Higher fetal insulin resistance in Chinese pregnant women with gestational diabetes mellitus and correlation with maternal insulin resistance.

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Qiuwei Wang

Full Text Available OBJECTIVE: The aim of this study was to determine the effect of gestational diabetes mellitus (GDM on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM. MEASUREMENTS: Maternal fasting blood and venous cord blood samples (reflecting fetal condition were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR and the proinsulin-to-insulin ratios (an indicator of fetal β-cell function were calculated in maternal and cord blood respectively. RESULTS: Both maternal and fetal levels of insulin, proinsulin and HOMA-IR but not proinsulin-to-insulin ratios were significantly higher in the GDM group than in the control group (maternal insulin, 24.8 vs. 15.4 µU/mL, P = 0.004, proinsulin, 23.3 vs. 16.2 pmol/L, P = 0.005, and HOMA-IR, 5.5 vs. 3.5, P = 0.041, respectively; fetal: insulin, 15.1 vs. 7.9 µU/mL, P<0.001, proinsulin, 25.8 vs. 15.1 pmol/L, P = 0.015, and HOMA-IR, 2.8 vs. 1.4, P = 0.017, respectively. Fetal HOMA-IR but not proinsulin-to-insulin ratios was significantly correlated to maternal HOMA-IR (r = 0.307, P = 0.019, in the pregnant women with GDM. CONCLUSIONS: Fetal insulin resistance was higher in Chinese pregnant women with GDM than control subjects, and correlated with maternal insulin resistance.

Fasting glucose, fasting insulin, and insulin resistance in the prediction of myocardial infarction and mortality at long-term follow-up

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Nielsen, M. L.; Pareek, M.; Leosdottir, M.

2015-01-01

Objective: To assess the additional prognostic value of fasting blood glucose (FBG), fasting plasma insulin (FPI), and homeostasis model assessment derived insulin resistance (HOMA-IR) for predicting incident myocardial infarction (MI) and all-cause mortality, independently of traditional...... measured at baseline. Subsequently, HOMA-IR was derived using the computerized HOMA calculator and ranked into quartiles due to the non-normal distribution and presumably non-linear biological effect of insulin resistance. Prognostic values of FBG, FPI, HOMA-IR, and traditional risk factors were tested.......1-48.3] years, whereas median [IQR] HOMA-IR was 0.9 [0.4-1.4]. Over a median follow-up time of 20 years, 1448 events occurred (11.3 per 1000 person-years). The simple prediction model, i.e. the model with traditional CV risk factors only, included age, gender, body mass index, systolic blood pressure, total...

Elevated fasting insulin levels increase the risk of abdominal obesity in Korean men.

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Park, Sung Keun; Oh, Chang-Mo; Jung, Taegi; Choi, Young-Jun; Chung, Ju Youn; Ryoo, Jae-Hong

2017-04-01

This study was designed to investigate whether an elevated fasting insulin level predicts abdominal obesity. A cohort study was conducted with 13,707 non-obese Korean men. They were categorized into 4 groups according to the quartile of fasting insulin level, and followed up from 2005 to 2010. Incidence rates of obesity were compared among the 4 groups during follow-up, and a Cox proportional hazards model was used to calculate hazard ratios (HRs) for abdominal obesity according to fasting insulin level. The overall incidence rate of obesity was 16.2%, but the rate increased in proportion to the fasting insulin level (quartiles 1-4: 9.8%, 12.4%, 16.9%, 25.5%, Pobesity increased proportionally to baseline fasting insulin level in an unadjusted model. However, after adjustment for covariates, including baseline waist circumference (WC), only in the quartile 4 group was the statistical significance of the association maintained [quartile 2-4; abdominal obesity: 0.89 (0.76-1.02), 1.00 (0.86-1.14) and 1.24 (1.08-1.43), P for trend obesity was highest in the group with the highest fasting insulin levels, an overall proportional relationship between fasting insulin level and incident abdominal obesity was not found. Additionally, this association was largely accounted for by baseline WC. Copyright © 2017 Elsevier B.V. All rights reserved.

Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade.

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Pedersen, Morten Høgild; Svart, Mads Vandsted; Lebeck, Janne; Bidlingmaier, Martin; Stødkilde-Jørgensen, Hans; Pedersen, Steen Bønløkke; Møller, Niels; Jessen, Niels; Jørgensen, Jens O L

2017-04-01

Insulin resistance and metabolic inflexibility are features of obesity and are amplified by fasting. Growth hormone (GH) secretion increases during fasting and GH causes insulin resistance. To study the metabolic effects of GH blockade during fasting in obese subjects. Nine obese males were studied thrice in a randomized design: (1) after an overnight fast (control), (2) after 72 hour fasting (fasting), and (3) after 72 hour fasting with GH blockade (pegvisomant) [fasting plus GH antagonist (GHA)]. Each study day consisted of a 4-hour basal period followed by a 2-hour hyperinsulinemic, euglycemic clamp combined with indirect calorimetry, assessment of glucose and palmitate turnover, and muscle and fat biopsies. GH levels increased with fasting (P fasting-induced reduction of serum insulin-like growth factor I was enhanced by GHA (P Fasting increased lipolysis and lipid oxidation independent of GHA, but fasting plus GHA caused a more pronounced suppression of lipid intermediates in response to hyperinsulinemic, euglycemic clamp. Fasting-induced insulin resistance was abrogated by GHA (P Fasting plus GHA also caused elevated glycerol levels and reduced levels of counterregulatory hormones. Fasting significantly reduced the expression of antilipolytic signals in adipose tissue independent of GHA. Suppression of GH activity during fasting in obese subjects reverses insulin resistance and amplifies insulin-stimulated suppression of lipid intermediates, indicating that GH is an important regulator of substrate metabolism, insulin sensitivity, and metabolic flexibility also in obese subjects. Copyright © 2017 by the Endocrine Society

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

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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.

Decreased insulin response in dairy cows following a four-day fast to induce hepatic lipidosis.

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Oikawa, S; Oetzel, G R

2006-08-01

Negative energy balance has been implicated in the development of fatty liver, insulin resistance, and impaired health in dairy cows. A 4-d fasting model previously was reported to increase liver triglycerides more than 2.5-fold. The purpose of the present study was to evaluate insulin response in this fasting model. Nonlactating, nonpregnant Holstein cows were fasted for 4 d (6 cows) or fed continuously as control cows (4 cows). Samples were collected 5 d before fasting, during fasting, and immediately after the 4-d fast, 8 d after the fast, and 16 d after the fast. Fasted cows had greater liver triglyceride content (49.4 vs. 16.2 mg/g, wet-weight basis) at the end of the fasting period compared with control cows. Fasted cows also had increased plasma nonesterified fatty acid (NEFA) concentrations (1.24 vs. 0.21 mmol/L) and increased plasma beta-hydroxybutyrate (BHBA) concentrations at the end of the fasting period. Liver triglyceride, plasma NEFA, and plasma BHBA in fasted cows returned to prefasting concentrations by the end of the experiment. Plasma glucose concentrations were not affected by fasting. Plasma insulin concentrations were decreased (6.3 vs. 14.1 microU/mL) and insulin-stimulated blood glucose reduction was decreased (24.9 vs. 48.6%) in the fasted cows compared with control cows at the end of the fast, indicating reduced insulin response. Insulin response was negatively correlated with plasma NEFA and liver triglycerides. Decreased insulin response may be an important complication of negative energy balance and hepatic lipidosis.

Intermittent fasting reduces body fat but exacerbates hepatic insulin resistance in young rats regardless of high protein and fat diets.

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Park, Sunmin; Yoo, Kyung Min; Hyun, Joo Suk; Kang, Suna

2017-02-01

Intermittent fasting (IMF) is a relatively new dietary approach to weight management, although the efficacy and adverse effects have not been full elucidated and the optimal diets for IMF are unknown. We tested the hypothesis that a one-meal-per-day intermittent fasting with high fat (HF) or protein (HP) diets can modify energy, lipid, and glucose metabolism in normal young male Sprague-Dawley rats with diet-induced obesity or overweight. Male rats aged 5 weeks received either HF (40% fat) or HP (26% protein) diets ad libitum (AL) or for 3 h at the beginning of the dark cycle (IMF) for 5 weeks. Epidydimal fat pads and fat deposits in the leg and abdomen were lower with HP and IMF. Energy expenditure at the beginning of the dark cycle, especially from fat oxidation, was higher with IMF than AL, possibly due to greater activity levels. Brown fat content was higher with IMF. Serum ghrelin levels were higher in HP-IMF than other groups, and accordingly, cumulative food intake was also higher in HP-IMF than HF-IMF. HF-IMF exhibited higher area under the curve (AUC) of serum glucose at the first part (0-40 min) during oral glucose tolerance test, whereas AUC of serum insulin levels in both parts were higher in IMF and HF. During intraperitoneal insulin tolerance test, serum glucose levels were higher with IMF than AL. Consistently, hepatic insulin signaling (GLUT2, pAkt) was attenuated and PEPCK expression was higher with IMF and HF than other groups, and HOMA-IR revealed significantly impaired attenuated insulin sensitivity in the IMF groups. However, surprisingly, hepatic and skeletal muscle glycogen storage was higher in IMF groups than AL. The higher glycogen storage in the IMF groups was associated with the lower expression of glycogen phosphorylase than the AL groups. In conclusion, IMF especially with HF increased insulin resistance, possibly by attenuating hepatic insulin signaling, and lowered glycogen phosphorylase expression despite decreased fat mass in young

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

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

2013-01-01

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

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

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

2015-01-01

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

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

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Yan Yan Chen

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

Association of fasting glucagon and proinsulin concentrations with insulin resistance

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Ferrannini, E; Muscelli, E; Natali, A

2007-01-01

AIMS/HYPOTHESIS: Hyperproinsulinaemia and relative hyperglucagonaemia are features of type 2 diabetes. We hypothesised that raised fasting glucagon and proinsulin concentrations may be associated with insulin resistance (IR) in non-diabetic individuals. METHODS: We measured IR [by a euglycaemic......, controlling for known determinants of insulin sensitivity (i.e. sex, age, BMI and glucose tolerance) as well as factors potentially affecting glucagon and proinsulin (i.e. fasting plasma glucose and C-peptide concentrations), glucagon and proinsulin were still positively associated, and adiponectin...

Cognitively impaired elderly exhibit insulin resistance and no memory improvement with infused insulin.

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Morris, Jill K; Vidoni, Eric D; Mahnken, Jonathan D; Montgomery, Robert N; Johnson, David K; Thyfault, John P; Burns, Jeffrey M

2016-03-01

Insulin resistance is a risk factor for Alzheimer's disease (AD), although its role in AD etiology is unclear. We assessed insulin resistance using fasting and insulin-stimulated measures in 51 elderly subjects with no dementia (ND; n = 37) and with cognitive impairment (CI; n = 14). CI subjects exhibited either mild CI or AD. Fasting insulin resistance was measured using the homeostatic model assessment of insulin resistance (HOMA-IR). Insulin-stimulated glucose disposal was assessed using the hyperinsulinemic-euglycemic clamp to calculate glucose disposal rate into lean mass, the primary site of insulin-stimulated glucose disposal. Because insulin crosses the blood-brain barrier, we also assessed whether insulin infusion would improve verbal episodic memory compared to baseline. Different but equivalent versions of cognitive tests were administered in counterbalanced order in the basal and insulin-stimulated state. Groups did not differ in age or body mass index. Cognitively impaired subjects exhibited greater insulin resistance as measured at fasting (HOMA-IR; ND: 1.09 [1.1] vs. CI: 2.01 [2.3], p = 0.028) and during the hyperinsulinemic clamp (glucose disposal rate into lean mass; ND: 9.9 (4.5) vs. AD 7.2 (3.2), p = 0.040). Cognitively impaired subjects also exhibited higher fasting insulin compared to ND subjects, (CI: 8.7 [7.8] vs. ND: 4.2 [3.8] μU/mL; p = 0.023) and higher fasting amylin (CI: 24.1 [39.1] vs. 8.37 [14.2]; p = 0.050) with no difference in fasting glucose. Insulin infusion elicited a detrimental effect on one test of verbal episodic memory (Free and Cued Selective Reminding Test) in both groups (p insulin resistance was observed in cognitively impaired subjects compared to ND controls, insulin infusion did not improve memory. Furthermore, a significant correlation between HOMA-IR and glucose disposal rate was present only in ND (p = 0.0002) but not in cognitively impaired (p = 0.884) subjects, indicating potentially important

Peripheral blood transcriptomic signatures of fasting glucose and insulin concentrations

NARCIS (Netherlands)

B.H. Chen (Brian); M.-F. Hivert (Marie-France); M.J. Peters (Marjolein); L.C. Pilling (Luke); Hogan, J.D. (John D.); Pham, L.M. (Lisa M.); L.W. Harries (Lorna); C.S. Fox (Caroline); S. Bandinelli (Stefania); A. Dehghan (Abbas); D.G. Hernandez (Dena); A. Hofman (Albert); J. Hong (Jaeyoung); R. Joehanes (Roby); A.D. Johnson (Andrew); P.J. Munson (Peter); D. Rybin (Denis); A. Singleton (Andrew); A.G. Uitterlinden (André); S.-X. Ying (Sai-Xia); D. Melzer (David); D. Levy (Daniel); J.B.J. van Meurs (Joyce); L. Ferrucci (Luigi); J.C. Florez (Jose); J. Dupuis (Josée); J.B. Meigs (James); Kolaczyk, E.D. (Eric D.)

2016-01-01

textabstractGenome-wide association studies (GWAS) have successfully identified genetic loci associated with glycemic traits. However, characterizing the functional significance of these loci has proven challenging. We sought to gain insights into the regulation of fasting insulin and fasting

Higher intramuscular triacylglycerol in women does not impair insulin sensitivity and proximal insulin signaling

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Høeg, Louise; Roepstorff, Carsten; Thiele, Maja

2009-01-01

that despite 47% higher IMTG levels in women in the follicular phase whole body as well as leg insulin sensitivity are higher than in matched men. This was not explained by sex differences in proximal insulin signalling in women. In women it seems that a high capillary density and type 1 muscle fiber...... expression may be important for insulin action. Key words: Muscle Triglycerides, gender, insulin action, sex paradox....

Deleterious effects of omitting breakfast on insulin sensitivity and fasting lipid profiles in healthy lean women.

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Farshchi, Hamid R; Taylor, Moira A; Macdonald, Ian A

2005-02-01

Breakfast consumption is recommended, despite inconclusive evidence of health benefits. The study's aim was to ascertain whether eating breakfast (EB) or omitting breakfast (OB) affects energy intake, energy expenditure, and circulating insulin, glucose, and lipid concentrations in healthy women. In a randomized crossover trial, 10 women [x+/-SD body mass index (BMI; in kg/m2): 23.2+/-1.4] underwent two 14-d EB or OB interventions separated by a 2-wk interval. In the EB period, subjects consumed breakfast cereal with 2%-fat milk before 0800 and a chocolate-covered cookie between 1030 and 1100. In the OB period, subjects consumed the cookie between 1030 and 1100 and the cereal and milk between 1200 and 1330. Subjects then consumed 4 additional meals with content similar to usual at predetermined times later in the day and recorded food intake on 3 d during each period. Fasting and posttest meal glucose, lipid, and insulin concentrations and resting energy expenditure were measured before and after each period. Reported energy intake was significantly lower in the EB period (P=0.001), and resting energy expenditure did not differ significantly between the 2 periods. OB was associated with significantly higher fasting total and LDL cholesterol than was EB (3.14 and 3.43 mmol/L and 1.55 and 1.82 mmol/L, respectively; P=0.001). The area under the curve of insulin response to the test meal was significantly lower after EB than after OB (P<0.01). OB impairs fasting lipids and postprandial insulin sensitivity and could lead to weight gain if the observed higher energy intake was sustained.

Metabolomics reveals differences in postprandial responses to breads and fasting metabolic characteristics associated with postprandial insulin demand in postmenopausal women.

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Moazzami, Ali A; Shrestha, Aahana; Morrison, David A; Poutanen, Kaisa; Mykkänen, Hannu

2014-06-01

Changes in serum metabolic profile after the intake of different food products (e.g., bread) can provide insight into their interaction with human metabolism. Postprandial metabolic responses were compared after the intake of refined wheat (RWB), whole-meal rye (WRB), and refined rye (RRB) breads. In addition, associations between the metabolic profile in fasting serum and the postprandial concentration of insulin in response to different breads were investigated. Nineteen postmenopausal women with normal fasting glucose and normal glucose tolerance participated in a randomized, controlled, crossover meal study. The test breads, RWB (control), RRB, and WRB, providing 50 g of available carbohydrate, were each served as a single meal. The postprandial metabolic profile was measured using nuclear magnetic resonance and targeted LC-mass spectrometry and was compared between different breads using ANOVA and multivariate models. Eight amino acids had a significant treatment effect (P insulin. Women with higher fasting concentrations of leucine and isoleucine and lower fasting concentrations of sphingomyelins and phosphatidylcholines had higher insulin responses despite similar glucose concentration after all kinds of bread (cross-validated ANOVA, P = 0.048). High blood concentration of branched-chain amino acids, i.e., leucine and isoleucine, has been associated with the increased risk of diabetes, which suggests that additional consideration should be given to bread proteins in understanding the beneficial health effects of different kinds of breads. The present study suggests that the fasting metabolic profile can be used to characterize the postprandial insulin demand in individuals with normal glucose metabolism that can be used for establishing strategies for the stratification of individuals in personalized nutrition. © 2014 American Society for Nutrition.

The effect of Ramadan fasting on glycaemic control in insulin dependent diabetic patients: A literature review.

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Alabbood, Majid H; Ho, Kenneth W; Simons, Mary R

Ramadan fasting is one of the five pillars of Islam. People with diabetes are exempted from fasting according to Islamic rules. However, many people with diabetes wish to fast. Physicians are asked frequently by their patients about their ability to fast and the possible impact of fasting on their glycaemic control. Studies about the effect of Ramadan on people with insulin-treated diabetes are scarce. This review aims to provide clinicians with the best recommendations for their patients with insulin-treated diabetes who wish to fast. Four databases (Medline, EMBASE, Scopus and PubMed) were searched using the following MeSH terms and keywords: "insulin dependent diabetes mellitus", "type 1 diabetes mellitus", 'Ramadan' "and" "fasting". In addition, a hand search of key journals and reference lists was performed. Sixteen full text articles were selected for review and critical analysis. All of the included studies except one found improvement or no change in glycaemic control parameters during Ramadan fasting. The incidence of major complications were negligible. Minor hypoglycaemic events were reported in some studies but did not adversely affect fasting. Postprandial hyperglycaemia was a major concern in other studies. However, the incidence of severe hyperglycaemia and diabetic ketoacidosis were trivial. Ramadan fasting is feasible for insulin dependent diabetic patient who wish to fast. Clinicians should advise their patients about the importance of adequate glycaemic control before Ramadan and frequent glucose monitoring during fasting. Certain types of Insulin seem to be more beneficial than other. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Low transferrin saturation is associated with impaired fasting glucose and insulin resistance in the South Korean adults: the 2010 Korean National Health and Nutrition Examination Survey.

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Park, R J; Moon, J D

2015-05-01

The associations of transferrin saturation with diabetes have not been well evaluated and conflicting results have been reported. The purpose of this study is to examine the association of iron indices (serum ferritin and transferrin saturation) with risk of impaired fasting glucose and insulin resistance. We conducted a cross-sectional study in 2413 individuals (1150 men and 1263 women) aged 20-50 years who participated in the 2010 Korean National Health and Nutrition Examination Survey. Participants were free of diabetes, malignancy, liver cirrhosis, chronic renal failure, anaemia, pregnancy and menopause. Fasting plasma glucose, insulin and the homeostasis model assessment of insulin resistance (HOMA-IR) were measured as the outcomes. Impaired fasting glucose was more prevalent in the highest compared with the lowest serum ferritin quartile among men (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.20-3.24) after adjustment for multiple covariates. Following the same adjustment, impaired fasting glucose was less prevalent in the highest compared with the lowest transferrin saturation quartile among men (OR, 0.45; 95% CI, 0.25-0.80) and women (OR, 0.33; 95% CI, 0.14-0.77). Moreover, a higher ferritin level was significantly associated with higher HOMA-IR after adjusting for confounders in men. Lower transferrin saturation was also significantly associated with higher insulin levels and HOMA-IR in both sexes. Lower transferrin saturations were associated with an increased risk of impaired fasting glucose and insulin resistance among general South Korean population. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Effect of intermittent fasting and refeeding on insulin action in healthy men

DEFF Research Database (Denmark)

Halberg, Nils; Henriksen, Morten; Söderhamn, Nathalie

2005-01-01

(mean +/- SE); body mass index: 25.7 +/- 0.4 kg/m(2)] by subjecting them to intermittent fasting every second day for 20 h for 15 days. Euglycemic hyperinsulinemic (40 mU.min(-1).m(-2)) clamps were performed before and after the intervention period. Subjects maintained body weight (86.4 +/- 2.3 kg...... with the basal levels before and after the intervention (5,922 +/- 991 vs. 3,860 +/- 784 ng/ml, P = 0.02). This experiment is the first in humans to show that intermittent fasting increases insulin-mediated glucose uptake rates, and the findings are compatible with the thrifty gene concept.......; coefficient of variation: 0.8 +/- 0.1%). Plasma free fatty acid and beta-hydroxybutyrate concentrations were 347 +/- 18 and 0.06 +/- 0.02 mM, respectively, after overnight fast but increased (P fasting, confirming that the subjects were fasting. Insulin...

The effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women

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Khoshdel, Abolfazl; Kheiri, Soleiman; Nasiri, Jafar; Tehran, Hoda Ahmari; Heidarian, Esfandiar

2014-01-01

Background: Many pregnant Muslim women choose to fast during Ramadan every year worldwide. This study aimed to examine the effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women and find whether fasting during pregnancy could have a negative effect on the health of mothers and fetuses. Methods: This cross-sectional study was conducted on 39 healthy volunteer fasting pregnant women. Serum leptin, neuropeptide Y, insulin levels, body mass index and weight were m...

Evaluation of fasting plasma insulin concentration as an estimate of insulin action in nondiabetic individuals: comparison with the homeostasis model assessment of insulin resistance (HOMA-IR).

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Abbasi, Fahim; Okeke, QueenDenise; Reaven, Gerald M

2014-04-01

Insulin-mediated glucose disposal varies severalfold in apparently healthy individuals, and approximately one-third of the most insulin resistant of these individuals is at increased risk to develop various adverse clinical syndromes. Since direct measurements of insulin sensitivity are not practical in a clinical setting, several surrogate estimates of insulin action have been proposed, including fasting plasma insulin (FPI) concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) calculated by a formula employing fasting plasma glucose (FPG) and FPI concentrations. The objective of this study was to compare FPI as an estimate of insulin-mediated glucose disposal with values generated by HOMA-IR in 758 apparently healthy nondiabetic individuals. Measurements were made of FPG, FPI, triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) concentrations, and insulin-mediated glucose uptake was quantified by determining steady-state plasma glucose (SSPG) concentration during the insulin suppression test. FPI and HOMA-IR were highly correlated (r = 0.98, P HOMA-IR (r = 0.64). Furthermore, the relationship between FPI and TG (r = 0.35) and HDL-C (r = -0.40) was comparable to that between HOMA-IR and TG (r = 0.39) and HDL-C (r = -0.41). In conclusion, FPI and HOMA-IR are highly correlated in nondiabetic individuals, with each estimate accounting for ~40% of the variability (variance) in a direct measure of insulin-mediated glucose disposal. Calculation of HOMA-IR does not provide a better surrogate estimate of insulin action, or of its associated dyslipidemia, than measurement of FPI.

The Comparison of Two Methods of Exercise (intense interval training and concurrent resistance- endurance training on Fasting Sugar, Insulin and Insulin Resistance in Women with Mellitus Diabetes

Directory of Open Access Journals (Sweden)

F Bazyar

2016-05-01

Full Text Available Background & aim: Exercise is an important component of health and an integral approach to the management of diabetes mellitus. The purpose of this study was to compare the effects of intense interval training and concurrent resistance- endurance training on fasting sugar, insulin and insulin resistance in women with mellitus diabetes.   Methods: Fifty-two overweight female diabetic type 2 patients (aged 45-60 years old with fasting blood glucose≥ 126 mg/dl were selected to participate in the present study. Participants were assigned to intense interval training group (N=17, concurrent resistance- endurance training group (N=17 and control group (N=18. The exercises incorporated 10 weeks of concurrent resistance- endurance training and intense interval training. Fasting blood sugar, serum insulin concentrations levels were measured. Concurrent training group trained eight weeks, three times a week of endurance training at 60% of maximum heart rate (MHR and two resistance training sessions per week with 70% of one repetition maximum (1-RM. Intense interval training group trained for eight weeks, three sessions per week for 4 to 10 repeats Wingate test on the ergometer 30s performed with maximum effort. The control group did no systematic exercise. At the end of experiment 42 subjects were succeed and completed the study period, and 10 subjects were removed due to illness and absence in the exercise sessions. Fasting blood sugar and insulin levels 24 hours before and 48 hours after the last training session was measured.   Results: The findings indicated that in periodic fasting, the blood sugar in intensive training group had a marked decrease (p= 0.000 however, the fasting blood sugar of exercise and power stamina groups reduced significantly (p=0.062. The results showed no significant difference between the groups (171/0 p =0.171. Fasting insulin (p <0.001 and insulin resistance (0001/0 = p=0.001 in periodic intensive training group were

Knockdown of angiopoietin-like 2 mimics the benefits of intermittent fasting on insulin responsiveness and weight loss.

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Martel, Cécile; Pinçon, Anthony; Bélanger, Alexandre Maxime; Luo, Xiaoyan; Gillis, Marc-Antoine; de Montgolfier, Olivia; Thorin-Trescases, Nathalie; Thorin, Éric

2018-01-01

Angiopoietin-like 2 (ANGPTL2) is an inflammatory adipokine linking obesity to insulin resistance. Intermittent fasting, on the other hand, is a lifestyle intervention able to prevent obesity and diabetes but difficult to implement and maintain. Our objectives were to characterize a link between ANGPTL2 and intermittent fasting and to investigate whether the knockdown of ANGPTL2 reproduces the benefits of intermittent fasting on weight gain and insulin responsiveness in knockdown and wild-type littermates mice. Intermittent fasting, access to food ad libitum once every other day, was initiated at the age of three months and maintained for four months. Intermittent fasting decreased by 63% (p < 0.05) gene expression of angptl2 in adipose tissue of wild-type mice. As expected, intermittent fasting improved insulin sensitivity (p < 0.05) and limited weight gain (p < 0.05) in wild-type mice. Knockdown mice fed ad libitum, however, were comparable to wild-type mice following the intermittent fasting regimen: insulin sensitivity and weight gain were identical, while intermittent fasting had no additional impact on these parameters in knockdown mice. Energy intake was similar between both wild-type fed intermittent fasting and ANGPTL2 knockdown mice fed ad libitum, suggesting that intermittent fasting and knockdown of ANGPTL2 equally lower feeding efficiency. These results suggest that the reduction of ANGPTL2 could be a useful and promising strategy to prevent obesity and insulin resistance, although further investigation of the mechanisms linking ANGPTL2 and intermittent fasting is warranted. Impact statement Intermittent fasting is an efficient diet pattern to prevent weight gain and improve insulin sensitivity. It is, however, a difficult regimen to follow and compliance is expected to be very low. In this work, we demonstrate that knockdown of ANGPTL2 in mice fed ad libitum mimics the beneficial effects of intermittent fasting on weight gain and insulin

Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups

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Soñanez-Organis, José G.; Viscarra, Jose A.; Jaques, John T.; MacKenzie, Duncan S.; Crocker, Daniel E.; Ortiz, Rudy M.

2016-01-01

Prolonged food deprivation in mammals typically reduces glucose, insulin, and thyroid hormone (TH) concentrations, as well as tissue deiodinase (DI) content and activity, which, collectively, suppress metabolism. However, in elephant seal pups, prolonged fasting does not suppress TH levels; it is associated with upregulation of adipose TH-mediated cellular mechanisms and adipose-specific insulin resistance. The functional relevance of this apparent paradox and the effects of glucose and insulin on TH-mediated signaling in an insulin-resistant tissue are not well defined. To address our hypothesis that insulin increases adipose TH signaling in pups during extended fasting, we assessed the changes in TH-associated genes in response to an insulin infusion in early- and late-fasted pups. In late fasting, insulin increased DI1, DI2, and THrβ-1 mRNA expression by 566%, 44%, and 267% at 60 min postinfusion, respectively, with levels decreasing by 120 min. Additionally, we performed a glucose challenge in late-fasted pups to differentiate between insulin- and glucose-mediated effects on TH signaling. In contrast to the insulin-induced effects, glucose infusion did not increase the expressions of DI1, DI2, and THrβ-1 until 120 min, suggesting that glucose delays the onset of the insulin-induced effects. The data also suggest that fasting duration increases the sensitivity of adipose TH-mediated mechanisms to insulin, some of which may be mediated by increased glucose. These responses appear to be unique among mammals and to have evolved in elephant seals to facilitate their adaptation to tolerate an extreme physiological condition. PMID:26739649

Fast-food habits, weight gain, and insulin resistance (the CARDIA study): 15-year prospective analysis.

