (n = 3,220), educational attainment (n = 3,598), and assets index (n = 3,601). Behavioral risk factors included current tobacco use, alcohol drinking, physical activity, daily intake of fruits and vegetables, and no control of salt intake. Cardiometabolic risk factors included obesity, elevated waist circumference, hypertension, insulin resistance, diabetes mellitus, low high-density lipoprotein cholesterol, and high triglyceride levels. Results In the overall population, 41.6% reported a monthly family income education. Important differences were noted between the socioeconomic indicators: for example, higher income and higher scores on an asset index were associated with greater risk of obesity, whereas higher levels of education were associated with lower risk of obesity. In contrast, higher SES according to all 3 indicators was associated with higher levels of triglycerides. Conclusions The association between SES and cardiometabolic risk factors varies depending on the SES indicator used. These results highlight the need to contextualize risk factors by socioeconomic groups in Latin American settings. PMID:27102029

  16. Diagnostic Usefulness of Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor Binding Protein 3 in Children with Suspected Pituitary Dwarfism.

    Science.gov (United States)

    Zelazowska-Rutkowska, Beata; Trusiak, Marta; Bossowski, Artur; Cylwik, Bogdan

    2018-05-01

    Pituitary dwarfism (also known as short stature) is a medical condition in which the pituitary gland does not produce enough growth hormone (GH). To confirm the diagnosis of growth hormone deficiency the overnight profile of GH secretion and GH provocative tests are usually performed; however, due to wide GH fluctuations throughout the day and night and the invasiveness of stimulation tests, their clinical utility is limited. Therefore, screening for IGF-1 (insulin-like growth factor 1) and IGFBP-3 (insulin-like growth factor binding protein type 3) is proposed, suggesting that these tests provide a more accurate reflection of the mean plasma GH level, although the results of these tests are still problematic. In this context, the aim of this study was to assess the diagnostic usefulness of IGF-1 and IGFBP-3 in children with suspected pituitary dwarfism. Studies were carried out in 127 children with abnormal growth and low spontaneous 24-hour plasma GH profiles and abnormal results of GH stimulation tests. Fasting serum IGF-1 and IGFBP-3 were determined by chemiluminescent quantitative measurement using the IMMULITE 1000 IGF-1 and IGFBP-3 kits (Siemens Healthcare Diagnostics, United Kingdom) on the IMMULITE 1000 analyzer (Siemens Healthcare Diagnostics, USA). Results were compared to the normal range by children's age. Mean serum IGF-1 concentrations were within the lower normal range (41.7% cases), and 58.3% results were below the normal reference range in the study group. The average serum IGFBP-3 levels were within the lower normal range. We conclude that IGF-1 test can be a useful tool in the diagnosis of pituitary dwarfism in children suspected of this condition, but due to relatively poor sensitivity the testing cannot be performed alone, but in combination with other tests. The IGFBP-3 test is not useful for the diagnosis of this disease.

  17. Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity.

    Science.gov (United States)

    Wang, Jiawei; Light, Kelly; Henderson, Mélanie; O'Loughlin, Jennifer; Mathieu, Marie-Eve; Paradis, Gilles; Gray-Donald, Katherine

    2014-01-01

    Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P added sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity.

  18. Survey of risk factors urinary tract infection

    OpenAIRE

    A Dehghani; M zahedi; M moezzi; M dafei; H Falahzadeh

    2016-01-01

    Introduction: Women are very susceptible to urinary tract infections and pregnancy raises the risk of urinary tract infection. In general, little information on the risk factors of urinary tract infection in pregnancy is underway. Urinary tract infection in pregnancy is an important risk factor for pregnancy dire consequences. The purpose of this study is to find risk factors associated with urinary tract infection in pregnant women. Methods: The study was observational and retrospective ...

  19. Natural Products for the Prevention and Alleviation of Risk Factors for Diabetes: Chromium and Cinnamon

    Science.gov (United States)

    Natural products are widespread for the alleviation and prevention of the risk factors of the metabolic syndrome and diabetes. We have shown that glucose, insulin, cholesterol, and hemoglobin A1c levels are all improved in people with type 2 diabetes following chromium supplementation in a double-b...

  20. Low birth weight. A risk factor for development of diabetic nephropathy?

    DEFF Research Database (Denmark)

    Rossing, P; Tarnow, L; Nielsen, F S

    1995-01-01

    for expression of renal disease after exposure to potentially injurious renal stimuli. The aim of this study was to determine if low birth weight is a risk factor for development of diabetic nephropathy. In a case-control study, we investigated 184 (110 men) insulin-dependent diabetes mellitus (IDDM) patients...

  1. History of preeclampsia is more predictive of cardiometabolic and cardiovascular risk factors than obesity

    NARCIS (Netherlands)

    Heidema, W.M.; Scholten, R.R.; Lotgering, F.K.; Spaanderman, M.E.A.

    2015-01-01

    OBJECTIVE: To determine to what extent a history of preeclampsia affects traditional cardiometabolic (insulin resistance and dyslipidemia) and cardiovascular (hypertension and micro-albuminuria) risk factors of the metabolic syndrome irrespective of BMI. STUDY DESIGN: In a retrospective case-control

  2. Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan

    Directory of Open Access Journals (Sweden)

    Nicole M. Templeman

    2017-07-01

    Full Text Available The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1 signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/− mice to Ins2+/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/− mice. Halving Ins2 lowered circulating insulin by 25%–34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan.

  3. Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.

    Science.gov (United States)

    Templeman, Nicole M; Flibotte, Stephane; Chik, Jenny H L; Sinha, Sunita; Lim, Gareth E; Foster, Leonard J; Nislow, Corey; Johnson, James D

    2017-07-11

    The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2 +/- mice to Ins2 +/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2 +/- mice. Halving Ins2 lowered circulating insulin by 25%-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Characterization of insulin-like growth factor I and insulin receptors on cultured bovine adrenal fasciculata cells. Role of these peptides on adrenal cell function

    International Nuclear Information System (INIS)

    Penhoat, A.; Chatelain, P.G.; Jaillard, C.; Saez, J.M.

    1988-01-01

    We have characterized insulin-like growth factor I (IGF-I) and insulin receptors in cultured bovine adrenal cells by binding and cross-linking affinity experiments. At equilibrium the dissociation constant and the number of binding sites per cell for IGF-I were 1.4 +/- (SE) 0.3 x 10(-9) M and 19,200 +/- 2,100, respectively. Under reduction conditions, disuccinimidyl suberate cross-linked [ 125 I]iodo-IGF-I to one receptor complex with an Mr of 125,000. Adrenal cells also contain specific insulin receptors with an apparent dissociation constant (Kd) of 10(-9) M. Under reduction conditions [ 125 I]iodo-insulin binds to one band with an approximate Mr of 125,000. IGF-I and insulin at micromolar concentrations, but not at nanomolar concentrations, slightly stimulated DNA synthesis, but markedly potentiated the mitogenic action of fibroblast growth factor. Adrenal cells cultured in a serum-free medium containing transferrin, ascorbic acid, and insulin (5 micrograms/ml) maintained fairly constant angiotensin-II (A-II) receptor concentration per cell and increased cAMP release on response to ACTH and their steroidogenic response to both ACTH and A-II. When the cells were cultured in the same medium without insulin, the number of A-II receptors significantly decreased to 65% and the increased responsiveness was blunted. Treatment of such cells for 3 days with increasing concentrations of IGF-I (1-100 ng/ml) produced a 2- to 3-fold increase in A-II receptors and enhanced the cAMP response (3- to 4-fold) to ACTH and the steroidogenic response (4- to 6-fold) to ACTH and A-II. These effects were time and dose dependent (ED50 approximately equal to 10(-9) M). Insulin at micromolar concentrations produced an effect similar to that of IGF-I, but at nanomolar concentrations the effect was far less

  5. Insulin-like growth factors act synergistically with basic fibroblast growth factor and nerve growth factor to promote chromaffin cell proliferation

    DEFF Research Database (Denmark)

    Frödin, M; Gammeltoft, S

    1994-01-01

    We have investigated the effects of insulin-like growth factors (IGFs), basic fibroblast growth factor (bFGF), and nerve growth factor (NGF) on DNA synthesis in cultured chromaffin cells from fetal, neonatal, and adult rats by using 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling for 24 or 48 h...... implications for improving the survival of chromaffin cell implants in diseased human brain....

  6. Treatment with insulin (analogues) and breast cancer risk in diabetics; a systematic review and meta-analysis of in vitro, animal and human evidence

    NARCIS (Netherlands)

    Bronsveld, Heleen K; ter Braak, Bas; Karlstad, Øystein; Vestergaard, Peter; Starup-Linde, Jakob; Bazelier, Marloes T; De Bruin, Marie L; de Boer, Anthonius; Siezen, Christine L E; van de Water, Bob; van der Laan, Jan Willem; Schmidt, Marjanka K

    2015-01-01

    INTRODUCTION: Several studies have suggested that anti-diabetic insulin analogue treatment might increase cancer risk. The aim of this study was to review the postulated association between insulin and insulin analogue treatment and breast cancer development, and plausible mechanisms. METHOD: A

  7. Insulin-like growth factor I/somatomedin C: a potent inducer of oligodendrocyte development

    International Nuclear Information System (INIS)

    McMorris, F.A.; Smith, T.M.; DeSalvo, S.; Furlanetto, R.W.

    1986-01-01

    Cell cultures established from cerebrum of 1-day-old rats were used to investigate hormonal regulation of the development of oligodendrocytes, which synthesize myelin in the central nervous system. The number of oligodendrocytes that developed was preferentially increased by insulin, or by insulin-like growth factor I (IGF-I), also known as somatomedin C. High concentrations of insulin were required for substantial induction of oligodendrocyte development, whereas only 3.3 ng of IGF-I per ml was needed for a 2-fold increase in oligodendrocyte numbers. At an IGF-I concentration of 100 ng/ml, oligodendrocyte numbers were increased 6-fold in cultures grown in the presence of 10% fetal bovine serum, or up to 60-fold in cultures maintained in serum-free medium. IGF-I produced less than a 2-fold increase in the number of nonoligodendroglial cells in the same cultures. Type I IGF receptors were identified on oligodendrocytes and on a putative oligodendrocyte precursor cell population identified by using mouse monoclonal antibody A2B5. Radioligand binding assays were done. These results indicate that IGF-I is a potent inducer of oligodendrocyte development and suggest a possible mechanism based on IGF deficiency for the hypomyelination that results from early postnatal malnutrition

  8. Obesity improves myocardial ischaemic tolerance and RISK signalling in insulin-insensitive rats

    Directory of Open Access Journals (Sweden)

    Daniel Donner

    2013-03-01

    Obesity with associated metabolic disturbances worsens ischaemic heart disease outcomes, and rodent studies confirm that obesity with insulin-resistance impairs myocardial resistance to ischemia-reperfusion (I-R injury. However, the effects of obesity per se are unclear, with some evidence for paradoxic cardioprotection (particularly in older subjects. We tested the impact of dietary obesity on I-R tolerance and reperfusion injury salvage kinase (RISK signalling in hearts from middle-aged (10 months old insulin-insensitive rats. Hearts from Wistar rats on either a 32-week control (CD or high carbohydrate obesogenic (OB diet were assessed for I-R resistance in vivo (45 minutes left anterior descending artery occlusion and 120 minutes reperfusion and ex vivo (25 minutes ischemia and 60 minutes reperfusion. Expression and δ-opioid receptor (δ-OR phospho-regulation of pro-survival (Akt/PKB, Erk1/2, eNOS and pro-injury (GSK3β enzymes were also examined. OB rats were heavier (764±25 versus 657±22 g for CD; P<0.05, hyperleptinaemic (11.1±0.7 versus 5.0±0.7 for CD; P<0.01 and comparably insulin-insensitive (HOMA-IR of 63.2±3.3 versus 63.2±1.6 for CD. In vivo infarction was more than halved in OB (20±3% versus CD rats (45±6% P<0.05, as was post-ischaemic lactate dehydrogenase efflux (0.4±0.3 mU/ml versus 5.6±0.5 mU/ml; P<0.02 and ex vivo contractile dysfunction (62±2% versus 44±6% recovery of ventricular force; P<0.05. OB hearts exhibited up to 60% higher Akt expression, with increased phosphorylation of eNOS (+100%, GSK3β (+45% and Erk1/2 (+15%. Pre-ischaemic δ-OR agonism with BW373U86 improved recoveries in CD hearts in association with phosphorylation of Akt (+40%, eNOS (+75% and GSK3β (+30%, yet failed to further enhance RISK-NOS activation or I-R outcomes in OB hearts. In summary, dietary obesity in the context of age-related insulin-insensitivity paradoxically improves myocardial I-R tolerance, in association with moderate hyperleptinaemic and

  9. Prevalence, risk factors and risk perception of tuberculosis infection ...

    African Journals Online (AJOL)

    Prevalence, risk factors and risk perception of tuberculosis infection among medical students and healthcare workers in Johannesburg, South Africa. A van Rie, K McCarthy, L Scott, A Dow, WDF Venter, WS Stevens ...

  10. Human blood-brain barrier insulin-like growth factor receptor

    International Nuclear Information System (INIS)

    Duffy, K.R.; Pardridge, W.M.; Rosenfeld, R.G.

    1988-01-01

    Insulin-like growth factor (IGF)-1 and IGF-2, may be important regulatory molecules in the CNS. Possible origins of IGFs in brain include either de novo synthesis or transport of circulating IGFs from blood into brain via receptor mediated transcytosis mechanisms at the brain capillary endothelial wall, ie, the blood-brain barrier (BBB). In the present studies, isolated human brain capillaries are used as an in vitro model system of the human BBB and the characteristics of IGF-1 or IGF-2 binding to this preparation were assessed. The total binding of IGF-2 at 37 degrees C exceeded 130% per mg protein and was threefold greater than the total binding for IGF-1. However, at 37 degrees C nonsaturable binding equaled total binding, suggesting that endocytosis is rate limiting at physiologic temperatures. Binding studies performed at 4 degrees C slowed endocytosis to a greater extent than membrane binding, and specific binding of either IGF-1 or IGF-2 was detectable. Scatchard plots for either peptide were linear and the molar dissociation constant of IGF-1 and IGF-2 binding was 2.1 +/- 0.4 and 1.1 +/- 0.1 nmol/L, respectively. Superphysiologic concentrations of porcine insulin inhibited the binding of both IGF-1 (ED50 = 2 micrograms/mL) and IGF-2 (ED50 = 0.5 microgram/mL). Affinity cross linking of 125 I-IGF-1, 125 I-IGF-2, and 125 I-insulin to isolated human brain capillaries was performed using disuccinimidylsuberate (DSS). These studies revealed a 141 kd binding site for both IGF-1 and IGF-2, and a 133 kd binding site for insulin

  11. Insulin-like growth factor I has independent effects on bone matrix formation and cell replication

    International Nuclear Information System (INIS)

    Hock, J.M.; Centrella, M.; Canalis, E.

    1988-01-01

    The effects of insulin-like growth factor-I (IGF-I) and insulin on bone matrix synthesis and bone cell replication were studied in cultured 21-day-old fetal rat calvariae. Histomorphometry techniques were developed to measure the incorporation of [2,3- 3 H]proline and [methyl- 3 H]thymidine into bone matrix and bone cell nuclei, respectively, using autoradiographs of sagittal sections of calvariae cultured with IGF-I, insulin, or vehicle for up to 96 h. To confirm an effect on bone formation, IGF-I was also studied for its effects on [ 3 H]proline incorporation into collagenase-digestible protein (CDP) and noncollagen protein and on [ 3 H]thymidine incorporation into acid-precipitable material (DNA). IGF-I at 10(-9)-10(-7) M significantly increased the rate of bone matrix apposition and CDP after 24 h by 45-50% and increased cell labeling by 8-fold in the osteoprogenitor cell zone, by 4-fold in the osteoblast cell zone, and by 2-fold in the periosteal fibroblast zone. Insulin at 10(-9)-10(-6) M also increased matrix apposition rate and CDP by 40-50%, but increased cell labeling by 2-fold only at a concentration of 10(-7) M or higher and then only in the osteoprogenitor cell zone. When hydroxyurea was added to IGF-I-treated bones, the effects of IGF-I on DNA synthesis were abolished, but the increase in bone matrix apposition induced by IGF-I was only partly diminished. In conclusion, IGF-I stimulates matrix synthesis in calvariae, an effect that is partly, although not completely, dependent on its stimulatory effect on DNA synthesis

  12. 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)

  13. Safety and efficacy of a basal-plus regimen with insulin glargine and insulin glulisine for elderly patients with high cardiovascular risk and type 2 diabetes mellitus.

    Science.gov (United States)

    Gómez-Huelgas, R; Sabán-Ruiz, J; García-Román, F J; Quintela-Fernández, N; Seguí-Ripoll, J M; Bonilla-Hernández, M V; Romero-Meliá, G

    2017-05-01

    To assess the safety and efficacy of a basal-plus (BP) regimen with insulin glargine (as basal insulin) and insulin glulisine (as prandial insulin) with the main meal for elderly patients with type 2 diabetes mellitus (DM2) and high cardiovascular risk, following standard clinical practice. An observational, retrospective study was conducted in 21 centres of internal medicine in Spain. The study included patients aged 65 years or older with DM2, undergoing treatment with a BP regimen for 4 to 12 months before inclusion in the study and a diagnosis of cardiovascular disease or high cardiovascular risk. The primary endpoint was the change in glycated haemoglobin (HbA1c) from the introduction of the glulisine to inclusion in the study. The study included 198 patients (mean age, 74±6.4 years; males, 52%). After at least 4 months of treatment with the BP regimen, started with the addition of glulisine, the mean HbA1c value decreased significantly (9±1.5% vs. 7.7±1.1%; P<.001), and almost 24% of the patients reached HbA1c levels of 7.5-8%. Furthermore, blood glucose levels under fasting conditions decreased significantly (190.6±73.2mg/dl vs. 138.9±38.2mg/dl; P<.001). A total of 35 patients (17.7%) had some hypoglycaemia during the month prior to the start of the study, and 2 cases (1.01%) of severe hypoglycaemia were detected. The BP strategy could significantly improve blood glucose control in patients 65 years of age or older with DM2 and high cardiovascular risk and is associated with a low risk of severe hypoglycaemia. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  14. Mecasermin rinfabate: insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3.