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Pereira, Mark A; Kartashov, Alex I; Ebbeling, Cara B; Van Horn, Linda; Slattery, Martha L; Jacobs, David R; Ludwig, David S

Fast-food consumption has increased greatly in the USA during the past three decades. However, the effect of fast food on risk of obesity and type 2 diabetes has received little attention. We aimed to investigate the association between reported fast-food habits and changes in bodyweight and insulin resistance over a 15-year period in the USA. Participants for the CARDIA study included 3031 young (age 18-30 years in 1985-86) black and white adults who were followed up with repeated dietary assessment. We used multiple linear regression models to investigate the association of frequency of fast-food restaurant visits (fast-food frequency) at baseline and follow-up with 15-year changes in bodyweight and the homoeostasis model (HOMA) for insulin resistance. Fast-food frequency was lowest for white women (about 1.3 times per week) compared with the other ethnic-sex groups (about twice a week). After adjustment for lifestyle factors, baseline fast-food frequency was directly associated with changes in bodyweight in both black (p=0.0050) and white people (p=0.0013). Change in fast-food frequency over 15 years was directly associated with changes in bodyweight in white individuals (pfast-food restaurant use at baseline and follow-up (n=203), those with frequent (more than twice a week) visits to fast-food restaurants at baseline and follow-up (n=87) gained an extra 4.5 kg of bodyweight (p=0.0054) and had a two-fold greater increase in insulin resistance (p=0.0083). Fast-food consumption has strong positive associations with weight gain and insulin resistance, suggesting that fast food increases the risk of obesity and type 2 diabetes.

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

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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.

Diminished hepatic insulin removal in obesity

International Nuclear Information System (INIS)

Cano, I.; Salvador, J.; Rodriguez, R.; Arraiza, M.C.; Goena, M.; Barberia, J.J.; Moncada, E.

1986-01-01

Peripheral insulin and C-peptide levels during oral glucose load were measured in 20 obese and 23 normal weight nondiabetic subjects. The fasting C-peptide to insulin molar ratios (Cp/I), as well as the relation between incremental areas of the two polypeptides (ACp-AI)/ACp, were used as relative measures of the hepatic insulin extraction (HIE). The insulin and C-peptide basal levels as well as incremental areas under plasma curves were higher in the obese subjects (P<0.001). HIE was lower in obeses than in controls assessed in the fasting state (P<0.05), as well as after glucose load (P<0.001). Nevertheless, obeses and controls with similar insulin fasting levels showed identical hepatic insulin extraction in fasting or after glucose load. HIE was independent of obesity degree, but was related to insulin basal levels (r=-0.60, P<0.01). This study suggests the hypothesis that the decreased hepatic insulin extraction in obeses is a result of the chronically increased insulin delivery to the liver and is not a consequence of obesity, although a contributory role cannot be ruled out

Diminished hepatic insulin removal in obesity

Energy Technology Data Exchange (ETDEWEB)

Cano, I; Salvador, J; Rodriguez, R; Arraiza, M C; Goena, M; Barberia, J J; Moncada, E

1986-01-01

Peripheral insulin and C-peptide levels during oral glucose load were measured in 20 obese and 23 normal weight nondiabetic subjects. The fasting C-peptide to insulin molar ratios (Cp/I), as well as the relation between incremental areas of the two polypeptides (ACp-AI)/ACp, were used as relative measures of the hepatic insulin extraction (HIE). The insulin and C-peptide basal levels as well as incremental areas under plasma curves were higher in the obese subjects (P<0.001). HIE was lower in obeses than in controls assessed in the fasting state (P<0.05), as well as after glucose load (P<0.001). Nevertheless, obeses and controls with similar insulin fasting levels showed identical hepatic insulin extraction in fasting or after glucose load. HIE was independent of obesity degree, but was related to insulin basal levels (r=-0.60, P<0.01). This study suggests the hypothesis that the decreased hepatic insulin extraction in obeses is a result of the chronically increased insulin delivery to the liver and is not a consequence of obesity, although a contributory role cannot be ruled out.

Higher fasting glucose is associated with poorer cognition among healthy young adults.

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Hawkins, Misty A W; Gunstad, John; Calvo, Dayana; Spitznagel, Mary Beth

2016-02-01

Obesity is associated with cognitive deficits; however, the mechanisms are unclear, especially among otherwise healthy adults. Our objectives were to examine (a) whether obesity is linked to elevations in fasting glucose and (b) whether these elevations are associated with cognitive impairment among otherwise healthy young adults. Participants were 35 normal weight adults and 35 young adults with obesity who completed a task from the Automated Neuropsychological Assessment Metrics-4 (ANAM-4). Measured body mass index (BMI) and fasting blood glucose levels (mg/dL) were examined. Persons with obesity had higher fasting glucose levels than normal weight persons (p = .03). After applying Bonferroni correction for multiple tests, higher fasting glucose predicted less accurate performance on tests of inhibitory control: Go/No-Go Commission Errors (β = .33, p = .004). No effects were observed for sustained attention or working memory (ps ≥. 049). Persons with glucose levels in the prediabetes range had nearly twice as many errors as those with normal glucose, a large effect that was independent of BMI. Young adults who were obese but otherwise healthy had higher fasting glucose levels compared with normal weight peers. Higher glucose levels were associated with poorer cognitive performance on tests of inhibitory control, especially among individuals with prediabetes levels. Thus, subclinical elevations in blood glucose may contribute to cognitive impairment and, ultimately, greater impulsivity-well in advance of the development of chronic disease states (e.g., insulin resistance or Type 2 diabetes) and independently of excess adiposity--though prospective studies are needed to determine directionality of this relationship. (c) 2016 APA, all rights reserved).

The effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women.

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Khoshdel, Abolfazl; Kheiri, Soleiman; Nasiri, Jafar; Tehran, Hoda Ahmari; Heidarian, Esfandiar

2014-01-01

Many pregnant Muslim women choose to fast during Ramadan every year worldwide. This study aimed to examine the effect of Ramadan fasting on serum leptin, neuropeptide Y and insulin in pregnant women and find whether fasting during pregnancy could have a negative effect on the health of mothers and fetuses. This cross-sectional study was conducted on 39 healthy volunteer fasting pregnant women. Serum leptin, neuropeptide Y, insulin levels, body mass index and weight were measured five times on 0, 7th, 14th and 28th days of Ramadan and on the 14th day post-Ramadan. The data were analyzed by SPSS software (version 11.5) using repeated measures ANOVA to find whether any changes occurred in the variables of interest during the study, and Pearson correlation coefficient was used to examine the relations among the variables. A significant change in fasting blood sugar, neuropeptide Y and leptin was observed during the study (pRamadan and increased after Ramadan, with the lowest value at the end of Ramadan. Neuropeptide Y increased both during Ramadan and two weeks after Ramadan. Also, leptin decreased significantly two weeks after Ramadan compared to the end of Ramadan. No significant change was observed in insulin level during the study (p>0.05). The result of this study revealed the important role of leptin and neuropeptide Y in the long term regulation of energy balance in pregnant women with chronic diurnal fasting, and it further revealed that Ramadan fasting did not significantly change the serum insulin level.

Evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.

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Silke A Herzberg-Schäfer

Full Text Available BACKGROUND: To date, fasting state- and different oral glucose tolerance test (OGTT-derived measures are used to estimate insulin release with reasonable effort in large human cohorts required, e.g., for genetic studies. Here, we evaluated twelve common (or recently introduced fasting state-/OGTT-derived indices for their suitability to detect genetically determined β-cell dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: A cohort of 1364 White European individuals at increased risk for type 2 diabetes was characterized by OGTT with glucose, insulin, and C-peptide measurements and genotyped for single nucleotide polymorphisms (SNPs known to affect glucose- and incretin-stimulated insulin secretion. One fasting state- and eleven OGTT-derived indices were calculated and statistically evaluated. After adjustment for confounding variables, all tested SNPs were significantly associated with at least two insulin secretion measures (p≤0.05. The indices were ranked according to their associations' statistical power, and the ranks an index obtained for its associations with all the tested SNPs (or a subset were summed up resulting in a final ranking. This approach revealed area under the curve (AUC(Insulin(0-30/AUC(Glucose(0-30 as the best-ranked index to detect SNP-dependent differences in insulin release. Moreover, AUC(Insulin(0-30/AUC(Glucose(0-30, corrected insulin response (CIR, AUC(C-Peptide(0-30/AUC(Glucose(0-30, AUC(C-Peptide(0-120/AUC(Glucose(0-120, two different formulas for the incremental insulin response from 0-30 min, i.e., the insulinogenic indices (IGI(2 and IGI(1, and insulin 30 min were significantly higher-ranked than homeostasis model assessment of β-cell function (HOMA-B; p<0.05. AUC(C-Peptide(0-120/AUC(Glucose(0-120 was best-ranked for the detection of SNPs involved in incretin-stimulated insulin secretion. In all analyses, HOMA-β displayed the highest rank sums and, thus, scored last. CONCLUSIONS/SIGNIFICANCE: With AUC(Insulin(0

Higher Fetal Insulin Resistance in Chinese Pregnant Women with Gestational Diabetes Mellitus and Correlation with Maternal Insulin Resistance

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Wang, Qiuwei; Huang, Ruiping; Yu, Bin; Cao, Fang; Wang, Huiyan; Zhang, Ming; Wang, Xinhong; Zhang, Bin; Zhou, Hong; Zhu, Ziqiang

2013-01-01

OBJECTIVE: The aim of this study was to determine the effect of gestational diabetes mellitus (GDM) on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM. MEASUREMENTS: Maternal fasting blood and venous cord blood samples (reflecting fetal condition) were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention) and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measur...

Fasting triglycerides as a predictor of incident diabetes, insulin resistance and β-cell function in a Canadian First Nation.

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Riediger, Natalie D; Clark, Kirsten; Lukianchuk, Virginia; Roulette, Joanne; Bruce, Sharon

2017-01-01

Diabetes prevalence is substantially higher among Canadian First Nations populations than the non-First Nation population. Fasting serum triglycerides have been found to be an important predictor of incident diabetes among non-indigenous populations. However, there is a great need to understand diabetes progression within specific ethnic groups, particularly First Nations populations. The purpose of this study was to test for an association between fasting serum triglycerides and incident diabetes, changes in insulin resistance and changes in β-cell function in a Manitoba First Nation cohort. Study data were from two diabetes screening studies in Sandy Bay First Nation in Manitoba, Canada, collected in 2002/2003 and 2011/2012. The cohort was composed of respondents to both screening studies (n=171). Fasting blood samples and anthropometric, health and demographic data were collected. A generalised linear model with Poisson distribution was used to test for an association between fasting triglycerides and incident diabetes. There were 35 incident cases of diabetes among 128 persons without diabetes at baseline. Participants who developed incident type 2 diabetes were significantly older and had significantly higher body mass index (BMI; p=0.012), total cholesterol (p=0.007), fasting triglycerides (ptriglyceride level was found to be a statistically significant positive predictor of incident diabetes independent of age, sex and waist circumference at baseline. Participants with triglycerides in the highest tertile (≥2.11 mmol/l) had a 4.0-times higher risk of developing incident diabetes compared to those in the lowest tertile (p=0.03). Notably, neither waist circumference nor BMI were significant predictors of incident diabetes independent of age, sex and triglycerides. Fasting triglycerides may be useful as a clinical predictor of insulin resistance and diabetes development among First Nations populations. Unlike other ethnic groups, BMI and waist circumference

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

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

2015-01-01

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

Prevalence of Non-responders for Glucose Control Markers after 10 Weeks of High-Intensity Interval Training in Adult Women with Higher and Lower Insulin Resistance

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Cristian Álvarez

2017-07-01

Full Text Available Background: Exercise training improves performance and biochemical parameters on average, but wide interindividual variability exists, with individuals classified as responders (R or non-responders (NRs, especially between populations with higher or lower levels of insulin resistance. This study assessed the effects of high-intensity interval training (HIIT and the prevalence of NRs in adult women with higher and lower levels of insulin resistance.Methods: Forty adult women were assigned to a HIIT program, and after training were analyzed in two groups; a group with higher insulin resistance (H-IR, 40 ± 6 years; BMI: 29.5 ± 3.7 kg/m2; n = 20 and a group with lower insulin resistance (L-IR, 35 ± 9 years; 27.8 ± 2.8 kg/m2; n = 20. Anthropometric, cardiovascular, metabolic, and performance variables were measured at baseline and after 10 weeks of training.Results: There were significant training-induced changes [delta percent (Δ%] in fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR scores in the H-IR group (−8.8, −26.5, −32.1%, p < 0.0001, whereas no significant changes were observed in the L-IR. Both groups showed significant pre-post changes in other anthropometric variables [waist circumference (−5.2, p < 0.010, and −3.8%, p = 0.046 and tricipital (−13.3, p < 0.010, and −13.6%, p < 0.0001, supra-iliac (−19.4, p < 0.0001, and −13.6%, p < 0.0001, and abdominal (−18.2, p < 0.0001, and −15.6%, p < 0.010 skinfold measurements]. Systolic blood pressure decreased significantly only in the L-IR group (−3.2%, p < 0.010. Both groups showed significant increases in 1RMLE (+12.9, p < 0.010, and +14.7%, p = 0.045. There were significant differences in the prevalence of NRs between the H-IR and L-IR groups for fasting glucose (25 vs. 95%, p < 0.0001 and fasting insulin (p = 0.025 but not for HOMA-IR (25 vs. 45%, p = 0.185.Conclusion: Independent of the “magnitude” of the

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

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Manning, Alisa K.; Hivert, Marie-France; Scott, Robert A.; Grimsby, Jonna L.; Bouatia-Naji, Nabila; Chen, Han; Rybin, Denis; Liu, Ching-Ti; Bielak, Lawrence F.; Prokopenko, Inga; Amin, Najaf; Barnes, Daniel; Cadby, Gemma; Hottenga, Jouke-Jan; Ingelsson, Erik; Jackson, Anne U.; Johnson, Toby; Kanoni, Stavroula; Ladenvall, Claes; Lagou, Vasiliki; Lahti, Jari; Lecoeur, Cecile; Liu, Yongmei; Martinez-Larrad, Maria Teresa; Montasser, May E.; Navarro, Pau; Perry, John R. B.; Rasmussen-Torvik, Laura J.; Salo, Perttu; Sattar, Naveed; Shungin, Dmitry; Strawbridge, Rona J.; Tanaka, Toshiko; van Duijn, Cornelia M.; An, Ping; de Andrade, Mariza; Andrews, Jeanette S.; Aspelund, Thor; Atalay, Mustafa; Aulchenko, Yurii; Balkau, Beverley; Bandinelli, Stefania; Beckmann, Jacques S.; Beilby, John P.; Bellis, Claire; Bergman, Richard N.; Blangero, John; Boban, Mladen; Boehnke, Michael; Boerwinkle, Eric; Bonnycastle, Lori L.; Boomsma, Dorret I.; Borecki, Ingrid B.; Böttcher, Yvonne; Bouchard, Claude; Brunner, Eric; Budimir, Danijela; Campbell, Harry; Carlson, Olga; Chines, Peter S.; Clarke, Robert; Collins, Francis S.; Corbatón-Anchuelo, Arturo; Couper, David; de Faire, Ulf; Dedoussis, George V; Deloukas, Panos; Dimitriou, Maria; Egan, Josephine M; Eiriksdottir, Gudny; Erdos, Michael R.; Eriksson, Johan G.; Eury, Elodie; Ferrucci, Luigi; Ford, Ian; Forouhi, Nita G.; Fox, Caroline S; Franzosi, Maria Grazia; Franks, Paul W; Frayling, Timothy M; Froguel, Philippe; Galan, Pilar; de Geus, Eco; Gigante, Bruna; Glazer, Nicole L.; Goel, Anuj; Groop, Leif; Gudnason, Vilmundur; Hallmans, Göran; Hamsten, Anders; Hansson, Ola; Harris, Tamara B.; Hayward, Caroline; Heath, Simon; Hercberg, Serge; Hicks, Andrew A.; Hingorani, Aroon; Hofman, Albert; Hui, Jennie; Hung, Joseph; Jarvelin, Marjo Riitta; Jhun, Min A.; Johnson, Paul C.D.; Jukema, J Wouter; Jula, Antti; Kao, W.H.; Kaprio, Jaakko; Kardia, Sharon L. R.; Keinanen-Kiukaanniemi, Sirkka; Kivimaki, Mika; Kolcic, Ivana; Kovacs, Peter; Kumari, Meena; Kuusisto, Johanna; Kyvik, Kirsten Ohm; Laakso, Markku; Lakka, Timo; Lannfelt, Lars; Lathrop, G Mark; Launer, Lenore J.; Leander, Karin; Li, Guo; Lind, Lars; Lindstrom, Jaana; Lobbens, Stéphane; Loos, Ruth J. F.; Luan, Jian’an; Lyssenko, Valeriya; Mägi, Reedik; Magnusson, Patrik K. E.; Marmot, Michael; Meneton, Pierre; Mohlke, Karen L.; Mooser, Vincent; Morken, Mario A.; Miljkovic, Iva; Narisu, Narisu; O’Connell, Jeff; Ong, Ken K.; Oostra, Ben A.; Palmer, Lyle J.; Palotie, Aarno; Pankow, James S.; Peden, John F.; Pedersen, Nancy L.; Pehlic, Marina; Peltonen, Leena; Penninx, Brenda; Pericic, Marijana; Perola, Markus; Perusse, Louis; Peyser, Patricia A; Polasek, Ozren; Pramstaller, Peter P.; Province, Michael A.; Räikkönen, Katri; Rauramaa, Rainer; Rehnberg, Emil; Rice, Ken; Rotter, Jerome I.; Rudan, Igor; Ruokonen, Aimo; Saaristo, Timo; Sabater-Lleal, Maria; Salomaa, Veikko; Savage, David B.; Saxena, Richa; Schwarz, Peter; Seedorf, Udo; Sennblad, Bengt; Serrano-Rios, Manuel; Shuldiner, Alan R.; Sijbrands, Eric J.G.; Siscovick, David S.; Smit, Johannes H.; Small, Kerrin S.; Smith, Nicholas L.; Smith, Albert Vernon; Stančáková, Alena; Stirrups, Kathleen; Stumvoll, Michael; Sun, Yan V.; Swift, Amy J.; Tönjes, Anke; Tuomilehto, Jaakko; Trompet, Stella; Uitterlinden, Andre G.; Uusitupa, Matti; Vikström, Max; Vitart, Veronique; Vohl, Marie-Claude; Voight, Benjamin F.; Vollenweider, Peter; Waeber, Gerard; Waterworth, Dawn M; Watkins, Hugh; Wheeler, Eleanor; Widen, Elisabeth; Wild, Sarah H.; Willems, Sara M.; Willemsen, Gonneke; Wilson, James F.; Witteman, Jacqueline C.M.; Wright, Alan F.; Yaghootkar, Hanieh; Zelenika, Diana; Zemunik, Tatijana; Zgaga, Lina; Wareham, Nicholas J.; McCarthy, Mark I.; Barroso, Ines; Watanabe, Richard M.; Florez, Jose C.; Dupuis, Josée; Meigs, James B.; Langenberg, Claudia

2013-01-01

Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction, but contributed little to our understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways may be uncovered by accounting for differences in body mass index (BMI) and potential interaction between BMI and genetic variants. We applied a novel joint meta-analytical approach to test associations with fasting insulin (FI) and glucose (FG) on a genome-wide scale. We present six previously unknown FI loci at P<5×10−8 in combined discovery and follow-up analyses of 52 studies comprising up to 96,496non-diabetic individuals. Risk variants were associated with higher triglyceride and lower HDL cholesterol levels, suggestive of a role for these FI loci in insulin resistance pathways. The localization of these additional loci will aid further characterization of the role of insulin resistance in T2D pathophysiology. PMID:22581228

In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

DEFF Research Database (Denmark)

Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R

2005-01-01

In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... endogenous insulin secretion, which was estimated by deconvolution of C-peptide concentrations. Hepatic extraction of insulin was calculated as 1 minus the ratio of fasting posthepatic insulin delivery rate to fasting endogenous insulin secretion rate. Compared with controls, LIPO displayed increased fasting...... insulin (130%, P Hepatic extraction of insulin was similar between groups (LIPO, 55%; controls, 57%; P > .8). In LIPO, HEXi and MCRi correlated inversely with fasting insulin (r = -0.56, P

Serum cortisol level and its correlation to serum insulin and fasting blood sugar levels in patients with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Chen Jianzhong; Zhang Jun

2004-01-01

Objective: To investigate the change of serum cortisol levels and its correlation to blood sugar and serum insulin levels in patients with type 2 diabetes mellitus. Methods: Blood sugar with oxidase method and serum cortisol insulin levels with RIA (8 AM fasting specimen) were measured in 26 patients with type 2 diabetes mellitus and 30 controls. Results: The serum cortisol levels in the diabetic patients were significantly higher than those in the controls (P<0.01). The cortisol levels were positively correlated to the blood sugar levels (r=0.32, p<0.01), but not correlated to insulin levels. Conclusion: There were cortisol secretion disturbances in patients with type 2 diabetes

Relationship between blood pressure and insulin resistance in patients with gestational diabetes

International Nuclear Information System (INIS)

Kan Shujuan; Zhang Sujuan

2008-01-01

Objective: To study the relationship existe between blood pressure level and degree of insulin resistance in patients with gestational diabetes. Methods: Ninety-five cases of gestational diabetes were diagnosed among 350 pregnant women. Of them, 55 were found to be hypertensive and 40 were normotensive. Fasting, 1,2, 3h post-prandial (75g glucose) blood sugar (with peroxidase method) levels and fasting insulin (with RIA) levels were measured in these patients and 85 normal pregnant women (as control). Results: Fasting, 1, 2, 3h post 75g glucose blood sugar and fasting insulin levels in the 55 hypertensive diabetics were significantly higher than those in the normotensives and controls (P<0.05). The calculated insulin sensitivity indices were significantly lower (P also < 0.05). Conclusion: A higher insulin resistance existed in hypertensive gestational diabetics which might be a risk factor of developing hypertension. (authors)

Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.

Science.gov (United States)

Nettleton, Jennifer A; McKeown, Nicola M; Kanoni, Stavroula; Lemaitre, Rozenn N; Hivert, Marie-France; Ngwa, Julius; van Rooij, Frank J A; Sonestedt, Emily; Wojczynski, Mary K; Ye, Zheng; Tanaka, Tosh; Garcia, Melissa; Anderson, Jennifer S; Follis, Jack L; Djousse, Luc; Mukamal, Kenneth; Papoutsakis, Constantina; Mozaffarian, Dariush; Zillikens, M Carola; Bandinelli, Stefania; Bennett, Amanda J; Borecki, Ingrid B; Feitosa, Mary F; Ferrucci, Luigi; Forouhi, Nita G; Groves, Christopher J; Hallmans, Goran; Harris, Tamara; Hofman, Albert; Houston, Denise K; Hu, Frank B; Johansson, Ingegerd; Kritchevsky, Stephen B; Langenberg, Claudia; Launer, Lenore; Liu, Yongmei; Loos, Ruth J; Nalls, Michael; Orho-Melander, Marju; Renstrom, Frida; Rice, Kenneth; Riserus, Ulf; Rolandsson, Olov; Rotter, Jerome I; Saylor, Georgia; Sijbrands, Eric J G; Sjogren, Per; Smith, Albert; Steingrímsdóttir, Laufey; Uitterlinden, André G; Wareham, Nicholas J; Prokopenko, Inga; Pankow, James S; van Duijn, Cornelia M; Florez, Jose C; Witteman, Jacqueline C M; Dupuis, Josée; Dedoussis, George V; Ordovas, Jose M; Ingelsson, Erik; Cupples, L Adrienne; Siscovick, David S; Franks, Paul W; Meigs, James B

2010-12-01

Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.

Thermogenesis induced by a high-carbohydrate meal in fasted lean and overweight young men: insulin, body fat, and sympathetic nervous system involvement.

Science.gov (United States)

Marques-Lopes, Iva; Forga, Luis; Martínez, J Alfredo

2003-01-01

This dietary trial was designed to evaluate the effect of an experimental short-term fasting period followed by a high-carbohydrate meal on energy expenditure, thermogenesis, and sympathetic nervous system activity in normal (body mass index 27 kg/m(2)) men who were healthy, non-diabetic or with no other endocrine disease, non-smokers, not taking oral prescription medications, and with a stable body weight for the previous 3 mo. Fasting and fed energy expenditures and diet-induced thermogenesis were measured after a high-carbohydrate meal in seven overweight and six lean young male subjects by indirect calorimetry. Heart rate, urinary excretion of catecholamines, serum glucose, and insulin were also measured over the experimental fasting (7.5 h) and postprandial (4 h) periods. After carbohydrate intake, overweight men showed a significantly higher energy production (kJ/kg of fat-free mass) than did lean individuals, and the diet-induced thermogenesis (percentage of energy intake) was positively correlated with body fat (kg), percentage of body fat, fat-free mass (kg), and fasting pre-meal serum insulin levels. Postprandial cumulative energy expenditure was directly associated with postprandial insulin response and with mean postprandial heart rate values. No significant differences in urinary catecholamines were found between lean and overweight men at basal conditions or during the study period. Overweight individuals showed similar short-term sympathetic nervous system responses induced by an experimental fasting period. Although diet-induced thermogenesis after carbohydrate intake was not statistically different between lean and overweight men, the postprandial insulin response and body fat content seemed to be involved in sympathetic nervous system activity.

Comparison of a carbohydrate-free diet vs. fasting on plasma glucose, insulin and glucagon in type 2 diabetes.

Science.gov (United States)

Nuttall, Frank Q; Almokayyad, Rami M; Gannon, Mary C

2015-02-01

Hyperglycemia improves when patients with type 2 diabetes are placed on a weight-loss diet. Improvement typically occurs soon after diet implementation. This rapid response could result from low fuel supply (calories), lower carbohydrate content of the weight-loss diet, and/or weight loss per se. To differentiate these effects, glucose, insulin, C-peptide and glucagon were determined during the last 24 h of a 3-day period without food (severe calorie restriction) and a calorie-sufficient, carbohydrate-free diet. Seven subjects with untreated type 2 diabetes were studied. A randomized-crossover design with a 4-week washout period between arms was used. Results from both the calorie-sufficient, carbohydrate-free diet and the 3-day fast were compared with the initial standard diet consisting of 55% carbohydrate, 15% protein and 30% fat. The overnight fasting glucose concentration decreased from 196 (standard diet) to 160 (carbohydrate-free diet) to 127 mg/dl (fasting). The 24 h glucose and insulin area responses decreased by 35% and 48% on day 3 of the carbohydrate-free diet, and by 49% and 69% after fasting. Overnight basal insulin and glucagon remained unchanged. Short-term fasting dramatically lowered overnight fasting and 24 h integrated glucose concentrations. Carbohydrate restriction per se could account for 71% of the reduction. Insulin could not entirely explain the glucose responses. In the absence of carbohydrate, the net insulin response was 28% of the standard diet. Glucagon did not contribute to the metabolic adaptations observed. Published by Elsevier Inc.

Hyperinsulinemia in the physiologic range is not superior to short-term fasting in suppressing insulin secretion in obese men.

Science.gov (United States)

Pincelli, A I; Brunani, A; Caumo, A; Scacchi, M; Pasqualinotto, L; Tibaldi, A; Dubini, A; Bonadonna, S; Cavagnini, F

2001-01-01

The negative-feedback control exerted by plasma insulin on beta-cell insulin release in normal-weight and obese subjects is still a matter of debate. Subjects submitted to a euglycemic insulin clamp undergo a suppression of insulin secretion that is due to both the infused insulin and the 2- to 3-hour fast during the procedure. We elected to elucidate the role of physiologic hyperinsulinemia per se in the insulin negative autofeedback in obese men. Ten men with massive uncomplicated obesity (age, 18 to 37 years; body mass index [BMI], 41 +/- 1.15 kg/m2) and 6 normal-weight healthy men (age, 22 to 30 years; BMI, 22 +/- 0.28 kg/m2) underwent 2 studies in random order: (1) a euglycemic-hyperinsulinemic glucose clamp with an insulin infusion rate of 1 mU/kg/min and (2) a control study with saline infusion. Serum C-peptide concentrations were significantly higher in obese versus control subjects at baseline (2.54 +/- 0.178 v 1.63 +/- 0.256 ng/mL, P < .05). Exogenous insulin infusion significantly suppressed serum C-peptide at steady state ([SS] last 30 minutes of insulin or saline infusion) in controls (mean of the last 4 measurements from 120 minutes to 150 minutes, 0.86 +/- 0.306 ng/mL, P < .05 vbaseline) but not in obese patients (2.03 +/- 0.26 ng/mL, nonsignificant [NS] v baseline). During the saline infusion studies, C-peptide levels slightly and similarly declined over time in both groups (2.71 +/- 0.350 at baseline v 2.31 +/- 0.300 ng/mL at SS in obese patients, NS, and 1.96 +/- 0.189 v 1.62 +/- 0.150 ng/mL in controls, NS). This study shows that in obese men hyperinsulinemia within the postprandial range is not superior to a 2.5-hour fast for the suppression of beta-cell activity, suggesting an impairment of the insulin negative autofeedback in this clinical condition.

High-fat diet feeding alters metabolic response to fasting/non fasting conditions. Effect on caveolin expression and insulin signalling.

Science.gov (United States)

Gómez-Ruiz, Ana; Milagro, Fermín I; Campión, Javier; Martínez, J Alfredo; de Miguel, Carlos

2011-04-13

The effect of food intake on caveolin expression in relation to insulin signalling was studied in skeletal muscle and adipocytes from retroperitoneal (RP) and subcutaneous (SC) adipose tissue, comparing fasted (F) to not fasted (NF) rats that had been fed a control or high-fat (HF) diet for 72 days. Serum glucose was analysed enzymatically and insulin and leptin by ELISA. Caveolins and insulin signalling intermediaries (IR, IRS-1 and 2 and GLUT4) were determined by RT-PCR and western blotting. Caveolin and IR phosphorylation was measured by immunoprecipitation. Data were analysed with Mann-Whitney U test. High-fat fed animals showed metabolic alterations and developed obesity and insulin resistance. In skeletal muscle, food intake (NF) induced activation of IR and increased expression of IRS-2 in control animals with normal metabolic response. HF animals became overweight, hyperglycaemic, hyperinsulinemic, hyperleptinemic and showed insulin resistance. In skeletal muscle of these animals, food intake (NF) also induced IRS-2 expression together with IR, although this was not active. Caveolin 3 expression in this tissue was increased by food intake (NF) in animals fed either diet. In RP adipocytes of control animals, food intake (NF) decreased IR and IRS-2 expression but increased that of GLUT4. A similar but less intense response was found in SC adipocytes. Food intake (NF) did not change caveolin expression in RP adipocytes with either diet, but in SC adipocytes of HF animals a reduction was observed. Food intake (NF) decreased caveolin-1 phosphorylation in RP but increased it in SC adipocytes of control animals, whereas it increased caveolin-2 phosphorylation in both types of adipocytes independently of the diet. Animals fed a control-diet show a normal response to food intake (NF), with activation of the insulin signalling pathway but without appreciable changes in caveolin expression, except a small increase of caveolin-3 in muscle. Animals fed a high-fat diet

Human milk insulin is related to maternal plasma insulin and BMI: but other components of human milk do not differ by BMI.

Science.gov (United States)

Young, B E; Patinkin, Z; Palmer, C; de la Houssaye, B; Barbour, L A; Hernandez, T; Friedman, J E; Krebs, N F

2017-09-01

The impact of maternal BMI and insulin sensitivity on bioactive components of human milk (HM) is not well understood. As the prevalence of obesity and diabetes rises, it is increasingly critical that we understand how maternal BMI and hormones associated with metabolic disease relate to concentrations of bioactive components in HM. This longitudinal cohort design followed 48 breastfeeding mothers through the first four months of lactation, collecting fasting morning HM samples at 2-weeks and 1, 2, 3 and 4-months, and fasting maternal blood at 2-weeks and 4-months. Insulin, glucose, adipokines leptin and adiponectin, appetite regulating hormone ghrelin, marker of oxidative stress 8OHdG and inflammatory cytokines (IL-6, IL-8, and TNF-a) were measured in HM and maternal plasma. A total of 26 normal weight (NW) (BMI=21.4±2.0 kg/m 2 ) and 22 overweight/obese (OW/Ob) (BMI=30.4±4.2 kg/m 2 ) were followed. Of all HM analytes measured, only insulin and leptin were different between groups - consistently higher in the OW/Ob group (leptin: P<0.001; insulin: P<0.03). HM insulin was 98% higher than maternal plasma insulin at 2-weeks and 32% higher at 4-months (P<0.001). Maternal fasting plasma insulin and HOMA-IR were positively related to HM insulin at 2-weeks (P<0.001, R 2 ⩾0.38, n=31), and 4-months (P⩽0.005, R 2 ⩾0.20, n=38). The concentrations of insulin in HM are higher than in maternal plasma and are related to maternal BMI and insulin sensitivity. With the exception of leptin, there were minimal other differences observed in HM composition across a wide range in maternal BMI.

Lack of relationship between plasma insulin and glucogen levels and angiographically-documented coronary atherosclerosis

Energy Technology Data Exchange (ETDEWEB)

Mookherjee, S; Potts, J L; Hill, N E; Warner, R; Raheja, K L; Patel, D G; Vardan, S; Smulyan, H [Upstate Medical Center, Syracuse, NY (USA)

1983-10-01

In 120 consecutive patients undergoing diagnostic coronary arteriography, fasting blood glucose, plasma insulin, glucagon, serum cholesterol and triglyceride concentrations were measured. The insulin-glucose ratio and insulin-glucagon ratio were calculated. Forty-five patients had normal coronary arteries, 19 had single vessel coronary artery disease and 56 patients had multiple vessel disease. Fasting blood glucose was >120 mg/100 ml in 37 patients (group A) and included 9 of the 10 known diabetics, 3 of whom were being treated with insulin. Seventy-seven patients included in group B had fasting blood glucose concentration <120 mg/100 ml. Patients with multiple vessel coronary disease in either group had higher blood glucose and cholesterol concentrations than those with normal coronary arteries or glucagon levels nor increased insulin-glucose or insulin-glucagon ratios. With comparable extent of coronary artery disease patients in group A had higher plasma insulin levels and insulin-glucagon ratios than those in group B, but no correlation exists between the presence of extent of coronary atherosclerosis and these variables in either group. Thus, neither fasting plasma insulin level nor insulin-glucagon ratio predicts the status of underlying coronary atherosclerosis in either diabetes or nondiabetes.

Decreases in fasting leptin and insulin concentrations after acute energy restriction and subsequent compensation in food intake.

Science.gov (United States)

Mars, Monica; de Graaf, Cees; de Groot, Lisette C P G M; Kok, Frans J

2005-03-01

The decrease in leptin after energy restriction is a starvation signal to the brain. Several studies have found an association between this decrease and subjective appetite; however, no solid data are available on the acute decrease in fasting leptin concentration and subsequent caloric compensation. The objective was to assess the effect of acute decreases in fasting leptin concentrations, induced by energy restriction, on subsequent energy intake compensation. We hypothesized that men with a large decrease in fasting leptin concentrations would have larger ad libitum energy intakes than would men with a small decrease in leptin. Thirty-four male unrestrained eaters [age: 23 +/- 3 y; body mass index (in kg/m(2)): 22.3 +/- 1.6] participated in a semicontrolled intervention study. Fasting serum leptin and insulin concentrations were measured before and 2 d after 62% energy restriction. Energy intake was measured on the 2 following days on which food was provided ad libitum. During energy restriction, fasting leptin and insulin concentrations decreased by 27.2% (95% CI: -34.4%, -19.9%) and 30.7% (95% CI: -41.0%, -20.4%), respectively. Subjects consumed 143 +/- 27% of their estimated energy requirements (18.3 +/- 2.9 MJ) on the first day and 124 +/- 20% (16.0 +/- 2.6 MJ) on the second day of ad libitum intake. No significant correlations were observed between decreases in fasting leptin or insulin concentrations and subsequent ad libitum energy intake; however, decreases in insulin were correlated with an increase in carbohydrate intake (r=-0.49, P < 0.01). Although fasting leptin concentrations decreased significantly during energy restriction and subjects showed compensatory behavior during subsequent ad libitum food intake, no association was observed between the decrease in fasting leptin concentrations and caloric compensation.

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

Science.gov (United States)

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

2015-01-01

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

Copeptin, a surrogate marker for arginine vasopressin secretion, is associated with higher glucose and insulin concentrations but not higher blood pressure in obese men

DEFF Research Database (Denmark)

Asferg, C L; Andersen, Ulrik Bjørn; Linneberg, A

2014-01-01

distribution. METHODS: In 103 obese men (mean age ± standard deviation: 49.4 ± 10.2 years) and 27 normal weight control men (mean age: 51.5 ± 8.4 years), taking no medication, we measured 24-h ambulatory blood pressure, fasting blood concentrations of copeptin, lipids, glucose and insulin, and determined body...... blood pressure (r = 0.11, P = 0.29), 24-h diastolic blood pressure (r = 0.11, P = 0.28), BMI (r = 0.09, P = 0.37), total body fatness percentage (r = 0.10, P = 0.33), android fat mass percentage (r = 0.04, P = 0.66) or serum triglyceride concentrations (r = 0.04; P = 0.68). In contrast, plasma copeptin......, and is associated with abnormalities in glucose and insulin metabolism, but not with higher blood pressure or an android fat distribution in obese men....

Association between HOMA-IR, fasting insulin and fasting glucose with coronary heart disease mortality in nondiabetic men: a 20-year observational study.

Science.gov (United States)

Kurl, Sudhir; Zaccardi, Francesco; Onaemo, Vivian N; Jae, Sae Young; Kauhanen, Jussi; Ronkainen, Kimmo; Laukkanen, Jari A

2015-02-01

Whether glucose and insulin are differently associated with the risk of coronary heart disease (CHD) mortality is unclear. We aimed to estimate the association between insulin resistance (estimated by the homeostasis model assessment for insulin resistance, HOMA-IR), fasting serum insulin (FI) and fasting plasma glucose (FPG) with incident CHD mortality in a prospective study including middle-aged nondiabetic Finnish men. During an average follow-up of 20 years, 273 (11 %) CHD deaths occurred. In a multivariable Cox regression analysis adjusted for age, body mass index, systolic blood pressure, serum LDL-cholesterol, cigarette smoking, history of CHD, alcohol consumption, blood leukocytes and plasma fibrinogen, the hazard ratios (HRs) for CHD mortality comparing top versus bottom quartiles were as follows: 1.69 (95 % CI: 1.15-2.48; p = 0.008) for HOMA-IR; 1.59 (1.09-2.32; p = 0.016) for FI; and 1.26 (0.90-1.76; p = 0.173) for FPG. These findings suggest that IR and FI, but not FPG, are independent risk factors for CHD mortality. Further studies could help clarify these results in terms of screening and risk stratification, causality of the associations, and therapeutical implications.

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

Lipid induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling

DEFF Research Database (Denmark)

Høeg, Louise D; Sjøberg, Kim Anker; Jeppesen, Jacob

2011-01-01

than men. We therefore hypothesized that women would be less prone to lipid induced insulin resistance. Research and design methods: Insulin sensitivity of whole body and leg glucose disposal was studied in 16 young well matched healthy men and women infused with intralipid or saline for 7h. Muscle...... ratio was decreased by intralipid. Conclusion: Intralipid infusion causes less insulin resistance of muscle glucose uptake in women than in men. This insulin resistance is not due to decreased canonical insulin signaling, accumulation of lipid intermediates, inflammation or direct inhibition of glucose......AbstractObjective: We have previously shown that overnight fasted women have higher insulin stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism...

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.

Effects of fasting on insulin action and glucose kinetics in lean and obese men and women.

Science.gov (United States)

Bergman, Bryan C; Cornier, Marc-Andre; Horton, Tracy J; Bessesen, Daniel H

2007-10-01

The development of insulin resistance in the obese individual could impair the ability to appropriately adjust metabolism to perturbations in energy balance. We investigated a 12- vs. 48-h fast on hepatic glucose production (R(a)), peripheral glucose uptake (R(d)), and skeletal muscle insulin signaling in lean and obese subjects. Healthy lean [n = 14; age = 28.0 +/- 1.4 yr; body mass index (BMI) = 22.8 +/- 0.42] and nondiabetic obese (n = 11; age = 34.6 +/- 2.3 yr; BMI = 36.1 +/- 1.5) subjects were studied following a 12- and 48-h fast during 2 h of rest and a 3-h 40 mUxm(-2)xmin(-1) hyperinsulinemic-euglycemic clamp (HEC). Basal glucose R(a) decreased significantly from the 12- to 48-h fast (lean 1.96 +/- 0.23 to 1.63 +/- 0.15; obese 1.23 +/- 0.07 to 1.07 +/- 0.07 mgxkg(-1)xmin(-1); P = 0.004) and was equally suppressed during the HEC after both fasts. The increase in glucose R(d) during the HEC after the 12-h fast was significantly decreased in lean and obese subjects after the 48-h fast (lean 9.03 +/- 1.17 to 4.16 +/- 0.34, obese 6.10 +/- 0.77 to 3.56 +/- 0.30 mgxkg FFM(-1)xmin(-1); P lean than obese subjects. We conclude that 1) 48 h of fasting produces a marked decline in peripheral insulin action, while suppression of hepatic glucose production is maintained in lean and obese men and women; and 2) the magnitude of this decline is greater in lean vs. obese subjects.

Higher magnesium intake is associated with lower fasting glucose and insulin, with no evidence of interaction with select genetic loci, in a meta-analysis of 15 charge consortium studies

Science.gov (United States)

Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) assoc...

Insulin resistance in Nigerians with essential hypertension | Akande ...

African Journals Online (AJOL)

Homeostasis model assessment (HOMA) was used to determine insulin resistance (IR). Results: The hypertensive subjects had significantly higher fasting insulin and HOMA-IR compared with normotensives (p =0.02 and 0.04) respectively. There were significant correlations between HOMA-IR, BMI, waist and hip ...

Insulin sensitivity, insulin release and glucagon-like peptide-1 levels in persons with impaired fasting glucose and/or impaired glucose tolerance in the EUGENE2 study

DEFF Research Database (Denmark)

Laakso, M; Zilinskaite, J; Hansen, T

2008-01-01

AIMS/HYPOTHESIS: We examined the phenotype of individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) with regard to insulin release and insulin resistance. METHODS: Non-diabetic offspring (n=874; mean age 40+/-10.4 years; BMI 26.6+/-4.9 kg/m(2)) of type 2 diabetic...

A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: the ACT NOW study.

Science.gov (United States)

Tripathy, Devjit; Cobb, Jeff E; Gall, Walter; Adam, Klaus-Peter; George, Tabitha; Schwenke, Dawn C; Banerji, MaryAnn; Bray, George A; Buchanan, Thomas A; Clement, Stephen C; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Ratner, Robert E; Stentz, Frankie B; Reaven, Peter D; Musi, Nicolas; Ferrannini, Ele; DeFronzo, Ralph A

2015-05-01

The objective was to test the clinical utility of Quantose M(Q) to monitor changes in insulin sensitivity after pioglitazone therapy in prediabetic subjects. Quantose M(Q) is derived from fasting measurements of insulin, α-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal. Participants were 428 of the total of 602 ACT NOW impaired glucose tolerance (IGT) subjects randomized to pioglitazone (45 mg/d) or placebo and followed for 2.4 years. At baseline and study end, fasting plasma metabolites required for determination of Quantose, glycated hemoglobin, and oral glucose tolerance test with frequent plasma insulin and glucose measurements to calculate the Matsuda index of insulin sensitivity were obtained. Pioglitazone treatment lowered IGT conversion to diabetes (hazard ratio = 0.25; 95% confidence interval = 0.13-0.50; P < .0001). Although glycated hemoglobin did not track with insulin sensitivity, Quantose M(Q) increased in pioglitazone-treated subjects (by 1.45 [3.45] mg·min(-1)·kgwbm(-1)) (median [interquartile range]) (P < .001 vs placebo), as did the Matsuda index (by 3.05 [4.77] units; P < .0001). Quantose M(Q) correlated with the Matsuda index at baseline and change in the Matsuda index from baseline (rho, 0.85 and 0.79, respectively; P < .0001) and was progressively higher across closeout glucose tolerance status (diabetes, IGT, normal glucose tolerance). In logistic models including only anthropometric and fasting measurements, Quantose M(Q) outperformed both Matsuda and fasting insulin in predicting incident diabetes. In IGT subjects, Quantose M(Q) parallels changes in insulin sensitivity and glucose tolerance with pioglitazone therapy. Due to its strong correlation with improved insulin sensitivity and its ease of use, Quantose M(Q) may serve as a useful clinical test to identify and monitor therapy in insulin-resistant patients.

A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

DEFF Research Database (Denmark)

Manning, Alisa K; Hivert, Marie-France; Scott, Robert A

2012-01-01

pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci...... associated with fasting insulin at P triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci...

Fasting Serum Taurine-Conjugated Bile Acids Are Elevated in Type 2 Diabetes and Do Not Change With Intensification of Insulin

Science.gov (United States)

Wewalka, Marlene; Patti, Mary-Elizabeth; Barbato, Corinne; Houten, Sander M.

2014-01-01

Context: Bile acids (BAs) are newly recognized signaling molecules in glucose and energy homeostasis. Differences in BA profiles with type 2 diabetes mellitus (T2D) remain incompletely understood. Objective: The objective of the study was to assess serum BA composition in impaired glucose-tolerant, T2D, and normal glucose-tolerant persons and to monitor the effects of improving glycemia on serum BA composition in T2D patients. Design and Setting: This was a cross-sectional cohort study in a general population (cohort 1) and nonrandomized intervention (cohort 2). Patients and Interventions: Ninety-nine volunteers underwent oral glucose tolerance testing, and 12 persons with T2D and hyperglycemia underwent 8 weeks of intensification of treatment. Main Outcome Measures: Serum free BA and respective taurine and glycine conjugates were measured by HPLC tandem mass spectrometry. Results: Oral glucose tolerance testing identified 62 normal-, 25 impaired glucose-tolerant, and 12 T2D persons. Concentrations of total taurine-conjugated BA were higher in T2D and intermediate in impaired- compared with normal glucose-tolerant persons (P = .009). Univariate regression revealed a positive association between total taurine-BA and fasting glucose (R = 0.37, P fasting insulin (R = 0.21, P = .03), and homeostatic model assessment-estimated insulin resistance (R = 0.26, P = .01) and an inverse association with oral disposition index (R = −0.36, P fasting serum total BA or BA composition. Conclusion: Fasting taurine-conjugated BA concentrations are higher in T2D and intermediate in impaired compared with normal glucose-tolerant persons and are associated with fasting and postload glucose. Serum BAs are not altered in T2D in response to improved glycemia. Further study may elucidate whether this pattern of taurine-BA conjugation can be targeted to provide novel therapeutic approaches to treat T2D. PMID:24432996

Kinetics of circulating endogenous insulin, C-peptide, and proinsulin in fasting nondiabetic man

DEFF Research Database (Denmark)

Henriksen, Jens Henrik Sahl; Tronier, B; Bülow, J B

1987-01-01

Plasma concentrations of insulin, C-peptide, and proinsulin were measured in different vascular beds in order to determine renal, hepatic, and systemic kinetics of the endogenous peptides in the fasting condition. Nineteen nondiabetic subjects were studied, two were normal, nine had minor vascular...

Insulin analogues: have they changed insulin treatment and improved glycaemic control?

DEFF Research Database (Denmark)

Madsbad, Sten

2002-01-01

To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studies....... This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin...... administered several times daily at mealtimes can improve glycaemic control without increasing the risk of hypoglycaemia. The fast-acting analogues are now also available as insulin mixed with NPH. Insulin glargine is a new long-acting insulin which is soluble and precipitates after injection, resulting...

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.

Low Prevalence of Insulin Resistance among Iranian Patients with Chronic Hepatitis C Virus Infection: A Case-Control Study.

Science.gov (United States)

Eshraghian, Kavous; Lankarani, Kamran B; Fattahi, Mohammad Reza; Esmailnejad, Atefeh; Peymani, Payam

2017-07-14

Association between chronic hepatitis C virus (CHC) infection and type 2 diabetes mellitus has been challenging in recent decades. Despite of extensive research in this area, there is no general agreement on the direct effect of HCV infection on insulin resistance. The study was performed in 52 CHC patients (mean age = 39.48) and 52 and sex‑matched healthy Iranian controls, referred to the Hepatitis Clinic, Department of Gastroenterohepatology, Shiraz University of medical sciences, Shiraz, Iran, from 2012 to 2015. Fasting blood glucose level, fasting insulin level and insulin resistance defined as a homeostasis model assessment of insulin resistance (HOMA-IR) index were determined and compared between two groups. Insulin resistance was present in 26.9% of CHC patients and 34.62% of healthy controls. Mean HOMA index was 1.93 in patients and 2.18 in controls. There were no statistically significant differences between patient and control groups with regard to fasting insulin level, fasting blood glucose, HOMA index and insulin resistance. HOMA index and fasting insulin level were significantly higher in IR CHC patients relative to IR controls. Fasting blood glucose was also significantly higher in controls younger than 40 years. Results obtained in this study showed that chronic hepatitis C cannot be considered as a risk factor for insulin resistance and diabetes in Iranian population. However, regular screening for insulin resistance is recommended in CHC patients with age ≥ 40 years and fasting blood glucose ≥ 100 mg/dl. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Relationship between insulin resistance and plasma endothelin in hypertension patients

International Nuclear Information System (INIS)

Duan Yongqiang; Wang Zuobing; Yu Hui; Cao Wei; Wang Jing; Li Xiaoqin

2011-01-01

To explore the relationship between plasma endothelin and hypertension insulin resistance, and the improvement of insulin resistance in hypertension patients treated with captopril and l-amlodipine, 25 patients with primary hypertension and impaired glucose tolerance were selected and treated by captopril and l-amlodipine. Systolic pressure, diastolic pressure, fasting blood glucose, insulin and insulin antibody were measured before and after treatment and compared with healthy controls. The results showed that the plasma ET-1 level in hypertension group was significantly higher than that of healthy controls (P<0.01), and he plasma ET-1 level was positively correlated with FPG, FINS, Anti-INS, HOMA-IR. The systolic pressure, diastolic pressure, fasting blood glucose, insulin, insulin antibody and insulin resistance index in hypertension patients were decreased significantly after treatment (P<0.05). There is a good correlation between endothelin and insulin resistance index in hypertension patients. Captopril and l-amlodipine had obvious improvement effect on insulin resistance in hypertension patients. (authors)

Decreased insulin clearance in individuals with elevated 1-h post-load plasma glucose levels.

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Maria Adelaide Marini

Full Text Available Reduced insulin clearance has been shown to predict the development of type 2 diabetes. Recently, it has been suggested that plasma glucose concentrations ≥ 8.6 mmol/l (155 mg/dl at 1 h during an oral glucose tolerance test (OGTT can identify individuals at high risk for type 2 diabetes among those who have normal glucose tolerance (NGT 1 h-high. The aim of this study was to examine whether NGT 1 h-high have a decrease in insulin clearance, as compared with NGT individuals with 1-h post-load glucose <8.6 mmol/l (l (155 mg/dl, NGT 1 h-low. To this end, 438 non-diabetic White individuals were subjected to OGTT and euglycemic-hyperinsulinemic clamp to evaluate insulin clearance and insulin sensitivity. As compared with NGT 1 h-low individuals, NGT 1 h-high had significantly higher 1-h and 2-h post-load plasma glucose and 2-h insulin levels as well as higher fasting glucose and insulin levels. NGT 1 h-high exhibited also a significant decrease in both insulin sensitivity (P<0.0001 and insulin clearance (P = 0.006 after adjusting for age, gender, adiposity measures, and insulin sensitivity. The differences in insulin clearance remained significant after adjustment for fasting glucose (P = 0.02 in addition to gender, age, and BMI. In univariate analyses adjusted for gender and age, insulin clearance was inversely correlated with body weight, body mass index, waist, fat mass, 1-h and 2-h post-load glucose levels, fasting, 1-h and 2-h post-load insulin levels, and insulin-stimulated glucose disposal. In conclusion, our data show that NGT 1 h-high have a reduction in insulin clearance as compared with NGT 1 h-low individuals; this suggests that impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia.

Beneficial effects on fasting insulin and postprandial responses through 7-day intake of New Zealand blackcurrant powder

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Mark Elisabeth Theodorus Willems

2017-07-01

Full Text Available Background: Blood glucose and insulin are elevated after intake of carbohydrate, with levels returning to normal in about 2-3 hours after ingestion. We examined the effects of daily New Zealand blackcurrant intake over 7 days on fasting glucose and insulin levels and the responses of glucose and insulin during an oral glucose tolerance test (i.e. OGTT. Methods: Seventeen healthy participants (9 males, 8 females, age: 24±8 years, body mass: 75.4±16.4 kg, height 172±11 cm, body mass index: 25.3±3.3 consumed 6 g·day-1 New Zealand blackcurrant (NZBC powder for 7 days. Every 6 g of the serving contained 138.6 mg anthocyanins, 49 mg vitamin C, and 5.2 g of carbohydrates with total phenolic content 271.6 mg. A cross-over design was used. Participants completed one OGTT before starting the supplementation (day 0 and another OGTT after 7 days of the supplementation (day 7. For the OGTT, participants were seated and consumed 75 g of glucose dissolved in 250 mL water. Finger prick capillary samples were taken before and every 30 minutes for a total of 120 minutes after consuming the glucose drink. Following duplicate glucose analysis, blood samples were centrifuged and then plasma was separated and frozen (-20°C for triplicate insulin analysis using a human 96-well insulin enzyme-linked immunosorbent assay (IBL international, Hamburg, Germany. Results: NZBC had no effect on fasting glucose (control: 4.46±0.45; NZBC: 4.41±0.44 mmol·L1, P=0.657, although there was a trend for fasting insulin to be 14.3% lower (control: 66.5±28.2; NZBC: 57.0±29.5 pmol·L-1 (P=0.091. HOMA-IR was not different between the control and NZBC (1.81±0.73 vs 1.58±0.83 (P=0.126. With NZBC during the OGTT, plasma glucose at 60 min was 8.1% lower (control: 6.68±1.13; NZBC: 6.14±1.41 mmol·L-1; P=0.016, insulin at 30 min was 18.4% lower (control: 337.1±228.3; NZBC: 275.0±136.4 pmol·L-1; P= 0.021, and insulin at 60 min was 39.2% lower (control: 297.8±154.3; NZBC: 181.2�

Baseline Levels, and Changes Over Time in Body Mass Index and Fasting Insulin, and Their Relationship to Change in Metabolic Trait Clustering

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Sullivan, Lisa M.; Fox, Caroline S.; Wilson, Peter W.F.; Nathan, David M.; Vasan, Ramachandran S.; D'Agostino, Ralph B.; Meigs, James B.

2014-01-01

Abstract Background: Multiple abnormal metabolic traits are found together or “cluster” within individuals more often than is predicted by chance. The individual and combined role of adiposity and insulin resistance (IR) on metabolic trait clustering is uncertain. We tested the hypothesis that change in trait clustering is a function of both baseline level and change in these measures. Methods: In 2616 nondiabetic Framingham Offspring Study participants, body mass index (BMI) and fasting insulin were related to a within-person 7-year change in a trait score of 0–4 Adult Treatment Panel III metabolic syndrome traits (hypertension, high triglycerides, low high-density lipoprotein cholesterol, hyperglycemia). Results: At baseline assessment, mean trait score was 1.4 traits, and 7-year mean (SEM) change in trait score was +0.25 (0.02) traits, Pfasting insulin were similarly related to trait score change. In models adjusted for age–sex–baseline cluster score, 7-year change in trait score was significantly related to both a 1-quintile difference in baseline BMI (0.07 traits) and fasting insulin (0.18 traits), and to both a 1-quintile 7-year increase in BMI (0.21 traits) and fasting insulin (0.18 traits). Conclusions: Change in metabolic trait clustering was significantly associated with baseline levels and changes in both BMI and fasting insulin, highlighting the importance of both obesity and IR in the clustering of metabolic traits. PMID:25007010

Insulin resistance in obesity can be reliably identified from fasting plasma insulin

NARCIS (Netherlands)

ter Horst, K. W.; Gilijamse, P. W.; Koopman, K. E.; de Weijer, B. A.; Brands, M.; Kootte, R. S.; Romijn, J. A.; Ackermans, M. T.; Nieuwdorp, M.; Soeters, M. R.; Serlie, M. J.

2015-01-01

Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely

Postmenopausal hypertension, abdominal obesity, apolipoprotein and insulin resistance.