    Science.gov (United States)

    2005-01-01

    Insmed is developing mecasermin rinfabate, a recombinant complex of insulin-like growth factor-I (rhIGF-I) and binding protein-3 (rhIGFBP-3) [insulin-like growth factor-I/insulin-like growth factor binding protein-3, rhIGF-I/rhIGFBP-3, SomatoKine], for a number of metabolic and endocrine indications. In the human body, IGF-I circulates in the blood bound to a binding protein-3 (IGFBP-3), which regulates the delivery of IGF-I to target tissues, and particular proteases clip them apart in response to stresses and release IGF-I as needed. IGF-I, a naturally occurring hormone, is necessary for normal growth and metabolism. For the treatment of IGF-I deficiency, it is desirable to administer IGF-I bound to IGFBP-3 to maintain the normal equilibrium of these proteins in the blood. Mecasermin rinfabate (rhIGF-I/rhIGFBP-3) mimics the effects of the natural protein complex in the bloodstream and would augment the natural supply of these linked compounds. The most advanced indication in development of mecasermin rinfabate is the treatment of severe growth disorders due to growth hormone insensitivity syndrome (GHIS), also called Laron syndrome. GHIS is a genetic condition in which patients do not produce adequate quantities of IGF because of a failure to respond to the growth hormone signal. This results in a slower growth rate and short stature. Mecasermin rinfabate also has potential as replacement therapy for IGF-I, which may become depleted in indications such as major surgery, organ damage/failure, traumatic injury, cachexia and severe burn trauma. It also has potential for the treatment of osteoporosis. Mecasermin rinfabate was developed by Celtrix using its proprietary recombinant protein production technology. Subsequently, Celtrix was acquired by Insmed Pharmaceuticals on 1 June 2000. Insmed and Avecia of the UK have signed an agreement for manufacturing mecasermin rinfabate and its components, rhIGF-1 and rhIGFBP-3. CGMP clinical production of mecasermin rinfabate

  15. Synthesizing Risk from Summary Evidence Across Multiple Risk Factors.

    Science.gov (United States)

    Shrier, Ian; Colditz, Graham A; Steele, Russell J

    2018-07-01

    Although meta-analyses provide summary effect estimates that help advise patient care, patients often want to compare their overall health to the general population. The Harvard Cancer Risk Index was published in 2004 and uses risk ratio estimates and prevalence estimates from original studies across many risk factors to provide an answer to this question. However, the published version of the formula only uses dichotomous risk factors and its derivation was not provided. The objective of this brief report was to provide the derivation of a more general form of the equation that allows the incorporation of risk factors with three or more levels.

  16. Cardiovascular risk factors in children.

    Science.gov (United States)

    Fraporti, Marisete Inês; Scherer Adami, Fernanda; Dutra Rosolen, Michele

    2017-10-01

    Systemic hypertension is one of the main risk factors for cardiovascular disease (CVD). Early diagnosis and treatment of hypertension in childhood can potentially have a significant impact on future adverse outcomes. To investigate the relationship of diastolic (DBP) and systolic blood pressure (SBP) with anthropometric data and area of residence of children in municipalities of Rio Grande do Sul state, Brazil. This is a cross-sectional study of 709 children between six and nine years of age. Blood pressure, weight, height and waist circumference (WC) were measured. Statistical tests had a maximum significance level of 5% (p≤0.05) and the software used was SPSS version 13.0. Obesity was significantly associated with pre-hypertension, and stage 1 and 2 hypertension as assessed by DBP and SBP (≤0.05); high WC was significantly associated with a classification of pre-hypertension and stage 1 hypertension based on DBP and a classification of stage 1 and 2 hypertension based on SBP (≤0.01). Children living in urban areas had significantly higher mean SBP than those living in rural areas. Those with high WC presented higher SBP and DBP compared to children with normal WC. Obese children showed higher mean SBP and DBP compared to those who were overweight or normal weight and mean SBP and DBP also increased with older age and higher mean body mass index and WC. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. CDC Behavioral Risk Factor Surveillance System (BRFSS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Behavioral Risk Factor Surveillance System (BRFSS) is a state-based system of health surveys that collects information on health risk behaviors, preventive...

  18. 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

    2012-02-01

    AIMS: 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. METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a London University teaching hospital. Maternal IGF-1, IGF-2 and IGFBP-3 were measured in maternal blood at booking and analyzed with respect to gestational age at delivery. RESULTS: There was no significant association between maternal IGF-1 or IGF-2 and preterm birth (PTB). A significant reduction in mean IGFBP-3 levels was noted with delivery <32 completed weeks (P=0.02). CONCLUSION: Maternal mean IGFBP-3 levels are significantly reduced in cases complicated by delivery <32 completed weeks.

  19. Impact of obesity and body fat distribution on cardiovascular risk factors in Hong Kong Chinese.

    Science.gov (United States)

    Thomas, G Neil; Ho, Sai-Yin; Lam, Karen S L; Janus, Edward D; Hedley, Anthony J; Lam, Tai Hing

    2004-11-01

    Body fat distribution has been reported to differentially contribute to the development of cardiovascular risk. We report the relative associations between general and central obesity and risk factors in 2893 Chinese subjects recruited from the Hong Kong population. Anthropometric parameters [waist circumference (WC) and BMI], surrogate measures of insulin resistance (fasting plasma glucose and insulin, oral glucose tolerance test, 2 hours glucose and insulin), fasting lipids (total, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides) and systolic and diastolic blood pressure were measured. General obesity was classified as BMI > or =25.0 kg/m(2) and central obesity as a WC > or =80 or > or =90 cm in women and men, respectively. A total of 39.2% of the population was found to be obese. Obesity per se increased the levels of the risk factors, but central adiposity contributed to a greater extent to adverse high-density lipoprotein-cholesterol, triglyceride, and insulin resistance levels. There was a continuous relationship between increasing obesity, both general and central, and cardiovascular risk, with lowest risk associated with the lowest indices of obesity. In the 1759 nonobese subjects divided into quartiles of BMI or WC, the levels of the cardiovascular risk factors still significantly increased with increasing quartiles of adiposity. Central adiposity appears to contribute to a greater extent than general adiposity to the development of cardiovascular risk in this population. The relationship between obesity parameters and risk is a continuum, with risk factors significantly increasing even at levels usually considered nonobese. These observations support the proposed redefinition of overweight and obesity in Asian populations using lower cut-off points.

  20. Macrophage Migration Inhibitory Factor: Critical Role in Obesity, Insulin Resistance, and Associated Comorbidities

    Directory of Open Access Journals (Sweden)

    Robert Kleemann

    2010-01-01

    Full Text Available Obesity is associated with insulin resistance, disturbed glucose homeostasis, low grade inflammation, and comorbidities such as type 2 diabetes and cardiovascular disease. The cytokine macrophage migration inhibitory factor (MIF is an ubiquitously expressed protein that plays a crucial role in many inflammatory and autoimmune disorders. Increasing evidence suggests that MIF also controls metabolic and inflammatory processes underlying the development of metabolic pathologies associated with obesity. This is a comprehensive summary of our current knowledge on the role of MIF in obesity and obesity-associated comorbidities, based on human clinical data as well as animal models of disease.

  1. The measurement of insulin-like growth factor 1 in sheep plasma.

    Science.gov (United States)

    Bruce, L A; Atkinson, T; Hutchinson, J S; Shakespear, R A; MacRae, J C

    1991-02-01

    A method is described for the radioimmunoassay (RIA) of insulin-like growth factor 1 (IGF-1) in neutralised formic acid-ethanol extracts of sheep plasma. The ability of the acid-ethanol pretreatment to remove the IGF-1 binding proteins (BPs), which interfere in the assay has been examined. Comparative plasma IGF-1 concentrations determined by the method correlated closely (P less than 0.001) with corresponding values where BPs were removed by acid gel filtration. The method has been applied to studies in which sheep were given exogenous growth hormone and indicated that plasma IGF-1 levels respond rapidly to the onset and termination of treatment.

  2. Insulin-like growth factors I and II in healthy women with and without established osteoporosis

    DEFF Research Database (Denmark)

    Ravn, Pernille; Spencer, E M; Christiansen, C

    1995-01-01

    .05) was seen in the nandrolone decanoate-treated group. The same tendency was seen for hormone replacement therapy, although it was not significant. In conclusion, the serum level of IGF-I is high in young women, when peak bone mass is attained, and low in postmenopausal women with established osteoporosis.......We measured serum concentrations of insulin-like growth factors I and II (IGF-I and IGF-II) by radioimmunoassay in 107 healthy women aged 28-78 years and in 116 women with established osteoporosis. The women with established osteoporosis were randomized to a 1-year double-blind, placebo...

  3. Study on serum insulin-like growth factor 1 and insulin-like growth factor-binding protein-3 in patients with benign prostatic hyperplasia

    International Nuclear Information System (INIS)

    Yu Jingping; Wu Xiumei; Yang Qixian; Chen Jianguo; Liu Weiming

    2003-01-01

    Objective: To determine the serum level changes of insulin-like growth factor-1 (IGF-I) and IGF binding protein-3 (IGFBP-3) in patients with benign prostatic hyperplasia (BPH) and to evaluate its significance. Methods: The serum IGF-1 and IGFBP-3 levels were measured with immunoradiometric assay (IRMA) in 64 cases of BPH and in 30 controls. The patients were divided into 3 groups according to the prostate volume (PV): Group 118 cases (PV ≤ 30 ml), Group 224 cases (PV 31-50 ml) and Group 322 cases (PV ≥ 50 ml). Results: Both IGF-1 and IGFBP-3 levels were no statistical difference between BPH and healthy subjects (Both p > 0.05). Both IGF-1 and IGFBP-3 levels in group 3 were significantly higher than those in group 1 (Both p < 0.05). A positive correlation existed between the serum levels of IGF-1, IGFBP-3 and PV (p < 0.05). Conclusion: These observations implicated that IGF-1 and IGFBP-3 were important factors in the pathogenesis of BPH

  4. Expression of insulin-like growth factor I, insulin-like growth factor binding proteins, and collagen mRNA in mechanically loaded plantaris tendon

    DEFF Research Database (Denmark)

    Olesen, Jens L; Heinemeier, Katja M; Haddad, Fadia

    2006-01-01

    Insulin-like growth factor I (IGF-I) is known to exert an anabolic effect on tendon fibroblast production of collagen. IGF-I's regulation is complex and involves six different IGF binding proteins (IGFBPs). Of these, IGFBP-4 and -5 could potentially influence the effect of IGF-I in the tendon...... because they both are produced in fibroblast; however, the response of IGFBP-4 and -5 to mechanical loading and their role in IGF-I regulation in tendinous tissue are unknown. A splice variant of IGF-I, mechano-growth factor (MGF) is upregulated and known to be important for adaptation in loaded muscle....... However, it is not known whether MGF is expressed and upregulated in mechanically loaded tendon. This study examined the effect of mechanical load on tendon collagen mRNA in relation to changes in the IGF-I systems mRNA expression. Data were collected at 2, 4, 8 and 16 days after surgical removal...

  5. Changes of insulin-like growth factor-Ⅱ and insulin-like growth factor binding protein-3 in cerebrospinal fluid of children with tuberculous meningitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Recent studies have found that insulin-like growth factors (IGFs) and insulin-like growth factor binding protein-3 (IGFBP-3) have stronger neurotrophic and neuroprotective effects. But whether their levels in cerebrospinal fluid could be used as an auxiliary indicator in differentially diagnosing tuberculous meningitis and viral encephalitis is not yet clear.OBJECTIVE: To explore the changes of insulin-like growth factor-Ⅱ (IGF-Ⅱ ) and IGFBP-3 in cerebrospinal fluid (CSF) of children with tuberculous meningitis and the significance of the changes.DESIGN: A non-randomized concurrent controlled study.SETTING: Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College.PARTICIPANTS: Thirty children with tuberculous meningitis (14 males and 16 females) were selected from the Department of Pediatric Internal Medicine, the First Affiliated Hospital of Xinxiang Medical College from January 2005 to December 2006. Tuberculous meningitis was diagnosed according to their clinical manifestations, the history of close contact with tuberculosis, typical cerebrospinal fluid changes of tuberculous meningitis, positive tuberculosis antibody and effective antituberculosis treatment. There were 30 children (13 males and 17 females) with viral encephalitis, and viral encephalitis was diagnosed according to epidemiological history, clinical manifestations, conventional and biochemical changes of cerebrospinal fluid, and negative bacteriology judgment. Meanwhile, 30 children (13 males and 17 females) without infectious and central nervous system disease were selected as the control group. Informed consent was obtained from the parents of all the enrolled children.METHODS: ① The lumbar puncture operation was implemented immediately to obtain cerebrospinal fluid (3 mL). The contents of IGF-Ⅱ and IGFBP-3 were detected with immunoradiometric assay. The concentrations of glucose and protein in cerebrospinal fluid were determined

  6. Circulating insulin-like growth factor-I, insulin-like growth factor binding protein-3 and terminal duct lobular unit involution of the breast: a cross-sectional study of women with benign breast disease.

    Science.gov (United States)

    Horne, Hisani N; Sherman, Mark E; Pfeiffer, Ruth M; Figueroa, Jonine D; Khodr, Zeina G; Falk, Roni T; Pollak, Michael; Patel, Deesha A; Palakal, Maya M; Linville, Laura; Papathomas, Daphne; Geller, Berta; Vacek, Pamela M; Weaver, Donald L; Chicoine, Rachael; Shepherd, John; Mahmoudzadeh, Amir Pasha; Wang, Jeff; Fan, Bo; Malkov, Serghei; Herschorn, Sally; Hewitt, Stephen M; Brinton, Louise A; Gierach, Gretchen L

    2016-02-18

    Terminal duct lobular units (TDLUs) are the primary structures from which breast cancers and their precursors arise. Decreased age-related TDLU involution and elevated mammographic density are both correlated and independently associated with increased breast cancer risk, suggesting that these characteristics of breast parenchyma might be linked to a common factor. Given data suggesting that increased circulating levels of insulin-like growth factors (IGFs) factors are related to reduced TDLU involution and increased mammographic density, we assessed these relationships using validated quantitative methods in a cross-sectional study of women with benign breast disease. Serum IGF-I, IGFBP-3 and IGF-I:IGFBP-3 molar ratios were measured in 228 women, ages 40-64, who underwent diagnostic breast biopsies yielding benign diagnoses at University of Vermont affiliated centers. Biopsies were assessed for three separate measures inversely related to TDLU involution: numbers of TDLUs per unit of tissue area ("TDLU count"), median TDLU diameter ("TDLU span"), and number of acini per TDLU ("acini count"). Regression models, stratified by menopausal status and adjusted for potential confounders, were used to assess the associations of TDLU count, median TDLU span and median acini count per TDLU with tertiles of circulating IGFs. Given that mammographic density is associated with both IGF levels and breast cancer risk, we also stratified these associations by mammographic density. Higher IGF-I levels among postmenopausal women and an elevated IGF-I:IGFBP-3 ratio among all women were associated with higher TDLU counts, a marker of decreased lobular involution (P-trend = 0.009 and breast cancer risk. If confirmed in prospective studies with cancer endpoints, these data may suggest that evaluation of IGF signaling and its downstream effects may have value for risk prediction and suggest strategies for breast cancer chemoprevention through inhibition of the IGF system.

  7. Predictive factors of insulin resistance resolution with adjustable gastric band surgery.

    Science.gov (United States)

    Colsa Gutiérrez, Pablo; Kharazmi Taghavi, Mahgol; Sosa Medina, Rocío; Gutiérrez Cabezas, José Manuel; Ovejero Gómez, Víctor Jacinto; Ruiz, José Luis; Ingelmo Setién, Alfredo

    2015-03-01

    The aim of the study was to evaluate preoperative factors associated with remission of diabetes and weight loss after laparoscopic gastric band surgery. A retrospective cohort of 95 patients who had an adjustable gastric band placed were included. A preliminary descriptive study of prognostic factors was performed using the logistic regression model with SPSS 17.0. The independent variables were age, sex, body mass index (BMI), diabetes status and degree of obesity; dependent variables were the proportion of weight loss, change in diabetes status score and percent changes in fasting sugar and glycosylated hemoglobin. The variables that were significantly associated with the percentage of changes in fasting blood sugar and glycated hemoglobin were: the degree of obesity in the first year; preoperative and diabetes status respectively. The analysis of the need for antidiabetic treatment using the modified diabetes status score showed preoperative BMI, age and gender as significant predictors. In patients undergoing gastric band surgery, weight loss is the fundamental mechanism by which insulin sensitivity increases. This improvement in glucose metabolism is influenced by factors such as sex, age, insulin treatment, duration of diabetes and degree of preoperative obesity. Copyright © 2014 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. The role of insulin-like growth factor-I in the physiopathology of hearing

    Directory of Open Access Journals (Sweden)

    Silvia eMurillo-Cuesta

    2011-07-01

    Full Text Available Insulin like growth factor I (IGF-I belongs to the family of polypeptides of insulin, which play a central role in embryonic development and adult nervous system homeostasis by endocrine, autocrine and paracrine mechanisms. IGF-I is fundamental for the regulation of cochlear development, growth and differentiation, and its mutations are associated with hearing loss in mice and men. Low levels of IGF-I have been shown to correlate with different human syndromes showing hearing loss and with presbyacusis. Animal models are fundamental to understand the genetic, epigenetic, and environmental factors that contribute to human hearing loss. In the mouse, IGF-I serum levels decrease with ageing and there is a concomitant hearing loss and retinal degeneration. In the Igf1-/- null mouse, hearing loss is due to neuronal loss, poor innervation of the sensory hair cells and age-related stria vascularis alterations. In the inner ear, IGF-I actions are mediated by intracellular signaling networks, RAF, AKT and p38 MAPK protein kinases modulate the expression and activity of transcription factors, as AP1, MEF2, FoxM1 and FoxP3, leading to the regulation of cell cycle and metabolism. Therapy with rhIGF-I has been approved in humans for the treatment of poor linear growth and certain neurodegenerative diseases. This review will discuss these findings and their implications in new IGF-I-based treatments for the protection or repair of hearing loss.

  9. The Risk Factors of Prostate Cancer and Its Prevention: A Literature Review

    Directory of Open Access Journals (Sweden)

    Noor Riza Perdana

    2016-11-01

    Numerous epidemiologic studies have linked PCa risk to various factors, i.e. age, ethnicity, family history, insulin like-growth factors, lifestyle, diet, environmental and occupational exposures. The results of epidemiological, In vivo, in vitro, and early clinical studies suggested that selected dietary products and supplementation may play a role in PCa prevention. More studies are still needed to explore and find the risk factors and preventive methods of PCa development. It is important for clinician to ellaborate these informations for education to lower PCa risks and prevent PCa.

  10. Cardiovascular Risk Factors in Children and Adolescents with Subclinical Hypothyroidism.

    Science.gov (United States)

    Yadav, Yogesh; Saikia, Uma Kaimal; Sarma, Dipti; Hazarika, Manoj

    2017-01-01

    Subclinical hypothyroidism (SCH) is a commonly encountered entity in day-to-day clinical practice and has been associated with adverse cardiovascular risk profile in adults and children. Data on children and adolescents with SCH, from India, are limited. This study was a cross-sectional case-control study, conducted at a tertiary care center in Northeast India. Twenty-seven children and adolescents aged 11 ± 2.4 years with SCH and thyroid-stimulating hormone >7.5 mIU/L were included in the study along with 20 age-, gender-, and height-matched controls. Multiple clinical, biochemical, and radiological cardiovascular risk factors were assessed and compared between the two groups. Body mass index (BMI) ( P = 0.048), waist circumference ( P = 0.008), waist to height ratio ( P = 0.007), low-density lipoprotein cholesterol ( P = 0.04), triglycerides (TGs) ( P = 0.038), TGs to high-density lipoprotein (HDL) cholesterol ratio ( P = 0.005), non-HDL cholesterol ( P = 0.019), fasting insulin ( P = 0.006), and homeostasis model assessment of insulin resistance ( P = 0.007) were found to be significantly higher while free T4 ( P = 0.002) and HDL cholesterol ( P = 0.019) were found to be significantly lower in SCH subjects compared to controls. On multiple regression analysis, BMI was found to have significant association with multiple cardiovascular risk factors. Children and adolescents with SCH were found to have adverse cardiovascular risk profile. Long-term follow-up studies are required to assess the clinical significance of these findings and requirement for therapy.