Science.gov (United States)

Ben Ali, Samir; Belfki-Benali, Hanen; Ahmed, Decy Ben; Haddad, Najet; Jmal, Awatef; Abdennebi, Monia; Romdhane, Habiba Ben

This study aimed to evaluate the association of abdominal obesity, apolipoprotein and insulin resistance (IR) with the risk of hypertension in postmenopausal women. We analyzed a total of 242 women aged between 35 and 70 years. Blood pressure (BP), anthropometric indices, lipid profile, fasting glucose, insulin, C-reactive protein (CRP) and apolipoprotein concentrations were measured. Homeostasis model assessment (HOMA) was used to assess IR. Hypertension was defined as a systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg or current treatment with antihypertensive drugs. Women with hypertension showed significantly higher mean values of age, SBP and DBP, waist circumference (WC), fasting plasma glucose (FPG), insulin, HOMAIR and the apolipoprotein B (apoB). When analyses were done according to the menopausal status, higher prevalence of hypertension was observed in postmenopausal women (72.8% vs. 26.0%, p menopause (p = 0.008) were significantly associated with higher risk for hypertension. These results suggest that changes in WC, apoB and IR accompanying menopause lead to a greater prevalence of hypertension in postmenopausal women.

High normal fasting glucose level in obese youth: a marker for insulin resistance and beta cell dysregulation.

LENUS (Irish Health Repository)

O'Malley, G

2010-06-01

A high but normal fasting plasma glucose level in adults is a risk factor for future development of type 2 diabetes mellitus and cardiovascular disease. We investigated whether normal fasting plasma glucose levels (<5.60 mmol\\/l) are associated with decreases in insulin sensitivity and beta cell function, as well as an adverse cardiovascular profile in obese youth.

Effects of meals rich in either monounsaturated or saturated fat on lipid concentrations and on insulin secretion and action in subjects with high fasting triglyceride concentrations.

Science.gov (United States)

Lopez, Sergio; Bermudez, Beatriz; Ortega, Almudena; Varela, Lourdes M; Pacheco, Yolanda M; Villar, Jose; Abia, Rocio; Muriana, Francisco J G

2011-03-01

The nature of dietary fats and fasting concentrations of triglycerides affect postprandial hypertriglyceridemia and glucose homeostasis. The objectives were to examine the effects of meals enriched in monounsaturated fatty acids (MUFAs) or saturated fatty acids (SFAs) on postprandial lipid, glucose, and insulin concentrations and to examine the extent of β cell function and insulin sensitivity in subjects with high fasting triglyceride concentrations. Fourteen men with fasting hypertriglyceridemia and normal glucose tolerance were given meals (≈10 kcal/kg body weight) containing MUFAs, SFAs, or no fat. Blood samples were collected at baseline and hourly over 8 h for analysis. The high-fat meals significantly increased postprandial concentrations of triglycerides, nonesterified fatty acids, and insulin and postprandial indexes of β cell function. However, postprandial indexes of insulin sensitivity decreased significantly. These effects were significantly attenuated with MUFAs relative to SFAs. MUFAs postprandially buffered β cell hyperactivity and insulin intolerance relative to SFAs in subjects with high fasting triglyceride concentrations. These data suggest that, in contrast with SFAs, MUFA-based strategies may provide cardiovascular benefits to persons at risk by limiting lipid and insulin excursions and may contribute to optimal glycemic control after meal challenges.

Insulin secretion and insulin action in non-insulin-dependent diabetes mellitus: which defect is primary?

Science.gov (United States)

Reaven, G M

1984-01-01

Defects in both insulin secretion and insulin action exist in patients with non-insulin-dependent diabetes mellitus (NIDDM). The loss of the acute plasma insulin response to intravenous glucose is seen in patients with relatively mild degrees of fasting hyperglycemia, but patients with severe fasting hyperglycemia also demonstrate absolute hypoinsulinemia in response to an oral glucose challenge. In contrast, day-long circulating insulin levels are within normal limits even in severely hyperglycemic patients with NIDDM. The relationship between NIDDM and insulin action in NIDDM is less complex, and is a characteristic feature of the syndrome. This metabolic defect is independent of obesity, and the severity of the resistance to insulin-stimulated glucose uptake increases with magnitude of hyperglycemia. Control of hyperglycemia with exogenous insulin ameliorates the degree of insulin resistance, and reduction of insulin resistance with weight loss in obese patients with NIDDM leads to an enhanced insulin response. Since neither therapeutic intervention is capable of restoring all metabolic abnormalities to normal, these observations do not tell us which of these two defects is primarily responsible for the development of NIDDM. Similarly, the observation that most patients with impaired glucose tolerance are hyperinsulinemic and insulin resistant does not prove that insulin resistance is the primary defect in NIDDM. In conclusion, reduction in both insulin secretion and action is seen in patients with NIDDM, and the relationship between these two metabolic abnormalities is very complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood pressure, serum lipids, fasting insulin, and adrenal hormones in 12-year-old children born with maternal preeclampsia.

Science.gov (United States)

Tenhola, Sirpa; Rahiala, Eero; Martikainen, Anneli; Halonen, Pirjo; Voutilainen, Raimo

2003-03-01

Women with prior preeclamptic pregnancies have an increased risk for metabolic syndrome and cardiovascular diseases. Maternal preeclampsia has been associated with elevated blood pressure (BP) in offspring during childhood. The aim of our study was to determine whether elevated BP pressure and metabolic changes, such as dyslipidemia, insulin resistance, and increased adrenal hormonal activity, are found in 12-yr-old children of preeclamptic mothers. Sixty children born after preeclamptic pregnancy (PRE) and 60 matched control subjects born after normotensive pregnancy (non-PRE) were studied at the age of 12 yr. The case-control pairs were matched for sex, gestational age (+/-1 wk), and size at birth. We measured BP and concentrations of blood glucose, serum fasting insulin, total and high density lipoprotein cholesterol, triglycerides, cortisol, dehydroepiandrosterone sulfate, and plasma epinephrine (E) and norepinephrine (NE). Low density lipoprotein cholesterol was calculated according to the Friedewald-Fredrickson formula. The PRE children had significantly higher mean systolic (116.4 vs. 113.2 mm Hg; P = 0.021) and diastolic (73.9 vs. 70.3 mm Hg; P = 0.022) BP than the non-PRE children, even when adjusted by current weight and height. At 12 yr of age, systolic BP values correlated inversely with birth weight (r = -0.459; P < 0.001) and length SD scores (r = -0.429; P = 0.001) in the PRE children. The mean concentrations of serum total, low density lipoprotein, and high density lipoprotein cholesterol; triglycerides; fasting insulin; blood glucose; serum cortisol; and dehydroepiandrosterone sulfate did not differ between the PRE and non-PRE groups. However, the mean plasma E concentration was higher in the PRE than in the non-PRE children (0.32 vs. 0.28 nmol/liter; P = 0.042), whereas the mean NE concentration did not differ between these two groups. In conclusion, 12-yr-old children born with maternal preeclampsia had elevated systolic and diastolic BPs and

Percentiles of fasting serum insulin, glucose, HbA1c and HOMA-IR in pre-pubertal normal weight European children from the IDEFICS cohort.

Science.gov (United States)

Peplies, J; Jiménez-Pavón, D; Savva, S C; Buck, C; Günther, K; Fraterman, A; Russo, P; Iacoviello, L; Veidebaum, T; Tornaritis, M; De Henauw, S; Mårild, S; Molnár, D; Moreno, L A; Ahrens, W

2014-09-01

The aim of this study is to present age- and sex-specific reference values of insulin, glucose, glycosylated haemoglobin (HbA1c) and the homeostasis model assessment to quantify insulin resistance (HOMA-IR) for pre-pubertal children. The reference population consists of 7074 normal weight 3- to 10.9-year-old pre-pubertal children from eight European countries who participated in at least one wave of the IDEFICS ('identification and prevention of dietary- and lifestyle-induced health effects in children and infants') surveys (2007-2010) and for whom standardised laboratory measurements were obtained. Percentile curves of insulin (measured by an electrochemiluminescence immunoassay), glucose, HbA1c and HOMA-IR were calculated as a function of age stratified by sex using the general additive model for location scale and shape (GAMLSS) method. Levels of insulin, fasting glucose and HOMA-IR continuously show an increasing trend with age, whereas HbA1c shows an upward trend only beyond the age of 8 years. Insulin and HOMA-IR values are higher in girls of all age groups, whereas glucose values are slightly higher in boys. Median serum levels of insulin range from 17.4 and 13.2 pmol l(-1) in 3-HOMA-IR, median values range from 0.5 and 0.4 in 3-<3.5-year-old girls and boys to 1.7 and 1.4 in 10.5-<11-year-old girls and boys, respectively. Our study provides the first standardised reference values for an international European children's population and provides the, up to now, largest data set of healthy pre-pubertal children to model reference percentiles for markers of insulin resistance. Our cohort shows higher values of Hb1Ac as compared with a single Swedish study while our percentiles for the other glucose metabolic markers are in good accordance with previous studies.

Fatty Acids, Obesity and Insulin Resistance

Directory of Open Access Journals (Sweden)

Peter Arner

2015-04-01

Full Text Available Objective: Although elevated free fatty acid (FFA levels in obesity have been considered to be of importance for insulin resistance, a recent meta-analysis suggested normal FFA levels in obese subjects. We investigated fasting circulating FFA and glycerol levels in a large cohort of non-obese and obese subjects. Methods: Subjects recruited for a study on obesity genetics were investigated in the morning after an overnight fast (n = 3,888. Serum FFA (n = 3,306, plasma glycerol (n = 3,776, and insulin sensitivity index (HOMA-IR,n = 3,469 were determined. Obesity was defined as BMI ≥ 30 kg/m2 and insulin resistance as HOMA-IR ≥ 2.21. Results: In obese subjects, circulating FFA and glycerol levels were higher than in non-obese individuals (by 26% and 47%, respectively; both p Conclusion: Circulating FFA and glycerol levels are markedly elevated in obesity but only marginally influenced by insulin resistance and type 2 diabetes. Whether these differences persist during diurnal variations in circulating FFA/glycerol, remains to be established.

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

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Shou-Kui Xiang

2012-01-01

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

Asian Adolescents with Excess Weight are at Higher Risk for Insulin Resistance than Non-Asian Peers.

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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.

Lower omental t-regulatory cell count is associated with higher fasting glucose and lower β-cell function in adults with obesity.

Science.gov (United States)

Gyllenhammer, Lauren E; Lam, Jonathan; Alderete, Tanya L; Allayee, Hooman; Akbari, Omid; Katkhouda, Namir; Goran, Michael I

2016-06-01

T-lymphocytes are potential initiators and regulators of adipose tissue (AT) inflammation, but there is limited human data on omental AT. The aim of this study was to assess the relationship between T cells, particularly Foxp3+ regulatory T (Treg) cells, in human subcutaneous (subQ) and omental AT and type 2 diabetes risk. SubQ and deep subQ (DsubQ) abdominal and omental AT biopsies were collected from 44 patients (body mass index, BMI ≥25) undergoing elective abdominal surgery. Flow cytometry was used to quantify CD4+ T cell (T effector and Treg) and macrophages (M1 and M2), and systemic inflammation was measured in fasting blood. Tregs were significantly lower in omental versus subQ and DsubQ AT, and M1 cell counts were significantly higher in the omental and DsubQ depot relative to the subQ. Only omental AT Tregs were negatively associated with fasting glucose and MCP-1 and positively associated with homeostasis model assessment (HOMA)-β. M1 and M2 cell counts across multiple depots had significant relationships with HOMA-insulin resistance, tumor necrosis factor-α, insulin, and HOMA-β. All relationships were consistent across ethnicities. Tregs were significantly lower in omental versus both subQ adipose depots. Fewer omental Tregs may have metabolic implications based on depot-specific relationships with higher fasting glucose and lower β-cell function. © 2016 The Obesity Society.

Alternate day fasting impacts the brain insulin-signaling pathway of young adult male C57BL/6 mice.

Science.gov (United States)

Lu, Jianghua; E, Lezi; Wang, Wenfang; Frontera, Jennifer; Zhu, Hao; Wang, Wen-Tung; Lee, Phil; Choi, In Young; Brooks, William M; Burns, Jeffrey M; Aires, Daniel; Swerdlow, Russell H

2011-04-01

Dietary restriction (DR) has recognized health benefits that may extend to brain. We examined how DR affects bioenergetics-relevant enzymes and signaling pathways in the brains of C57BL/6 mice. Five-month-old male mice were placed in ad libitum or one of two repeated fasting and refeeding (RFR) groups, an alternate day (intermittent fed; IF) or alternate day plus antioxidants (blueberry, pomegranate, and green tea extracts) (IF + AO) fed group. During the 24-h fast blood glucose levels initially fell but stabilized within 6 h of starting the fast, thus avoiding frank hypoglycemia. DR in general appeared to enhance insulin sensitivity. After six weeks brain AKT and glycogen synthase kinase 3 beta phosphorylation were lower in the RFR mice, suggesting RFR reduced brain insulin-signaling pathway activity. Pathways that mediate mitochondrial biogenesis were not activated; AMP kinase phosphorylation, silent information regulator 2 phosphorylation, peroxisomal proliferator-activated receptor-gamma coactivator 1 alpha levels, and cytochrome oxidase subunit 4 levels did not change. ATP levels also did not decline, which suggests the RFR protocols did not directly impact brain bioenergetics. Antioxidant supplementation did not affect the brain parameters we evaluated. Our data indicate in young adult male C57BL/6 mice, RFR primarily affects brain energy metabolism by reducing brain insulin signaling, which potentially results indirectly as a consequence of reduced peripheral insulin production. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Higher insulin sensitivity in vegans is not associated with higher mitochondrial density.

Science.gov (United States)

Gojda, J; Patková, J; Jaček, M; Potočková, J; Trnka, J; Kraml, P; Anděl, M

2013-12-01

Vegans have a lower incidence of insulin resistance (IR)-associated diseases and a higher insulin sensitivity (IS) compared with omnivores. The aim of this study was to examine whether the higher IS in vegans relates to markers of mitochondrial biogenesis and to intramyocellular lipid (IMCL) content. Eleven vegans and 10 matched (race, age, sex, body mass index, physical activity and energy intake) omnivorous controls were enrolled in a case-control study. Anthropometry, bioimpedance (BIA), ultrasound measurement of visceral and subcutaneous fat layer, parameters of glucose and lipid homeostasis, hyperinsulinemic euglycemic clamp and muscle biopsies were performed. Citrate synthase (CS) activity, mitochondrial DNA (mtDNA) and IMCL content were assessed in skeletal muscle samples. Both groups were comparable in anthropometric and BIA parameters, physical activity and protein-energy intake. Vegans had significantly higher glucose disposal (M-value, vegans 8.11±1.51 vs controls 6.31±1.57 mg/kg/min, 95% confidence interval: 0.402 to 3.212, P=0.014), slightly lower IMCL content (vegans 13.91 (7.8 to 44.0) vs controls 17.36 (12.4 to 78.5) mg/g of muscle, 95% confidence interval: -7.594 to 24.550, P=0.193) and slightly higher relative muscle mtDNA amount (vegans 1.36±0.31 vs controls 1.13±0.36, 95% confidence interval:-0.078 to 0.537, P=0.135). No significant differences were found in CS activity (vegans 18.43±5.05 vs controls 18.16±5.41 μmol/g/min, 95% confidence interval: -4.503 to 5.050, P=0.906). Vegans have a higher IS, but comparable mitochondrial density and IMCL content with omnivores. This suggests that a decrease in whole-body glucose disposal may precede muscle lipid accumulation and mitochondrial dysfunction in IR development.

Insulin analogs with improved pharmacokinetic profiles.

Science.gov (United States)

Brange; Vølund

1999-02-01

The aim of insulin replacement therapy is to normalize blood glucose in order to reduce the complications of diabetes. The pharmacokinetics of the traditional insulin preparations, however, do not match the profiles of physiological insulin secretion. The introduction of the rDNA technology 20 years ago opened new ways to create insulin analogs with altered properties. Fast-acting analogs are based on the idea that an insulin with less tendency to self-association than human insulin would be more readily absorbed into the systemic circulation. Protracted-acting analogs have been created to mimic the slow, steady rate of insulin secretion in the fasting state. The present paper provides a historical review of the efforts to change the physicochemical and pharmacological properties of insulin in order to improve insulin therapy. The available clinical studies of the new insulins are surveyed and show, together with modeling results, that new strategies for optimal basal-bolus treatment are required for utilization of the new fast-acting analogs.

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

Directory of Open Access Journals (Sweden)

Dorian S Houser

2013-11-01

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

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

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

2013-11-01

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

Fasting plasma chenodeoxycholic acid and cholic acid concentrations are inversely correlated with insulin sensitivity in adults

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Laville Martine

2011-07-01

Full Text Available Abstract Background Accumulating data suggest a novel role for bile acids (BAs in modulating metabolic homeostasis. BA treatment has been shown to improve glucose tolerance and to increase energy expenditure in mice. Here, we investigated the relationship between fasting plasma BAs concentrations and metabolic parameters in humans. Findings Fasting plasma glucose, insulin and lipid profile were measured in 14 healthy volunteers, 20 patients with type 2 diabetes (T2D, and 22 non-diabetic abdominally obese subjects. Insulin sensitivity was also assessed by the determination of the glucose infusion rate (GIR during a hyperinsulinemic-euglycemic clamp in a subgroup of patients (9 healthy and 16 T2D subjects. Energy expenditure was measured by indirect calorimetry. Plasma cholic acid (CA, chenodeoxycholic acid (CDCA and deoxycholic acid (DCA concentrations were analyzed by gas chromatograph-mass spectrometry. In univariable analysis, a positive association was found between HOMA-IR and plasma CDCA (β = 0.09, p = 0.001, CA (β = 0.03, p = 0.09 and DCA concentrations (β = 0.07, p Conclusions Both plasma CDCA, CA and DCA concentrations were negatively associated with insulin sensitivity in a wide range of subjects.

Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice.

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Ong, Qi-Rui; Chan, Elizabeth S; Lim, Mei-Li; Cole, Gregory M; Wong, Boon-Seng

2014-01-17

Human ApoE4 accelerates memory decline in ageing and in Alzheimer's disease. Although intranasal insulin can improve cognition, this has little effect in ApoE4 subjects. To understand this ApoE genotype-dependent effect, we examined brain insulin signaling in huApoE3 and huApoE4 targeted replacement (TR) mice. At 32 weeks, lower insulin receptor substrate 1 (IRS1) at S636/639 and Akt phosphorylation at T308 were detected in fasting huApoE4 TR mice as compared to fasting huApoE3 TR mice. These changes in fasting huApoE4 TR mice were linked to lower brain glucose content and have no effect on plasma glucose level. However, at 72 weeks of age, these early changes were accompanied by reduction in IRS2 expression, IRS1 phosphorylation at Y608, Akt phosphorylation at S473, and MAPK (p38 and p44/42) activation in the fasting huApoE4 TR mice. The lower brain glucose was significantly associated with higher brain insulin in the aged huApoE4 TR mice. These results show that ApoE4 reduces brain insulin signaling and glucose level leading to higher insulin content.

Relationship of serum resistin with insulin resistance and obesity

International Nuclear Information System (INIS)

Zaidi, S.I.Z.

2015-01-01

Background: Adipokines have been implicated in the modulation of insulin sensitivity and glucose tolerance and have thus gained importance in the study of Type 2 diabetes mellitus (T2DM). Resistin, a unique signalling molecule, is being proposed as a significant factor in the pathogenesis of obesity-related insulin resistance. However, its relevance to human diabetes mellitus remains uncertain and controversial. This study was therefore planned to compare and correlate the potential role of resistin in obese patients with T2DM and obese non-diabetic controls and also to evaluate the correlation between resistin and marker of obesity and glycaemic parameters. Method: Fasting serum resistin, glucose and insulin were measured in forty obese diabetics (mean±SD BMI 35±5 kg/m2) and forty obese non-diabetics (mean±SD BMI 33±3 kg/m2). Insulin resistance was assessed using the HOMA-IR formula derived from fasting insulin and glucose levels. Results: Serum resistin levels (38±8 ng/ml) were significantly higher in type 2 diabetic patients as compared with the controls. Fasting blood glucose (164±46 mg/dl), serum insulin (37±7 μU/ml) and insulin resistance (19±8), were considerably higher among the studied diabetics than in the controls. Pearson's correlation analysis revealed positive correlation between serum resistin and BMI (p=0.001) and HOMA-IR (p=0.561) in diabetic subjects. Similarly, a correlation also existed between serum resistin and BMI (p=0.016) and HOMA-IR (p=0.307) in control obese subjects. However, it was highly significant in diabetics as compared to non-diabetic controls. Conclusion: A significant BMI-dependent association exists between resistin and insulin resistance in patients with T2DM. It appears that resistin may play a role in the pathogenesis of obesity and insulin resistance and that both of these may contribute to the development of T2DM. (author)

Fasting and Systemic Insulin Signaling Regulate Phosphorylation of Brain Proteins That Modulate Cell Morphology and Link to Neurological Disorders*

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Li, Min; Quan, Chao; Toth, Rachel; Campbell, David G.; MacKintosh, Carol; Wang, Hong Yu; Chen, Shuai

2015-01-01

Diabetes is strongly associated with cognitive decline, but the molecular reasons are unknown. We found that fasting and peripheral insulin promote phosphorylation and dephosphorylation, respectively, of specific residues on brain proteins including cytoskeletal regulators such as slit-robo GTPase-activating protein 3 (srGAP3) and microtubule affinity-regulating protein kinases (MARKs), in which deficiency or dysregulation is linked to neurological disorders. Fasting activates protein kinase A (PKA) but not PKB/Akt signaling in the brain, and PKA can phosphorylate the purified srGAP3. The phosphorylation of srGAP3 and MARKs were increased when PKA signaling was activated in primary neurons. Knockdown of PKA decreased the phosphorylation of srGAP3. Furthermore, WAVE1, a protein kinase A-anchoring protein, formed a complex with srGAP3 and PKA in the brain of fasted mice to facilitate the phosphorylation of srGAP3 by PKA. Although brain cells have insulin receptors, our findings are inconsistent with the down-regulation of phosphorylation of target proteins being mediated by insulin signaling within the brain. Rather, our findings infer that systemic insulin, through a yet unknown mechanism, inhibits PKA or protein kinase(s) with similar specificity and/or activates an unknown phosphatase in the brain. Ser858 of srGAP3 was identified as a key regulatory residue in which phosphorylation by PKA enhanced the GAP activity of srGAP3 toward its substrate, Rac1, in cells, thereby inhibiting the action of this GTPase in cytoskeletal regulation. Our findings reveal novel mechanisms linking peripheral insulin sensitivity with cytoskeletal remodeling in neurons, which may help to explain the association of diabetes with neurological disorders such as Alzheimer disease. PMID:26499801

Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels.

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Mahendran, Yuvaraj; Jonsson, Anna; Have, Christian T; Allin, Kristine H; Witte, Daniel R; Jørgensen, Marit E; Grarup, Niels; Pedersen, Oluf; Kilpeläinen, Tuomas O; Hansen, Torben

2017-05-01

Fasting plasma levels of branched-chain amino acids (BCAAs) are associated with insulin resistance, but it remains unclear whether there is a causal relation between the two. We aimed to disentangle the causal relations by performing a Mendelian randomisation study using genetic variants associated with circulating BCAA levels and insulin resistance as instrumental variables. We measured circulating BCAA levels in blood plasma by NMR spectroscopy in 1,321 individuals from the ADDITION-PRO cohort. We complemented our analyses by using previously published genome-wide association study (GWAS) results from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n = 46,186) and from a GWAS of serum BCAA levels (n = 24,925). We used a genetic risk score (GRS), calculated using ten established fasting serum insulin associated variants, as an instrumental variable for insulin resistance. A GRS of three variants increasing circulating BCAA levels was used as an instrumental variable for circulating BCAA levels. Fasting plasma BCAA levels were associated with higher HOMA-IR in ADDITION-PRO (β 0.137 [95% CI 0.08, 0.19] p = 6 × 10 -7 ). However, the GRS for circulating BCAA levels was not associated with fasting insulin levels or HOMA-IR in ADDITION-PRO (β -0.011 [95% CI -0.053, 0.032] p = 0.6 and β -0.011 [95% CI -0.054, 0.031] p = 0.6, respectively) or in GWAS results for HOMA-IR from MAGIC (β for valine-increasing GRS -0.012 [95% CI -0.069, 0.045] p = 0.7). By contrast, the insulin-resistance-increasing GRS was significantly associated with increased BCAA levels in ADDITION-PRO (β 0.027 [95% CI 0.005, 0.048] p = 0.01) and in GWAS results for serum BCAA levels (β 1.22 [95% CI 0.71, 1.73] p = 4 × 10 -6 , β 0.96 [95% CI 0.45, 1.47] p = 3 × 10 -4 , and β 0.67 [95% CI 0.16, 1.18] p = 0.01 for isoleucine, leucine and valine levels, respectively) and instrumental variable analyses in ADDITION

Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

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Vora, J P; Owens, D R; Dolben, J; Atiea, J A; Dean, J D; Kang, S; Burch, A; Brange, J

1988-11-12

To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. Study in normal people at a diabetes research unit and a university department of medical physics. Seven healthy male volunteers aged 20-39 not receiving any other drugs. After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and

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

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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.

The Association of Fasting Glucose, Insulin, and C-Peptide, with 19-Year Incidence of Coronary Heart Disease in Older Japanese-American Men; the Honolulu Heart Program

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Nazneem Wahab

2018-04-01

Full Text Available The role of fasting glucose, insulin levels, and C-peptide in coronary heart disease (CHD in non-diabetic individuals remains uncertain. We examined the association between fasting glucose, insulin and C-peptide with the long-term incidence of CHD in Japanese-American men. In 1980–1982, from a random sample of the Honolulu Heart Program men (n = 1378, aged 61–81 years, data on several CHD and metabolic risk factors were obtained to examine the relation of fasting glucose, insulin and C-peptide to 19-year CHD incidence. Age-adjusted incidence of CHD increased with increasing quintiles of glucose, insulin and C-peptide. Age-adjusted CHD rates in the glucose quintiles were 11.9, 11.6, 14.4, 18.1 and 24.1 per 1000 person-years (trend p < 0.001. In individual Cox models (lowest quintiles of glucose, insulin and C-peptide as reference the relative risks (95% confidence interval of CHD incidence for the glucose quintiles adjusting for age, smoking, hypertension, cholesterol, physical activity, and body mass index, were 0.9 (0.6–1.4, 1.2 (0.8–1.8, 1.4 (0.9–2.2, and 1.7 (1.1–2.6, respectively (trend p = 0.004. Insulin and C-peptide were not significantly associated with CHD on multivariate analysis. Fasting glucose remained the only significant predictor of increased CHD risk (p = 0.003 in a model combining all 3 metabolic variables. In this cohort, only fasting glucose independently predicts long-term incidence of CHD. Age-adjusted insulin and C-peptide levels were associated with CHD incidence, but after adjustment for other risk factors, do not independently predict CHD.

Fasting and Systemic Insulin Signaling Regulate Phosphorylation of Brain Proteins That Modulate Cell Morphology and Link to Neurological Disorders.

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Li, Min; Quan, Chao; Toth, Rachel; Campbell, David G; MacKintosh, Carol; Wang, Hong Yu; Chen, Shuai

2015-12-11

Diabetes is strongly associated with cognitive decline, but the molecular reasons are unknown. We found that fasting and peripheral insulin promote phosphorylation and dephosphorylation, respectively, of specific residues on brain proteins including cytoskeletal regulators such as slit-robo GTPase-activating protein 3 (srGAP3) and microtubule affinity-regulating protein kinases (MARKs), in which deficiency or dysregulation is linked to neurological disorders. Fasting activates protein kinase A (PKA) but not PKB/Akt signaling in the brain, and PKA can phosphorylate the purified srGAP3. The phosphorylation of srGAP3 and MARKs were increased when PKA signaling was activated in primary neurons. Knockdown of PKA decreased the phosphorylation of srGAP3. Furthermore, WAVE1, a protein kinase A-anchoring protein, formed a complex with srGAP3 and PKA in the brain of fasted mice to facilitate the phosphorylation of srGAP3 by PKA. Although brain cells have insulin receptors, our findings are inconsistent with the down-regulation of phosphorylation of target proteins being mediated by insulin signaling within the brain. Rather, our findings infer that systemic insulin, through a yet unknown mechanism, inhibits PKA or protein kinase(s) with similar specificity and/or activates an unknown phosphatase in the brain. Ser(858) of srGAP3 was identified as a key regulatory residue in which phosphorylation by PKA enhanced the GAP activity of srGAP3 toward its substrate, Rac1, in cells, thereby inhibiting the action of this GTPase in cytoskeletal regulation. Our findings reveal novel mechanisms linking peripheral insulin sensitivity with cytoskeletal remodeling in neurons, which may help to explain the association of diabetes with neurological disorders such as Alzheimer disease. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Observations on the presence of insulin resistance in patients with essential hypertension and coronary heart disease

International Nuclear Information System (INIS)

Zhu Mei; Wu Guo

2006-01-01

Objective: To investigate the presence of insulin resistance in patients with essential hypertension (EH) and coronary heart disease (CHD). Methods: Fasting and 2h post oral 75g glucose blood sugar (with oxidase method), insulin and C-peptide (with RIA) levels were examined in 52 patients with EH, 40 patients with CHD and 35 controls. Results: The fasting and 2h post o- ral glucose serum levels of glucose, insulin and C-peptide in the patients were significantly higher than those in the controls (P < 0.01), suggesting presence of impaired glucose tolerance and insulin resistance. Conclusion: Impaired glucose tolerance due to insulin resistance was demonstrated in the studied patients with EH or CHD. (authors)

Fasting and feeding variations of insulin requirements and insulin binding to erythrocytes at different times of the day in insulin dependent diabetics--assessed under the condition of glucose-controlled insulin infusion.