  11. Cardiovascular risk factors in children and adolescents with subclinical hypothyroidism

    Directory of Open Access Journals (Sweden)

    Yogesh Yadav

    2017-01-01

    Full Text Available Background: Subclinical hypothyroidism (SCH is a commonly encountered entity in day-to-day clinical practice and has been associated with adverse cardiovascular risk profile in adults and children. Data on children and adolescents with SCH, from India, are limited. Materials and Methods: This study was a cross-sectional case–control study, conducted at a tertiary care center in Northeast India. Twenty-seven children and adolescents aged 11 ± 2.4 years with SCH and thyroid-stimulating hormone >7.5 mIU/L were included in the study along with 20 age-, gender-, and height-matched controls. Multiple clinical, biochemical, and radiological cardiovascular risk factors were assessed and compared between the two groups. Results: Body mass index (BMI (P = 0.048, waist circumference (P = 0.008, waist to height ratio (P = 0.007, low-density lipoprotein cholesterol (P = 0.04, triglycerides (TGs (P = 0.038, TGs to high-density lipoprotein (HDL cholesterol ratio (P = 0.005, non-HDL cholesterol (P = 0.019, fasting insulin (P = 0.006, and homeostasis model assessment of insulin resistance (P = 0.007 were found to be significantly higher while free T4 (P = 0.002 and HDL cholesterol (P = 0.019 were found to be significantly lower in SCH subjects compared to controls. On multiple regression analysis, BMI was found to have significant association with multiple cardiovascular risk factors. Conclusion: Children and adolescents with SCH were found to have adverse cardiovascular risk profile. Long-term follow-up studies are required to assess the clinical significance of these findings and requirement for therapy.

  12. Effect of discontinuation of long-term growth hormone treatment on carbohydrate metabolism and risk factors for cardiovascular disease in girls with Turner syndrome

    NARCIS (Netherlands)

    Y.K. van Pareren (Yvonne); S.M.P.F. de Muinck Keizer-Schrama (Sabine); Th. Stijnen (Theo); T.C.J. Sas (Theo); S.L.S. Drop (Stenvert)

    2002-01-01

    textabstractGH treatment increases insulin levels in girls with Turner syndrome (TS), who are already predisposed to develop diabetes mellitus and other risk factors for developing cardiovascular disease. Therefore, in the present study, we investigated carbohydrate metabolism and

  13. Relationship of Polycystic Ovarian Syndrome with Cardiovascular Risk Factors.

    Science.gov (United States)

    Bilal, Muhammad; Haseeb, Abdul; Rehman, Abdur

    2018-05-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age. The two main documented pathogenic mechanisms are hyperinsulinemia and hyperandrogenemia but there is growing evidence for increased predisposition to cardiovascular disease, dyslipidemia, and type 2 diabetes mellitus. Our study aims to analyze the association of PCOS with cardiovascular risk factors. This is a prospective study which targeted 100 PCOS patients from Civil Hospital Karachi over a period of one year (July 2016 to July 2017). An equal number of age-matched healthy control participants were also included in the study. The student's t-test was used to assess the significance of differences using SPSS version (19). The statistical significance was set at a p-value of PCOS was primary infertility seen in 72% of the patients. Mean arterial pressure, fasting glucose and insulin levels and insulin resistance was found to be significantly different in PCOS patients as compared to their controls. A classic atherosclerotic lipid profile demonstrating elevated total cholesterol and low-density lipoprotein-C (LDL-C) levels and decreased serum high density lipoprotein-C(HDL-C) was observed in our study. This study established a significant yet independent association of PCOS with major cardiovascular risk factors. This association can effectively progress into CVD outcomes which necessitates early intervention programs and preventative strategies to reduce mortality from cardiovascular events. This study lays out the framework for conducting further researches on the PCOS women while exploring novel cardiovascular risk factors. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  14. Somatomedin-C/insulin-like growth factor-I and Insulin-like growth factor-II mRNAs in rate fetal and adult tissues

    International Nuclear Information System (INIS)

    Lund, P.K.; Moats-Staats, B.M.; Hynes, M.A.; Simmons, J.G.; Jansen, M.; D'ercole, A.J.; Van Wyk, J.J.

    1986-01-01

    Somatomedin-C or insulin-like growth factor I (Sm-C/IGF-I) and insulin-like growth factor II (IGF-II) have been implicated in the regulation of fetal growth and development. In the present study 32 P-labeled complementary DNA probes encoding human and mouse Sm-C/IGF-I and human IGF-II were used in Northern blot hybridizations to analyze rat Sm-C/IGF-I and IGF-II mRNAs in poly(A + ) RNAs from intestine, liver, lung, and brain of adult rats and fetal rats between day 14 and 17 of gestation. In fetal rats, all four tissues contained a major mRNA of 1.7 kilobase (kb) that hybridized with the human Sm-C/IGF-I cDNA and mRNAs of 7.5, 4.7, 1.7, and 1.2 kb that hybridized with the mouse Sm-C/IGF-I cDNA. Adult rat intestine, liver, and lung also contained these mRNAs but Sm-C/IGF-I mRNAs were not detected in adult rat brain. These findings provide direct support for prior observations that multiple tissues in the fetus synthesize immunoreactive Sm-C/IGF-I and imply a role for Sm-C/IGF-I in fetal development as well as postnatally. Multiple IGF-II mRNAs of estimated sizes 4.7, 3.9, 2.2, 1.75, and 1.2 kb were observed in fetal rat intestine, liver, lung, and brain. The 4.7- and 3.9-kb mRNAs were the major hybridizing IGF-II mRNAs in all fetal tissues. Higher abundance of IGF-II mRNAs in rat fetal tissues compared with adult tissues supports prior hypotheses, based on serum IGF-II concentrations, that IGF-II is predominantly a fetal somatomedin. IGF-II mRNAs are present, however, in some poly(A + ) RNAs from adult rat tissues. The brain was the only tissue in the adult rat where the 4.7- and 3.9-kb IGF-II mRNAs were consistently detected. These findings suggest that a role for IGF-II in the adult rat, particularly in the central nervous system, cannot be excluded

  15. Effect of 10 days of bedrest on metabolic and vascular insulin action: a study in individuals at risk for type 2 diabetes

    DEFF Research Database (Denmark)

    Sonne, Mette P; Alibegovic, Amra C; Højbjerre, Lise

    2010-01-01

    Physical inactivity is a known risk factor for type 2 diabetes. We studied whole body and forearm insulin sensitivity in subjects at increased risk for type 2 diabetes [persons with low birth weight (LBW group; n = 20) and first-degree relatives to type 2 diabetic patients (FDR group; n = 13......)] as well as a control (CON) group (n = 20) matched for body mass index, age, and physical activity levels before and after 10 days of bedrest. Subjects were studied by hyperinsulinemic isoglycemic clamp combined with arterial and deep venous catheterization of the forearm. Forearm blood flow (FBF...

  16. Association of polycystic ovary syndrome with cardiovascular risk factors.

    Science.gov (United States)

    Akram, Tanzeela; Hasan, Shahid; Imran, Muhammad; Karim, Asima; Arslan, Muhammad

    2010-01-01

    Polycystic ovary syndrome (PCOS), also clinically known as Stein-Leventhal syndrome, is an endocrine disorder that affects 5-10% of women. To evaluate the risk factors for developing early onset of cardiovascular disease (CVD) in young patients with PCOS from our local population. Case-control study. Fifty women with PCOS selected by history and transvaginal ultrasounds and 30 age-matched healthy women (controls). The case subjects and controls were further divided into two age categories comprising of equal number of subjects, of 20-29 and 30-39 years of age. The subjects underwent a detailed medical history, general physical examination, systolic (SBP) and diastolic blood pressures (DBP). Fasting blood samples were analyzed for glucose, insulin, triacylglycerides (TAG), total cholesterol, high density lipoprotein-C (HDL-C), low density lipoprotein-C (LDL-C), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Women with the PCOS had significantly higher mean arterial pressure (MAP), serum TAG, LDL-C, insulin, and LH levels when compared with the age-matched control subjects. No significant differences were observed between serum cholesterol, glucose, and FSH levels between cases and controls. However, no marked differences were observed in biochemical parameters between the two age groups of PCOS patients. Younger women with PCOS are equally at risk of developing CVD as older women.

  17. Insulin Signaling and Heart Failure

    Science.gov (United States)

    Riehle, Christian; Abel, E. Dale

    2016-01-01

    Heart failure is associated with generalized insulin resistance. Moreover, insulin resistant states such as type 2 diabetes and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes alters the systemic and neurohumoral milieu leading to changes in metabolism and signaling pathways in the heart that may contribute to myocardial dysfunction. In addition, changes in insulin signaling within cardiomyocytes develop in the failing heart. The changes range from activation of proximal insulin signaling pathways that may contribute to adverse left ventricular remodeling and mitochondrial dysfunction to repression of distal elements of insulin signaling pathways such as forkhead (FOXO) transcriptional signaling or glucose transport which may also impair cardiac metabolism, structure and function. This article will review the complexities of insulin signaling within the myocardium and ways in which these pathways are altered in heart failure or in conditions associated with generalized insulin resistance. The implications of these changes for therapeutic approaches to treating or preventing heart failure will be discussed. PMID:27034277

  18. Insulin Promoter Factor 1 variation is associated with type 2 diabetes in African Americans

    Directory of Open Access Journals (Sweden)

    Wang Xiaoqin

    2005-10-01

    Full Text Available Abstract Background Defective insulin secretion is a key defect in the pathogenesis of type 2 diabetes (T2DM. The β-cell specific transcription factor, insulin promoter factor 1 gene (IPF1, is essential to pancreatic development and the maintenance of β-cell mass. We hypothesized that regulatory or coding variants in IPF1 contribute to defective insulin secretion and thus T2DM. Methods We screened 71 Caucasian and 69 African American individuals for genetic variants in the promoter region, three highly conserved upstream regulatory sequences (PH1, PH2 and PH3, the human β-cell specific enhancer, and the two exons with adjacent introns. We tested for an association of each variant with T2DM Caucasians (192 cases and 192 controls and African Americans (341 cases and 186 controls. Results We identified 8 variants in the two populations, including a 3 bp insertion in exon 2 (InsCCG243 in African Americans that resulted in an in-frame proline insertion in the transactivation domain. No variant was associated with T2DM in Caucasians, but polymorphisms at -3766 in the human β-cell enhancer, at -2877 bp in the PH1 domain, and at -108 bp in the promoter region were associated with T2DM in African American subjects (p Conculsion The common alleles of regulatory variants in the 5' enhancer and promoter regions of the IPF1 gene increase susceptibility to type 2 diabetes among African American individuals, likely as a result of gene-gene or gene-environment interactions. In contrast, IPF1 is not a cause of type 2 diabetes in Caucasians. A previously described InsCCG243 variant may contribute to diabetes susceptibility in African American individuals, but is of low penetrance.

  19. Role of the Insulin-Like Growth Factor Type 1 Receptor in the Pathogenesis of Diabetic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Duo Zhang

    2015-01-01

    Full Text Available Defective cognitive function is common in patients with diabetes, suggesting that insulin normally exerts anabolic actions in neuron, namely, diabetic encephalopathy. However, because insulin can cross-activate the insulin-like growth factor type 1 receptor (IGF-1R, which also functions in most of tissues, such as muscle and bone, it has been difficult to establish the direct (IGF-1-independent actions of insulin in the pathogenesis of diabetic encephalopathy. To overcome this problem, we examined insulin signaling and action in primary PC-12 cells engineered for conditional disruption of the IGF-1 receptor (ΔIGF-1R. The results showed that the lower glucose metabolism and high expression of IGF-1R occurred in the brain of the DE rat model. The results also showed the defect of IGF-1R could significantly improve the ability of glucose consumption and enhance sensitivity to insulin-induced IR and Akt phosphorylation in PC12 cells. And meanwhile, IGF-1R allele gene knockout (IGF-1Rneo mice treated with HFD/STZ had better cognitive abilities than those of wild mice. Those results indicate that insulin exerts direct anabolic actions in neuron-like cells by activation of its cognate receptor and prove that IGF-1R plays an important role in the pathogenesis of diabetic encephalopathy.

  20. Interleukin-Driven Insulin-Like Growth Factor Promotes Prostatic Inflammatory Hyperplasia

    Science.gov (United States)

    Hahn, Alana M.; Myers, Jason D.; McFarland, Eliza K.; Lee, Sanghee

    2014-01-01

    Prostatic inflammation is of considerable importance to urologic research because of its association with benign prostatic hyperplasia and prostate cancer. However, the mechanisms by which inflammation leads to proliferation and growth remain obscure. Here, we show that insulin-like growth factors (IGFs), previously known as critical developmental growth factors during prostate organogenesis, are induced by inflammation as part of the proliferative recovery to inflammation. Using genetic models and in vivo IGF receptor blockade, we demonstrate that the hyperplastic response to inflammation depends on interleukin-1–driven IGF signaling. We show that human prostatic hyperplasia is associated with IGF pathway activation specifically localized to foci of inflammation. This demonstrates that mechanisms of inflammation-induced epithelial proliferation and hyperplasia involve the induction of developmental growth factors, further establishing a link between inflammatory and developmental signals and providing a mechanistic basis for the management of proliferative diseases by IGF pathway modulation. PMID:25292180

  1. Evaluation of insulin-like growth factor-1 and insulin like growth factor binding protein-3 in diagnosis of growth hormone deficiency in short-stature children

    International Nuclear Information System (INIS)

    Ali, A.; Hashim, R.; Khan, F.A.; Sattar, A.; Ijaz, A.; Manzoor, S.M.; Younas, M.

    2009-01-01

    Growth Hormone Deficiency (GHD) is conventionally diagnosed and confirmed by diminished peak Growth Hormone (GH) levels to provocative testing. Serum Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) are under the influence of GH and reflect the spontaneous endogenous GH secretion. Owing to the absence of a circadian rhythm, it is possible to take individual measurements of IGF-1 and IGFBP-3 at any time of the day for evaluation of GH status instead of subjecting the individual to cumbersome provocative tests. Objectives of this study were to compare IGF-1 and IGFBP-3 assays with Exercise and L-Dopa stimulation tests in the diagnosis of growth hormone deficiency in short stature children using ITT as gold standard. Methods: This validation study was conducted at Department of Chemical Pathology and Endocrinology, AFIP, Rawalpindi, from November 2005 to October 2006. Fifty-two short stature children were included in the study. Basal samples for GH levels and simultaneous IGF-1 and IGFBP-3 measurements were obtained and afterwards all children were subjected to sequential exercise and LDopa stimulation tests. Insulin Tolerance Test (ITT) was performed one week later with all the necessary precautionary measures. On the basis of ITT results, children were divided into two groups, i.e., 31 growth hormone deficient and 21 Normal Variant Short Stature (NVSS). Results: The diagnostic value of exercise stimulation test remained highest with sensitivity 90.3%, specificity 76.0%, Positive Predictive Value (PPV) 84.84%, Negative Predictive Value (NPV) 84.2% and accuracy 84.6%. The conventional L-Dopa stimulation had sensitivity 96.7%, specificity 38.0%, PPV 69.7%, NPV 88.8 % and accuracy 73.0%. The serum IGF-1 and IGFBP-3 levels were positively correlated with post ITT peak GH levels (r= 0.527, r=0.464 respectively, both p<0.001). The diagnostic value of IGF-1 had sensitivity 83.87%, specificity 76.2%, PPV 83.87%, NPV 76.2% and

  2. Collagen and Stretch Modulate Autocrine Secretion of Insulin-like Growth Factor-1 and Insulin-like Growth Factor Binding Proteins from Differentiated Skeletal Muscle Cells

    Science.gov (United States)

    Perrone, Carmen E.; Fenwick-Smith, Daniela; Vandenburgh, Herman H.

    1995-01-01

    Stretch-induced skeletal muscle growth may involve increased autocrine secretion of insulin-like growth factor-1 (IGF-1) since IGF-1 is a potent growth factor for skeletal muscle hypertrophy, and stretch elevates IGF-1 mRNA levels in vivo. In tissue cultures of differentiated avian pectoralis skeletal muscle cells, nanomolar concentrations of exogenous IGF-1 stimulated growth in mechanically stretched but not static cultures. These cultures released up to 100 pg of endogenously produced IGF-1/micro-g of protein/day, as well as three major IGF binding proteins of 31, 36, and 43 kilodaltons (kDa). IGF-1 was secreted from both myofibers and fibroblasts coexisting in the muscle cultures. Repetitive stretch/relaxation of the differentiated skeletal muscle cells stimulated the acute release of IGF-1 during the first 4 h after initiating mechanical activity, but caused no increase in the long-term secretion over 24-72 h of IGF-1, or its binding proteins. Varying the intensity and frequency of stretch had no effect on the long-term efflux of IGF-1. In contrast to stretch, embedding the differentiated muscle cells in a three-dimensional collagen (Type I) matrix resulted in a 2-5-fold increase in long-term IGF-1 efflux over 24-72 h. Collagen also caused a 2-5-fold increase in the release of the IGF binding proteins. Thus, both the extracellular matrix protein type I collagen and stretch stimulate the autocrine secretion of IGF-1, but with different time kinetics. This endogenously produced growth factor may be important for the growth response of skeletal myofibers to both types of external stimuli.

  3. Influence of Insulin-like Growth Factor 1 on Nuclear Maturation of Germinal Vesicle Mouse Oocytes

    Directory of Open Access Journals (Sweden)

    R mahmoudi

    2014-09-01

    Full Text Available Background & aim: In vitro maturation and fertilization of oocytes play an important role in reproductive biotechnology. The aim of this study is to define the IGF-1 effect on in vitro maturation, fertilization and development of mice immature oocytes to 2-cells in TCM199 medium cultures. Methods: In this study 4 week old NMRI mice were used. Ovaries stimulation carried out using PMSG. GV oocytes with or without cumulus cells were isolated from ovaries and cultured in TCM199 in presence of 100 ng IGF-1 for 24hr.The oocytes (MII were inseminated with sperm in T6 medium for fertilization and development of 2-cells stage and they were investigated under inverted microscope. Data analysis was performed by using Chi- 2 test. Results: In cumulus cell group and in the presence of insulin-like growth factor fertilization of oocytes, forming embryos and the formation of 2-cells compared to the group without cumulus cells significantly increased (p < 0.05. Conclusion: As the results showed oocytes with cumulus cells in the presence of insulin-like growth factor enhances maturation, fertilization and embryonic development in 2-cells oocytes compared to group without cumulus cells TCM199.

  4. The insulin-like growth factor axis and collagen turnover during prednisolone treatment

    DEFF Research Database (Denmark)

    Wolthers, O D; Juul, A; Hansen, M

    1994-01-01

    Serum concentrations of insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3), the carboxyterminal propeptide of type I collagen (PICP), the carboxyterminal pyridinoline crosslinked telopeptide of type I collagen (ICTP), and the aminoterminal propeptide...... of type III procollagen (PIIINP) were studied in 10 prepubertal children with asthma (mean age 9.0 years). The children were treated with 2.5 and 5.0 mg/day prednisolone in a randomised double blind crossover trial with run in, treatment, and washout periods of two weeks. No statistically significant...... effects on serum concentrations of IGF-I and IGFBP-3 were found. Dose related reductions of PICP, ICTP, and PIIINP were observed: the mean (SEM) reduction in PICP was 33.4 (26.3) and 68.4 (20.6) micrograms/l, in ICTP 2.5 (0.5) and 2.9 (0.6) micrograms/l, and in PIIINP 2.1 (0.7) and 3.1 (1.8) micrograms...