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Hung, C T; Beyer, J; Schulz, G

1986-07-01

Nine insulin-dependent diabetic patients were examined for insulin requirement, counterregulatory hormones, and receptor binding during their connection to glucose-controlled insulin infusion system. They were of 103% ideal body weight. A diet of 45% carbohydrate, 20% protein and 35% fat was divided into three meals and three snacks averaging the daily calorie intake of 1859 kcal. Following an equilibrating phase of 14 hours after the connection to the glucose-controlled insulin infusion system the blood samples were taken at 0800, 1200 and 1800. The insulin infusion rate increased at 0300 in the early morning from 0.128 mU/kg/min to 0.221 mU/kg/min (P less than 0.02). The postprandial insulin infusion rate jumped from 0.7 U/h (0700-0800) to 7.5 U/h (0800-0900). The calorie related and carbohydrate related insulin demands after breakfast were also highest and declined after lunch respectively (1.16 uU/kg/min kj vs. 0.61 uU/kg/min kj, P less than 0.05 and 236 mU/g CHO vs. 129 mU/g CHO and 143 mU/g CHO). Of the counterregulatory hormones the cortisol showed a significant diurnal rhythm to insulin demands. The insulin tracer binding was higher at 0800 before breakfast than that at 1200 before lunch (P less than 0.05). The increased binding could be better attributed to receptor concentration change than to affinity change. The cause of insulin relative insensitivity in the morning could be due to altered liver response to the cortisol peak in type 1 diabetics. The preserved variation of insulin binding in our patients might be referred to feeding.

Association of paraoxonase-1 gene polymorphisms with insulin resistance in South Indian population.

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Gomathi, Panneerselvam; Iyer, Anandi Chandramouli; Murugan, Ponniah Senthil; Sasikumar, Sundaresan; Raj, Nancy Bright Arul Joseph; Ganesan, Divya; Nallaperumal, Sivagnanam; Murugan, Maruthamuthu; Selvam, Govindan Sadasivam

2018-04-15

Insulin resistance plays a crucial role in the pathogenesis of type 2 diabetes and cardiovascular diseases. Recently, paraoxonase-1(PON1) is reported to have an ability to reduce insulin resistance by promoting glucose transporter-4 (GLUT-4) expression in vitro. Single nucleotide polymorphism (SNP) in PON1 is associated with variability in enzyme activity and concentration. Based on this we aimed to investigate the association of PON1 (Q192R and L55M) polymorphisms with the risk of developing insulin resistance in adult South Indian population. Two hundred and eighty seven (287) Type 2 diabetes patients and 293 healthy controls were enrolled in this study. All the study subjects were genotyped for PON1 (Q192R and L55M) missense polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) method. Fasting serum insulin level was measured by ELISA. The distribution of QR/RR and LM/MM genotypes were significantly higher in type 2 diabetes patients compared with healthy controls. Moreover, the R and M alleles were significantly associated with type 2 diabetes with an Odds Ratio of 1.68 (P  R genotypes were found to be significantly associated with higher BMI, cholesterol, triglycerides, LDL, fasting serum insulin and HOMA-IR. Further, the mutant allele or genotypes of PON1 L55M were associated with higher BMI, triglycerides, VLDL, fasting serum insulin and HOMA-IR among adult type 2 diabetes patients. PON1 (Q192R and L55M) polymorphisms may play a crucial role in pathogenesis and susceptibility of insulin resistance thus leads to the development of type 2 diabetes in South Indian population. Copyright © 2018 Elsevier B.V. All rights reserved.

Association Between Insulin Resistance and Bone Structure in Nondiabetic Postmenopausal Women

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Shanbhogue, Vikram V; Finkelstein, Joel S; Bouxsein, Mary L

2016-01-01

computed tomography was used to assess bone density and microstructure at the distal radius and tibia. Fasting insulin and glucose was measured and insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR) with higher values indicating greater insulin resistance....... RESULTS: There was a negative association between HOMA-IR and bone size and a positive association between HOMA-IR and total vBMD, trabecular vBMD, trabecular thickness and cortical thickness at the radius and tibia. These relationships remained even after adjusting for body weight and other potential...

The Relationship between Serum 25-Hydroxyvitamin D Concentration, Cardiorespiratory Fitness, and Insulin Resistance in Japanese Men

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Xiaomin Sun

2014-12-01

Full Text Available Here, we aim to investigate the independent and combined associations of serum 25-hydroxyvitamin D (25(OHD and cardiorespiratory fitness (CRF with glucose metabolism. Fasting blood samples of 107 men aged 40–79 years were analyzed for 25(OHD, glucose, insulin, glycated hemoglobin, and lipid profile. Homeostasis model assessment of insulin resistance index (HOMA-IR was calculated from the fasting concentrations of glucose and insulin. Visceral fat area (VFA was determined by magnetic resonance imaging and CRF by measuring maximal oxygen uptake. Median 25(OHD concentration was 36.3 nmol/L, while the prevalence of 25(OHD deficiency was 74.8%. Participants with high CRF had significantly lower HOMA-IR, glycated hemoglobin, and insulin values than participants with low CRF (p < 0.05. Higher 25(OHD concentration was strongly correlated with lower HOMA-IR and insulin values independent of VFA (p < 0.01 but significantly affected by CRF. In the high CRF group, participants with higher 25(OHD concentration had lower HOMA-IR values than participants with low 25(OHD concentration (p < 0.05. Higher 25(OHD and CRF are crucial for reducing insulin resistance regardless of abdominal fat. In addition, higher 25(OHD concentration may strengthen the effect of CRF on reducing insulin resistance in middle-aged and elderly Japanese men with high CRF.

Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in non-obese patients with type 2 diabetes

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Lund, Søren S; Tarnow, Lise; Frandsen, Merete

2008-01-01

metformin than repaglinide (mean (95% confidence intervals), LDL cholesterol difference metformin versus repaglinide: AUC: -0.17 mmol/l (-0.26; -0.08)). AUC differences remained significant after adjusting for fasting levels. CONCLUSIONS: In non-obese T2DM patients, metformin reduced postprandial levels...... of glycaemia, triglycerides and FFA similarly compared to the prandial insulin secretagogue, repaglinide. Furthermore, metformin reduced fasting and postprandial cholesterolaemia and insulinaemia compared with repaglinide. These data support prescription of metformin as the preferred drug in non-obese patients......OBJECTIVE: Non-obese patients with type 2 diabetes (T2DM) are characterized by predominant defective insulin secretion. However, in non-obese T2DM patients, metformin, targeting insulin resistance, is non-inferior to the prandial insulin secretagogue, repaglinide, controlling overall glycaemia (Hb...

Effect of insulin resistance on intracellular signal transduction of vessels in diabetic

International Nuclear Information System (INIS)

Cen Rongguang; Wei Shaoying; Mo Xingju

2003-01-01

To investigate the relationship between the insulin resistance (IR) and the intracellular signal transduction of vessels, changes in fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), total cholesterol (TC), inositol triphosphate (IP 3 ), protein kinase C(PKC) and intracellular total calcium concentration in 31 diabetic patients were compared with those of 39 normal controls. The levels of FBG, FINS, TG and TC in diabetic patients were significantly higher than those of normal controls (P 3 and PKC in diabetic patients were significantly lower than those of normal controls (P<0.01). The results suggest that there is a causal relation between insulin resistance and abnormalities of cellular calcium metabolism and intracellular signal transduction of vessels

[Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy].

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Pesić, Milica; Zivić, Sasa; Radenković, Sasa; Velojić, Milena; Dimić, Dragan; Antić, Slobodan

2007-04-01

Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin) for basal insulin supply in patients with type 1 diabetes. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IT) were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15); 2. NPH insulin twice daily (n = 15); 3. insulin glargine once daily (n = 18). Meal time insulin aspart was continued in all groups. Fasting blood glucose (FBG) was lower in the glargine group (7.30+/-0.98 mmol/1) than in the twice daily NPH group (7.47+/-1.06 mmol/1), but without significant difference. FBG was significantly higher in the once daily NPH group (8.44+/-0.85 mmol/l; p < 0.05). HbAlc after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72+/-0.86% to 6.87+/-0.50%), as well as in the twice daily NPH group (from 7.80+/-0.83% to 7.01+/-0.63%). Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56+/-2.09) than in both NPH groups (9.0+/-1.65 in twice daily NPH group and 8.13+/-1.30 in other NPH group) (episodes/patients-month, p < 0.05). Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbAlc and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Regular meal frequency creates more appropriate insulin sensitivity and lipid profiles compared with irregular meal frequency in healthy lean women.

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Farshchi, H R; Taylor, M A; Macdonald, I A

2004-07-01

To investigate the impact of irregular meal frequency on circulating lipids, insulin, glucose and uric acid concentrations which are known cardiovascular risk factors. A randomised crossover dietary intervention study. Nottingham, UK--Healthy free-living women. A total of nine lean healthy women aged 18-42 y recruited via advertisement. A randomised crossover trial with two phases of 14 days each. In Phase 1, subjects consumed their normal diet on either 6 occasions per day (regular) or by following a variable meal frequency (3-9 meals/day, irregular). In Phase 2, subjects followed the alternative meal pattern to that followed in Phase 1, after a 2-week (wash-out) period. Subjects were asked to come to the laboratory after an overnight fast at the start and end of each phase. Blood samples were taken for measurement of circulating glucose, lipids, insulin and uric acid concentrations before and for 3 h after consumption of a high-carbohydrate test meal. Fasting glucose and insulin values were not affected by meal frequency, but peak insulin and AUC of insulin responses to the test meal were higher after the irregular compared to the regular eating patterns (P meal frequency was associated with higher fasting total (P meal frequency appears to produce a degree of insulin resistance and higher fasting lipid profiles, which may indicate a deleterious effect on these cardiovascular risk factors. : The Ministry of Health and Medical Education, IR Iran.

Relationships between endothelin and insulin receptor of red blood cell and insulin resistance in patients with hypertension

International Nuclear Information System (INIS)

Tong Qian; Zheng Yang; Xu Hui

2004-01-01

Objective: To find the relationships between endothelin (ET) and insulin resistance (IR) and insulin receptor (INSR) in patients with essential hypertension. Methods: Forty patients including 20 cases of essential hypertension disease (EHD) and 20 health persons were divided into experimental group and control group. Blood glucose, serum insulin, ET and the number of erythrocyte INSR in all patients during fasting condition were detected by radioimmunoassay and radiometric analysis. Results: Both insulin sensitivity index (ISI) and the number of INSR in EHD group were much less than that of control group, on the contrary, ET level of EHD group was significantly higher than that of control group (P<0.05). Statistical analysis demonstrated a negative correlation between ET and ISI and INSR number existed in EHD group. Conclusion: IR is a common phenomenon in patient with EHD and possibly due to decrease of INSR number. The ET levels are higher in patients with EHD than that in health people and correlate with INSR, and the change of INSR number is the possible mediator for their relationship

Oral insulin improves metabolic parameters in high fat diet fed rats

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LEANDRO C. LIPINSKI

2017-08-01

Full Text Available ABSTRACT Introduction/Aim: The gut has shown to have a pivotal role on the pathophysiology of metabolic disease. Food stimulation of distal intestinal segments promotes enterohormones secretion influencing insulin metabolism. In diabetic rats, oral insulin has potential to change intestinal epithelium behavior. This macromolecule promotes positive effects on laboratorial metabolic parameters and decreases diabetic intestinal hypertrophy. This study aims to test if oral insulin can influence metabolic parameters and intestinal weight in obese non-diabetic rats. Methods: Twelve weeks old Wistar rats were divided in 3 groups: control (CTRL standard chow group; high fat diet low carbohydrates group (HFD and HFD plus daily oral 20U insulin gavage (HFD+INS. Weight and food consumption were weekly obtained. After eight weeks, fasting blood samples were collected for laboratorial analysis. After euthanasia gut samples were isolated. Results: Rat oral insulin treatment decreased body weight gain (p<0,001, fasting glucose and triglycerides serum levels (p<0,05 an increased intestinal weight of distal ileum (P<0,05. Animal submitted to high fat diet presented higher levels of HOMA-IR although significant difference to CT was not achieved. HOMA-beta were significantly higher (p<0.05 in HFD+INS. Visceral fat was 10% lower in HFD+INS but the difference was not significant. Conclusions: In non-diabetic obese rats, oral insulin improves metabolic malfunction associated to rescue of beta-cell activity.

Hydrocortisone and insulin effect on oxidative phosphorylation in mitochondria of liver and spleen th rats exposed to fast neutrons

International Nuclear Information System (INIS)

Sutkovoj, D.A.; Alferov, A.N.; Letov, V.N.

1979-01-01

Total-body exposure of rats to fast neutrons (100 rad) elicits an increase in the content of 11-oxycorticosteroids in blood plasma and an appreciable decrease in the respiratory and phosphorylation activity of liver and spleen mitochondria. Administration of hydrocortisone (50 mg/kg) and particularly insulin (2 units/kg) intensifies energy generation in the liver. In the spleen, a beneficial effect was only produced by insulin. Glucocorticoid considerably aggravates the postradiation impairment of oxidative phosphorylation

Circulating glucagon to ghrelin ratio as a determinant of insulin resistance in hyperthyroidism.

Science.gov (United States)

Ağbaht, Kemal; Erdogan, Murat Faik; Emral, Rifat; Baskal, Nilgun; Güllü, Sevim

2014-02-01

Due to stimulated overall metabolism, a state of nutritional inadequacy often ensues, during thyrotoxicosis. We aimed to investigate circulating levels of some major components of the system that regulates energy stores, glucose, and fat metabolism, during thyrotoxicosis compared to euthyroidism. Fasting serum ghrelin, leptin, adiponectin, insulin, glucagon, glucose, as well as body fat composition were analyzed during thyrotoxicosis in 40 hyperthyroid patients (50.5 ± 15.2 years old, 22 females, 31 with Graves disease, and 9 with toxic nodular goiter). The same measurements were repeated an average 3 months later, when all patients achieved euthyroidism. Compared to euthyroidism, in thyrotoxicosis, patients had lower ghrelin and fat mass; had comparable insulin, HOMA-IR, glucagon, and leptin levels; higher levels of circulating adiponectin. Fasting serum glucose tended to be higher during thyrotoxicosis. The unique correlation of HOMA-IR was with the-glucagon to ghrelin ratio-(r = 0.801, p hyperthyroidism. The fasting HOMA-IR tends to be higher, despite the decreased adiposity in hyperthyroidism. The-glucagon to ghrelin ratio-strongly correlates with fasting HOMA-IR in hyperthyroidism.

Relationship between insulin resistance and tissue blood flow in preeclampsia.

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Anim-Nyame, Nick; Gamble, John; Sooranna, Suren R; Johnson, Mark R; Steer, Philip J

2015-05-01

Preeclampsia is characterized by generalized endothelial dysfunction and impaired maternal tissue perfusion, and insulin resistance is a prominent feature of this disease. The aim of this study was to test the hypothesis that insulin resistance in preeclampsia is related to the reduced resting tissue blood flow. We used venous occlusion plethysmography to compare the resting calf muscle blood flow (measured as QaU) in 20 nulliparous women with preeclampsia and 20 normal pregnant controls matched for maternal age, gestational age, parity and BMI during the third trimester. Fasting blood samples were obtained to measure the plasma concentrations of insulin and glucose, and to calculate the fasting insulin resistance index (FIRI), a measure of insulin resistance in both groups of women. Calf blood flow was significantly reduced in the preeclampsia group (1.93 ± 0.86 QaU), compared with normal pregnant controls (3.94 ± 1.1 QaU, P insulin concentrations and Insulin Resistance Index were significantly higher in preeclampsia compared with normal pregnancy (P insulin concentrations (r = -0.57, P = 0.008) and FIRI (r = -0.59, P = 0.006) in preeclampsia, but not in normal pregnancy. These findings support our hypothesis and raise the possibility that reduced tissue blood flow may a play a role in the increased insulin resistance seen in preeclampsia.

High serum fasting peptide YY (3-36) is associated with obesity-associated insulin resistance and type 2 diabetes.

Science.gov (United States)

Ukkola, Olavi H; Puurunen, Veli-Pekka; Piira, Olli-Pekka; Niva, Jarkko T; Lepojärvi, E Samuli; Tulppo, Mikko P; Huikuri, Heikki V

2011-10-10

We studied whether serum fasting levels of active form of peptide YY (PYY), PYY(3-36), are associated with obesity and related phenotypes. The study population consisted of 428 patients with coronary artery disease and diagnosed type 2 diabetes and 440 patients with coronary artery disease but without evidence of diabetes from the ARTEMIS study. The patients were recruited from the consecutive series of patients undergoing coronary angiography in the Oulu University Hospital. The patients without diabetes underwent a 2-hour oral glucose tolerance test. PYY(3-36) levels were analyzed by human PYY(3-36) specific radioimmunoassay. Result suggested that when PYY(3-36) tertiles were considered, high serum fasting PYY(3-36) concentration was associated with high body mass index, waist circumference, hemoglobin A1c, fasting blood glucose, leptin, triglyceride (p for all p ≤ 0.001), serum insulin (p=0.013) and with a low high-density lipoprotein cholesterol (p=0.004) concentrations in the analyses adjusted for age, sex and study group. The link high PYY(3-36)-high insulin level was evident in subjects with normal glucose tolerance (pfasting glucose, impaired glucose tolerance and normal glucose tolerance (pfasting PYY(3-36) concentrations in type 2 diabetic subjects are high. Although high PYY(3-36) is strongly linked to obesity and associated insulin resistance, the relation between PYY(3-36) and type 2 diabetes is independent of body fatness. Copyright © 2011 Elsevier B.V. All rights reserved.

Treatment of severe insulin resistance in pregnancy with 500 units per milliliter of concentrated insulin.

Science.gov (United States)

Mendez-Figueroa, Hector; Maggio, Lindsay; Dahlke, Joshua D; Daley, Julie; Lopes, Vrishali V; Coustan, Donald R; Rouse, Dwight J

2013-07-01

To evaluate glycemic control and pregnancy outcomes among pregnant women with severe insulin resistance treated with 500 units/mL concentrated insulin. Retrospective analysis of gravid women with severe insulin resistance (need for greater than 100 units of insulin per injection or greater than 200 units/d) treated with either 500 units/mL concentrated insulin or conventional insulin therapy. We performed a two-part analysis: 1) between gravid women treated with and without 500 units/mL concentrated insulin; and 2) among gravid women treated with 500 units/mL concentrated insulin, comparing glycemic control before and after its initiation. Seventy-three pregnant women with severe insulin resistance were treated with 500 units/mL concentrated insulin and 78 with conventional insulin regimens. Patients treated with 500 units/mL concentrated insulin were older and more likely to have type 2 diabetes mellitus. Average body mass index was comparable between both groups (38.6 compared with 40.4, P=.11) as were obstetric and perinatal outcomes and glycemic control during the last week of gestation. Within the 500 units/mL concentrated insulin cohort, after initiation of this medication, fasting and postprandial blood glucose concentrations improved. However, the rates of blood glucose values less than 60 mg/dL and less than 50 mg/dL were higher in the 500 units/mL concentrated insulin group after initiation than before, 4.8% compared with 2.0% (Pinsulin in severely obese insulin-resistant pregnant women confers similar glycemic control compared with traditional insulin regimens but may increase the risk of hypoglycemia. II.

Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: A meta-analysis of 50,345 Caucasians

NARCIS (Netherlands)

A.M. Fretts (Amanda M.); J.L. Follis (Jack ); J.A. Nettleton (Jennifer ); R.N. Lemaitre (Rozenn ); J.S. Ngwa; M.K. Wojczynski (Mary ); I.-P. Kalafati (Ioanna-Panagiota); T.V. Varga (Tibor V.); A.C. Frazier-Wood (Alexis C.); D.K. Houston (Denise); J. Lahti (Jari); U. Ericson (Ulrika); E.H. van den Hooven (Edith); V. Mikkilä (Vera); J.C. Kiefte-de Jong (Jessica); D. Mozaffarian (Dariush); K.M. Rice (Kenneth); F. Renström (Frida); K.E. North (Kari); N.M. McKeown (Nicola ); M.F. Feitosa (Mary Furlan); S. Kanoni (Stavroula); C.E. Smith (Caren); M. Garcia (Melissa); A.-M. Tiainen (Anna-Maija); E. Sonestedt (Emily); A. Manichaikul (Ani); F.J.A. van Rooij (Frank); M. Dimitriou (Maria); O. Raitakari (Olli); J.S. Pankow (James); L. Djoussé (Luc); M.A. Province (Mike); F.B. Hu (Frank); C.-Q. Lai (Chao-Qiang); M.F. Keller (Margaux); M.-M. Perälä (Mia-Maria); J.I. Rotter (Jerome I.); A. Hofman (Albert); M.J. Graff (Maud J.L.); M. Kähönen (Mika); K. Mukamal (Kenneth); I. Johansson (Ingegerd); J.M. Ordovas (Jose); Y. Liu (YongMei); S. Männistö (Satu); A.G. Uitterlinden (André); P. Deloukas (Panagiotis); I. Seppälä (Ilkka); B.M. Psaty (Bruce); L.A. Cupples (Adrienne); I.B. Borecki (Ingrid); P.W. Franks (Paul W.); D.K. Arnett (Donna); M.A. Nalls (Michael); K. Hagen (Knut); M. Orho-Melander (Marju); O.H. Franco (Oscar); T. Lehtimäki (Terho); G.V. Dedoussis (George); J.B. Meigs (James); D.S. Siscovick (David)

2015-01-01

textabstractBackground: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. Objective: We investigated the

Serum LBP Is Associated with Insulin Resistance in Women with PCOS.

Science.gov (United States)

Zhu, Qibo; Zhou, Huang; Zhang, Aipin; Gao, Rufei; Yang, Shumin; Zhao, Changhong; Wang, Yue; Hu, Jinbo; Goswami, Richa; Gong, Lilin; Li, Qifu

2016-01-01

Lipopolysaccharide-binding protein (LBP) is closely associated with many metabolic disorders. However, no study has been done to explore the relationship between LBP and polycystic ovary syndrome (PCOS). The objective of this study was to investigate whether the serum LBP level is elevated and associated with insulin resistance (IR) in PCOS. In this cross-sectional study, 117 PCOS patients and 121 age-matched controls were recruited. Hyperinsulinemic-euglycemic clamp was performed with an expression of M value for insulin sensitivity. Fasting serum samples were collected to detect LBP, lipids, insulin, sex hormones and high sensitive C reactive protein (hs-CRP). Pearson's correlation and multiple linear regression was used to analyze the associations between M value and LBP level. The study was performed in a clinical research center. Compared with controls, PCOS subjects had a significantly higher LBP concentration (33.03±14.59 vs. 24.35±10.31 μg/ml, plean and overweight/obese individuals, serum LBP level was higher in PCOS subjects than that in controls. M value was negatively correlated with body mass index (BMI), fasting serum insulin, triglycerides, low-density lipoprotein cholesterol (LDL-c), free testosterone, high sensitive C reactive protein (hs-CRP) and LBP, whereas positively correlated with high-density lipoprotein cholesterol (HDL-c) and sex hormone binding globulin (SHBG). Serum LBP level was associated with M value after adjusting for BMI, fasting serum insulin, SHBG, as well as hs-CRP. Serum LBP level significantly is elevated in PCOS, and is independently associated with IR in PCOS.

Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

NARCIS (Netherlands)

Liu, Ching-Ti; Raghavan, Sridharan; Maruthur, Nisa; Kabagambe, Edmond Kato; Hong, Jaeyoung; Ng, Maggie C. Y.; Hivert, Marie-France; Lu, Yingchang; An, Ping; Bentley, Amy R.; Drolet, Anne M.; Gaulton, Kyle J.; Guo, Xiuqing; Armstrong, Loren L.; Irvin, Marguerite R.; Li, Man; Lipovich, Leonard; Rybin, Denis V.; Taylor, Kent D.; Agyemang, Charles; Palmer, Nicholette D.; Cade, Brian E.; Chen, Wei-Min; Dauriz, Marco; Delaney, Joseph A. C.; Edwards, Todd L.; Evans, Daniel S.; Evans, Michele K.; Lange, Leslie A.; Leong, Aaron; Liu, Jingmin; Liu, Yongmei; Nayak, Uma; Patel, Sanjay R.; Porneala, Bianca C.; Rasmussen-Torvik, Laura J.; Snijder, Marieke B.; Stallings, Sarah C.; Tanaka, Toshiko; Yanek, Lisa R.; Zhao, Wei; Becker, Diane M.; Bielak, Lawrence F.; Biggs, Mary L.; Bottinger, Erwin P.; Bowden, Donald W.; Chen, Guanjie; Correa, Adolfo; Couper, David J.; Crawford, Dana C.; Cushman, Mary; Eicher, John D.; Fornage, Myriam; Franceschini, Nora; Fu, Yi-Ping; Goodarzi, Mark O.; Gottesman, Omri; Hara, Kazuo; Harris, Tamara B.; Jensen, Richard A.; Johnson, Andrew D.; Jhun, Min A.; Karter, Andrew J.; Keller, Margaux F.; Kho, Abel N.; Kizer, Jorge R.; Krauss, Ronald M.; Langefeld, Carl D.; Li, Xiaohui; Liang, Jingling; Liu, Simin; Lowe, William L.; Mosley, Thomas H.; North, Kari E.; Pacheco, Jennifer A.; Peyser, Patricia A.; Patrick, Alan L.; Rice, Kenneth M.; Selvin, Elizabeth; Sims, Mario; Smith, Jennifer A.; Tajuddin, Salman M.; Vaidya, Dhananjay; Wren, Mary P.; Yao, Jie; Zhu, Xiaofeng; Ziegler, Julie T.; Zmuda, Joseph M.; Zonderman, Alan B.; Zwinderman, Aeilko H.; Adeyemo, Adebowale; Boerwinkle, Eric; Ferrucci, Luigi; Hayes, M. Geoffrey; Kardia, Sharon L. R.; Miljkovic, Iva; Pankow, James S.; Rotimi, Charles N.; Sale, Michele M.; Wagenknecht, Lynne E.; Arnett, Donna K.; Chen, Yii-Der Ida; Nalls, Michael A.; Province, Michael A.; Kao, W. H. Linda; Siscovick, David S.; Psaty, Bruce M.; Wilson, James G.; Loos, Ruth J. F.; Dupuis, Josée; Rich, Stephen S.; Florez, Jose C.; Rotter, Jerome I.; Morris, Andrew P.; Meigs, James B.

2016-01-01

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA)

A maternal high-fat, high-sucrose diet alters insulin sensitivity and expression of insulin signalling and lipid metabolism genes and proteins in male rat offspring: effect of folic acid supplementation.

Science.gov (United States)

Cuthbert, Candace E; Foster, Jerome E; Ramdath, D Dan

2017-10-01

A maternal high-fat, high-sucrose (HFS) diet alters offspring glucose and lipid homoeostasis through unknown mechanisms and may be modulated by folic acid. We investigated the effect of a maternal HFS diet on glucose homoeostasis, expression of genes and proteins associated with insulin signalling and lipid metabolism and the effect of prenatal folic acid supplementation (HFS/F) in male rat offspring. Pregnant Sprague-Dawley rats were randomly fed control (CON), HFS or HFS/F diets. Offspring were weaned on CON; at postnatal day 70, fasting plasma insulin and glucose and liver and skeletal muscle gene and protein expression were measured. Treatment effects were assessed by one-way ANOVA. Maternal HFS diet induced higher fasting glucose in offspring v. HFS/F (P=0·027) and down-regulation (Pinsulin resistance v. CON (P=0·030) and HFS/F was associated with higher insulin (P=0·016) and lower glucose (P=0·025). Maternal HFS diet alters offspring insulin sensitivity and de novo hepatic lipogenesis via altered gene and protein expression, which appears to be potentiated by folate supplementation.

Evaluation of chronic kidney disease patients for insulin resistance in tertiary care hospital

International Nuclear Information System (INIS)

Tahir, S.; Hayat, A.; Khan, S.A.; Ahmad, T.M.; Majeed, N.