  5. Insulin-like growth factor receptor inhibitors: baby or the bathwater?

    Science.gov (United States)

    Yee, Douglas

    2012-07-03

    The success of targeted therapies for cancer is undisputed; strong preclinical evidence has resulted in the approval of several new agents for cancer treatment. The type I insulin-like growth factor receptor (IGF1R) appeared to be one of these promising new targets. Substantial population and preclinical data have all pointed toward this pathway as an important regulator of tumor cell biology. Although early results from clinical trials that targeted the IGF1R showed some evidence of response, larger randomized phase III trials have not shown clear clinical benefit of targeting this pathway in combination with conventional strategies. These disappointing results have resulted in the discontinuation of several anti-IGF1R programs. However, the conduct of these trials has brought to the forefront several important factors that need to be considered in the conduct of future clinical trials. The need to develop biomarkers, a clearer understanding of insulin receptor function, and defining rational combination regimens all require further consideration. In this commentary, the current state of IGF1R inhibitors in cancer therapy is reviewed.

  6. Insulin-like Growth Factor Binding Protein 7 Mediates Glioma Cell Growth and Migration

    Directory of Open Access Journals (Sweden)

    Wei Jiang

    2008-12-01

    Full Text Available Insulin-like growth factor binding protein 7 (IGFBP-7 is the only member of the IGFBP superfamily that binds strongly to insulin, suggesting that IGFBP-7 may have different functions from other IGFBPs. Unlike other IGFBPs, the expression and functions of IGFBP-7 in glioma tumors have not been reported. Using cDNA microarray analysis, we found that expression of IGFBP-7 correlated with the grade of glioma tumors and the overall patient survival. This finding was further validated by real-time reverse transcription-polymerase chain reaction and Western blot analysis. We used RNAi to examine the role of IGFBP-7 in glioma cells, inhibiting IGFBP-7 expression by short interfering RNA transfection. Cell proliferation was suppressed after IGFBP-7 expression was inhibited for 5 days, and glioma cell growth was stimulated consistently by the addition of recombinant IGFBP-7 protein. Moreover, glioma cell migration was attenuated by IGFBP-7 depletion but enhanced by IGFBP-7 overexpression and addition. Overexpression of AKT1 in IGFBP-7-overxpressed cells attenuated the IGFBP-7-promoted migration and further enhanced inhibition of IGFBP-7 depletion on the migration. Phosphorylation of AKT and Erk1/2 was also inversely regulated by IGFBP-7 expression. These two factors together suggest that IGFBP-7 can regulate glioma cell migration through the AKT-ERK pathway, thereby playing an important role in glioma growth and migration.

  7. Transforming growth factor-beta1 stimulates the production of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in human bone marrow stromal osteoblast progenitors

    DEFF Research Database (Denmark)

    Kveiborg, Marie; Flyvbjerg, Allan; Eriksen, E F

    2001-01-01

    While transforming growth factor-beta1 (TGF-beta1) regulates proliferation and differentiation of human osteoblast precursor cells, the mechanisms underlying these effects are not known. Several hormones and locally acting growth factors regulate osteoblast functions through changes in the insulin......-like growth factors (IGFs) and IGF-binding proteins (IGFBPs). Thus, we studied the effects of TGF-beta1 on IGFs and IGFBPs in human marrow stromal (hMS) osteoblast precursor cells. TGF-beta1 increased the steady-state mRNA level of IGF-I up to 8.5+/-0.6-fold (P...

  8. Gene expression of tumour necrosis factor and insulin signalling-related factors in subcutaneous adipose tissue during the dry period and in early lactation in dairy cows.

    Science.gov (United States)

    Sadri, H; Bruckmaier, R M; Rahmani, H R; Ghorbani, G R; Morel, I; van Dorland, H A

    2010-10-01

    Gene expression of adipose factors, which may be part of the mechanisms that underlie insulin sensitivity, were studied in dairy cows around parturition. Subcutaneous fat biopsies and blood samples were taken from 27 dairy cows in week 8 antepartum (a.p.), on day 1 postpartum (p.p.) and in week 5 p.p. In the adipose tissue samples, mRNA was quantified by real-time reverse transcription polymerase chain reaction for tumour necrosis factor alpha (TNFα), insulin-independent glucose transporter (GLUT1), insulin-responsive glucose transporter (GLUT4), insulin receptor, insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), regulatory subunit of phosphatidylinositol-3 kinase (p85) and catalytic subunit of phosphatidylinositol-3 kinase. Blood plasma was assayed for concentrations of glucose, β-hydroxybutyric acid, non-esterified fatty acids (NEFA) and insulin. Plasma parameters followed a pattern typically observed in dairy cows. Gene expression changes were observed, but there were no changes in TNFα concentrations, which may indicate its local involvement in catabolic adaptation of adipose tissue. Changes in GLUT4 and GLUT1 mRNA abundance may reflect their involvement in reduced insulin sensitivity and in sparing glucose for milk synthesis in early lactation. Unchanged gene expression of IRS1, IRS2 and p85 over time may imply a lack of their involvement in terms of insulin sensitivity dynamics. Alternatively, it may indicate that post-transcriptional modifications of these factors came into play and may have concealed an involvement. © 2010 Blackwell Verlag GmbH.

  9. Expression of insulin-like growth factor-1 and insulin-like growth factor-1 receptors in EL4 lymphoma cells overexpressing growth hormone.

    Science.gov (United States)

    Weigent, Douglas A; Arnold, Robyn E

    2005-03-01

    Almost all of the previous studies with growth hormone (GH) have been done with exogenously supplied GH and, therefore, involve actions of the hormone through its receptor. However, the actions of endogenous or lymphocyte GH are still unclear. In a previous study, we showed that overexpression of GH (GHo) in a lymphoid cell line resulted in protection of the cells to apoptosis mediated by nitric oxide (NO). In the present study, we show that the protection from apoptosis could be transferred to control cells with culture fluids obtained from GHo cells and blocked by antibodies to the insulin-like growth factor-1 (IGF-1) or antibodies to the IGF-1-receptor (IGF-1R). Northern and Western blot analysis detected significantly higher levels of IGF-1 in cells overexpressing GH. An increase in the expression of the IGF-1R in GHo cells was also detected by Western blot analysis, (125)I-IGF-1 binding and analysis of IGF-1R promoter luciferase constructs. Transfection of GHo cells with a dominant negative IGF-1R mutant construct blocked the generation of NO and activation of Akt seen in GHo cells compared to vector alone control EL4 cells. The results suggest that one of the consequences of the overexpression of GH, in cells lacking the GH receptor, is an increase in the expression of IGF-1 and the IGF-1R which mediate the protection of EL4 lymphoma cells from apoptosis.

  10. Risk Factors for Depression : Differential Across Age?

    NARCIS (Netherlands)

    Schaakxs, Roxanne; Comijs, Hannie C; van der Mast, Roos C; Schoevers, Robert A; Beekman, Aartjan T F; Penninx, Brenda W J H

    INTRODUCTION: The occurrence of well-established risk factors for depression differs across the lifespan. Risk factors may be more strongly associated with depression at ages when occurrence, and therefore expectance, is relatively low ("on-time off-time" hypothesis). This large-scale study examined

  11. Physical risk factors for neck pain

    NARCIS (Netherlands)

    Ariëns, Geertje A M; Van Mechelen, Willem; Bongers, Paulien M.; Bouter, Lex M.; Van Der Wal, Gerrit

    2000-01-01

    To identify physical risk factors for neck pain, a systematic review of the literature was carried out. Based on methodological quality and study design, 4 levels of evidence were defined to establish the strength of evidence for the relationship between risk factors and neck pain. Altogether, 22

  12. Data collection on risk factors in pregnancy

    NARCIS (Netherlands)

    Zetstra-van der Woude, Alethea Priscilla

    2016-01-01

    This thesis aims to investigate the different methods of data collection of risk factors in pregnancy. Several observational epidemiologic study designs were used to assess associations between risk factors and negative birth outcomes. We especially looked at the use of folic acid around pregnancy

  13. Fatty liver is associated with insulin resistance, risk of coronary heart disease, and early atherosclerosis in a large European population

    DEFF Research Database (Denmark)

    Gastaldelli, Amalia; Kozakova, Michaela; Højlund, Kurt

    2009-01-01

    Patients with fatty liver (FL) disease have a high risk of developing diabetes and cardiovascular diseases. The aim was to evaluate the association between FL, insulin resistance (IR), coronary heart disease (CHD) risk, and early atherosclerosis in a large European population (RISC Study). In 1...... cholesterol (r = 0.33), alanine aminotransferase (r = 0.48), aspartate aminotransferase (r = 0.25), systolic blood pressure (r = 0.39) and IMT (r = 0.30), and reduced insulin sensitivity (r = -0.43), high-density lipoprotein cholesterol (r = -0.50), adiponectin (r = -0.42), and physical activity (r = -0...

  14. Impact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin.

    Science.gov (United States)

    Kemp, Michael G; Spandau, Dan F; Travers, Jeffrey B

    2017-02-26

    The growing incidence of non-melanoma skin cancer (NMSC) necessitates a thorough understanding of its primary risk factors, which include exposure to ultraviolet (UV) wavelengths of sunlight and age. Whereas UV radiation (UVR) has long been known to generate photoproducts in genomic DNA that promote genetic mutations that drive skin carcinogenesis, the mechanism by which age contributes to disease pathogenesis is less understood and has not been sufficiently studied. In this review, we highlight studies that have considered age as a variable in examining DNA damage responses in UV-irradiated skin and then discuss emerging evidence that the reduced production of insulin-like growth factor-1 (IGF-1) by senescent fibroblasts in the dermis of geriatric skin creates an environment that negatively impacts how epidermal keratinocytes respond to UVR-induced DNA damage. In particular, recent data suggest that two principle components of the cellular response to DNA damage, including nucleotide excision repair and DNA damage checkpoint signaling, are both partially defective in keratinocytes with inactive IGF-1 receptors. Overcoming these tumor-promoting conditions in aged skin may therefore provide a way to lower aging-associated skin cancer risk, and thus we will consider how dermal wounding and related clinical interventions may work to rejuvenate the skin, re-activate IGF-1 signaling, and prevent the initiation of NMSC.

  15. Impact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin

    Directory of Open Access Journals (Sweden)

    Michael G. Kemp

    2017-02-01

    Full Text Available The growing incidence of non-melanoma skin cancer (NMSC necessitates a thorough understanding of its primary risk factors, which include exposure to ultraviolet (UV wavelengths of sunlight and age. Whereas UV radiation (UVR has long been known to generate photoproducts in genomic DNA that promote genetic mutations that drive skin carcinogenesis, the mechanism by which age contributes to disease pathogenesis is less understood and has not been sufficiently studied. In this review, we highlight studies that have considered age as a variable in examining DNA damage responses in UV-irradiated skin and then discuss emerging evidence that the reduced production of insulin-like growth factor-1 (IGF-1 by senescent fibroblasts in the dermis of geriatric skin creates an environment that negatively impacts how epidermal keratinocytes respond to UVR-induced DNA damage. In particular, recent data suggest that two principle components of the cellular response to DNA damage, including nucleotide excision repair and DNA damage checkpoint signaling, are both partially defective in keratinocytes with inactive IGF-1 receptors. Overcoming these tumor-promoting conditions in aged skin may therefore provide a way to lower aging-associated skin cancer risk, and thus we will consider how dermal wounding and related clinical interventions may work to rejuvenate the skin, re-activate IGF-1 signaling, and prevent the initiation of NMSC.

  16. Transient risk factors of acute occupational injuries

    DEFF Research Database (Denmark)

    Østerlund, Anna H; Lander, Flemming; Nielsen, Kent

    2017-01-01

    Objectives The objectives of this study were to (i) identify transient risk factors of occupational injuries and (ii) determine if the risk varies with age, injury severity, job task, and industry risk level. Method A case-crossover design was used to examine the effect of seven specific transient...... risk factors (time pressure, disagreement with someone, feeling sick, being distracted by someone, non-routine task, altered surroundings, and broken machinery and materials) for occupational injuries. In the study, 1693 patients with occupational injuries were recruited from a total of 4002...... in relation to sex, age, job task, industry risk level, or injury severity. Conclusion Use of a case-crossover design identified several worker-related transient risk factors (time pressure, feeling sick, being distracted by someone) that led to significantly increased risks for occupational injuries...

  17. Risk factors of recurrent anal sphincter ruptures

    DEFF Research Database (Denmark)

    Jangö, Hanna; Langhoff-Roos, J; Rosthøj, Steen

    2012-01-01

    Please cite this paper as: Jangö H, Langhoff-Roos J, Rosthøj S, Sakse A. Risk factors of recurrent anal sphincter ruptures: a population-based cohort study. BJOG 2012;00:000-000 DOI: 10.1111/j.1471-0528.2012.03486.x. Objective  To determine the incidence and risk factors of recurrent anal sphincter...... were used to determine risk factors of recurrent ASR. Main outcome measures  The incidence of recurrent ASR and odds ratios for possible risk factors of recurrent ASR: age, body mass index, grade of ASR, birthweight, head circumference, gestational age, presentation, induction of labour, oxytocin...... augmentation, epidural, episiotomy, vacuum extraction, forceps, shoulder dystocia, delivery interval and year of second delivery. Results  Out of 159 446 women, 7336 (4.6%) experienced an ASR at first delivery, and 521 (7.1%) had a recurrent ASR (OR 5.91). The risk factors of recurrent ASR in the multivariate...

  18. Salivary factors in children and adolescents with insulin-dependent diabetes mellitus.

    Science.gov (United States)

    Karjalainen, K M; Knuuttila, M L; Käär, M L

    1996-01-01

    To determine whether hyperglycemia in IDDM (insulin-dependent diabetes mellitus) could interfere with salivary secretion rates, salivary glucose levels, and salivary microbial counts, we studied salivary factors in two groups of children and adolescents with IDDM. One study group included 14 children with newly diagnosed IDDM )mean age 11 years, SD +/- 2.4 years). Samples of saliva were collected on admission to hospital and after 2 weeks on insulin treatment. The other study group were 50 IDDM children (mean age 14.4 years, SD +/- 1.7 years, mean duration of diabetes 6.2 years, SD +/- 1.4 years) visiting the outpatient diabetic clinic. Samples of saliva were collected during two visits, approximately 3 months apart. In the newly diagnosed IDDM cases, mean salivary glucose level decreased from 54.1 +/- 31.7 mg/l to 35.2 +/- 29.5 mg/l (P = 0.096) after beginning insulin treatment. During hyperglycemia, salivary glucose levels correlated with mean blood glucose levels for the day concerned (r = 0.65, P salivary glucose levels. Stimulated saliva secretion increased significantly from 5.4 +/- 3.3 ml/5 min to 7.3 +/- 2.6 ml/5 min (P salivary flow rates and salivary glucose levels were not significantly related to the glycosylated hemoglobin (HbA1) values. Salivary glucose levels and salivary secretion rates were inversely correlated (P salivary secretion and high salivary glucose levels. As a consequence, salivary lactobacilli and yeast counts tended to increase.

  19. Contextual factors in liquidity risk

    NARCIS (Netherlands)

    Bonner, C.; van Lelyveld, I.P.P.; Zymek, R.

    2015-01-01

    We assess the determinants of banks’ liquidity holdings using data for nearly 7000 banks from 25 OECD countries. We highlight the role of several bank-specific, institutional and policy variables in shaping banks’ liquidity risk management. Our main question is whether liquidity regulation

  20. Basal insulin persistence, associated factors, and outcomes after treatment initiation among people with type 2 diabetes mellitus in the US.

    Science.gov (United States)

    Perez-Nieves, Magaly; Kabul, Samaneh; Desai, Urvi; Ivanova, Jasmina I; Kirson, Noam Y; Cummings, Alice Kate; Birnbaum, Howard G; Duan, Ran; Cao, Dachuang; Hadjiyianni, Irene

    2016-01-01

    To assess basal insulin persistence, associated factors, and economic outcomes for insulin-naïve people with type 2 diabetes mellitus (T2DM) in the US. People aged ≥18 years diagnosed with T2DM initiating basal insulin between April 2006 and March 2012 (index date), no prior insulin use, and continuous insurance coverage for 6 months before (baseline) and 24 months after index date (follow-up period) were selected using de-identified administrative claims data in the US. Based on whether there were ≥30 day gaps in basal insulin use in the first year post-index, patients were classified as continuers (no gap), interrupters (≥1 prescription after gap), and discontinuers (no prescription after gap). Factors associated with persistence - assessed using multinomial logistic regression model; annual healthcare resource use and costs during follow-up period - compared separately between continuers and interrupters, and continuers and discontinuers. Of the 19,110 people included in the sample (mean age: 59 years, ∼60% male), 20% continued to use basal insulin, 62% had ≥1 interruption, and 18% discontinued therapy in the year after initiation. Older age, multiple antihyperglycemic drug use, and injectable antihyperglycemic use during baseline were associated with significantly higher likelihoods of continuing basal insulin. Relative to interrupters and discontinuers, continuers had fewer emergency department visits, shorter hospital stays, and lower medical costs (continuers: $10,890, interrupters: $13,674, discontinuers: $13,021), but higher pharmacy costs (continuers: $7449, interrupters: $5239, discontinuers: $4857) in the first year post-index (p US. In addition, persistence patterns were assessed using administrative claims as opposed to actual medication-taking behavior and did not account for measures of glycemic control. Further research is needed to understand the reasons behind basal insulin persistence and the implications thereof, to help

  1. Intrinsic Risk Factors of Falls in Elderly

    Directory of Open Access Journals (Sweden)

    Yasmin Amatullah

    2016-09-01

    Full Text Available Background: Falls are common geriatric problems. The risk factors of falls are the intrinsic and extrinsic risk factors. Studies on falls are scarcely conducted in Indonesia, especially in Bandung. Therefore, this study was conducted to identify the intrinsic risk factors of falls among elderly. Methods: A descriptive study was carried out from August to October 2013 at the Geriatric Clinic of Dr. Hasan Sadikin General Hospital Bandung. Fifty three participants were selected according to the inclusion and exclusion criteria using consecutive sampling. The determined variables in this study were classification of the risk of falls, demographic profile, history of falls, disease, and medications. After the selection, the participants were tested by Timed up-and-go test (TUGT. Moreover, an interview and analysis of medical records were carried out to discover the risk factors of falls. The collected data were analyzed and presented in the form of percentages shown in tables. Results: From 53 patients, women (35.66% were considered to have higher risk of fall than men (18.34%. The majority of patients (66% with the risk of fall were from the age group 60–74 years. The major diseases suffered by patients were hypertension, osteoarthritis and diabetes mellitus. Drugs that were widely used were antihypertensive drugs; analgesic and antipyretic drugs and antidiabetic drugs. Conclusions: There are various intrinsic risk factors of falls in elderly and each of the elderly has more than one intrinsic risk factor of falls.

  2. Insulin-like growth factor I enhances collagen synthesis in engineered human tendon tissue

    DEFF Research Database (Denmark)

    Herchenhan, Andreas; Bayer, Monika L.; Eliasson, Pernilla

    2015-01-01

    OBJECTIVE: Isolated human tendon cells form 3D tendon constructs that demonstrate collagen fibrillogenesis and feature structural similarities to tendon when cultured under tensile load. The exact role of circulating growth factors for collagen formation in tendon is sparsely examined. We...... investigated the influence of insulin-like growth factor I (IGF-I) on tendon construct formation in 3D cell culture. DESIGN: Tendon constructs were grown in 0.5 or 10% FBS with or without IGF-I (250 mg/ml) supplementation. Collagen content (fluorometric), mRNA levels (PCR) and fibril diameter (transmission...... electron microscopy) were determined at 7, 10, 14, 21 and 28 days. RESULTS: IGF-I revealed a stimulating effect on fibril diameter (up to day 21), mRNA for collagen (to day 28), tenomodulin (to day 28) and scleraxis (at days 10 and 14), and on overall collagen content. 10% FBS diminished the development...

  3. 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....

  4. Systemic administration of insulin-like growth factor I (IGF-I) causes growth of the rat prostate

    DEFF Research Database (Denmark)

    Tørring, N; Vinter-Jensen, L; Pedersen, S B

    1997-01-01

    PURPOSE: To investigate the effects of insulin-like growth factor I (IGF-I) and epidermal growth factor (EGF) on the rat prostate. In addition, we investigated the effect of ornithine decarboxylase (ODC) inhibition with alpha-diflouromethylornitine (DFMO) on the expected growth of the prostate.MA...

  5. Are hypertriglyceridemia and low HDL causal factors in the development of insulin resistance?

    NARCIS (Netherlands)

    Li, Naishi; Fu, Jingyuan; Koonen, Debby P.; Kuivenhoven, Jan Albert; Snieder, Harold; Hofker, Marten H.

    Insulin resistance often occurs with dyslipidemia as part of the metabolic syndrome and the current dominant paradigm is that insulin resistance leads to dyslipidemia. However, dyslipidemia may also cause insulin resistance; this was postulated 30 years ago, but has never been substantiated.

  6. Urinary catecholamines, plasma insulin and environmental factors in relation to body fat distribution.

    Science.gov (United States)

    Leonetti, D L; Bergstrom, R W; Shuman, W P; Wahl, P W; Jenner, D A; Harrison, G A; Fujimoto, W Y

    1991-05-01

    The relationship of body fat distribution to insulin and the catecholamines, hormones that affect lipolysis differentially by fat site, was examined within an environmental context, including factors of medication use, physical activity, dietary intake, educational attainment, and age. Four cross-sectional body fat areas (cm2) were determined by three computed tomography (CT) scans (subcutaneous chest fat at the level of the nipples, subcutaneous and intra-abdominal fat at the level of the umbilicus, and subcutaneous left mid-thigh fat) in 191 second-generation Japanese-American men aged 45-74 years. The site-specific fat measurements were first examined in relation to use of beta-adrenergic antagonists, then to fasting plasma insulin and C-peptide levels and to urinary epinephrine and norepinephrine levels from a 24-h urine collection made during usual daily activities. Greater fat stores in the intra-abdominal area, even after adjustment for body mass index (BMI, weight/height2) and presence of coronary heart disease, were found to be related to use of beta-adrenergic antagonists. In men taking no adrenergic antagonists (n = 157), after adjustment for BMI, truncal fat measurements of the chest (partial r = -0.16, P less than 0.05) and intra-abdominal area (partial r = -0.21, P less than 0.05) were found to be inversely related to epinephrine, and intra-abdominal fat (partial r = 0.25, P less than 0.01) alone was directly related to fasting plasma insulin. With respect to other environmental variables, the significant inverse relationship of intra-abdominal fat (adjusted for BMI) with physical activity (partial r = -0.17, P less than 0.05) and the significant difference in intra-abdominal fat by educational attainment (college 102.3 +/- 5.7 vs no college 115.7 +/- 6.1 cm2, P = 0.03) became non-significant with adjustment, using multiple regression analysis, for insulin in the case of physical activity and epinephrine in the case of educational attainment. Thus

  7. Antepartal insulin-like growth factor 1 and insulin-like growth factor binding protein 2 concentrations are indicative of ketosis in dairy cows.

    Science.gov (United States)

    Piechotta, M; Mysegades, W; Ligges, U; Lilienthal, J; Hoeflich, A; Miyamoto, A; Bollwein, H

    2015-05-01

    A study involving a small number of cows found that the concentrations of insulin-like growth hormone 1 (IGF1) may be a useful predictor of metabolic disease. Further, IGF1 may provide also a pathophysiological link to metabolic diseases such as ketosis. The objective of the current study was to test whether the low antepartal total IGF1 or IGF1 binding protein (IGFBP) concentrations might predict ketosis under field conditions. Clinical examinations and blood sampling were performed antepartum (262-270 d after artificial insemination) on 377 pluriparous pregnant Holstein Friesian cows. The presence of postpartum diseases were recorded (ketosis, fatty liver, displacement of the abomasum, hypocalcemia, mastitis, retention of fetal membranes, and clinical metritis or endometritis), and the concentrations of IGF1, IGFBP2, IGFBP3, and nonesterified fatty acids were measured. Cows with postpartum clinical ketosis had lower IGF1 concentrations antepartum than healthy cows. The sensitivity of antepartal IGF1 as a marker for postpartum ketosis was 0.87, and the specificity was 0.43; a positive predictive value of 0.91 and a negative predictive value of 0.35 were calculated. The cows with ketosis and retained fetal membranes had lower IGFBP2 concentrations compared with the healthy cows. It can be speculated that lower IGF1 production in the liver during late pregnancy may increase growth hormone secretions and lipolysis, thereby increasing the risk of ketosis. Lower IGFBP2 concentrations may reflect the suppression of IGFBP2 levels through higher growth hormone secretion. In conclusion, compared with nonesterified fatty acids as a predictive parameter, IGF1 and IGFBP2 may represent earlier biomarkers of inadequate metabolic adaptation to the high energy demand required postpartum. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. Importance of high triglycerides levels between novel coronary risk factors

    Directory of Open Access Journals (Sweden)

    Valmore Bermúdez

    2017-11-01

    Full Text Available Introduction: The analysis of new cardiovascular risk factors is under an extensive debate in the cardiology and metabolic research fields. Objective: To determine the main factors that contribute to the classification of individuals with higher coronary risk in the adult population from Maracaibo, Venezuela. Methods: A descriptive, cross-sectional study with multistage random sampling in 1379 individuals belonging to the Maracaibo City Metabolic Syndrome Prevalence Study (MMSPS was performed. They were classified according to the coronary risk by Framingham-Wilson equation adapted to our population. The association between various risk factors was evaluated by ordinal logistic regression models. Results: 1,379 subjects (females 55.9%; n = 771 were evaluated, 66.2% (n = 913 were classified with low coronary risk. In univariate (χ2 = 112.35; p < 0.00001 and multivariate analysis [OR: 3.98 (2.39-6.63; p < 0.01], the main factors associated to be classified as the highest risk category were hypertriglyceridemia. Conclusion: There are several factors that should be included in predictive models use worldwide. The most important in our population were dyslipidemia such as hypertriglyceridemia, hyperlipoproteinemia (a and insulin resistance. Resumen: Introducción: El análisis de nuevos factores de riesgo cardiovascular constituye un tema de amplio debate en la investigación cardio-metabólica. Objetivo: Determinar los principales factores que contribuyen a la clasificación de sujetos en las categorías de mayor riesgo coronario en individuos adultos de la ciudad de Maracaibo, Venezuela. Métodos: Estudio descriptivo, trasversal con muestreo aleatorio multietapas en 1.379 individuos pertenecientes al Estudio de Prevalencia de Síndrome Metabólico de la Ciudad de Maracaibo (EPSMM. Estos fueron clasificaron de acuerdo con el riesgo coronario mediante la fórmula Framingham-Wilson adaptada para

  9. Paternal Insulin-like Growth Factor 2 (Igf2) Regulates Stem Cell Activity During Adulthood.

    Science.gov (United States)

    Barroca, Vilma; Lewandowski, Daniel; Jaracz-Ros, Agnieszka; Hardouin, Sylvie-Nathalie

    2017-02-01

    Insulin-like Growth Factor 2 (IGF2) belongs to the IGF/Insulin pathway, a highly conserved evolutionarily network that regulates growth, aging and lifespan. Igf2 is highly expressed in the embryo and in cancer cells. During mouse development, Igf2 is expressed in all sites where hematopoietic stem cells (HSC) successively expand, then its expression drops at weaning and becomes undetectable when adult HSC have reached their niches in bones and start to self-renew. In the present study, we aim to discover the role of IGF2 during adulthood. We show that Igf2 is specifically expressed in adult HSC and we analyze HSC from adult mice deficient in Igf2 transcripts. We demonstrate that Igf2 deficiency avoids the age-related attrition of the HSC pool and that Igf2 is necessary for tissue homeostasis and regeneration. Our study reveals that the expression level of Igf2 is critical to maintain the balance between stem cell self-renewal and differentiation, presumably by regulating the interaction between HSC and their niche. Our data have major clinical interest for transplantation: understanding the changes in adult stem cells and their environments will improve the efficacy of regenerative medicine and impact health- and life-span. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Paternal Insulin-like Growth Factor 2 (Igf2 Regulates Stem Cell Activity During Adulthood

    Directory of Open Access Journals (Sweden)

    Vilma Barroca

    2017-02-01

    Full Text Available Insulin-like Growth Factor 2 (IGF2 belongs to the IGF/Insulin pathway, a highly conserved evolutionarily network that regulates growth, aging and lifespan. Igf2 is highly expressed in the embryo and in cancer cells. During mouse development, Igf2 is expressed in all sites where hematopoietic stem cells (HSC successively expand, then its expression drops at weaning and becomes undetectable when adult HSC have reached their niches in bones and start to self-renew. In the present study, we aim to discover the role of IGF2 during adulthood. We show that Igf2 is specifically expressed in adult HSC and we analyze HSC from adult mice deficient in Igf2 transcripts. We demonstrate that Igf2 deficiency avoids the age-related attrition of the HSC pool and that Igf2 is necessary for tissue homeostasis and regeneration. Our study reveals that the expression level of Igf2 is critical to maintain the balance between stem cell self-renewal and differentiation, presumably by regulating the interaction between HSC and their niche. Our data have major clinical interest for transplantation: understanding the changes in adult stem cells and their environments will improve the efficacy of regenerative medicine and impact health- and life-span.

  11. Smoldering multiple myeloma risk factors for progression

    DEFF Research Database (Denmark)

    Sørrig, Rasmus; Klausen, Tobias W; Salomo, Morten

    2016-01-01

    Several risk scores for disease progression in Smoldering Multiple Myeloma (SMM) patients have been proposed, however, all have been developed using single center registries. To examine risk factors for time to progression (TTP) to Multiple Myeloma (MM) for SMM we analyzed a nationwide population......-based cohort of 321 newly diagnosed SMM patients registered within the Danish Multiple Myeloma Registry between 2005 and 2014. Significant univariable risk factors for TTP were selected for multivariable Cox regression analyses. We found that both an M-protein ≥ 30g/l and immunoparesis significantly influenced......-high risk of transformation to MM. Using only immunoparesis and M-protein ≥ 30g/l, we created a scoring system to identify low, intermediate and high risk SMM. This first population-based study of SMM patients confirms that an M-protein ≥ 30g/l and immunoparesis remain important risk factors for progression...

  12. Musculoskeletal Risk Factors in the Young Athlete.

    Science.gov (United States)

    Moskwa, C A; Nicholas, J A; Goldberg, B

    1989-11-01

    In brief: Many children and adolescents participate in sports that put them at risk for musculoskeletal injuries. Underlying physical conditions, or risk factors, may predispose them to particular types of sports injuries. Research shows that these risk factors fall into five categories: body type, flexibility, muscle strength, inadequate rehabilitation of a previous injury, and skeletal malalignment and anomalies. Some findings show, for example, that youthful football players who are also heavy have an increased rate of injury, sprains and strains are less common in flexible athletes, and patellar pain or subluxation may be related to a variety of malalignment factors. The authors recommend using a systematic, integrated approach to risk assessment of the athlete, both for detecting risk factors and determining their potential for con tribu ting to a sports injury.

  13. HUMAN PROSTATE CANCER RISK FACTORS

    Science.gov (United States)

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  14. Psychological Risk Factors in Headache

    Science.gov (United States)

    Nicholson, Robert A.; Houle, Timothy T.; Rhudy, Jamie L.; Norton, Peter J.

    2008-01-01

    Headache is a chronic disease that occurs with varying frequency and results in varying levels of disability. To date, the majority of research and clinical focus has been on the role of biological factors in headache and headache-related disability. However, reliance on a purely biomedical model of headache does not account for all aspects of headache and associated disability. Using a biopsychosocial framework, the current manuscript expands the view of what factors influence headache by considering the role psychological (i.e., cognitive and affective) factors have in the development, course, and consequences of headache. The manuscript initially reviews evidence showing that neural circuits responsible for cognitive–affective phenomena are highly interconnected with the circuitry responsible for headache pain. The manuscript then reviews the influence cognitions (locus of control and self-efficacy) and negative affect (depression, anxiety, and anger) have on the development of headache attacks, perception of headache pain, adherence to prescribed treatment, headache treatment outcome, and headache-related disability. The manuscript concludes with a discussion of the clinical implications of considering psychological factors when treating headache. PMID:17371358

  15. Pathophysiology, risk factors, and screening methods for prediabetes in women with polycystic ovary syndrome.

    Science.gov (United States)

    Gourgari, Evgenia; Spanakis, Elias; Dobs, Adrian Sandra

    2016-01-01

    Polycystic ovary syndrome (PCOS) is a syndrome associated with insulin resistance (IR), obesity, infertility, and increased cardiometabolic risk. This is a descriptive review of several mechanisms that can explain the IR among women with PCOS, other risk factors for the development of diabetes, and the screening methods used for the detection of glucose intolerance in women with PCOS. Few mechanisms can explain IR in women with PCOS such as obesity, insulin receptor signaling defects, and inhibition of insulin-mediated glucose uptake in adipocytes. Women with PCOS have additional risk factors for the development of glucose intolerance such as family history of diabetes, use of oral contraceptives, anovulation, and age. The Androgen Society in 2007 and the Endocrine Society in 2013 recommended using oral glucose tolerance test as a screening tool for abnormal glucose tolerance in all women with PCOS. The approach to detection of glucose intolerance among women with PCOS varies among health care providers. Large prospective studies are still needed for the development of guidelines with strong evidence. When assessing risk of future diabetes in women with PCOS, it is important to take into account the method used for screening as well as other risk factors that these women might have.

  16. Seismic Risk Perception compared with seismic Risk Factors

    Science.gov (United States)

    Crescimbene, Massimo; La Longa, Federica; Pessina, Vera; Pino, Nicola Alessandro; Peruzza, Laura

    2016-04-01

    The communication of natural hazards and their consequences is one of the more relevant ethical issues faced by scientists. In the last years, social studies have provided evidence that risk communication is strongly influenced by the risk perception of people. In order to develop effective information and risk communication strategies, the perception of risks and the influencing factors should be known. A theory that offers an integrative approach to understanding and explaining risk perception is still missing. To explain risk perception, it is necessary to consider several perspectives: social, psychological and cultural perspectives and their interactions. This paper presents the results of the CATI survey on seismic risk perception in Italy, conducted by INGV researchers on funding by the DPC. We built a questionnaire to assess seismic risk perception, with a particular attention to compare hazard, vulnerability and exposure perception with the real data of the same factors. The Seismic Risk Perception Questionnaire (SRP-Q) is designed by semantic differential method, using opposite terms on a Likert scale to seven points. The questionnaire allows to obtain the scores of five risk indicators: Hazard, Exposure, Vulnerability, People and Community, Earthquake Phenomenon. The questionnaire was administered by telephone interview (C.A.T.I.) on a statistical sample at national level of over 4,000 people, in the period January -February 2015. Results show that risk perception seems be underestimated for all indicators considered. In particular scores of seismic Vulnerability factor are extremely low compared with house information data of the respondents. Other data collected by the questionnaire regard Earthquake information level, Sources of information, Earthquake occurrence with respect to other natural hazards, participation at risk reduction activities and level of involvement. Research on risk perception aims to aid risk analysis and policy-making by

  17. Using risk factors for detection and prognostication of uveal melanoma

    Directory of Open Access Journals (Sweden)

    Pukhraj Rishi

    2015-01-01

    Full Text Available The early detection of malignancy, particularly uveal melanoma, is crucial in protecting visual acuity, salvaging the eye, and preventing metastasis. Risk factors for early detection of uveal melanoma have been clearly delineated in the literature and allow identification of melanoma when it is tiny and simulates a nevus. These factors include thickness >2 mm, presence of subretinal fluid (SRF, symptoms, the orange pigment, margin near optic disc, acoustic hollowness, surrounding halo, and absence of drusen. The importance of early detection is realized when one considers melanoma thickness, as each millimeter increase in melanoma thickness imparts 5% increased risk for metastatic disease. Newer imaging modalities like enhanced depth imaging optical coherence tomography and fundus autoflouroscence facilitate in detection of SRF and orange pigment. Additional molecular biomarkers and cytological features have been identified which can predict the clinical behavior of a small melanocytic lesion. Features that suggest a poor prognosis include higher blood levels of tyrosinase m-RNA, vascular endothelial growth factor, insulin-like growth factor; monosomy 3 and gains in chromosome 8. Management of uveal melanoma includes enucleation (for large, local eye wall resection, brachytherapy, charged particle irradiation, and thermotherapy (for small to medium tumors. Although the role of a good clinical evaluation cannot be underestimated, it is advisable to evaluate the various radiological, molecular, and cytological features, to enhance the accuracy of early diagnosis and improved prognosis.

  18. High cardiometabolic risk in healthy Chilean adolescents: associations with anthropometric, biological and lifestyle factors.

    Science.gov (United States)

    Burrows, Raquel; Correa-Burrows, Paulina; Reyes, Marcela; Blanco, Estela; Albala, Cecilia; Gahagan, Sheila

    2016-02-01

    To analyse the prevalence of cardiovascular risk factors in healthy adolescents of low to middle socio-economic status and to study the influence of anthropometric, biological and lifestyle factors on the risk of metabolic syndrome (MetS). Cross-sectional study. BMI, waist circumference, blood pressure, fat and lean mass (by dual-energy X-ray absorptiometry), TAG, HDL-cholesterol, glucose, insulin, homeostatic model assessment-insulin resistance index (HOMA-IR), food intake and physical activity were measured. Cardiovascular risk factors were defined using the International Diabetes Federation criteria and insulin resistance using HOMA-IR ≥2.6. Bivariate and multivariate regressions examined the associations between MetS and anthropometric, biological and lifestyle factors. Observational cohort study including Chilean adolescents, who were part of a follow-up study beginning in infancy. Adolescents aged 16-17 years (n 667). In the sample, 16.2% had obesity and 9.5% had MetS. Low HDL-cholesterol (69.9%), abdominal obesity (33.3%) and fasting hyperglycaemia (8.7%) were the most prevalent cardiovascular risk factors. In males, obesity (OR=3.7; 95% CI 1.2, 10.8), insulin resistance (OR=3.0; 95% CI 1.1, 8.2), physical inactivity (OR=2.9; 95% CI 1.1, 7.7) and sarcopenia (OR=21.2; 95% CI 4.2, 107.5) significantly increased the risk of MetS. In females, insulin resistance (OR=4.9; 95% CI 1.9, 12.6) and sarcopenia (OR=3.6; 95% CI 1.1, 11.9) were significantly associated with MetS. High prevalences of obesity, abdominal obesity, dyslipidaemia, fasting hyperglycaemia and MetS were found in healthy adolescents. In both sexes, sarcopenia and insulin resistance were important risk factors of MetS. Promotion of active lifestyles at the school level and regulation of the sale of energy-dense foods are needed.