2018-01-01

Objective: To evaluate the patients of chronic kidney disease for insulin resistance. Study Design: Cross sectional observational study. Place and Duration of Study: The study was conducted in the chemical pathology department of Army Medical College/Military Hospital Rawalpindi, from Nov 2016 to Apr 2017. Material and Methods: Fifty patients were recruited for this study with deranged renal functions and/or having any structural renal abnormality for more than 3 months. These patients did not have any history of diabetes and dialysis. Fifty ages matched healthy individuals were included as controls. Renal function tests, lipid profile, complete blood count, fasting plasma glucose and serum insulin levels were performed in all subjects. Insulin resistance was calculated by using homeostatic model for assessment of insulin resistance (HOMA-IR). Results of this study were analyzed on SPSS version 23. Results: Fasting insulin levels were much higher in the patient with chronic kidney disease as compared to controls (p-value=0.001). HOMA-IR in cases was also significantly higher. Statistical comparison of lipid profile showed significant difference of only triglycerides level. Conclusion: HOMA-IR is markedly raised in the patients of chronic kidney disease. This indicates a significant association of chronic kidney disease with insulin resistance. (author)

Study on the phenomenon of insulin resistance (IR) in patients with acute cerebral infarction

International Nuclear Information System (INIS)

Chen Xinhua; Wang Genfa; Yu Lihua

2007-01-01

Objective: To investigate the presence of insulin resistance (IR) in patients with cerebral infarction and the indication for insulin therapy. Methods: Fasting blood glucose (FPG) (with biochemistry), fasting serum insulin (FINS) and cortisol (with RIA) levels were measured in 50 patients with cerebral infarction and 80 controls. Insulin sensitivity index (ISI) was calculated and correlation with the score of neurologic impairment as well as the size of lesion was studied. Results: FPG, FINS and cortisol levels in the patients were significantly higher than those in the controls (P<0.001 ) while the ISI was significantly lower (P <0.001 ) than that in the controls. Levels of there parameters were significantly higher in patients with moderate-severe lesions than those in patients with only mild lesion (P<0.001, P<0.01, P<0.05 respectively). ISI was negatively correlated to the size of infarction (r=-0.313, P<0.05) and also to the score of neurologic impairment (r=-0.317, P<0.05). The mortality and morbidity in the moderate severe group were naturally higher than those in the mild group. Conclusion: Insulin resistance does exist during the acute stage of cerebral infarction. Degree of hyperinsulinaemia and severity of the resistance are related to the course and prognosis of the disease process. Insulin therapy should be considered in those patients with hyperglycemia. (authors)

Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians

Science.gov (United States)

Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. We investigated the associations of meat intake and the intera...

Preliminary evidence for obesity and elevations in fasting insulin mediating associations between cortisol awakening response and hippocampal volumes and frontal atrophy.

Science.gov (United States)

Ursache, Alexandra; Wedin, William; Tirsi, Aziz; Convit, Antonio

2012-08-01

Recent studies have demonstrated alterations in the cortisol awakening response (CAR) and brain abnormalities in adults with obesity and type 2 diabetes mellitus (T2DM). While adolescents with T2DM exhibit similar brain abnormalities, less is known about whether brain impairments and hypothalamic-pituitary-adrenal (HPA) axis abnormalities are already present in adolescents with pre-diabetic conditions such as insulin resistance (IR). This study included 33 adolescents with IR and 20 without IR. Adolescents with IR had a blunted CAR, smaller hippocampal volumes, and greater frontal lobe atrophy compared to controls. Mediation analyses indicated pathways whereby a smaller CAR was associated with higher BMI which was in turn associated with fasting insulin levels, which in turn was related to smaller hippocampal volume and greater frontal lobe atrophy. While we had hypothesized that HPA dysregulation may result from brain abnormalities, our findings suggest that HPA dysregulation may also impact brain structures through associations with metabolic abnormalities. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy

Directory of Open Access Journals (Sweden)

Pešić Milica

2007-01-01

Full Text Available Background/Aim. Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin for basal insulin supply in patients with type 1 diabetes. Methods. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IIT were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15; 2. NPH insulin twice daily (n = 15; 3. insulin glargine once daily (n = 18. Meal time insulin aspart was continued in all groups. Results. Fasting blood glucose (FBG was lower in the glargine group (7.30±0.98 mmol/l than in the twice daily NPH group (7.47±1.06 mmol/l, but without significant difference. FBG was significantly higher in the once daily NPH group (8.44±0.85 mmol/l; p < 0.05. HbA1c after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72±0.86% to 6.87±0.50%, as well as in the twice daily NPH group (from 7.80±0.83% to 7.01±0.63%. Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56±2.09 than in both NPH groups (9.0±1.65 in twice daily NPH group and 8.13±1.30 in other NPH group (episodes/patients-month, p < 0.05. Conclusion. Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbA1c and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Fasting Ghrelin Levels Are Decreased in Obese Subjects and Are Significantly Related With Insulin Resistance and Body Mass Index

Directory of Open Access Journals (Sweden)

Dimitrios Papandreou

2017-10-01

CONCLUSION: Obese subjects have low fasting ghrelin levels that they are significantly related to insulin resistance and body mass index. More prospective studies are needed to establish the role of ghrelin in the pathogenesis of human obesity.

Use of the oral sugar test in ponies when performed with or without prior fasting.

Science.gov (United States)

Knowles, E J; Harris, P A; Elliott, J; Menzies-Gow, N J

2017-07-01

It is recommended that the oral sugar test (OST) for insulin dysregulation (ID) be performed after an overnight fast, but fasting is impractical in ponies kept solely at pasture. There are few data on OST repeatability and reliability in ponies. To report 1) whether OST results obtained in the morning after an overnight fast or without fasting in the afternoon (FASTING/FED) can be used interchangeably, 2) time of highest insulin concentration T max [insulin], repeatability and reliability of insulin response to the OST when FASTING or FED and 3) dichotomous agreement (ID/normal) within a small sample when FASTING or FED. Method comparison study. Oral sugar tests were performed on four occasions in 10 adult native British ponies, twice FASTING and twice FED. Insulin concentrations were measured by radioimmunoassay at 0-120 min (T 0,30,60,75,90,120 ). Differences between FASTING and FED results were assessed using mixed effects models. Indices of repeatability and reliability were calculated; dichotomous agreement was reported using kappa statistics. Serum [insulin] was significantly (P≤0.05) higher at T 60 -T 90 with prior fasting (estimated differences [95% confidence intervals]): T 60 : 23.5 μiu/ml (8.7-38.4 μiu/ml), T 75 : 27.1 μiu/ml (12.3-41.8 μiu/ml), T 90 : 15.1 (0.36-29.9 μiu/ml). Most frequently, T max [ins] occurred at T 30 . At any single time point, within-subject coefficients of variation were: FASTING: 40% and FED: 31%. The 95% limits for repeatability were FASTING: 29-340%, FED: 41-240%. Test reliabilities were FASTING: 0.70 and FED: 0.67. For dichotomous interpretation similar results (kappa = 0.7) were obtained using cut-offs of [Insulin] >60 μiu/ml at T 60 or T 90 for FASTING and [Insulin] >51 μiu/ml at T 30 or T 60 for FED samples. Oral sugar tests were performed on a small number of animals on one pasture during one season (spring). Clinicians should beware of interpreting changes in absolute OST results owing to poor repeatability. When

Effect of insulin degludec versus insulin glargine on glycemic control and daily fasting blood glucose variability in insulin-naïve Japanese patients with type 2 diabetes: I'D GOT trial.

Science.gov (United States)

Aso, Yoshimasa; Suzuki, Kunihiro; Chiba, Yasuko; Sato, Minoru; Fujita, Nobuya; Takada, Yoshihisa; Murano, Shunichi; Kuroda, Hisamoto

2017-08-01

Insulin degludec (IDeg) is an ultra-long-acting insulin that has a smooth time/action profile over more than 42h. The present study compared the effects of IDeg and insulin glargine (IGlar) on HbA1c reduction and on within-subject day-to-day variability of fasting blood glucose (FBG) in insulin-naïve patients with type 2 diabetes. Eligible patients were randomly allocated at a 3:1 ratio to receive once-daily IDeg (n=31) or IGlar (n=12). Both basal insulins were administered before breakfast and titrated to achieve a target FBG <110mg/dl. The primary endpoints were the change in HbA1c from baseline to 24weeks of treatment, as well as the standard deviation (SD) and coefficient of variation (CV) of FBG from 8 to 12weeks and from 20 to 24weeks. Secondary endpoints included the QOL evaluated by the Diabetes Therapy-Related QOL questionnaire. After 24weeks, HbA1c was decreased by 1.6% in the IDeg group and 1.7% in the IGlar at the same insulin dosage. At 24weeks, FBG was significantly lower in the IDeg group than in the IGlar group and the CV of FBG was significantly smaller in the IDeg group. The frequency of total and severe hypoglycemic episodes did not differ between the groups. In the IDeg group, QOL showed significant improvement regarding anxiety and dissatisfaction with treatment. Treatment with IDeg or IGlar achieved similar improvement in glycemic control in insulin-naïve patients with type 2 diabetes. The day-to-day variation of FBG was smaller in patients receiving IDeg. Copyright © 2017. Published by Elsevier B.V.

Insulin resistance and lipid profile during an oral glucose tolerance test in women with and without gestational diabetes mellitus.

Science.gov (United States)

Liang, Zx; Wu, Y; Zhu, Xy; Fang, Q; Chen, Dq

2016-01-01

We aimed to compare changes in insulin levels during an oral glucose tolerance test (OGTT) between women with normal glucose tolerance (NGT) during pregnancy and those with gestational diabetes mellitus (GDM). Overall, 105 pregnant women between 24 and 28 weeks' gestation, 50 with NGT and 55 with GDM according to NDDG standard, were enrolled into the study. The levels of fasting blood glucose, insulin, triglyceride (TG) and total cholesterol (TC) and the insulin levels, blood glucose levels at 1, 2 and 3 hours post oral glucose administration during an OGTT (5.8, 10.6, 9.2 and 8.1 mmol/L, respectively) were measured. Then, insulin resistance (IR) index was calculated. There was no significant difference in fasting, 3-h insulin levels and 3-h blood glucose levels between those with NGT and those with GDM (P > 0.05). However, 1-h and 2-h insulin levels, fasting and 1-h and 2-h blood glucose levels in women with GDM were significantly higher than those in the NGT group (P < 0.05). Fasting TC and TG levels in the GDM group were significantly higher than those with NGT (P = 0.031 and P = 0.025, respectively). Correlation analysis showed that TG and TC levels were positively correlated with homoeostasis model assessment-IR (HOMA-IR) (r = 0.67 and r = 0.78, respectively; P < 0.05). Our findings suggest that insulin sensitivity in women with GDM was significantly lower than that observed in those with NGT. Reducing IR and blood lipids in women with GDM could potentially improve maternal and foetal outcomes.

Impaired fasting glycaemia vs impaired glucose tolerance: similar impairment of pancreatic alpha and beta cell function but differential roles of incretin hormones and insulin action

DEFF Research Database (Denmark)

Faerch, K; Vaag, A; Holst, Jens Juul

2008-01-01

.892) compared with NGT. Hepatic insulin sensitivity was normal in i-IFG and i-IGT individuals (p > or = 0.179). Individuals with i-IGT had peripheral insulin resistance (p = 0.003 vs NGT), and consequently the disposition index (DI; insulin secretion x insulin sensitivity) during IVGTT (DI(IVGTT))) was reduced......AIMS/HYPOTHESIS: The impact of strategies for prevention of type 2 diabetes in isolated impaired fasting glycaemia (i-IFG) vs isolated impaired glucose tolerance (i-IGT) may differ depending on the underlying pathophysiology. We examined insulin secretion during OGTTs and IVGTTs, hepatic...

Fast Food Pattern and Cardiometabolic Disorders: A Review of Current Studies.

Science.gov (United States)

Bahadoran, Zahra; Mirmiran, Parvin; Azizi, Fereidoun

2015-01-01

There are growing concern globally regarding the alarming trend of fast food consumption and its related cardiometabolic outcomes including overweight and obesity. This study aimed to review the current evidences available in relation to adverse effects of fast food pattern on cardiometa-bolic risk factors. Relevant articles including epidemiological and clinical studies with appropriate design and good quality were obtained through searches of the Medline, PubMed, Scopus databases and Google scholar with related key words including "fast foods", "processed foods", "obesity", "overweight", "insulin resistance", "diabetes", "cardiovascular disease", "metabolic syndrome", "dyslipidemia" and "hypertension". Fast food consumption and out-of-home eating behavior is a main risk factor for lower diet quality, higher calorie and fat intake and lower micronutrients density of diet. Frequent consumption of fast foods was accompanied with overweight and abdominal fat gain, impaired insulin and glucose homeostasis, lipid and lipoprotein disorders, induction of systemic inflammation and oxidative stress. Higher fast food consumption also increases the risk of developmental diabetes, metabolic syndrome and cardiovascular disease. This review provides further evidence warning us against the irreparable effects of fast food consumption on public health especially the increasing global burden of obesity and cardiovascu-lar diseases.

Glucose tolerance, insulin release, and insulin binding to monocytes in kidney transplant recipients

International Nuclear Information System (INIS)

Briggs, W.A.; Wielechowski, K.S.; Mahajan, S.K.; Migdal, S.D.; McDonald, F.D.

1982-01-01

In order to evaluate glucose tolerance following renal transplantation, intravenous glucose tolerance tests (IVGTT), with evaluation of hormonal responses to the intravenous glucose load and percent specific 125 I-insulin binding to peripheral blood monocytes, were studied in eight clinically stable kidney transplant recipients. For comparison purposes, identical studies were done in eight control subjects and seven clinically stable hemodialysis patients. One transplant recipient was glucose intolerant, with fasting hyperglycemia, elevated HbA1C, and abnormal glucose decay constant. Impaired pancreatic insulin release appeared to be the major factor accounting for his glucose intolerance. The seven glucose-tolerant transplant recipients had significantly increased insulin release during IVGTT compared to control subjects, and significant correlations were found among insulin release, glucose decay constant, and fasting blood sugar in those patients. Insulin binding to monocytes was significantly greater in transplant recipients than control subjects due to an increase in insulin binding capacity per cell. A significant correlation was found between percent specific 125 I-insulin binding and steroid dose, expressed as mg/kg body weight/day, in those patients. Thus, chronic steroid administration does not cause glucose intolerance in transplant recipients who manifest steroid-associated increases in pancreatic insulin release and cellular insulin binding capacity

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

Insulin resistance and glucose levels in subjects with subclinical hypothyroidism

International Nuclear Information System (INIS)

Kahn, S.H.; Fazal, N.; Yasir, M.; Asif, N.; Rafi, T.

2017-01-01

To compare insulin resistance and glycemic indicators among subjects with euthyroidism and subclinical hypothyroidism. Study Design: Comparative cross-sectional study. Place and Duration of Study: Department of Pathology and Medicine, PNS Hafeez, Islamabad, in collaboration with the Department of Chemical Pathology and Endocrinology at the Armed Forces Institute of Pathology (AFIP), Rawalpindi, from December 2015 to September 2016. Methodology: Subjects referred for executive screening of apparently healthy population (without any known history of diabetes, hypertension, heart disease or other chronic ailments), were included. Subjects were grouped as euthyroidism and subclinical hypothyroidism. Results: Median (IQR) insulin resistance indices including fasting insulin and Homeostasis Model Assessment for Insulin Resistance in subjects with group-1 (n=176, 87%, Thyroid Stimulating Hormone: 0.5 - 3.5 mIU/L) and group-2 (n=26, 13%, Thyroid Stimulating Hormone: 3.51 - 15 mIU/L) were 7.6 (6.70) vs. 11.4 (13.72, p=0.040) and 1.77 (1.79) vs. 2.8 (3.07, p=0.071). The median differences for fasting plasma glucose were 5.0 (1.0) in group-1 vs. 5.0 (1.47) for Group-2 [p=0.618], and glycated hemoglobin was 5.60 (1.1) vs. 5.60 (1.7, p=0.824). Homeostasis Model Assessment for beta sensitivity index in paradox showed slightly higher values for group-2 [median (IQR) 86.67 (92.94)] than group-1 [111.6 (189.64, p= 0.040)]. Conclusion: Measures of insulin resistance including Homeostasis Model Assessment for Insulin Resistance and fasting insulin levels were significantly different between subjects with euthyroidism and having subclinical hypothyroidism. (author)

The relationship between insulin resistance and the change of cytosol free calcium concentration in gestational diabetes mellitus

International Nuclear Information System (INIS)

Li Pu; Zheng Lei; Cen Rongguang; Song Yangxiu

2004-01-01

To investigate the relationship between the insulin resistance (IR) and abnormalities of cellular calcium metabolism in gestational diabetes mellitus, the changes in the [Ca 2+ ]i and the insulin receptor tyrosine kinase activity in circulating erythrocytes of 32 cases gestational diabetes were compared with those of 47 normal pregnant and 43 non pregnant women. The level of [Ca 2+ ]i in circulating erythrocyte in gestational diabetes mellitus women was significantly higher than that in the pregnant and non pregnant women (P 2+ ]i in circulating erythrocytes in gestational diabetes mellitus was positively correlated with fasting blood glucose and fasting insulin, negatively with the insulin receptor tyrosine kisase activity (P 2+ ]i level during the gastational period might be one of the possible factor in the insulin resistance of gestaional diabetes mellitus. (authors)

Brain natriuretic peptide and insulin resistance in older adults.

Science.gov (United States)

Kim, F; Biggs, M L; Kizer, J R; Brutsaert, E F; de Filippi, C; Newman, A B; Kronmal, R A; Tracy, R P; Gottdiener, J S; Djoussé, L; de Boer, I H; Psaty, B M; Siscovick, D S; Mukamal, K J

2017-02-01

Higher levels of brain natriuretic peptide (BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established. N-terminal of the pro hormone brain natriuretic peptide (NT-pro BNP) was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-proBNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-proBNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-proBNP levels on insulin resistance. Lower NT-proBNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors (P insulin resistance (P = 0.38; P = 0.01 for comparison with the association of measured levels of NT-proBNP). In older adults, lower NT-proBNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study. © 2016 Diabetes UK.

Intermittent fasting modulation of the diabetic syndrome in sand rats. III. Post-mortem investigations.

Science.gov (United States)

Belkacemi, Louiza; Selselet-Attou, Ghalem; Bulur, Nurdan; Louchami, Karim; Sener, Abdullah; Malaisse, Willy J

2011-01-01

The present report concerns several post-mortem variables examined in sand rats that were either maintained on a vegetal diet (control animals) or exposed first during a 20-day transition period to a mixed diet consisting of a fixed amount of a hypercaloric food and decreasing amounts of the vegetal food and then to a 30-day experimental period of exposure to the hypercaloric food. During the latter period, all animals were either given free access to food or fasting daily for 15 h, i.e. from 5.00 p.m. to 8.00 a.m. The body weight, liver wet weight, pancreas wet weight, plasma glucose and haemoglobin A1c concentration, plasma insulin concentration, insulinogenic index, insulin resistance HOMA, plasma cholesterol and triglyceride concentration, liver triglyceride and phospholipid content were all measured. Pancreatic islet (insulin, GLUT2) and liver (lipid droplets) histology were also examined. The main findings consisted in a lower body weight of fasting than non-fasting animals, a higher liver weight in non-diabetic and diabetic rats than in control non-fasting (but not so in fasting) animals, a decrease of pancreas weight in non-diabetic and diabetic as distinct from control animals, a fasting-induced decrease in plasma glucose, plasma insulin and insulin resistance HOMA, plasma cholesterol and triglyceride concentration and triglyceride liver content.

Insulin and C peptide response, and antibody levels in hepatitis C related chronic liver disease

International Nuclear Information System (INIS)

Abbas, Z.; Tariq, N.; Iqbal, M.; Shah, M.A.

2002-01-01

Objective: Patients with cirrhosis due to hepatitis C (HC) have an increased prevalence of diabetes mellitus. The pathogenic mechanism by which HC predisposes to DM is not clear. The objective of this study was to determine the insulin and C-peptide response to 75 gram oral glucose load and measure anti phospholipid antibody levels in patients with chronic liver disease due to HC. Design: a prospective study. Place and duration of study: This study was conducted at the department of medicine, Jinnah postgraduate medical centre over period of three months. Subjects and methods: An analytical case control study was carried out on 37 patients (m-18,f=19); none of these patients had received interferon. They were divided into four groups: (a) HC cirrhosis with DM (n=9 ), (b) HC cirrhosis without DM (n=11), (c) hepatitis B (HB) cirrhosis without DM (n=7), (d) chronic hepatitis C without DM (n=10). Group C and D were taken as controls. Fasting blood samples were taken and repeated after 2 hours of 75 gram oral glucose load (2 h PG). Result: mean ages of group A,B,C and D were (yr +- SD) 51.3 +- 7.6,48.9 +- 2.4, 33.7 +-10.8 and 31.7 +- 8.8 respectively. There was no statistically significant difference in the age, Pugh score and body mass index of HC cirrhotic patients with and without DM. Patients of group A had higher fasting and 2 h PG glucose levels (P=0.003 and 0.000) and higher fasting insulin level (p=0.045). However, increments in insulin and c peptide levels 2 h PG were much less (p=0.048 and 0.003). HB cirrhotics without diabetes (group C behaved just like HC cirrhotic without diabetes (group B). Patients of group D had normal glucose tolerance and insulin and C peptide levels. All four groups had normal anti phospholipid antibody levels. Conclusion: Patients with cirrhosis due to HC nd HB show evidence of glucose intolerance in spite of hyperinsulinaemia probably due to insulin resistance. HC cirrhotics with diabetes have fasting hyperglycemia in spite of

Association of serum sparc with insulin resistance in type-2 diabetes mellitus

International Nuclear Information System (INIS)

Nadeem, K.; Ahmed, U.; Arif, H.

2017-01-01

Objective: To determine the association of serum SPARC with insulin resistance in type-2 diabetes. Study Design: Descriptive study. Place and Duration of Study: Physiology department and CREAM lab, Army medical college, Rawalpindi, in collaboration with Military Hospital Rawalpindi, from Feb 2016 to Oct 2016. Material and Methods: Sixty individuals were recruited in this descriptive study. Thirty diagnosed cases of type- 2 DM were included, while thirty age and gender matched healthy individuals were included as controls through non-probability purposive sampling. Controls were labelled as group A, while cases were labelled as group B. Patients with type-1 DM, type-2 DM on insulin therapy, hyperglycemic states other than DM and inflammatory disorders were excluded from the study. Data were collected after informed and written consent. Blood samples were withdrawn under strict aseptic measures and serum was stored at -20 degree C. Serum insulin levels and serum SPARC levels were analyzed by enzyme linked immunosorbent assay (ELISA). Insulin resistance was determined using homeostasis model assessment of insulin resistance (HOMA-IR), and its value >1.5 was considered significant. Results: Fasting insulin levels were significantly higher in group B as compared with group A, supporting the diagnosis of type-2 DM. HOMA-IR values were greater than 1.5 in group B, thus establishing significant insulin resistance. Serum SPARC levels were significantly higher in group B than group A (17.7 ± 1.14 vs 8.7 ± 1.08 ng/ml) with p-value<0.001. Serum SPARC levels showed positive correlation with fasting insulin levels and HOMA-IR values. Conclusion: Our study showed a positive correlation between serum SPARC levels and insulin resistance, which indicates that SPARC plays an important role in the development of insulin resistance in type-2 diabetes mellitus. (author)

Red meat intake, insulin resistance, and markers of endothelial function among Iranian women.

Science.gov (United States)

Barak, Farzaneh; Falahi, Ebrahim; Keshteli, Ammar Hassanzadeh; Yazdannik, Ahmadreza; Saneei, Parvane; Esmaillzadeh, Ahmad

2015-02-01

Few data, with conflicting findings, are available linking red meat consumption to indicators of insulin resistance and endothelial dysfunction. This study aimed to investigate the association of red meat consumption with insulin resistance and endothelial dysfunction among a sample of female nurses in Isfahan, Iran. This cross-sectional study was carried out among 420 female nurses who were selected by a multistage cluster random sampling method. Usual dietary intakes were assessed using a validated food frequency questionnaire. Red meat intake was calculated by summing up the consumption of all kinds of red meat in foods and processed meat in sausages and fast foods. To measure serum concentrations of adhesion molecules and glycemic indexes, a fasting blood sample was taken. After adjustment for potential confounders, high red meat intake was significantly associated with higher fasting plasma glucose, homeostasis model assessment of insulin resistance, and lower quantitative insulin sensitivity check index. Although high red meat intake was significantly associated with higher serum insulin levels and lower homeostasis model assessment of beta-cell function in the crude model, after controlling for BMI, the association was no longer significant. Red meat consumption was associated with high concentrations of E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble intercellular adhesion molecule-1 (sICAM-1) after adjustment for different potential confounders. We found that increased red meat intake was associated with high concentrations of plasma endothelial dysfunction biomarkers and abnormal glucose homeostasis among Iranian women. Prospective studies are required to confirm these findings. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Triglycerides/glucose index is a useful surrogate marker of insulin resistance among adolescents.

Science.gov (United States)

Kang, B; Yang, Y; Lee, E Y; Yang, H K; Kim, H-S; Lim, S-Y; Lee, J-H; Lee, S-S; Suh, B-K; Yoon, K-H

2017-05-01

Our aim was to investigate the association between the triglycerides/glucose index (TyG index) and the homeostasis model assessment-estimated insulin resistance (HOMA-IR) in the prediction of insulin resistance (IR) among adolescents. We conducted a cross-sectional study among 221 Korean adolescents (168 males and 53 females aged 9-13 years) from May to June 2014 in Chung-ju city. The TyG index was calculated as ln [triglycerides (mg dl -1 ) × fasting glucose (mg dl -1 )/2]. IR was defined using HOMA-IR >95th percentile for age and sex. In the IR group, weight, body mass index (BMI), waist circumference, body fat, fasting insulin, fasting plasma glucose, triglyceride levels and triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) were significantly higher than that in the non-IR group. The TG index was significantly different between the IR group (n=22) and non-IR group (n=199), at 8.43±0.45 and 8.05±0.41, respectively (Pindex was well correlated with HOMA-IR (r=0.41; Pindex for diagnosis of insulin resistance was 8.18. The TyG index is a simple, cost-effective surrogate marker of insulin resistance among adolescents compared with HOMA-IR.

Insulin sensitivity is reduced in children with high body-fat regardless of BMI

DEFF Research Database (Denmark)

Fairchild, Timothy J; Klakk, Heidi; Heidemann, Malene

2018-01-01

BF% was measured by dual-energy X-ray absorptiometry (DXA). Fasting plasma glucose and insulin concentrations were measured and the homoeostatic model assessment of insulin resistance (HOMA-IR) used to assess insulin sensitivity. RESULTS: Approximately 8% of children classified as normal weight...... by BMI had high BF% (NW + Adipose). Children with high BF% had significantly higher insulin (NW + adipose: 32.3%; OW/OB + Adipose: 52.2%) and HOMA-IR scores (NW + Adipose: 32.3%; OW/OB + Adipose: 55.3%) than children classified as NW without high BF% (reference group; NW + NonAdipose). Adjusting for CRF...

Insulin aspart in diabetic pregnancy

DEFF Research Database (Denmark)

Mathiesen, Elisabeth R

2008-01-01

in insulin requirements during pregnancy necessitate short-acting insulins for postprandial control of hyperglycemia. The fast-acting insulin analogue insulin aspart has been tested in a large, randomized trial of pregnant women with Type 1 diabetes and offers benefits in control of postprandial...... hyperglycemia with a tendency towards fewer episodes of severe hypoglycemia compared with human insulin. Treatment with insulin aspart was associated with a tendency toward fewer fetal losses and preterm deliveries than treatment with human insulin. Insulin aspart could not be detected in the fetal circulation...... and no increase in insulin antibodies was found. Thus, the use of insulin aspart in pregnancy is regarded safe....

In nondiabetic, human immunodeficiency virus-infected patients with lipodystrophy, hepatic insulin extraction and posthepatic insulin clearance rate are decreased in proportion to insulin resistance

DEFF Research Database (Denmark)

Haugaard, Steen B; Andersen, Ove; Hansen, Birgitte R

2005-01-01

In healthy, nondiabetic individuals with insulin resistance, fasting insulin is inversely correlated to the posthepatic insulin clearance rate (MCRi) and the hepatic insulin extraction (HEXi). We investigated whether similar early mechanisms to facilitate glucose homeostasis exist in nondiabetic...... > .1). Our data suggest that HEXi and MCRi are decreased in proportion to the degree of insulin resistance in nondiabetic HIV-infected patients with lipodystrophy....... insulin clearance rate was estimated as the ratio of posthepatic insulin appearance rate to steady-state plasma insulin concentration during a euglycemic hyperinsulinemic clamp (40 mU.m-2 .min-1). Posthepatic insulin appearance rate during the clamp was calculated, taking into account the remnant...

Some metabolic and anthropometric variables in obes children by measuring serum insulin, and leptin

International Nuclear Information System (INIS)

Nour Eldin, A.M.