  19. Risk factors of coercion among psychiatric inpatients

    DEFF Research Database (Denmark)

    Thomsen, Christoffer; Starkopf, Liis; Hastrup, Lene Halling

    2017-01-01

    PURPOSE: Reducing the use of coercion among patients with mental disorders has long been a political priority. However, risk factors for coercive measures have primarily been investigated in smaller studies. To reduce the use of coercion, it is crucial to identify people at risk which we aim to do...... and having children, reduced the risk of being subjected to coercive measure (all p risk factors associated with coercive measures. Our findings can assist researchers in identifying patients at risk of coercion and thereby help...... measure (21.9%). Clinical characteristics were the foremost predictors of coercion and patients with organic mental disorder had the highest increased risk of being subjected to a coercive measure (OR = 5.56; 95% CI = 5.04, 6.14). The risk of coercion was the highest in the first admission and decreased...

  20. Predictors of mortality in insulin dependent diabetes

    DEFF Research Database (Denmark)

    Rossing, P; Hougaard, P; Borch-Johnsen, K

    1996-01-01

    OBJECTIVE: To evaluate the prognostic significance of microalbuminuria and overt diabetic nephropathy and other putative risk factors for cardiovascular and all cause mortality in insulin dependent diabetes. DESIGN: Ten year observational follow up study. SETTING: Outpatient diabetic clinic...... in a tertiary referral centre. SUBJECTS: All 939 adults with insulin dependent diabetes (duration of diabetes five years or more) attending the clinic in 1984; 593 had normal urinary albumin excretion ( or = 300 mg...... and other potentially modifiable risk factors such as hypertension, smoking, poor glycaemic control, and social class predict increased mortality in insulin dependent diabetes. Microalbuminuria by itself confers only a small increase in mortality. The prognosis of patients with overt diabetic nephropathy...

  1. Free and total insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and IGFBP-3 and their relationships to the presence of diabetic retinopathy and glomerular hyperfiltration in insulin-dependent diabetes mellitus

    NARCIS (Netherlands)

    J.A.M.J.L. Janssen (Joseph); M.L. Jacobs (Marloes); F.H.M. Derkx (Frans); R.F.A. Weber (Rob); A-J. van der Lely (Aart-Jan); S.W.J. Lamberts (Steven)

    1997-01-01

    textabstractThe existing literature on serum insulin-like growth factor I (IGF-I) levels in insulin-dependent diabetes mellitus (IDDM) is conflicting. Free IGF-I may have greater physiological and clinical relevance than total IGF- I. Recently, a validated method has been developed to measure free

  2. Free and total insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and IGFBP-3 and their relationships to the presence of diabetic retinopathy and glomerular hyperfiltration in insulin-dependent diabetes mellitus

    NARCIS (Netherlands)

    J.A.M.J.L. Janssen (Joseph); M.L. Jacobs (Marloes); F.H.M. Derkx (Frans); R.F.A. Weber (Robert); A-J. van der Lely (Aart-Jan); S.W.J. Lamberts (Steven)

    1997-01-01

    textabstractThe existing literature on serum insulin-like growth factor I (IGF-I) levels in insulin-dependent diabetes mellitus (IDDM) is conflicting. Free IGF-I may have greater physiological and clinical relevance than total IGF-I. Recently, a validated method has

  3. Skeletal muscle hypertrophy and regeneration: interplay between the myogenic regulatory factors (MRFs) and insulin-like growth factors (IGFs) pathways.

    Science.gov (United States)

    Zanou, Nadège; Gailly, Philippe

    2013-11-01

    Adult skeletal muscle can regenerate in response to muscle damage. This ability is conferred by the presence of myogenic stem cells called satellite cells. In response to stimuli such as injury or exercise, these cells become activated and express myogenic regulatory factors (MRFs), i.e., transcription factors of the myogenic lineage including Myf5, MyoD, myogenin, and Mrf4 to proliferate and differentiate into myofibers. The MRF family of proteins controls the transcription of important muscle-specific proteins such as myosin heavy chain and muscle creatine kinase. Different growth factors are secreted during muscle repair among which insulin-like growth factors (IGFs) are the only ones that promote both muscle cell proliferation and differentiation and that play a key role in muscle regeneration and hypertrophy. Different isoforms of IGFs are expressed during muscle repair: IGF-IEa, IGF-IEb, or IGF-IEc (also known as mechano growth factor, MGF) and IGF-II. MGF is expressed first and is observed in satellite cells and in proliferating myoblasts whereas IGF-Ia and IGF-II expression occurs at the state of muscle fiber formation. Interestingly, several studies report the induction of MRFs in response to IGFs stimulation. Inversely, IGFs expression may also be regulated by MRFs. Various mechanisms are proposed to support these interactions. In this review, we describe the general process of muscle hypertrophy and regeneration and decipher the interactions between the two groups of factors involved in the process.

  4. The insulin-like growth factor axis and collagen turnover in asthmatic children treated with inhaled budesonide

    DEFF Research Database (Denmark)

    Wolthers, O D; Juul, A; Hansen, M

    1995-01-01

    Serum concentrations of growth hormone-dependent insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3), the carboxy terminal propeptide of type I procollagen (PICP), the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP......) and the amino terminal propeptide of type III procollagen (PIIINP) were studied in 14 prepubertal children with asthma (mean age 9.7 years) during treatment with inhaled budesonide. The study design was a randomized, crossover trial with two double-blind treatment periods (200 and 800 micrograms) and one open...

  5. The insulin-like growth factor axis and collagen turnover in asthmatic children treated with inhaled budesonide

    DEFF Research Database (Denmark)

    Wolthers, O D; Juul, A; Hansen, M

    1995-01-01

    Serum concentrations of growth hormone-dependent insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3), the carboxy terminal propeptide of type I procollagen (PICP), the carboxy terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) and ...... the calculations (p reduced synthesis of type III collagen. A similar trend was observed in ICTP levels when the 400 micrograms period was excluded from the calculations (p = 0.05; z = -1.9). No other statistically significant variations were seen....

  6. H19 RNA binds four molecules of insulin-like growth factor II mRNA-binding protein

    DEFF Research Database (Denmark)

    Runge, Steffen; Nielsen, Finn Cilius; Nielsen, Jacob

    2000-01-01

    H19 RNA is a major oncofetal 2.5-kilobase untranslated RNA of unknown function. The maternally expressed H19 gene is located 90 kilobase pairs downstream from the paternally expressed insulin-like growth factor II (IGF-II) gene on human chromosome 11 and mouse chromosome 7; and due to their recip......H19 RNA is a major oncofetal 2.5-kilobase untranslated RNA of unknown function. The maternally expressed H19 gene is located 90 kilobase pairs downstream from the paternally expressed insulin-like growth factor II (IGF-II) gene on human chromosome 11 and mouse chromosome 7; and due...

  7. Depressive symptoms, insulin sensitivity and insulin secretion in the RISC cohort study

    DEFF Research Database (Denmark)

    Bot, M; Pouwer, F; De Jonge, P

    2013-01-01

    Sensitivity and Cardiovascular Disease Risk (RISC) study. Presence of significant depressive symptoms was defined as a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16. Standard oral glucose tolerance tests were performed. Insulin sensitivity was assessed with the oral glucose insulin......AIM: This study explored the association of depressive symptoms with indices of insulin sensitivity and insulin secretion in a cohort of non-diabetic men and women aged 30 to 64 years. METHODS: The study population was derived from the 3-year follow-up of the Relationship between Insulin...... sensitivity (OGIS) index. Insulin secretion was estimated using three model-based parameters of insulin secretion (beta-cell glucose sensitivity, the potentiation factor ratio, and beta-cell rate sensitivity). RESULTS: A total of 162 out of 1027 participants (16%) had significant depressive symptoms. Having...

  8. The insulin-like growth factor system is modulated by exercise in breast cancer survivors: a systematic review and meta-analysis.

    Science.gov (United States)

    Meneses-Echávez, José Francisco; Jiménez, Emilio González; Río-Valle, Jacqueline Schmidt; Correa-Bautista, Jorge Enrique; Izquierdo, Mikel; Ramírez-Vélez, Robinson

    2016-08-25

    Insulin-like growth factors (IGF´s) play a crucial role in controlling cancer cell proliferation, differentiation and apoptosis. Exercise has been postulated as an effective intervention in improving cancer-related outcomes and survival, although its effects on IGF´s are not well understood. This meta-analysis aimed to determine the effects of exercise in modulating IGF´s system in breast cancer survivors. Databases of PuMed, EMBASE, Cochrane Central Register of Controlled Trials, EMBASE, ClinicalTrials.gov, SPORTDiscus, LILACS and Scopus were systematically searched up to November 2014. Effect estimates were calculated through a random-effects model of meta-analysis according to the DerSimonian and Laird method. Heterogeneity was evaluated with the I (2) test. Risk of bias and methodological quality were evaluated using the PEDro score. Five randomized controlled trials (n = 235) were included. Most women were post-menopausal. High-quality and low risk of bias were found (mean PEDro score = 6.2 ± 1). Exercise resulted in significant improvements on IGF-I, IGF-II, IGFBP-I, IGFBP-3, Insulin and Insulin resistance (P breast cancer survivors. These findings provide novel insight regarding the molecular effects of exercise on tumoral microenvironment, apoptosis and survival in breast cancer survivors.

  9. Metabolic syndrome as a risk factor for neurological disorders.

    Science.gov (United States)

    Farooqui, Akhlaq A; Farooqui, Tahira; Panza, Francesco; Frisardi, Vincenza

    2012-03-01

    The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the hypothalamic 'bodyweight/appetite/satiety set point,' resulting in the initiation and development of metabolic syndrome. Metabolic syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer's disease. The molecular mechanism underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However, it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders such as stroke, Alzheimer's disease and depression. The purpose of this review is not only to describe the involvement of brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical changes in stroke, Alzheimer's disease and depression to a wider audience of neuroscientists with the hope that this discussion will initiate more studies on the relationship between metabolic syndrome and neurological disorders. © Springer Basel AG 2011

  10. Obesity as a Major Risk Factor for Cancer

    Directory of Open Access Journals (Sweden)

    Giovanni De Pergola

    2013-01-01

    Full Text Available The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution together with physical activity. Reports from the International Agency for Research into Cancer and the World Cancer Research Fund (WCRF have shown that the strongest evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal, whereas the less common malignancies are leukemia, non-Hodgkin’s lymphoma, multiple myeloma, malignant melanoma, and thyroid tumours. To be able to develop novel methods in prevention and treatment, we first must understand the underlying processes which link cancer to obesity. Four main systems have been identified as potential producers of cancer in obesity: insulin, insulin-like growth factor-I, sex steroids, and adipokines. Various novel candidate mechanisms have been proposed: chronic inflammation, oxidative stress, crosstalk between tumour cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and the functional defeat of immune function. Herein, we review the major pathogenic links between obesity and susceptibility to cancer.

  11. Insulin/insulin like growth factors in cancer: new roles for the aryl hydrocarbon receptor, tumor resistance mechanisms and new blocking strategies

    Directory of Open Access Journals (Sweden)

    Travis B Salisbury

    2015-02-01

    Full Text Available The insulin-like growth factor 1 receptor (IGF1R and the insulin receptor (IR are receptor tyrosine kinases (RTKs that are expressed in cancer cells. The results of different studies indicate that tumor proliferation and survival is dependent on the IGF1R and IR, and that their inhibition leads to reductions in proliferation and increases in cell death. Molecular targeting therapies that have been used in solid tumors include: anti-IGF1R antibodies, anti-IGF1/IGF2 antibodies and small molecule inhibitors that suppress IGF1R and IR kinase activity. New advances in the molecular basis of anti-IGF1R blocking antibodies reveal they are biased agonists and promote the binding of IGF1 to integrin β3 receptors in some cancer cells. Our recent reports indicate that pharmacological aryl hydrocarbon receptor (AHR ligands inhibit breast cancer cell responses to IGFs, suggesting that targeting AHR may have benefit in cancers whose proliferation and survival are dependent on insulin/IGF signaling. Novel aspects of IGF1R/IR in cancer, such as biased agonism, integrin β3 signaling, AHR and new therapeutic targeting strategies will be discussed.

  12. 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.

  13. Doxorubicin impairs the insulin-like growth factor-1 system and causes insulin-like growth factor-1 resistance in cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Patrizia Fabbi

    Full Text Available Insulin-like growth factor-1 (IGF-1 promotes the survival of cardiomyocytes by activating type 1 IGF receptor (IGF-1R. Within the myocardium, IGF-1 action is modulated by IGF binding protein-3 (IGFBP-3, which sequesters IGF-1 away from IGF-1R. Since cardiomyocyte apoptosis is implicated in anthracycline cardiotoxicity, we investigated the effects of the anthracycline, doxorubicin, on the IGF-1 system in H9c2 cardiomyocytes.Besides inducing apoptosis, concentrations of doxorubicin comparable to those observed in patients after bolus infusion (0.1-1 µM caused a progressive decrease in IGF-1R and increase in IGFBP-3 expression. Exogenous IGF-1 was capable to rescue cardiomyocytes from apoptosis triggered by 0.1 and 0.5 µM, but not 1 µM doxorubicin. The loss of response to IGF-1 was paralleled by a significant reduction in IGF-1 availability and signaling, as assessed by free hormone levels in conditioned media and Akt phosphorylation in cell lysates, respectively. Doxorubicin also dose-dependently induced p53, which is known to repress the transcription of IGF1R and induce that of IGFBP3. Pre-treatment with the p53 inhibitor, pifithrin-α, prevented apoptosis and the changes in IGF-1R and IGFBP-3 elicited by doxorubicin. The decrease in IGF-1R and increase in IGFBP-3, as well as apoptosis, were also antagonized by pre-treatment with the antioxidant agents, N-acetylcysteine, dexrazoxane, and carvedilol.Doxorubicin down-regulates IGF-1R and up-regulates IGFBP-3 via p53 and oxidative stress in H9c2 cells. This leads to resistance to IGF-1 that may contribute to doxorubicin-initiated apoptosis. Further studies are needed to confirm these findings in human cardiomyocytes and explore the possibility of manipulating the IGF-1 axis to protect against anthracycline cardiotoxicity.

  14. Insulin-like growth factor binding protein-2: contributions of the C-terminal domain to insulin-like growth factor-1 binding.

    Science.gov (United States)

    Kibbey, Megan M; Jameson, Mark J; Eaton, Erin M; Rosenzweig, Steven A

    2006-03-01

    Signaling by the insulin-like growth factor (IGF)-1 receptor (IGF-1R) has been implicated in the promotion and aggressiveness of breast, prostate, colorectal, and lung cancers. The IGF binding proteins (IGFBPs) represent a class of natural IGF antagonists that bind to and sequester IGF-1/2 from the IGF-1R, making them attractive candidates as therapeutics for cancer prevention and control. Recombinant human IGFBP-2 significantly attenuated IGF-1-stimulated MCF-7 cell proliferation with coaddition of 20 or 100 nM IGFBP-2 (50 or 80% inhibition, respectively). We previously identified IGF-1 contact sites both upstream and downstream of the CWCV motif (residues 247-250) in human IGFBP-2 (J Biol Chem 276:2880-2889, 2001). To further test their contributions to IGFBP-2 function, the single tryptophan in human IGFBP-2, Trp-248, was selectively cleaved with 2-(2'nitrophenylsulfenyl)-3-methyl-3 bromoindolenine (BNPS-skatole) and the BNPS-skatole products IGFBP-2(1-248) and IGFBP-2(249-289) as well as IGFBP-2(1-190) were expressed as glutathione S-transferase-fusion proteins and purified. Based on competition binding analysis, deletion of residues 249 to 289 caused an approximately 20-fold decrease in IGF-1 binding affinity (IGFBP-2 EC50 = 0.35 nM and IGFBP-2(1-248) = 7 nM). Removal of the remainder of the C-terminal domain had no further effect on affinity (IGFBP-2(1-190) EC50 = 9.2 nM). In kinetic assays, IGFBP-2(1-248) and IGFBP-2(1-190) exhibited more rapid association and dissociation rates than full-length IGFBP-2. These results confirm that regions upstream and downstream of the CWCV motif participate in IGF-1 binding. They further support the development of full-length IGFBP-2 as a cancer therapeutic.

  15. Association of an APOC3 promoter variant with type 2 diabetes risk and need for insulin treatment in lean persons

    NARCIS (Netherlands)

    M. van Hoek (Mandy); T.W. van Herpt (Thijs); A. Dehghan (Abbas); A. Hofman (Albert); A. Lieverse (Aloysius); C.M. van Duijn (Cornelia); J.C.M. Witteman (Jacqueline); E.J.G. Sijbrands (Eric)

    2011-01-01

    textabstractAims/hypothesis: An APOC3 promoter haplotype has been previously associated with type 1 diabetes. In this population-based study, we investigated whether APOC3 polymorphisms increase type 2 diabetes risk and need for insulin treatment in lean participants. Methods: In the Rotterdam

  16. Biomarkers for insulin resistance and inflammation and the risk for all-cause dementia and Alzheimer disease

    Science.gov (United States)

    Our aim was to investigate the contribution of biomarkers of glucose homeostasis (adiponectin, glucose, glycated albumin, and insulin levels) and inflammation (high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A(2) levels) to the risk of developing Alzheimer disease (AD) a...

  17. Levels of insulin, insulin-like growth factor-I and thyroid hormones in relation to the body condition score changes in periparturient dairy cows

    Directory of Open Access Journals (Sweden)

    Fratrić Natalija

    2013-01-01

    Full Text Available The objective of this study was to determine the levels of insulin, insulin like growth factor I (IGF-I and thyroid hormones in relation to the body condition score (BCS of periparturient dairy cows. The study was carried out on twenty Holstein-Friesian dairy cows with average milk production of 7000 L/305 days in the previous lactation, parity ranging from 2-4. All cows were BCS scored during the early dry period, 7±3 days before and after parturition. Based on the BCS at the early dry period, cows were divided in two groups: cows with high BCS (3.75- 4.25, HBCS, n=10, and cows with moderate BCS (2.75-3.75, MBCS, n=10. Blood samples were taken at the time of BCS evaluation. Concentrations of insulin, IGF-I, triiodothyroinine (T3 and thyroxine (T4 were determined by radioimmunoassay (RIA, INEP-Zemun, Serbia. Statistical differences between mean values were determined using Student t-test (p0.05. IGF-I level in HBCS cows at days 7±3 before calving was significantly higher (16.28±3.07:11.76±2.28, p<0.01, with a reverse relationship after calving (3.77±1.64:8.46±2.37, p<0.01. Insulin level was significantly lower at 7±3 days before calving in HBCS cows (16.26±4.60:20.18±4.96mIU/L, p<0.05. Thyroid hormones levels were significantly lower in HBCS group et all examined periods. [Projekat Ministarstva nauke Republike Srbije, br. III 46002 i br. 31003

  18. Epidemiology and risk factors of schizophrenia.

    Science.gov (United States)

    Janoutová, Jana; Janácková, Petra; Serý, Omar; Zeman, Tomás; Ambroz, Petr; Kovalová, Martina; Varechová, Katerina; Hosák, Ladislav; Jirík, Vitezslav; Janout, Vladimír

    2016-01-01

    Schizophrenia is a severe mental disorder that affects approximately one percent of the general population. The pathogenesis of schizophrenia is influenced by many risk factors, both environmental and genetic. The environmental factors include the date of birth, place of birth and seasonal effects, infectious diseases, complications during pregnancy and delivery, substance abuse and stress. At the present time, in addition to environmental factors, genetic factors are assumed to play a role in the development of the schizophrenia. The heritability of schizo- phrenia is up to 80%. If one parent suffers from the condition, the probability that it will be passed down to the offspring is 13%. If it is present in both parents, the risk is more than 20%. The opinions are varied as to the risk factors affecting the development of schizophrenia. Knowing these factors may greatly contribute to prevention of the condition.

  19. Direct demonstration of rapid insulin-like growth factor II receptor internalization and recycling in rat adipocytes. Insulin stimulates 125I-insulin-like growth factor II degradation by modulating the IGF-II receptor recycling process

    International Nuclear Information System (INIS)

    Oka, Y.; Rozek, L.M.; Czech, M.P.

    1985-01-01

    The photoactive insulin-like growth factor (IGF)-II analogue 4-azidobenzoyl- 125 I-IGF-II was synthesized and used to label specifically and covalently the Mr = 250,000 Type II IGF receptor. When rat adipocytes are irradiated after a 10-min incubation with 4-azidobenzoyl- 125 I-IGF-II at 10 degrees C and immediately homogenized, most of the labeled IGF-II receptors are associated with the plasma membrane fraction, indicating that receptors accessible to the labeling reagent at low temperature are on the cell surface. However, when the photolabeled cells are incubated at 37 degrees C for various times before homogenization, labeled IGF-II receptors are rapidly internalized with a half-time of 3.5 min as evidenced by a loss from the plasma membrane fraction and a concomitant appearance in the low density microsome fraction. The steady state level of cell surface IGF-II receptors in the presence or absence of IGF-II remains constant under these conditions, demonstrating that IGF-II receptors rapidly recycle back to the cell surface at the same rate as receptor internalization. Using the above methodology, it is shown that acute insulin action: 1) increases the steady state number of cell surface IGF-II receptors; 2) increases the number of ligand-bound IGF-II receptors that are internalized per unit of time; and 3) increases the rate of cellular 125 I-IGF-II degradation by a process that is blocked by anti-IGF-II receptor antibody

  20. Asian Adolescents with Excess Weight are at Higher Risk for Insulin Resistance than Non-Asian Peers.

    Science.gov (United States)

    Elsamadony, Ahmed; Yates, Kathy F; Sweat, Victoria; Yau, Po Lai; Mangone, Alex; Joseph, Adriana; Fierman, Arthur; Convit, Antonio

    2017-11-01

    The purpose of this study was to evaluate whether Asian American adolescents have higher metabolic risk from excess weight than non-Asians. Seven hundred thirty-three students, aged 14 to 19 years old, completed a school-based health screening. The 427 Asian and 306 non-Asian students were overall equivalent on age, sex, and family income. Height, weight, waist circumference, percent body fat, and blood pressure were measured. Fasting triglycerides, high- and low-density lipoproteins, glucose, and insulin levels were measured. Asian and non-Asians in lean or overweight/obesity groups were contrasted on the five factors that make up the metabolic syndrome. Asian adolescents carrying excess weight had significantly higher insulin resistance (IR), triglyceride levels, and waist-height ratios (W/H), despite a significantly lower overall BMI than corresponding non-Asians. Similarly, Asians had a stronger relationship between W/H and the degree of IR than non-Asian counterparts; 35% and 18% of the variances were explained (R 2  = 0.35, R 2  = 0.18) respectively, resulting in a significant W/H by racial group interaction (F change [1,236] = 11.56, P Asians have higher IR and triglyceride levels from excess weight than their non-Asian counterparts. One-size-fits-all public health policies targeting youth should be reconsidered and attention paid to Asian adolescents, including those with mild degrees of excess weight. © 2017 The Obesity Society.

  1. Insulin-Like Growth Factor Axis Expression in Dental Pulp Cells Derived From Carious Teeth

    Directory of Open Access Journals (Sweden)

    Hanaa Esa Alkharobi

    2018-04-01

    Full Text Available The insulin-like growth factor (IGF axis plays an important role in dental tissue regeneration and most components of this axis are expressed in human dental pulp cells (DPCs. In our previous study, we analyzed IGF axis gene expression in DPCs and demonstrated a novel role of IGF binding protein (IGFBP-2 and -3 in coordinating mineralized matrix formation in differentiating DPCs. A more recent study from our laboratory partially characterized dental pulp stem cells from teeth with superficial caries (cDPCs and showed that their potential to differentiate odontoblasts and/or into osteoblasts is enhanced by exposure to the mild inflammatory conditions characteristic of superficial caries. In the present study, we examine whether changes apparent in IGF axis expression during osteogenic differentiation of healthy DPCs are also apparent in DPCs derived from carious affected teeth.

  2. Dissociation between plasma concentrations of thyroxine and insulin-like growth factor-I.

    Science.gov (United States)

    Dauncey, M J; Morovat, A; Rudd, B T; Shakespear, R A

    1990-09-01

    The relation between plasma concentrations of thyroxine (T4) and insulin-like growth factor-I (IGF-I) has been examined in young, growing pigs under controlled conditions of energy intake. Compared with euthyroid controls, plasma levels of IGF-I were significantly elevated (P less than 0.005) both in hypothyroid animals on the same food intake and in hyperthyroid animals on double the food intake. There was however no increase in IGF-I in a hyperthyroid group on the control level of intake. Contrary to previous reports in which energy intake was not controlled, it is concluded that there is no simple correlation between plasma concentrations of T4 and IGF-I.

  3. Enhanced insulin-like growth factor I gene expression in regenerating rat pancreas

    International Nuclear Information System (INIS)

    Smith, F.E.; Rosen, K.M.; Villa-Komaroff, L.; Weir, G.C.; Bonner-Weir, S.

    1991-01-01

    Insulin-like growth factor I (IGF-I) mRNA expression was studied after 90% partial pancreatectomy in the rat to determine whether IGF-I was associated with pancreatic regeneration. The level of IGF-I mRNA was maximally increased (4-fold above control value) 3 days after pancreatectomy, but thereafter gradually decreased, returning to control levels by 14 days after surgery. By in situ hybridization, IGF-I mRNA in both pancreatectomized and sham-operated rats was localized to capillary endothelial cells, indicating that this is the site of IGF-I expression in the normal rat pancreas. However, enhanced IGF-I mRNA expression was localized to focal areas of regeneration unique to pancreatectomized rats. In these areas, epithelial cells of proliferating ductules and individual connective tissue cells expressed IGF-I, suggesting that IGF-I may play an important role in the growth or differentiation of pancreatic tissue

  4. Enhanced insulin-like growth factor I gene expression in regenerating rat pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Smith, F.E.; Rosen, K.M.; Villa-Komaroff, L.; Weir, G.C.; Bonner-Weir, S. (E. P. Joslin Research Laboratory, Joslin Diabetes Center, Harvard Medical School, Boston, MA (USA))

    1991-07-15

    Insulin-like growth factor I (IGF-I) mRNA expression was studied after 90% partial pancreatectomy in the rat to determine whether IGF-I was associated with pancreatic regeneration. The level of IGF-I mRNA was maximally increased (4-fold above control value) 3 days after pancreatectomy, but thereafter gradually decreased, returning to control levels by 14 days after surgery. By in situ hybridization, IGF-I mRNA in both pancreatectomized and sham-operated rats was localized to capillary endothelial cells, indicating that this is the site of IGF-I expression in the normal rat pancreas. However, enhanced IGF-I mRNA expression was localized to focal areas of regeneration unique to pancreatectomized rats. In these areas, epithelial cells of proliferating ductules and individual connective tissue cells expressed IGF-I, suggesting that IGF-I may play an important role in the growth or differentiation of pancreatic tissue.

  5. Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults

    DEFF Research Database (Denmark)

    Juul, A; Bang, P; Hertel, Niels

    1994-01-01

    Serum levels of insulin-like growth factor-I (IGF-I) increase with age and pubertal development. The large variation in circulating IGF-I levels in adolescence makes it difficult to use the IGF-I value of a single child in the assessment of his growth status. In addition, the interference of IGF......-binding proteins in many IGF-I assays contributes to this problem. We measured IGF-I in acid-ethanol-extracted serum from 1030 healthy children, adolescents, and adults, employing a RIA that reduces interference of IGF-binding proteins by using monoiodinated Tyr31-[125I]des-(1-3)IGF-I as radioligand. Mean serum...... volume. Multiple regression analysis revealed that serum IGF-I levels predicted height velocity in the following year (r = 0.33; P

  6. Two insulin-like growth factor I messenger RNAs are expressed in human liver

    International Nuclear Information System (INIS)

    Rotwein, P.

    1986-01-01

    Through use of a synthetic radiolabelled oligonucleotide probe, human insulin-like growth factor I (IGF-I) cDNA clones were isolated from a liver library. Two types of cDNAs were defined by restriction enzyme analysis and DNA sequencing. Both encode IGF-I precursors of either 195 or 153 amino acids. The two predicted protein precursors are identical from their amino terminus to a lysine residue 16 codons beyond the IGF-I sequence, and then they diverge. Both cDNAs predict additional unique carboxyl-terminal extension peptides. Since there is only one IGF-I gene in the human genome, the finding of two different cDNAs suggests that alternative RNA processing plays a role in IGF-I gene expression. The functions of the different extension peptides remain to be elucidates

  7. Insulin-Like Growth Factors in the Pathogenesis of Neurological Diseases in Children.

    Science.gov (United States)

    Riikonen, Raili

    2017-09-26

    Insulin-like growth factors play a key role for neuronal growth, differentiation, the survival of neurons and synaptic formation. The action of IGF-1 is most pronounced in the developing brain. In this paper we will try to give an answer to the following questions: Why are studies in children important? What clinical studies in neonatal asphyxia, infantile spasms, progressive encephalopathy-hypsarrhythmia-optical atrophy (PEHO) syndrome, infantile ceroid lipofuscinosis (INCL), autistic spectrum disorders (ASD) and subacute sclerosing encephalopathy (SSPE) have been carried out? What are IGF-based therapeutic strategies? What are the therapeutic approaches? We conclude that there are now great hopes for the therapeutic use of IGF-1 for some neurological disorders (particularly ASD).

  8. Serum insulin-like growth factor II (IGF-II) in chronic heart failure

    International Nuclear Information System (INIS)

    Tong Lijun; Chen Donghai; Ji Naijun; Fan Bifu; Wang Chengyao; Mei Yibin; Li Fuyuan; Kao Yan

    2004-01-01

    Objective: To investigate the clinical significance of changes of serum insulin-like growth factor II (IGF-II) levels in patients with chronic heart failure. Methods: Serum IGF-II levels were measured with RIA in 132 cases of chronic heart failure and 45 controls. Results: Serum IGF-II levels were significantly higher in patients with chronic heart failure than those in the controls (t=0.033, P<0.001). IGF-II levels were highest in grade IV CHF patients (vs grade II t=3.963, P<0.01; vs grade III, t=3.578, P<0.01). In the twelve patients died in hospital, the serum IGF-II levels were significantly higher than those patients recovered (t=7.141, P<0.01). Conclusion: Serum IGF-II levels were increased in CHF patients and were highest in the most severe cases. (authors)

  9. Retinopathy of prematurity and serum level of insulin-like growth factor-1.

    Science.gov (United States)

    Banjac, Lidija; Bokan, Vesna

    2012-06-01

    The aim of our study was to measure and compare serum insulin-like growth factor-1 (IGF-1) levels at postmenstrual age of 33 weeks between preterm infants with and without retinopathy of prematurity (ROP). ROP occurs in two phases. Low serum levels of IGF-1 during ROP phase 1 have been found to correlate with the severity of ROP. ROP phase 2 begins around postmenstrual week 33. We conducted a prospective cohort study to measure serum IGF-1 levels in premature infants at postmenstrual age of 33 weeks. The study included all premature infants (N = 74), gestational age large controlled study with repeated measurement of IGF-1 level in the neonatal period is needed to confirm that restoration of IGF-I level occurs in ROP phase 2, i.e. that the low level of IGF-1 is only a feature of ROP phase 1.

  10. Circulating concentrations of insulin-like growth factor-1 in dogs with naturally occurring mitral regurgitation

    DEFF Research Database (Denmark)

    Pedersen, Henrik Duelund; Falk, Bo Torkel; Häggström, Jens

    2005-01-01

    Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth hormone, has effects on cardiac mass and function, and plays an important role in the regulation of vascular tone. In humans, an inverse relationship between degree of heart failure (HF) and circulating IGF-1 concentrations...... has been found in several studies. In dogs with HF, few studies have focused on IGF-1. We examined circulating IGF-1 concentrations in dogs with mitral regurgitation (MR) caused by myxomatous mitral valve disease. Study 1 included 88 Cavalier King Charles Spaniels (CKCSs) with a broad range...... of asymptomatic MR (median serum IGF-1: 76.7 µg/L; 25-75 percentile, 59.8-104.9 µg/L). As expected, standard body weight and percentage under- or overweight correlated directly with IGF-1. MR (assessed in 4 different ways) did not correlate with IGF-1. In study 2, 28 dogs with severe MR and stable, treated...

  11. Protein kinase C is differentially regulated by thrombin, insulin, and epidermal growth factor in human mammary tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Gomez, M.L.; Tellez-Inon, M.T. (Instituto de Ingenieria Genetica y Biologia Molecular, Buenos Aires (Argentina)); Medrano, E.E.; Cafferatta, E.G.A. (Instituto de Investigaciones Bioquimicas Fundacion Campomar, Buenos Aires (Argentina))

    1988-03-01

    The exposure of serum-deprived mammary tumor cells MCF-7 and T-47D to insulin, thrombin, and epidermal growth factor (EGF) resulted in dramatic modifications in the activity and in the translocation capacity of protein kinase C from cytosol to membrane fractions. Insulin induces a 600% activation of the enzyme after 5 h of exposure to the hormone in MCF-7 cells; thrombin either activates (200% in MCF-7) or down-regulates (in T-47D), and EGF exerts only a moderate effect. Thus, the growth factors studied modulate differentially the protein kinase C activity in human mammary tumor cells. The physiological significance of the results obtained are discussed in terms of the growth response elicited by insulin, thrombin, and EGF.

  12. 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.

  13. Liver inflammation is a Risk Factor for Prediabetes in At-Risk Latinos with and without Hepatitis C Infection

    Science.gov (United States)

    Burman, Blaire E; Bacchetti, Peter; Ayala, Claudia E.; Gelman, Nicholas; Melgar, Jennifer; Khalili, Mandana

    2014-01-01

    Background and Aims Early recognition of prediabetes can lead to timely clinical interventions to prevent type 2 diabetes. Both Latino ethnicity and chronic hepatitis C (HCV) have been identified as diabetic risk factors. We aimed to investigate predictors of impaired fasting glucose (IFG), a common prediabetic state, among Latinos with and without HCV. Methods One hundred Latino adults with no history of diabetes or cirrhosis underwent clinical, laboratory, and metabolic evaluation, including oral glucose tolerance testing (OGTT) and insulin suppression testing to quantify directly measured insulin resistance (IR). Isolated IFG was defined as fasting glucose ≥100mg/dL and prediabetes among Latinos with and without HCV. Among HCV-infected individuals, early antiviral therapy could mitigate the effect of inflammation and represent an important intervention to prevent diabetes in this at-risk population. PMID:25156890

  14. Diabetic ketoacidosis: risk factors, mechanisms and management ...

    African Journals Online (AJOL)

    Diabetic ketoacidosis: risk factors, mechanisms and management strategies in sub-Saharan Africa: a review. ... ketoacidosis is the most common hyperglycaemic emergency in patients with diabetes mellitus, especially type 1 diabetes.

  15. risk factors for abnormal tubal hysterosalpingographic findings

    African Journals Online (AJOL)

    Administrator

    So many presumed risk factors for female tubal infertility are seen among. Nigerian women. ... strategies such as health awareness campaigns against unwanted pregnancy, promotion of responsible ..... of CT findings in acute pyogenic pelvic.

  16. Shoulder Dystocia: Incidence and Risk Factors.

    Science.gov (United States)

    Ouzounian, Joseph G

    2016-12-01

    Shoulder dystocia complicates ∼1% of vaginal births. Although fetal macrosomia and maternal diabetes are risk factors for shoulder dystocia, for the most part its occurrence remains largely unpredictable and unpreventable.

  17. Risk Factors for Developing Atopic Dermatitis

    DEFF Research Database (Denmark)

    G. Carson, Charlotte

    2013-01-01

    The aim of this thesis was to investigate possible risk factors affecting the development of AD. AD is a frequent disease among children and has a substantial impact on the lives of both the child and its family. A better understanding of the disease would enable better treatment, prevention...... and information to the families involved. Previous risk factor studies have been hampered by an unsuitable study design and/or difficulties in standardization when diagnosing AD, which limit their conclusions. In paper I, we conducted a traditional cross-sectional analysis testing 40 possible risk factors...... exposure to dog was the only environmental exposure that significantly reduced the disease manifestation, suggesting other, yet unknown environmental factors affecting the increasing prevalence of AD in children. Length at birth was shown to be inversely associated with the risk of later developing AD...

  18. Awareness of risk factors for cancer

    DEFF Research Database (Denmark)

    Lagerlund, Magdalena; Hvidberg, Line; Hajdarevic, Senada

    2015-01-01

    Background: Sweden and Denmark are neighbouring countries with similarities in culture, healthcare, and economics, yet notable differences in cancer statistics. A crucial component of primary prevention is high awareness of risk factors in the general public. We aimed to determine and compare...... awareness of risk factors for cancer between a Danish and a Swedish population sample, and to examine whether there are differences in awareness across age groups. Methods: Data derive from Module 2 of the International Cancer Benchmarking Partnership. Telephone interviews were conducted with 3000 adults...... in Denmark and 3070 in Sweden using the Awareness and Beliefs about Cancer measure. Data reported here relate to awareness of 13 prompted risk factors for cancer. Prevalence ratios with 95 % confidence intervals were calculated to examine associations between country, age, and awareness of risk factors...

  19. THE RISK FACTORS FOR INITIAL REPRODUCTIVE LOSS

    Directory of Open Access Journals (Sweden)

    Екатерина Игоревна Лебедева

    2017-09-01

    Conclusion. Mixed somatic and gynecological pathology, abnormalities in hemostasis, combination of inherited and acquired thrombogenic risk factors dominates in women with initial reproductive loss, though only 37,3 % such pregnancies have favorable outcome.

  20. Insulin-like growth factor binding protein-2, 28 kDa an 24 kDa insulin-like growth factor binding protein levels are decreased in fluid of dominant follicles, obtained from normal and polycystic ovaries

    NARCIS (Netherlands)

    A.G.P. Schuller (Alwin); D.J. Lindenbergh-Kortleve (Dicky); T.D. Pache; E.C. Zwarthoff (Ellen); B.C.J.M. Fauser (Bart); S.L.S. Drop (Stenvert)

    1993-01-01

    textabstractIn order to investigate potential changes in insulin-like growth factor binding proteins (IGFBPs) during human follicle maturation, we examined the IGFBP profiles in follicular fluid from follicles in different stages of maturation. Samples were obtained from ovaries of women with

  1. Cow placenta extract promotes murine hair growth through enhancing the insulin - like growth factor-1

    Directory of Open Access Journals (Sweden)

    Dongliang Zhang

    2011-01-01

    Full Text Available Background: Hair loss is seen as an irreversible process. Most research concentrates on how to elongate the anagen, reduce the negative factors of obstructing hair growth and improve the hair number and size. Aim: In our experiment, we tried to prove that the cow placenta extract can promote hair growth by elongating hair shaft and increasing hair follicle number. Materials and Methods: Cow placenta extract (CPE, water and minoxidil applied separately on the back of depilated B57CL/6 mice for the case, negative and positive control respectively. We checked the proliferation of cells which are resident in hair sheath, and the expression of a few growth factors which stimulate hair growth. Results: Result shows that placenta extract more efficiently accelerates cell division and growth factor expression, by raising the insulin-like growth factor (IGF-1 mRNA and protein level to increase HF size and hair length. Conclusions: The extract is not a purified product; so, it is less effective than minoxidil, which is approved by the US FDA for the treatment of male pattern baldness. If refinement is done, the placenta extract would be a good candidate medicine for hair loss.