2004-01-01

The present study aimed to assess serum leptin level in obese children to study its correlation with some metabolic variables as serum insulin and serum glucose. The study was conducted on 30 obese children of age from 9-14 years with body mass index (BMI) > 27.8 Kg/m 2 . All children were subjected to history taking, clinical examination, anthropometric measurements and laboratory investigations including fasting serum leptin, insulin and blood glucose. Serum leptin was significantly higher in obese children (102.3± 56.2 ng/ml) compared to non-obese ones (48.15±26.1 ng/ml). The relation between serum leptin and anthropometric measurements and laboratory investigations including fasting serum insulin and blood glucose. Serum leptin was significantly higher in obese children (102.3± 56.2 ng/ml)compared to non-obese ones (48.15±26.1 ng/ml). The relation between serum leptin and anthropometric variables was positively correlated with BMI r s = 0.68, (p s = 0.59.(p<0.01). It is concluded that serum leptin is increased in obesity and its concentration effects the size of the body. Moreover, the relation of leptin and insulin suggests a positive role of leptin in insulin resistance, which are common metabolic disorders associated with obesity

Serum LBP Is Associated with Insulin Resistance in Women with PCOS.

Directory of Open Access Journals (Sweden)

Qibo Zhu

Full Text Available Lipopolysaccharide-binding protein (LBP is closely associated with many metabolic disorders. However, no study has been done to explore the relationship between LBP and polycystic ovary syndrome (PCOS. The objective of this study was to investigate whether the serum LBP level is elevated and associated with insulin resistance (IR in PCOS.In this cross-sectional study, 117 PCOS patients and 121 age-matched controls were recruited. Hyperinsulinemic-euglycemic clamp was performed with an expression of M value for insulin sensitivity. Fasting serum samples were collected to detect LBP, lipids, insulin, sex hormones and high sensitive C reactive protein (hs-CRP. Pearson's correlation and multiple linear regression was used to analyze the associations between M value and LBP level.The study was performed in a clinical research center.Compared with controls, PCOS subjects had a significantly higher LBP concentration (33.03±14.59 vs. 24.35±10.31 μg/ml, p<0.001, and lower M value (8.21±3.06 vs. 12.31±1.72 mg/min/kg, p<0.001. Both in lean and overweight/obese individuals, serum LBP level was higher in PCOS subjects than that in controls. M value was negatively correlated with body mass index (BMI, fasting serum insulin, triglycerides, low-density lipoprotein cholesterol (LDL-c, free testosterone, high sensitive C reactive protein (hs-CRP and LBP, whereas positively correlated with high-density lipoprotein cholesterol (HDL-c and sex hormone binding globulin (SHBG. Serum LBP level was associated with M value after adjusting for BMI, fasting serum insulin, SHBG, as well as hs-CRP.Serum LBP level significantly is elevated in PCOS, and is independently associated with IR in PCOS.

Adiposity, insulin and lipid metabolism in post-menopausal women.

Science.gov (United States)

Lovegrove, J A; Silva, K D R R; Wright, J W; Williams, C M

2002-04-01

To investigate relationships between body fat and its distribution and carbohydrate and lipid tolerance using statistical comparisons in post-menopausal women. Sequential meal, postprandial study (600 min) which included a mixed standard breakfast (30 g fat) and lunch (44 g fat) given at 0 and 270 min, respectively, after an overnight fast. Twenty-eight post-menopausal women with a diverse range of body weight (body mass index (BMI), mean 27.2, range 20.5-38.8 kg/m2) and abdominal fat deposition (waist, mean 86.4, range 63.5-124.0 cm). Women with BMI 37 kg/m2, age > 80 y and taking hormone replacement therapy (HRT) were excluded. Anthropometric measurements were performed to assess total and regional fat deposits. The concentrations of plasma total cholesterol, high density lipoprotein (HDL) cholesterol, triacylglycerol (TAG), glucose, insulin (ins), non-esterified fatty acids (NEFA) and apolipoprotein (apo) B-48 were analysed in plasma collected at baseline (fasted state) and at 13 postprandial time points for a 600 min period. Insulin concentrations in the fasted and fed state were significantly correlated with all measures of adiposity (BMI, waist, waist-hip ratio (W/H), waist-height ratio (W/Ht) and sum of skinfold thickness (SSk)). After controlling for BMI, waist remained significantly and positively associated with fasted insulin (r=0.559) with waist contributing 53% to the variability after multiple regression analysis. After controlling for waist, BMI remained significantly correlated with postprandial (IAUC) insulin (r=0.535) contributing 66% of the variability of this measurement. No association was found between any measures of adiposity and glucose concentrations, although insulin concentration in relation to glucose concentration (glucose-insulin ratio) was significantly negatively correlated with all measures of adiposity. A significant positive correlation was found between fasted TAG and BMI (r=0.416), waist (r=0.393) and Ssk (r=0.457) and

Fast Food Pattern and Cardiometabolic Disorders: A Review of Current Studies

Directory of Open Access Journals (Sweden)

Zahra Bahadoran

2015-12-01

Full Text Available Background: There are growing concern globally regarding the alarming trend of fast food consump­tion and its related cardiometabolic outcomes including overweight and obesity. This study aimed to review the current evidences available in relation to adverse effects of fast food pattern on cardiometa­bolic risk factors. Methods: Relevant articles including epidemiological and clinical studies with appropriate design and good quality were obtained through searches of the Medline, PubMed, Scopus databases and Google scholar with related key words including "fast foods", "processed foods", "obesity", "overweight", "insulin resistance", "diabetes", "cardiovascular disease", "metabolic syndrome", "dyslipidemia" and "hypertension". Results: Fast food consumption and out-of-home eating behavior is a main risk factor for lower diet quality, higher calorie and fat intake and lower micronutrients density of diet. Frequent consumption of fast foods was accompanied with overweight and abdominal fat gain, impaired insulin and glucose homeostasis, lipid and lipoprotein disorders, induction of systemic inflammation and oxidative stress. Higher fast food consumption also increases the risk of developmental diabetes, metabolic syndrome and cardiovascular disease. Conclusion: This review provides further evidence warning us against the irreparable effects of fast food consumption on public health especially the increasing global burden of obesity and cardiovascu­lar diseases.

A low-frequency inactivating AKT2 variant enriched in the Finnish population is associated with fasting insulin levels and type 2 diabetes risk

Science.gov (United States)

Grarup, Niels; Rivas, Manuel A; Mahajan, Anubha; Locke, Adam E; Cingolani, Pablo; Pers, Tune H; Viñuela, Ana; Brown, Andrew A; Wu, Ying; Flannick, Jason; Fuchsberger, Christian; Gamazon, Eric R; Gaulton, Kyle J; Im, Hae Kyung; Teslovich, Tanya M; Blackwell, Thomas W; Bork-Jensen, Jette; Burtt, Noël P; Chen, Yuhui; Green, Todd; Hartl, Christopher; Kang, Hyun Min; Kumar, Ashish; Ladenvall, Claes; Ma, Clement; Moutsianas, Loukas; Pearson, Richard D; Perry, John R B; Rayner, N William; Robertson, Neil R; Scott, Laura J; van de Bunt, Martijn; Eriksson, Johan G; Jula, Antti; Koskinen, Seppo; Lehtimäki, Terho; Palotie, Aarno; Raitakari, Olli T; Jacobs, Suzanne BR; Wessel, Jennifer; Chu, Audrey Y; Scott, Robert A; Goodarzi, Mark O; Blancher, Christine; Buck, Gemma; Buck, David; Chines, Peter S; Gabriel, Stacey; Gjesing, Anette P; Groves, Christopher J; Hollensted, Mette; Huyghe, Jeroen R; Jackson, Anne U; Jun, Goo; Justesen, Johanne Marie; Mangino, Massimo; Murphy, Jacquelyn; Neville, Matt; Onofrio, Robert; Small, Kerrin S; Stringham, Heather M; Trakalo, Joseph; Banks, Eric; Carey, Jason; Carneiro, Mauricio O; DePristo, Mark; Farjoun, Yossi; Fennell, Timothy; Goldstein, Jacqueline I; Grant, George; de Angelis, Martin Hrabé; Maguire, Jared; Neale, Benjamin M; Poplin, Ryan; Purcell, Shaun; Schwarzmayr, Thomas; Shakir, Khalid; Smith, Joshua D; Strom, Tim M; Wieland, Thomas; Lindstrom, Jaana; Brandslund, Ivan; Christensen, Cramer; Surdulescu, Gabriela L; Lakka, Timo A; Doney, Alex S F; Nilsson, Peter; Wareham, Nicholas J; Langenberg, Claudia; Varga, Tibor V; Franks, Paul W; Rolandsson, Olov; Rosengren, Anders H; Farook, Vidya S; Thameem, Farook; Puppala, Sobha; Kumar, Satish; Lehman, Donna M; Jenkinson, Christopher P; Curran, Joanne E; Hale, Daniel Esten; Fowler, Sharon P; Arya, Rector; DeFronzo, Ralph A; Abboud, Hanna E; Syvänen, Ann-Christine; Hicks, Pamela J; Palmer, Nicholette D; Ng, Maggie C Y; Bowden, Donald W; Freedman, Barry I; Esko, Tõnu; Mägi, Reedik; Milani, Lili; Mihailov, Evelin; Metspalu, Andres; Narisu, Narisu; Kinnunen, Leena; Bonnycastle, Lori L; Swift, Amy; Pasko, Dorota; Wood, Andrew R; Fadista, João; Pollin, Toni I; Barzilai, Nir; Atzmon, Gil; Glaser, Benjamin; Thorand, Barbara; Strauch, Konstantin; Peters, Annette; Roden, Michael; Müller-Nurasyid, Martina; Liang, Liming; Kriebel, Jennifer; Illig, Thomas; Grallert, Harald; Gieger, Christian; Meisinger, Christa; Lannfelt, Lars; Musani, Solomon K; Griswold, Michael; Taylor, Herman A; Wilson, Gregory; Correa, Adolfo; Oksa, Heikki; Scott, William R; Afzal, Uzma; Tan, Sian-Tsung; Loh, Marie; Chambers, John C; Sehmi, Jobanpreet; Kooner, Jaspal Singh; Lehne, Benjamin; Cho, Yoon Shin; Lee, Jong-Young; Han, Bok-Ghee; Käräjämäki, Annemari; Qi, Qibin; Qi, Lu; Huang, Jinyan; Hu, Frank B; Melander, Olle; Orho-Melander, Marju; Below, Jennifer E; Aguilar, David; Wong, Tien Yin; Liu, Jianjun; Khor, Chiea-Chuen; Chia, Kee Seng; Lim, Wei Yen; Cheng, Ching-Yu; Chan, Edmund; Tai, E Shyong; Aung, Tin; Linneberg, Allan; Isomaa, Bo; Meitinger, Thomas; Tuomi, Tiinamaija; Hakaste, Liisa; Kravic, Jasmina; Jørgensen, Marit E; Lauritzen, Torsten; Deloukas, Panos; Stirrups, Kathleen E; Owen, Katharine R; Farmer, Andrew J; Frayling, Timothy M; O'Rahilly, Stephen P; Walker, Mark; Levy, Jonathan C; Hodgkiss, Dylan; Hattersley, Andrew T; Kuulasmaa, Teemu; Stančáková, Alena; Barroso, Inês; Bharadwaj, Dwaipayan; Chan, Juliana; Chandak, Giriraj R; Daly, Mark J; Donnelly, Peter J; Ebrahim, Shah B; Elliott, Paul; Fingerlin, Tasha; Froguel, Philippe; Hu, Cheng; Jia, Weiping; Ma, Ronald C W; McVean, Gilean; Park, Taesung; Prabhakaran, Dorairaj; Sandhu, Manjinder; Scott, James; Sladek, Rob; Tandon, Nikhil; Teo, Yik Ying; Zeggini, Eleftheria; Watanabe, Richard M; Koistinen, Heikki A; Kesaniemi, Y Antero; Uusitupa, Matti; Spector, Timothy D; Salomaa, Veikko; Rauramaa, Rainer; Palmer, Colin N A; Prokopenko, Inga; Morris, Andrew D; Bergman, Richard N; Collins, Francis S; Lind, Lars; Ingelsson, Erik; Tuomilehto, Jaakko; Karpe, Fredrik; Groop, Leif; Jørgensen, Torben; Hansen, Torben; Pedersen, Oluf; Kuusisto, Johanna; Abecasis, Gonçalo; Bell, Graeme I; Blangero, John; Cox, Nancy J; Duggirala, Ravindranath; Seielstad, Mark; Wilson, James G; Dupuis, Josee; Ripatti, Samuli; Hanis, Craig L; Florez, Jose C; Mohlke, Karen L; Meigs, James B; Laakso, Markku; Morris, Andrew P; Boehnke, Michael; Altshuler, David; McCarthy, Mark I; Gloyn, Anna L; Lindgren, Cecilia M

2017-01-01

To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting insulin, a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in fasting plasma insulin (FI) levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-hour insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio=1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2. PMID:28341696

Reference intervals for glucose, beta-cell polypeptides and counterregulatory factors during prolonged fasting

DEFF Research Database (Denmark)

Højlund, Kurt; Wildner-Christensen, M; Eshøj, O

2001-01-01

To establish reference intervals for the pancreatic beta-cell response and the counterregulatory hormone response to prolonged fasting, we studied 33 healthy subjects (16 males, 17 females) during a 72-h fast. Glucose, insulin, C-peptide, and proinsulin levels decreased (P ... of counterregulatory factors increased during the fast [P fasting (P ... decreased from the second to third day of fasting (P = 0.03). Males had higher glucose and glucagon levels and lower FFA levels during the fast (P

Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age

DEFF Research Database (Denmark)

Akintola, Abimbola A; van den Berg, Annette; van Buchem, Mark A

2015-01-01

[fasted glucose and glucose area-under-the-curve (AUC)], insulin resistance [fasted insulin, AUCinsulin, and homeostatic model assessment of insulin resistance (HOMA-IR)], and pancreatic Beta cell secretory capacity (insulinogenic index). 3 Tesla MRI and Magnetization Transfer (MT) imaging MT-ratio (MTR......-height in gray and white matter was inversely associated with AUCinsulin, fasted insulin, HOMA-IR and insulinogenic-index (all p 65 years): in younger controls, significantly stronger inverse associations were observed between MTR peak-height and fasted glucose......, AUCglucose, fasted insulin, AUCinsulin and HOMA-IR in gray matter; and for AUCglucose, fasted insulin and HOMA-IR in white matter (all P-interaction

Validation of insulin resistance indexes in a stable renal transplant population

NARCIS (Netherlands)

Oterdoom, Leendert H.; de Vries, Aiko P. J.; van Son, Willem J.; Homan van der Heide, Jaap J.; Ploeg, Rutger J.; Gansevoort, Ron T.; de Jong, Paul E.; Gans, Rijk O. B.; Bakker, Stephan J. L.

2005-01-01

The purpose of this study was to investigate the validity of established insulin resistance indexes, based on fasting blood parameters, in a stable renal transplant population. Fasting insulin, homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI), and

Validation of insulin resistance indexes in a stable renal transplant population

NARCIS (Netherlands)

Oterdoom, LH; De Vries, APJ; Van Son, WJ; Van Der Heide, JJH; Ploeg, RJ; Gansevoort, RT; De Jong, PE; Gans, ROB; Bakker, SJL

2005-01-01

OBJECTIVE - The purpose of this study was to investigate the validity of established insulin resistance indexes, based on fasting blood parameters, in a stable renal transplant population. RESEARCH DESIGN AND METHODS - Fasting insulin, homeostasis model assessment (HOMA), the quantitative insulin

Clinical significance of changes of serum true insulin and proinsulin levels in relations of patients with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Tian Xiaoping; Huang Huijian; Huang Haibo; Wu Yan; He Haoming

2004-01-01

Objective: To explore the degree of insulin resistance and β-cell secretory function impairment in close (1st degree) relations of patients with type 2 diabetes (DMII). Methods: Serum true insulin (TI), pro-insulin (PI), immunoreactive insulin (IRI) levels at fasting and after oral 75g glucose loading were determined in: 1) patients with DM 2, n=65 2)relations of DM 2 patients with impaired glucose tolerance (IGT), n=34 3) relations of DM 2 patients with normal glucose tolerance (NGT), n=66 and 4) controls, n=48. HOMA-IR and HOMA-β cell secretory indices were calculated from the data. Results: Fasting serum PI levels were significantly higher in DM 2 patients, relations with IGT and NGT than those in the controls (t=2.38, t=2.16, t=1.95, P 1 C percentages were significantly higher in DM 2 patients and IGT, NGT groups than those in controls (t=3.67, t=2.45, t=1.97, P 1 C percentage, fasting TI and IRI levels. Conclusion: Insulin resistance was already obvious in those relations of DM 2 patients with normal glucose tolerance and β-cell secretory function impairment was also present. Early intervention in these subjects might be beneficial. (authors)

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.

Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan

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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.

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.

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.

Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin resistant phenotypes

DEFF Research Database (Denmark)

Malin, Steven K; Haus, Jacob M; Solomon, Thomas

2013-01-01

Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance, however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilizati...

Increased plasma levels of FABP4 and PTEN is associated with more severe insulin resistance in women with gestational diabetes mellitus.

Science.gov (United States)

Li, Yuan-yuan; Xiao, Rui; Li, Cai-ping; Huangfu, Jian; Mao, Jiang-feng

2015-02-08

The aim of this study was to investigate the relationship between plasma fatty acid binding protein 4 (FABP4), phosphatase and tensin homolog (PTEN), and insulin resistance in patients with gestational diabetes mellitus (GDM). Plasma FABP4 and PTEN were determined by ELISA in GDM patients (GDM group, n=30) and in euglycemic pregnant women (control group, n=30). The clinical features, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and lipid profiles were compared between the 2 groups. The influence of risk factors on insulin resistance, including BMI, lipid profiles, FABP4, and PTEN, were further investigated by multiple-factor stepwise regression analysis. Higher levels of BMI, ΔBMI, triglyceride (TG), fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), fasting insulin, HOMA-IR, FABP4, PTEN, and lower level of high-density lipoprotein cholesterol (HDL-C) were found in the GDM patients than in the controls (all Pinsulin resistance. GDM patients have more severe insulin resistance compared to euglycemic pregnant women. Higher levels of plasma FABP4 and PTEN are associated with increased insulin resistance and may participate in the pathogenesis of insulin resistance during gestation.

Trajectories of BMI change impact glucose and insulin metabolism.

Science.gov (United States)

Walsh, E I; Shaw, J; Cherbuin, N

2018-03-01

The aim of this study was to examine, in a community setting, whether trajectory of weight change over twelve years is associated with glucose and insulin metabolism at twelve years. Participants were 532 community-living middle-aged and elderly adults from the Personality and Total Health (PATH) Through Life study. They spanned the full weight range (underweight/normal/overweight/obese). Latent class analysis and multivariate generalised linear models were used to investigate the association of Body Mass Index (BMI, kg/m 2 ) trajectory over twelve years with plasma insulin (μlU/ml), plasma glucose (mmol/L), and HOMA2 insulin resistance and beta cell function at follow-up. All models were adjusted for age, gender, hypertension, pre-clinical diabetes status (normal fasting glucose or impaired fasting glucose) and physical activity. Four weight trajectories were extracted; constant normal (mean baseline BMI = 25; follow-up BMI = 25), constant high (mean baseline BMI = 36; follow-up BMI = 37), increase (mean baseline BMI = 26; follow-up BMI = 32) and decrease (mean baseline BMI = 34; follow-up BMI = 28). At any given current BMI, individuals in the constant high and increase trajectories had significantly higher plasma insulin, greater insulin resistance, and higher beta cell function than those in the constant normal trajectory. Individuals in the decrease trajectory did not differ from the constant normal trajectory. Current BMI significantly interacted with preceding BMI trajectory in its association with plasma insulin, insulin resistance, and beta cell function. The trajectory of preceding weight has an independent effect on blood glucose metabolism beyond body weight measured at any given point in time. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier

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

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H Rashidi

2016-12-01

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

A Paleolithic diet confers higher insulin sensitivity, lower C-reactive protein and lower blood pressure than a cereal-based diet in domestic pigs

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Ugander Martin

2006-11-01

Full Text Available Abstract Background A Paleolithic diet has been suggested to be more in concordance with human evolutionary legacy than a cereal based diet. This might explain the lower incidence among hunter-gatherers of diseases of affluence such as type 2 diabetes, obesity and cardiovascular disease. The aim of this study was to experimentally study the long-term effect of a Paleolithic diet on risk factors for these diseases in domestic pigs. We examined glucose tolerance, post-challenge insulin response, plasma C-reactive protein and blood pressure after 15 months on Paleolithic diet in comparison with a cereal based swine feed. Methods Upon weaning twenty-four piglets were randomly allocated either to cereal based swine feed (Cereal group or cereal free Paleolithic diet consisting of vegetables, fruit, meat and a small amount of tubers (Paleolithic group. At 17 months of age an intravenous glucose tolerance test was performed and pancreas specimens were collected for immunohistochemistry. Group comparisons of continuous variables were made by use of the t-test. P Results At the end of the study the Paleolithic group weighed 22% less and had 43% lower subcutaneous fat thickness at mid sternum. No significant difference was seen in fasting glucose between groups. Dynamic insulin sensitivity was significantly higher (p = 0.004 and the insulin response was significantly lower in the Paleolithic group (p = 0.001. The geometric mean of C-reactive protein was 82% lower (p = 0.0007 and intra-arterial diastolic blood pressure was 13% lower in the Paleolithic group (p = 0.007. In evaluations of multivariate correlations, diet emerged as the strongest explanatory variable for the variations in dynamic insulin sensitivity, insulin response, C-reactive protein and diastolic blood pressure when compared to other relevant variables such as weight and subcutaneous fat thickness at mid sternum. There was no obvious immunohistochemical difference in pancreatic islets

Sociodemographic differences in fast food price sensitivity

Science.gov (United States)

Meyer, Katie A.; Guilkey, David K.; Ng, Shu Wen; Duffey, Kiyah J.; Popkin, Barry M.; Kiefe, Catarina I.; Steffen, Lyn M.; Shikany, James M.; Gordon-Larsen, Penny

2014-01-01

Importance Fiscal food policies (e.g., taxation) are increasingly proposed to improve population-level health, but their impact on health disparities is unknown. Objective We estimated subgroup-specific effects of fast food price changes on fast food consumption and cardio-metabolic outcomes, hypothesizing inverse associations between fast food price with fast food consumption, BMI, and insulin resistance and stronger associations among blacks (vs. whites) and participants with relatively lower education or income. Design 20-year follow-up (5 exams) in a biracial U.S. prospective cohort: Coronary Artery Risk Development in Young Adults (CARDIA) (1985/86–2005/06, baseline n=5,115). Participants Aged 18–30 at baseline; designed for equal recruitment by race (black/white), educational attainment, age, and gender. Exposures Community-level price data from the Council for Community and Economic Research (C2ER) temporally- and geographically-linked to study participants’ home address at each exam. Main outcome and measures Participant-reported number of fast food eating occasions per week; BMI (kg/m2) from clinical assessment of weight and height; homeostatic model assessment insulin resistance (HOMA-IR) from fasting glucose and insulin. Covariates included individual- and community-level social and demographic factors. Results In repeated measures regression, multivariable-adjusted associations between fast food price and consumption were non-linear (quadratic, pconsumption at higher prices; estimates varied according to race (interaction term p=0.04), income (p=0.07), and education (p=0.03). For example, at the 10th percentile of price ($1.25/serving), blacks and whites had mean fast food consumption (times/week) of 2.2 (95% CI: 2.1–2.3) and 1.6 (1.5–1.7), respectively, while at the 90th percentile of price ($1.53/serving), respective mean consumption estimates were 1.9 (1.8–2.0) and 1.5 (1.4–1.6). We observed differential price effects on HOMA

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.

Observations on the insulin-secretion function in the offsprings of patients with type II diabetes

International Nuclear Information System (INIS)

Xu Shujie; Tian Xiaoping; Wu Yan

2004-01-01

Objective: To investigate the disturbance of insulin-secretion function in the offsprings of patients with type II diabetes. Methods: Blood sugar (with oxidase method) and insulin (with RIA) levels were measured after overnight fasting and repeatedly measured 2h after 75g glucose per oral in the following subjects: 1) Group A, 23 non-obese offsprings of type II diabetics 2) group B, 18 obese offsprings (BMI ≥25kg/m 2 ) and 3) 27 controls. Homeostatic model assessment-insulin resistance (HOMA-IR) and β-cell function index (HCI) were calculated from the data (glucose and insulin levels) obtained. Results: For Group A subjects, the fasting blood sugar (FPG) levels were significantly higher and HBCI significantly lower than those in te controls (both P<0.05). For Group B obese subjects, in addition to the above two parameters (with HBCI P<0.01), 2h PG levels as well as HOMA-IR were also significantly higher (both P<0.05). Conclusion: Present study showed that in the offsprings of diabetics, HBCI was already lowered before definite impaired glucose tolerance (IGT) could be demonstrated, especially in the obese ones. (authors)

Observations on the insulin-secretion function in the offsprings of patients with type II diabetes

Energy Technology Data Exchange (ETDEWEB)

Shujie, Xu; Xiaoping, Tian; Yan, Wu [The First People' s Hospital of Lianyungang (China)

2004-10-01

Objective: To investigate the disturbance of insulin-secretion function in the offsprings of patients with type II diabetes. Methods: Blood sugar (with oxidase method) and insulin (with RIA) levels were measured after overnight fasting and repeatedly measured 2h after 75g glucose per oral in the following subjects: 1) Group A, 23 non-obese offsprings of type II diabetics 2) group B, 18 obese offsprings (BMI {>=}25kg/m{sup 2} ) and 3) 27 controls. Homeostatic model assessment-insulin resistance (HOMA-IR) and {beta}-cell function index (HCI) were calculated from the data (glucose and insulin levels) obtained. Results: For Group A subjects, the fasting blood sugar (FPG) levels were significantly higher and HBCI significantly lower than those in te controls (both P<0.05). For Group B obese subjects, in addition to the above two parameters (with HBCI P<0.01), 2h PG levels as well as HOMA-IR were also significantly higher (both P<0.05). Conclusion: Present study showed that in the offsprings of diabetics, HBCI was already lowered before definite impaired glucose tolerance (IGT) could be demonstrated, especially in the obese ones. (authors)

Relationship of dopamine type 2 receptor binding potential with fasting neuroendocrine hormones and insulin sensitivity in human obesity.

Science.gov (United States)

Dunn, Julia P; Kessler, Robert M; Feurer, Irene D; Volkow, Nora D; Patterson, Bruce W; Ansari, Mohammad S; Li, Rui; Marks-Shulman, Pamela; Abumrad, Naji N

2012-05-01

Midbrain dopamine (DA) neurons, which are involved with reward and motivation, are modulated by hormones that regulate food intake (insulin, leptin, and acyl ghrelin [AG]). We hypothesized that these hormones are associated with deficits in DA signaling in obesity. We assessed the relationships between fasting levels of insulin and leptin, and AG, BMI, and insulin sensitivity index (S(I)) with the availability of central DA type 2 receptor (D2R). We measured D2R availability using positron emission tomography and [(18)F]fallypride (radioligand that competes with endogenous DA) in lean (n = 8) and obese (n = 14) females. Fasting hormones were collected prior to scanning and S(I) was determined by modified oral glucose tolerance test. Parametric image analyses revealed associations between each metabolic measure and D2R. The most extensive findings were negative associations of AG with clusters involving the striatum and inferior temporal cortices. Regional regression analyses also found extensive negative relationships between AG and D2R in the caudate, putamen, ventral striatum (VS), amygdala, and temporal lobes. S(I) was negatively associated with D2R in the VS, while insulin was not. In the caudate, BMI and leptin were positively associated with D2R availability. The direction of associations of leptin and AG with D2R availability are consistent with their opposite effects on DA levels (decreasing and increasing, respectively). After adjusting for BMI, AG maintained a significant relationship in the VS. We hypothesize that the increased D2R availability in obese subjects reflects relatively reduced DA levels competing with the radioligand. Our findings provide evidence for an association between the neuroendocrine hormones and DA brain signaling in obese females.

[Normal plasma insulin and HOMA values among Chilean children and adolescents].

Science.gov (United States)

Barja, Salesa; Arnaiz, Pilar; Domínguez, Angélica; Villarroel, Luis; Cassis, Berta; Castillo, Oscar; Salomó, Gianina; Farías, Marcelo; Goycoolea, Manuela; Quiroga, Teresa; Mardones, Francisco

2011-11-01

Plasma insulin and HOMA (homeostasis model assessment) index, used to determine insulin resistance, do not have local standard values for children and adolescents in Chile. To establish the normal reference intervals for insulin and HOMA in children and adolescents aged 10-15 years, according to sex and puberal maturation. A cross-sectional study of 2,153 children and adolescents from Puente Alto County was performed, during 2009 and 2010. Anthropometry and self-report of puberal maturation were assessed. Fasting glucose (hexoquinase) and insulin blood levels (chemiluminiscence), were determined and HOMA index was calculated. Percentile distributions of these variables were calculated. The reference group included only subjects with normal body mass index and fasting blood glucose (n = 1,192). Girls had higher insulin and HOMA values than boys (12.5 ± 6.0 and 9.1 ± 4.9 μϋ/mL (p HOMA mean values than subjects with Tanner III and IV (9.0 ± 4.3 and 12.5 ± 6.2μϋ/ml (p HOMA distributions according to sex and maturation, was selected as the upper cut-off point to identify individuals with insulin resistance. HOMA cutoff point for Tanner I and II boys was 3.2, for Tanner I and II girls was 4.1, for Tanner III and IV boys was 4.2 and for Tanner III and IV girls was 5.0.