  2. Preventing Cardiovascular Disease Risk Factors through Aerobic ...

    African Journals Online (AJOL)

    This paper focused on the reduction of cardiovascular disease risk factors, through aerobic exercises. The central argument here is that through exercise there is the tendency for increased strength of the heart muscles. When this is the case, what follows is a reduction in body weight and ultimately less risk on the ...

  3. Risk factors in prevention of drug dependences

    NARCIS (Netherlands)

    Orosova, Ol'ga; Gajdosova, Beata; Madarasova-Geckova, Andrea; Van Dijk, Jitse P.

    2007-01-01

    The study presents the state-of-art of knowledge of risk factors of drug use as a form of risk behaviour in adolescents in individual, interpersonal, and environmental domain (family, school, society). The attention is paid to general deviation syndrome and to the construct of general tendency to

  4. Risk factors for QTc interval prolongation

    NARCIS (Netherlands)

    Heemskerk, Charlotte P.M.; Pereboom, Marieke; van Stralen, Karlijn; Berger, Florine A.; van den Bemt, Patricia M.L.A.; Kuijper, Aaf F.M.; van der Hoeven, Ruud T M; Mantel-Teeuwisse, Aukje K.; Becker, Matthijs L

    2018-01-01

    Purpose: Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. In

  5. Osteoporosis Risk Factors in Eighth Grade Students.

    Science.gov (United States)

    Lysen, Victoria C.; Walker, Robert

    1997-01-01

    Presents findings from food frequency questionnaires and surveys of 138 Midwestern eighth-grade student-parent pairs. The study examined the incidence of modifiable and nonmodifiable osteoporosis risk factors and compared gender differences. Data analysis indicated that many adolescents possessed several modifiable and nonmodifiable risk factors…

  6. Risk Factors for Homelessness Among US Veterans

    Science.gov (United States)

    Tsai, Jack; Rosenheck, Robert A.

    2015-01-01

    Homelessness among US veterans has been a focus of research for over 3 decades. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this is the first systematic review to summarize research on risk factors for homelessness among US veterans and to evaluate the evidence for these risk factors. Thirty-one studies published from 1987 to 2014 were divided into 3 categories: more rigorous studies, less rigorous studies, and studies comparing homeless veterans with homeless nonveterans. The strongest and most consistent risk factors were substance use disorders and mental illness, followed by low income and other income-related factors. There was some evidence that social isolation, adverse childhood experiences, and past incarceration were also important risk factors. Veterans, especially those who served since the advent of the all-volunteer force, were at greater risk for homelessness than other adults. Homeless veterans were generally older, better educated, and more likely to be male, married/have been married, and to have health insurance coverage than other homeless adults. More studies simultaneously addressing premilitary, military, and postmilitary risk factors for veteran homelessness are needed. This review identifies substance use disorders, mental illness, and low income as targets for policies and programs in efforts to end homelessness among veterans. PMID:25595171

  7. Risk factors predisposing to congenital heart defects

    International Nuclear Information System (INIS)

    Ul Haq, Faheem; Jalil, Fatima; Hashmi, Saman; Jumani, Maliha Iqbal; Imdad, Aamer; Jabeen, Mehnaz; Hashmi, Javad Tauseef; Irfan, Furqan Bin; Imran, Muhammad; Atiq, Mehnaz

    2011-01-01

    Congenital heart disease (CHD) is associated with multiple risk factors, consanguinity may be one such significant factor. The role of consanguinity in the etiology of CHD is supported by inbreeding studies, which demonstrate an autosomal recessive pattern of inheritance of some congenital heart defects. This study was done to find out the risk factors for CHD. A case-control study was done on pediatric patients at a tertiary care hospital, Aga Khan University Hospital, located in Karachi, Pakistan. A total of 500 patients, 250 cases and 250 controls were included in the study. Amongst the 250 cases (i.e. those diagnosed with CHD), 122 patients (48.8%) were born of consanguineous marriages while in the controls (i.e. non-CHD) only 72 patients (28.9%) showed a consanguinity amongst parents. On multivariate analysis, consanguinity emerged as an independent risk factor for CHD; adjusted odds ratio 2.59 (95% C. I. 1.73 - 3.87). Other risk factors included low birth weight, maternal co-morbidities, family history of CHD and first born child. On the other hand, medications used by the mother during the index pregnancy, maternal age and gender of the child did not significantly increase the risk of developing CHD. Analyses of our results show that parental consanguinity, family history of CHD, maternal co-morbidities, first born child and low birth weight are independent risk factors for CHD

  8. Significance of platelet-activating factor acetylhydrolase in patients with non-insulin-dependent (type 2) diabetes mellitus.

    Science.gov (United States)

    Serban, M; Tanaseanu, Cristina; Kosaka, T; Vidulescu, Cristina; Stoian, Irina; Marta, Daciana S; Tanaseanu, S; Moldoveanu, Elena

    2002-01-01

    Non-insulin dependent diabetes mellitus (NIDDM) represents an independent risk factor for cardiovascular diseases (CVD), being characterized by a continuous low-grade inflammation and endothelial activation state. Plasma platelet - activating factor - acetylhydrolases (PAF-AHs) are a subgroup of Ca(2+)-independent phospholipase A(2) family (also known as lipoprotein-associated phospholipases A(2)) that hydrolyze and inactivate the lipid mediator platelet-activating factor (PAF) and/or oxidized phospholipids. This enzyme is considered to play an important role in inflammatory diseases and atherosclerosis. The present study aims to investigate the relations between the levels of PAF-AH activity and LDL-cholesterol / HDL-cholesterol (LDL-ch / HDL-ch) ratio in NIDDM patients as compared to controls. serum PAF-AH activity was measured in 50 patients with dyslipidemia, in 50 NIDDM patients and in 50 controls (normal lipid and glucose levels). Total cholesterol, LDL-ch, HDL-ch, triglyceride and blood glucose were determined in all subjects. All NIDDM patients display hiperlipidemia, with increased LDL-ch and triglyceride levels. There is a significant correlation between LDL-ch levels (especially LDL-ch / HDL-ch ratio) and PAF-AH activity in dyslipidemic and NIDDM patients. Diabetic and dyslipidemic patients have an increased plasma PAF-AH activity correlated with their LDL-ch levels and mainly with LDL-ch / HDL-ch ratio. Plasma PAF-AH high levels appear to be important as a risk marker for endothelial dysfunction in patients with NIDDM.

  9. Concentrated insulins: the new basal insulins

    Directory of Open Access Journals (Sweden)

    Lamos EM

    2016-03-01

    Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

  10. Atrial fibrillation and bleeding complication - risk factors and risk marker

    NARCIS (Netherlands)

    Breithardt, G.; Ravens, U.; Kirchhof, P.; van Gelder, I. C.

    2012-01-01

    The development of atrial fibrillation (AF) is closely linked to risk factors like hypertension and heart failure, diabetes mellitus, myocardial infarction and valvular heart disease. These factors partly overlap with those which determine the progression of atrial fibrillation and the incidence of

  11. Metritis in dairy cows: risk factors and reproductive performance.

    Science.gov (United States)

    Giuliodori, M J; Magnasco, R P; Becu-Villalobos, D; Lacau-Mengido, I M; Risco, C A; de la Sota, R L

    2013-06-01

    The objectives of this study were to assess the risk factors for metritis, its effects on milk yield and on reproductive performance, and the efficacy of ceftiofur therapy in Holstein dairy cows. Cows (n=303) from a commercial dairy herd in Argentina were studied. Cows were scored for body condition, and blood samples were collected on d -14, 7, 21, 31, 41, and 50 relative to parturition. Cows having a watery, purulent, or brown, and fetid vaginal discharge (VD) and rectal temperature ≤ 39.2°C were diagnosed as having clinical metritis, and those having a similar VD and rectal temperature >39.2°C were diagnosed as having puerperal metritis. Both clinical and puerperal metritis cows were randomly assigned to control (no treatment) or ceftiofur group (2.2mg/kg×3 consecutive days). Cure was declared if clear VD was observed at 21 d in milk (DIM). Blood samples were analyzed for nonesterified fatty acids, β-hydroxybutyrate, and blood urea nitrogen using commercial kits, and for insulin-like growth factor-1, insulin, and leptin by RIA. Data were analyzed with PROC MIXED, GENMOD, PHREG, and LIFETEST from SAS (SAS Institute Inc., Cary, NC). The risk for metritis increased with dystocia, retained fetal membranes, and dead calf [AOR (adjusted odds ratio)=2.58, 95% CI: 1.189-5.559], and as prepartum nonesterified fatty acids levels increased (AOR=1.001, 95% CI: 0.999-1.002). Conversely, risk decreased as prepartum insulin-like growth factor-1 increased (AOR=0.65, 95% CI: 0.349-1.219). Cows having either clinical or puerperal metritis produced less milk by 90 DIM than did healthy cows (2,236 ± 172 vs. 2,367 ± 77 vs. 2,647 ± 82 kg, respectively). Cows with puerperal metritis had lower risk for pregnancy by 100 DIM (AOR=0.189, 95% CI: 0.070-0.479) and a lower hazard rate for pregnancy by 150 DIM (hazard rate: 0.753, 95% CI: 0.621-0.911), and took longer to get pregnant (129 vs. 111 vs. 109 d, for puerperal metritis, clinical metritis, and healthy cows, respectively

  12. 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.

  13. Insulin Sensitivity and Plasma Glucose Response to Aerobic Exercise in Pregnant Women at Risk for Gestational Diabetes Mellitus.

    Science.gov (United States)

    Embaby, Heba; Elsayed, Enas; Fawzy, Mohamed

    2016-09-01

    Gestational diabetes mellitus (GDM) is one of the common complications that occur during pregnancy. Early intervention is essential to prevent the development of the disease in the non-pregnant state but also helpful in preventing the occurrence of GDM. The aim of the study was to assess the effect of aerobic exercises on insulin sensitivity and fasting plasma glucose level in pregnant women with risk for gestational diabetes mellitus. Forty multigravidae women between 20-24 weeks of gestation with risk for GDM were randomly selected (age range was 25-35 years), body mass index ranged from 30-35 kg/m 2 . Women were divided into two equal groups: intervention group (A), which followed an aerobic exercise program in the form of walking on treadmill, three times weekly until the end of 37 weeks of gestation in addition to diet control. Control group (B) which received diet control with usual care given by obstetricians and midwives. Evaluation of the women in both groups was carried out before and after treatment program through assessment of fasting blood glucose and insulin levels. There was a highly statistically significance decrease in fasting blood glucose level, fasting insulin level in both groups where the p value was 0.0001 favoring group (A). Moderate intensity of aerobic exercises were effective in reducing fasting blood glucose level and fasting insulin level in pregnant women with risk for gestational diabetes mellitus.

  14. Insulin secretion and action in North Indian women during pregnancy.

    Science.gov (United States)

    Arora, G P; Almgren, P; Thaman, R G; Pal, A; Groop, L; Vaag, A; Prasad, R B; Brøns, C

    2017-10-01

    The relative roles(s) of impaired insulin secretion vs. insulin resistance in the development of gestational diabetes mellitus depend upon multiple risk factors and diagnostic criteria. Here, we explored their relative contribution to gestational diabetes as defined by the WHO 1999 (GDM1999) and adapted WHO 2013 (GDM2013) criteria, excluding the 1-h glucose value, in a high-risk Indian population from Punjab. Insulin secretion (HOMA2-B) and insulin action (HOMA2-IR) were assessed in 4665 Indian women with or without gestational diabetes defined by the GDM1999 or adapted GDM2013 criteria. Gestational diabetes defined using both criteria was associated with decreased insulin secretion compared with pregnant women with normal glucose tolerance. Women with gestational diabetes defined by the adapted GDM2013, but not GDM1999 criteria, were more insulin resistant than pregnant women with normal glucose tolerance, and furthermore displayed lower insulin secretion than GDM1999 women. Urban habitat, illiteracy, high age and low BMI were independently associated with reduced insulin secretion, whereas Sikh religion, increasing age and BMI, as well as a family history of diabetes were independently associated with increased insulin resistance. Gestational diabetes risk factors influence insulin secretion and action in North Indian women in a differential manner. Gestational diabetes classified using the adapted GDM2013 compared with GDM1999 criteria is associated with more severe impairments of insulin secretion and action. © 2017 Diabetes UK.

  15. Do insulin cartridges really provide a lower risk of potential diabetes complications than traditional vials?

    Science.gov (United States)

    Al-Sharayri, Mohammad G; Aljbori, Tariq M; Migdadi, Qusai M; Al-Omoush, Marwa B; Jaarah, Ayman R

    2014-09-01

    Recently, many publicly funded healthcare organizations suffered from an economical crisis. This forced some organizations to utilize less costly alternatives where possible. Insulin cartridges and vials are examples. Many patients are questioning the difference between the two alternatives as they contain the same active ingredient. To find out if insulin cartridges really provide a lower risk of potential diabetes complications than traditional vials. A questionnaire was used to ask two random samples of diabetic patients about the development of some diabetes complications. The first sample (n = 41) consisted of patients using cartridges; the second sample (n = 40) consisted of patients using vials. Patients were randomly selected from the endocrine clinic and the out-patient pharmacy in Al-Hussein Hospital in King Hussein Medical Center in Amman- Jordan. 44% of respondents in the first sample did not suffer from any complication; on the other hand, the percentage was only 15% of respondents in the second sample. All respondents (100%) in the first sample suffered from only 2 complications or less; however, 25% of the respondents in the second sample suffered from 3 or more complications. Nephropathy complications, were slightly higher in the first sample; 22% compared to 15% in the second sample. On the other hand, all complications reported in the second sample were higher; 30% for neuropathy, 65% for retinopathy complications and 42.5% for extremities damage compared to only 9.7%, 7.3% and 26.8% respectively in the first sample. In general, respondents who were using cartridges reported a lesser incidence of diabetes complications. Although many organizations suffered from an economical crisis, the cost-effectiveness aspect should be taken into consideration when purchasing medical alternatives. This will provide higher quality of life for patients and eventually lower hidden and future costs for the organizations.

  16. Insulin-Like Growth Factor-1 Inscribes a Gene Expression Profile for Angiogenic Factors and Cancer Progression in Breast Epithelial Cells

    Directory of Open Access Journals (Sweden)

    J.S. Oh

    2002-01-01

    Full Text Available Activation of the insulin-like growth factor-1 receptor (IGF-11R by IGF-1 is associated with the risk and progression of many types of cancer, although despite this it remains unclear how activated IGF-1 R contributes to cancer progression. In this study, gene expression changes elicited by IGF-1 were profiled in breast epithelial cells. We noted that many genes are functionally linked to cancer progression and angiogenesis. To validate some of the changes observed, the RNA and/or protein was confirmed for c-fos, cytochrome P4501Al, cytochrome P450 1131, interleukin-1 beta, fas ligand, vascular endothelial growth factor, and urokinase plasminogen activator. Nuclear proteins were also temporally monitored to address how gene expression changes were regulated. We found that IGF-1 stimulated the nuclear translocation of phosphorylated AKT, hypoxic-inducible factor-1 alpha, and phosphorylated cAMP-responsive element-binding protein, which correlated with temporal changes in gene expression. Next, the promoter regions of IGF-1-regulated genes were searched in silico. The promoters of genes that clustered together had similar regulatory regions. In summary, IGF-1 inscribes a gene expression profile relevant to cancer progression, and this study provides insight into the mechanism(s whereby some of these changes occur.

  17. Modifiable risk factors for schizophrenia and autism--shared risk factors impacting on brain development.

    Science.gov (United States)

    Hamlyn, Jess; Duhig, Michael; McGrath, John; Scott, James

    2013-05-01

    Schizophrenia and autism are two poorly understood clinical syndromes that differ in age of onset and clinical profile. However, recent genetic and epidemiological research suggests that these two neurodevelopmental disorders share certain risk factors. The aims of this review are to describe modifiable risk factors that have been identified in both disorders, and, where available, collate salient systematic reviews and meta-analyses that have examined shared risk factors. Based on searches of Medline, Embase and PsycINFO, inspection of review articles and expert opinion, we first compiled a set of candidate modifiable risk factors associated with autism. Where available, we next collated systematic-reviews (with or without meta-analyses) related to modifiable risk factors associated with both autism and schizophrenia. We identified three modifiable risk factors that have been examined in systematic reviews for both autism and schizophrenia. Advanced paternal age was reported as a risk factor for schizophrenia in a single meta-analysis and as a risk factor in two meta-analyses for autism. With respect to pregnancy and birth complications, for autism one meta-analysis identified maternal diabetes and bleeding during pregnancy as risks factors for autism whilst a meta-analysis of eight studies identified obstetric complications as a risk factor for schizophrenia. Migrant status was identified as a risk factor for both autism and schizophrenia. Two separate meta-analyses were identified for each disorder. Despite distinct clinical phenotypes, the evidence suggests that at least some non-genetic risk factors are shared between these two syndromes. In particular, exposure to drugs, nutritional excesses or deficiencies and infectious agents lend themselves to public health interventions. Studies are now needed to quantify any increase in risk of either autism or schizophrenia that is associated with these modifiable environmental factors. Copyright © 2012 Elsevier Inc

  18. Risk factors in neuroleptic malignant syndrome.

    Science.gov (United States)

    Gupta, Vinay; Magon, Rakesh; Mishra, B P; Sidhu, G B S; Mahajan, Ranjiv

    2003-01-01

    Neuroleptic malignant syndrome (NMS) is an uncommon but potentially serious idiosyncratic response to neuroleptic antipsychotics. It usually affects young males, but the risk has been seen to increase with certain factors including the administration practices of antipsychotic neuroleptics in these individuals. Even though no predictors for NMS are yet known, this article highlights the findings on certain risk factors as seen from a series of fifteen patients who developed NMS. Cautious use of neuroleptics in those at risk, early recognition and institution of immediate management is important.

  19. Epidemiology and risk factors of schizophrenia

    Czech Academy of Sciences Publication Activity Database

    Janoutová, J.; Janáčková, P.; Šerý, Omar; Zeman, T.; Ambrož, P.; Kovalová, M.; Vařechová, K.; Hosák, L.; Jiřík, V.; Janout, V.

    2016-01-01

    Roč. 37, č. 1 (2016), s. 1-8 ISSN 0172-780X R&D Projects: GA MZd NT14504 Institutional support: RVO:67985904 Keywords : schizophrenia * risk factors * epidemiology Subject RIV: FQ - Public Health Care, Social Medicine Impact factor: 0.918, year: 2016

  20. Osteonecrosis. Part 1. Risk factors and pathogenesis

    Directory of Open Access Journals (Sweden)

    Ekaterina Valeriyevna Ilyinykh

    2013-01-01

    Full Text Available The paper considers different risk factors for osteonecrosis (ON and some aspects of its pathogenesis: impairments in the differentiation of stromal cells, the vascular provision of intraand extravasal genesis, the quality of proper bone tissue due to generalized or local osteoporosis, intravascular coagulation factors contributing to microthrombogenesis. The basic types of ON are identified.