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

Changes of serum leptin and their relationships with insulin resistance in patients with simple obesity and patients with type 2 diabetes mellitus complicated with obesity

International Nuclear Information System (INIS)

Zhang Lei; Changzhou Wujin People's Hospital of Jiangsu Province, Changzhou; Shi Linlin; Lu Dan; Zhang Lei; Wang Qing; Yao Wenhua

2005-01-01

Objective: To study the changes of serum leptin in patients with simple obesity and patients with type 2 diabetes mellitus complicated with obesity in order to explore the relationship of leptin and insulin resistance and the role of leptin in the occurrence of type 2 diabetes mellitus. Methods: 60 cases of simple obesity, 60 cases of type 2 diabetes mellitus and 30 cases of normal control were included according to the diagnostic criteria of obesity and type 2 diabetes mellitus. the levels of fasting serum leptin, fasting serum insulin, fasting glucose, fasting blood lipid were measured in all cases. The body mass index (BMI) and insulin action index were calculated. Results: The level of BMI, serum leptin, serum insulin, blood lipid were significantly higher in patients with simple obesity and with type 2 diabetes mellitus complicated with obesity than in normal control cases, while (IAI) was significantly lower. The levels of free serum leptin, serum insulin, free glucose, and blood lipid were significantly higher in patients with type 2 diabetes mellitus complicated with obesity than in patients with simple obesity, while IAI was significantly lower. The level of serum leptin was positively correlated with BMI (r=0.48, P<0.55) and fasting serum leptin (r=0.55, P<0.05) and negatively correlated with IAI (r=-0.47, P<0.05) in patients with type 2 diabetes complicated with obesity. Conclusion: The overexpression of serum leptin may play an important role in the occurrence of the insulin resistance and type 2 diabetes mellitus in obesity patients. (authors)

Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog

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Chih-Ting Su

2016-11-01

Full Text Available Insulin antibodies (IA associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA found in insulin autoimmune syndrome (IAS, which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Examinations of serial sera disclosed a high titre of insulin antibodies (33%, normal <5%, high insulin concentration (111.9 IU/mL and undetectable C-peptide when hypoglycemia occurred. An oral glucose tolerance test revealed persistent high serum levels of total insulin and undetectable C-peptide. Image studies of the pancreas were unremarkable, which excluded the diagnosis of insulinoma. The patient does not take any of the medications containing sulfhydryl compounds, which had been reported to cause IAS. After administering oral prednisolone for 3 weeks, hypoglycemic episodes markedly improved, and he was discharged smoothly.

Characterisation of insulin analogues therapeutically available to patients

KAUST Repository

Adams, Gary G.

2018-03-29

The structure and function of clinical dosage insulin and its analogues were assessed. This included \\'native insulins\\' (human recombinant, bovine, porcine), \\'fast-acting analogues\\' (aspart, glulisine, lispro) and \\'slow-acting analogues\\' (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein.

C-Peptide, Baseline and Postprandial Insulin Resistance after a Carbohydrate-Rich Test Meal - Evidence for an Increased Insulin Clearance in PCOS Patients?

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Stassek, J; Erdmann, J; Ohnolz, F; Berg, F D; Kiechle, M; Seifert-Klauss, V

2017-01-01

Introduction Known characteristics of patients with PCOS include infertility, menstrual disorders, hirsutism and also often insulin resistance. These symptoms increase with increasing body weight. In the LIPCOS study ( L ifestyle I ntervention for Patients with Polycystic Ovary Syndrome [ PCOS ]) long-term changes of the PCOS in dependence on pregnancy and parenthood were systematically assessed. In the framework of the LIPCOS study, PCOS patients were given a standardised carbohydrate-rich test meal in order to examine glucose homeostasis and insulin secretion. The results were compared with those of a eumenorrhoeic control group who all had corresponding BMI values and corresponding ages. Methods and Patients 41 PCOS patients (without diabetes) and 68 controls received a standardised carbohydrate-rich test meal (260 kcal, 62 % carbohydrates, 32 % fat, 6 % proteins) in order to generate a submaximal insulin and glucose stimulation. The values were determined at baseline and postprandial after 60, 120 and 180 minutes. In addition, the corresponding C-peptide levels were recorded. Results In the PCOS patients (n = 41), the insulin secretion test after a standardised test meal showed almost identical baseline and postprandial insulin levels when compared with those of the age- and BMI-matched eumenorrhoeic controls (n = 68). In the PCOS patients, the baseline and postprandial glucose levels were significantly elevated (92.88 ± 10.28 [PCOS] vs. 85.07 ± 9.42 mg/dL [controls]; p PCOS patients formally exhibit a higher fasting insulin resistance than controls. In spite of the higher stimulated C-peptide levels, the insulin levels did not increase more strongly with increasing glucose levels than in controls which may be indicative of a higher insulin clearance in PCOS patients.

Women With Gestational Diabetes Mellitus Randomized to a Higher-Complex Carbohydrate/Low-Fat Diet Manifest Lower Adipose Tissue Insulin Resistance, Inflammation, Glucose, and Free Fatty Acids: A Pilot Study.

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Hernandez, Teri L; Van Pelt, Rachael E; Anderson, Molly A; Reece, Melanie S; Reynolds, Regina M; de la Houssaye, Becky A; Heerwagen, Margaret; Donahoo, William T; Daniels, Linda J; Chartier-Logan, Catherine; Janssen, Rachel C; Friedman, Jacob E; Barbour, Linda A

2016-01-01

Diet therapy in gestational diabetes mellitus (GDM) has focused on carbohydrate restriction but is poorly substantiated. In this pilot randomized clinical trial, we challenged the conventional low-carbohydrate/higher-fat (LC/CONV) diet, hypothesizing that a higher-complex carbohydrate/lower-fat (CHOICE) diet would improve maternal insulin resistance (IR), adipose tissue (AT) lipolysis, and infant adiposity. At 31 weeks, 12 diet-controlled overweight/obese women with GDM were randomized to an isocaloric LC/CONV (40% carbohydrate/45% fat/15% protein; n = 6) or CHOICE (60%/25%/15%; n = 6) diet. All meals were provided. AT was biopsied at 37 weeks. After ∼7 weeks, fasting glucose (P = 0.03) and free fatty acids (P = 0.06) decreased on CHOICE, whereas fasting glucose increased on LC/CONV (P = 0.03). Insulin suppression of AT lipolysis was improved on CHOICE versus LC/CONV (56 vs. 31%, P = 0.005), consistent with improved IR. AT expression of multiple proinflammatory genes was lower on CHOICE (P vs. 12.6 ± 2%, respectively). A CHOICE diet may improve maternal IR and infant adiposity, challenging recommendations for a LC/CONV diet. © 2016 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.

Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes

DEFF Research Database (Denmark)

Hulman, Adam; Simmons, Rebecca K; Brunner, Eric J

2017-01-01

AIMS/HYPOTHESIS: South Asian individuals have reduced insulin sensitivity and increased risk of type 2 diabetes compared with white individuals. Temporal changes in glycaemic traits during middle age suggest that impaired insulin secretion is a particular feature of diabetes development among South...... Asians. We therefore aimed to examine ethnic differences in early changes in glucose metabolism prior to incident type 2 diabetes. METHODS: In a prospective British occupational cohort, subject to 5 yearly clinical examinations, we examined ethnic differences in trajectories of fasting plasma glucose...... (FPG), 2 h post-load plasma glucose (2hPG), fasting serum insulin (FSI), 2 h post-load serum insulin (2hSI), HOMA of insulin sensitivity (HOMA2-S) and secretion (HOMA2-B), and the Gutt insulin sensitivity index (ISI0,120) among 120 South Asian and 867 white participants who developed diabetes during...

Characterization of the chicken muscle insulin receptor

International Nuclear Information System (INIS)

Adamo, M.; Simon, J.; Rosebrough, R.W.; McMurtry, J.P.; Steele, N.C.; LeRoith, D.

1987-01-01

Insulin receptors are present in chicken skeletal muscle. Crude membrane preparations demonstrated specific 125 I-insulin binding. The nonspecific binding was high (36-55% of total binding) and slightly lower affinity receptors were found than are typically observed for crude membrane insulin binding in other chicken tissues. Affinity crosslinking of 125 I-insulin to crude membranes revealed insulin receptor alpha-subunits of Mr 128K, intermediate between those of liver (134K) and brain (124K). When solubilized and partially purified on wheat germ agglutinin (WGA) affinity columns, chicken muscle insulin receptors exhibited typical high affinity binding, with approximately 10(-10) M unlabeled insulin producing 50% inhibition of the specific 125 I-insulin binding. WGA purified chicken muscle insulin receptors also exhibited insulin-stimulated autophosphorylation of the beta-subunit, which appeared as phosphorylated bands of 92- and 81K. Both bands were immunoprecipitated by anti-receptor antiserum (B10). WGA purified membranes also demonstrated dose-dependent insulin-stimulated phosphorylation of the exogenous substrate poly(Glu,Tyr)4:1. However, unlike chicken liver, chicken muscle insulin receptor number and tyrosine kinase activity were unaltered by 48 hr of fasting or 48 hr of fasting and 24 hr of refeeding. Thus, despite the presence of insulin receptors in chicken muscle showing normal coupling to receptor tyrosine kinase activity, nutritional alterations modulate these parameters in a tissue-specific manner in chickens

Possible metabolic impact of Ramadan fasting in healthy men.

Science.gov (United States)

Vardarli, Mustafa Cumhur; Hammes, Hans-Peter; Vardarli, İrfan

2014-01-01

Insulin sensitivity and β-cell function during Ramadan fasting in healthy male subjects have not been investigated so far. We assessed the changes of these and other metabolic parameters to judge the potential metabolic benefits of Ramadan fasting. Twenty-four healthy males of Turkish origin living in Germany, with normal glucose tolerance, participated in this study during Ramadan of 2009; 19 who completed fasting were analyzed. Blood was drawn at sunset after a period of fasting lasting approximately 15 h on days 0, 16, and 30 of Ramadan, as well as 7 and 28 days later. Insulin sensitivity (Homeostasis Model Assessment, HOMA), β-cell function, and other parameters were assessed. Ramadan fasting was associated with a significant reduction (-) or increment (+) for the following variables: insulin sensitivity (-20%; P = 0.04), β-cell function (+10%; P = 0.049), high-density lipoprotein cholesterol (-23%; P = 0.0003), low-density lipoprotein cholesterol (+14%; P = 0.007), nonesterified fatty acids (-62%; P Ramadan fasting is associated with transiently impaired insulin sensitivity, compensated for by an increased β-cell function. However, the pattern of insulin resistance-mediating adipocytokines suggests a potentially beneficial metabolic effect of Ramadan fasting.

Chronic hepatitis C infection is associated with insulin resistance and lipid profiles.

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Dai, Chia-Yen; Yeh, Ming-Lun; Huang, Chung-Feng; Hou, Chen-Hsiu; Hsieh, Ming-Yen; Huang, Jee-Fu; Lin, I-Ling; Lin, Zu-Yau; Chen, Shinn-Chern; Wang, Liang-Yen; Chuang, Wan-Long; Yu, Ming-Lung; Tung, Hung-Da

2015-05-01

Chronic hepatitis C virus (HCV) infection has been suggested to be associated with non-insulin-dependent diabetes mellitus and lipid profiles. This study aimed to investigate the possible relationships of insulin resistance (IR) and lipid profiles with chronic hepatitis C (CHC) patients in Taiwan. We enrolled 160 hospital-based CHC patients with liver biopsy and the 480 controlled individuals without CHC and chronic hepatitis B from communities without known history of non-insulin-dependent diabetes mellitus. Fasting plasma glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), alanine aminotransferase, and serum insulin levels, and homeostasis model assessment (HOMA-IR) were tested. When comparing factors between CHC patients, and sex- and age-matched controls who had no HCV infection, patients with HCV infection had a significantly higher alanine aminotransferase level, fasting plasma glucose level, insulin level, and HOMA-IR (P C and LDL-C levels (all P  2.5]), a high body mass index, TGs, and HCV RNA level are independent factors significantly associated with high HOMA-IR in multivariate logistic analyses. Chronic HCV infection was associated with metabolic characteristics including IR and lipid profile. IR was also associated with virological characteristics. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Association between chilli food habits with iron status and insulin resistance in a Chinese population.

Science.gov (United States)

Li, Jiang; Wang, Rui; Xiao, Cheng

2014-04-01

Some studies have indicated that the consumption of chilli-containing foods can influence iron absorption and affect serum insulin and glucose concentrations, which may help to alleviate diabetes or prediabetes. The objective of this study was to explore the relationship between chilli food habits with iron status and insulin resistance in the Chinese population. Fasting blood samples, anthropometric data, and chilli food habit data collected from 8433 adults (aged 18 to 99), in 2009, as part of the China Health and Nutrition Survey, a large-scale longitudinal, household-based survey in China. Chilli food habits were assessed using chilli food eating frequencies (no eating, sometimes eating, often eating, and usually eating) and chilli food types (a little bit hot, moderately hot, and very hot). Fasting serum ferritin, insulin, and fasting plasma glucose were also measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to estimate insulin resistance. Compared with the chilli-eating group, the no eating group had higher HOMA-IR levels for both men and women (Pfood types. However, there was no significant difference in the ferritin level and HOMA-IR components for different chilli food eating frequencies in both sex groups. Chilli food habits, especially the different hotness levels of chilli food, were associated with iron status and insulin resistance in the Chinese population. Additional studies are needed to elucidate mechanisms of action and to establish causal inference.

Berberine improves insulin resistance induced by high fat diet in rats

International Nuclear Information System (INIS)

Zhou Libin; Yang Ying; Shang Wenbin; Li Fengying; Tang Jinfeng; Wang Xiao; Liu Shangquan; Yuan Guoyue; Chen Mingdao

2005-01-01

Objective: To observe the effect of berberine on insulin resistance induced by high fat diet in rats. Methods: Normal male SD rats (8 weeks old) were divided into two groups taking either normal chow (NC, n=9) or high fat diet (HF, n=20). After fourteen weeks, HF rats were divided into two groups. Ten rats continued to take high fat diet. Another ten rats took additional berberine gavage (HF+B, 150mg/kg weight once a day). Six weeks later, oral glucose tolerance test and insulin tolerance test were performed for estimating insulin sensitivity. Results: The body weight, liver weight and epididyaml fat pads weight of HF group were significantly higher than those of HF+B group and NC group (all P<0.01). Fasting plasma glucose, insulin and plasma glucose, insulin 2h after taking glucose in HF+B rats were significantly lower than those in HF rats (all P<0.01). Plasma glucose and insulin levels at all time points in HF rats were significantly higher than those in NC rats. Homa-IR of HF group was markedly higher than that of HF+B group (P<0.01). The glucose-lowering effects after the administration of insuin (0.5u/kg intrapenitoneally) at all time points in HF+B rats were stronger than those in HF rats with 23% and 7% reduction at 15min respectively. Conclusion: Long term high fat diet resulted in insulin resistance. Berberine was able to reverse insulin resistance through promoting peripheral tissue up taking of glucose and decreasing insulin, which would be quite ideal for the intervention of IGT. (authors)

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

Science.gov (United States)

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

2017-10-01

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

Preliminary evidence for obesity-associated insulin resistance in adolescents without elevations of inflammatory cytokines

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Cohen Jessica I

2012-06-01

Full Text Available Abstract Background To ascertain whether the associations between obesity, inflammation, and insulin resistance established in human adult studies are found among adolescents. Methods We contrasted 36 obese and 24 lean youth on fasting glucose, insulin levels, lipid profile, hemoglobin A1C, markers of hepatic function, white blood cell count, C-reactive protein (CRP and fibrinogen levels. The cytokines IL-6, TNF-α, IFN-γ, IL-10 and IL-4 and the adipokines leptin, resistin, and adiponectin were also compared between the two groups. The fasting glucose and insulin values were used to estimate the degree of insulin resistance with the homeostatic model assessment of insulin resistance (HOMA-IR. T-tests and correlations were run to examine group differences and associations between groups. In addition, regression analyses were used to ascertain whether the markers of inflammation were predictive of the degree of insulin resistance. Results Although obese adolescents had clear evidence of insulin resistance, only CRP, fibrinogen and leptin were elevated; there were no group differences in pro- or anti-inflammatory cytokines nor adiponectin and resistin. Anthropometric measures of obesity and level of insulin resistance were highly correlated to the acute phase reactants CRP and fibrinogen; however, the degree of insulin resistance was not predicted by the pro- or anti-inflammatory cytokine markers. Obese adolescents had higher white blood cell counts. In addition they had higher circulating alanine aminotransferase concentrations and lower circulating albumin and total protein than lean adolescents, possibly as a result of hepatocyte damage from fatty liver. Conclusion Unlike rodent or adult studies, we found that wide-spread systemic inflammation is not necessarily associated with insulin resistance among adolescents. This finding does not support the current paradigm that the associations between obesity and insulin resistance are, to a

Effect of Human Myotubes-Derived Media on Glucose-Stimulated Insulin Secretion

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Maria L. Mizgier

2017-01-01

Full Text Available Fasting to postprandial transition requires a tight adjustment of insulin secretion to its demand, so tissue (e.g., skeletal muscle glucose supply is assured while hypo-/hyperglycemia are prevented. High muscle glucose disposal after meals is pivotal for adapting to increased glycemia and might drive insulin secretion through muscle-released factors (e.g., myokines. We hypothesized that insulin influences myokine secretion and then increases glucose-stimulated insulin secretion (GSIS. In conditioned media from human myotubes incubated with/without insulin (100 nmol/L for 24 h, myokines were qualitatively and quantitatively characterized using an antibody-based array and ELISA-based technology, respectively. C57BL6/J mice islets and Wistar rat beta cells were incubated for 24 h with control and conditioned media from noninsulin- and insulin-treated myotubes prior to GSIS determination. Conditioned media from insulin-treated versus nontreated myotubes had higher RANTES but lower IL6, IL8, and MCP1 concentration. Qualitative analyses revealed that conditioned media from noninsulin- and insulin-treated myotubes expressed 32 and 23 out of 80 myokines, respectively. Islets incubated with conditioned media from noninsulin-treated myotubes had higher GSIS versus control islets (p<0.05. Meanwhile, conditioned media from insulin-treated myotubes did not influence GSIS. In beta cells, GSIS was similar across conditions. In conclusion, factors being present in noninsulin-stimulated muscle cell-derived media appear to influence GSIS in mice islets.

Meta-analysis investigating associations between healthy diet and fasting glucose and insulin levels and modification by loci associated with glucose homeostasis in data from 15 cohorts

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Whether loci that influence fasting glucose (FG) and fasting insulin (FI) levels, as identified by genome-wide association studies, modify associations of diet with FG or FI is unknown. We utilized data from 15 US and European cohort studies comprising 51,289 persons without diabetes to test whether...

Expression of glycogen synthase and phosphofructokinase in muscle from type 1 (insulin-dependent) diabetic patients before and after intensive insulin treatment

DEFF Research Database (Denmark)

Vestergaard, H; Andersen, P H; Lund, S

1994-01-01

The aim of the present study was to determine whether short-term appropriate insulinization of Type 1 (insulin-dependent) diabetic patients in long-term poor glycaemic control (HbA1C > 9.5%) was associated with an adaptive regulation of the activity and gene expression of key proteins in muscle...... glycogen storage and glycolysis: glycogen synthase and phosphofructokinase, respectively. In nine diabetic patients biopsies of quadriceps muscle were taken before and 24-h after intensified insulin therapy and compared to findings in eight control subjects. Subcutaneous injections of rapid acting insulin...... were given at 3-h intervals to improve glycaemic control in diabetic patients (fasting plasma glucose decreased from 20.8 +/- 0.8 to 8.7 +/- 0.8 mmol/l whereas fasting serum insulin increased from 59 +/- 8 to 173 +/- 3 pmol/l). Before intensified insulin therapy, analysis of muscle biopsies from...

Enhanced hepatic insulin signaling in the livers of high altitude native rats under basal conditions and in the livers of low altitude native rats under insulin stimulation: a mechanistic study.

Science.gov (United States)

Al Dera, Hussain; Eleawa, Samy M; Al-Hashem, Fahaid H; Mahzari, Moeber M; Hoja, Ibrahim; Al Khateeb, Mahmoud

2017-07-01

This study was designed to investigate the role of the liver in lowering fasting blood glucose levels (FBG) in rats native to high (HA) and low altitude (LA) areas. As compared with LA natives, besides the improved insulin and glucose tolerance, HA native rats had lower FBG, at least mediated by inhibition of hepatic gluconeogenesis and activation of glycogen synthesis. An effect that is mediated by the enhancement of hepatic insulin signaling mediated by the decreased phosphorylation of TSC induced inhibition of mTOR function. Such effect was independent of activation of AMPK nor stabilization of HIF1α, but most probably due to oxidative stress induced REDD1 expression. However, under insulin stimulation, and in spite of the less activated mTOR function in HA native rats, LA native rats had higher glycogen content and reduced levels of gluconeogenic enzymes with a more enhanced insulin signaling, mainly due to higher levels of p-IRS1 (tyr612).

Effect of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats

International Nuclear Information System (INIS)

Anwar, M. K.; Hussain, M. M.; Khan, M. A.; Ahmad, T.

2013-01-01

Objective: To compare the effects of combined and individual supplementation of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats. Methods: The randomised controlled trial was conducted at the Department of Physiology, Army Medical College, Rawalpindi, between October 2010 and April 2011. It comprised 80 healthy Sprague Dawley rats who were divided into four groups (n = 20 each). Rats were fed high-fat diet for 2 weeks followed by an intraperitoneal injection of streptozocin to induce type 2 diabetes mellitus. Group I served as diabetic control; group II was given cholecalciferol; group III; levo carnitine; and group IV was administered cholecalciferol and levo carnitine together. After 6 days of supplementation, terminal intracardiac blood extraction was done and samples were analysed for fasting plasma glucose and plasma insulin. Insulin resistance was calculated by homeostatic model assessment for insulin resistance. SPSS 17.0 was used for statistical analysis. Results: Fasting plasma glucose levels were significantly decreased (p <0.001) in the combined supplementation group compared to the diabetic control and individual supplementation groups. Combined supplementation showed a significant increase in fasting plasma insulin levels when compared with diabetic control and levo carnitine groups (p <0.001), and the effect of combined supplementation on ameliorating insulin resistance was significantly better (p <0.001) as compared to the individual supplementation of cholecalciferol and levo carnitine. Conclusions: The combined supplementation of cholecalciferol and levo carnitine for 6 days markedly improved the glycaemic control, insulin secretion and insulin resistance in type 2 diabetic rats on high-fat diet. A prolonged supplementation by both the compounds along with caloric restriction may yield a more promising outcome. (author)

A web-based study of the relationship of duration of insulin pump infusion set use and fasting blood glucose level in adults with type 1 diabetes.

Science.gov (United States)

Sampson Perrin, Alysa J; Guzzetta, Russell C; Miller, Kellee M; Foster, Nicole C; Lee, Anna; Lee, Joyce M; Block, Jennifer M; Beck, Roy W

2015-05-01

To evaluate the impact of infusion set use duration on glycemic control, we conducted an Internet-based study using the T1D Exchange's online patient community, Glu ( myGlu.org ). For 14 days, 243 electronically consented adults with type 1 diabetes (T1D) entered online that day's fasting blood glucose (FBG) level, the prior day's total daily insulin (TDI) dose, and whether the infusion set was changed. Mean duration of infusion set use was 3.0 days. Mean FBG level was higher with each successive day of infusion set use, increasing from 126 mg/dL on Day 1 to 133 mg/dL on Day 3 to 147 mg/dL on Day 5 (P<0.001). TDI dose did not vary with increased duration of infusion set use. Internet-based data collection was used to rapidly conduct the study at low cost. The results indicate that FBG levels increase with each additional day of insulin pump infusion set use.

Acupuncture Alters Expression of Insulin Signaling Related Molecules and Improves Insulin Resistance in OLETF Rats

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Xin-Yu Huang

2016-01-01

Full Text Available To determine effect of acupuncture on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF rats and to evaluate expression of insulin signaling components. Rats were divided into three groups: Sprague-Dawley (SD rats, OLETF rats, and acupuncture+OLETF rats. Acupuncture was subcutaneously applied to Neiguan (PC6, Zusanli (ST36, and Sanyinjiao (SP6; in contrast, acupuncture to Shenshu (BL23 was administered perpendicularly. For Neiguan (PC6 and Zusanli (ST36, needles were connected to an electroacupuncture (EA apparatus. Fasting blood glucose (FPG was measured by glucose oxidase method. Plasma fasting insulin (FINS and serum C peptide (C-P were determined by ELISA. Protein and mRNA expressions of insulin signaling molecules were determined by Western blot and real-time RT-PCR, respectively. OLETF rats exhibit increased levels of FPG, FINS, C-P, and homeostasis model assessment-estimated insulin resistance (HOMA-IR, which were effectively decreased by acupuncture treatment. mRNA expressions of several insulin signaling related molecules IRS1, IRS2, Akt2, aPKCζ, and GLUT4 were decreased in OLETF rats compared to SD controls. Expression of these molecules was restored back to normal levels upon acupuncture administration. PI3K-p85α was increased in OLETF rats; this increase was also reversed by acupuncture treatment. Acupuncture improves insulin resistance in OLETF rats, possibly via regulating expression of key insulin signaling related molecules.

Intranasal insulin therapy: the clinical realities

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Hilsted, J; Madsbad, Sten; Hvidberg, A

1995-01-01

To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

[Metabolic profile in obese patients with obstructive sleep apnea. A comparison between patients with insulin resistance and with insulin sensitivity].

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Dumitrache-Rujinski, Stefan; Dinu, Ioana; Călcăianu, George; Erhan, Ionela; Cocieru, Alexandru; Zaharia, Dragoş; Toma, Claudia Lucia; Bogdan, Miron Alexandru

2014-01-01

Obstructive sleep apnea syndrome (OSAS) may induce metabolic abnormalities through intermittent hypoxemia and simpathetic activation. It is difficult to demonstrate an independent role of OSAS in the occurrence of metabolic abnormalities, as obesity represents an important risk factor for both OSAS and metabolic abnormalities. to assess the relations between insulin resistance (IR), insulin sensitivity (IS), OSAS severity and nocturnal oxyhaemoglobin levels in obese, nondiabetic patients with daytime sleepiness. We evaluated 99 consecutive, obese, nondiabetic patients (fasting glycemia 5/hour and daytime sleepiness) by an ambulatory six channel cardio-respiratory polygraphy. Hight, weight serum triglycerides (TG), high density lipoprotein-cholesterol (HDL-C) levels were evaluated. Correlations between Apneea Hypopnea Index (AHI), Oxygen Desaturation Index (ODI), average and lowest oxyhaemoglobin saturation (SaO), body mass index (BMI) and insulin resistance or sensitivity were assesed. IR was defined as a TG/ HDL-Cratio > 3, and insulin sensitivity (IS) as a TG/HDL-C ratio obese nondiabetic patients. Preserving insulin sensitivity is more likely when oxyhaemoglobin levels are higher and ODI is lower. Mean lowest nocturnal SaO2 levels seems to be independently involved in the development of insulin resistance as no statistically significant differences were found for BMI between the two groups.

Identifying metabolic syndrome in African American children using fasting HOMA-IR in place of glucose.

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Sharma, Sushma; Lustig, Robert H; Fleming, Sharon E

2011-05-01

Metabolic syndrome (MetS) is increasing among young people. We compared the use of homeostasis model assessment of insulin resistance (HOMA-IR) with the use of fasting blood glucose to identify MetS in African American children. We performed a cross-sectional analysis of data from a sample of 105 children (45 boys, 60 girls) aged 9 to 13 years with body mass indexes at or above the 85th percentile for age and sex. Waist circumference, blood pressure, and fasting levels of blood glucose, insulin, triglycerides, and high-density lipoprotein cholesterol were measured. We found that HOMA-IR is a stronger indicator of MetS in children than blood glucose. Using HOMA-IR as 1 of the 5 components, we found a 38% prevalence of MetS in this sample of African American children and the proportion of false negatives decreased from 94% with blood glucose alone to 13% with HOMA-IR. The prevalence of MetS was higher in obese than overweight children and higher among girls than boys. Using HOMA-IR was preferred to fasting blood glucose because insulin resistance was more significantly interrelated with the other 4 MetS components.

Effects of GCK, GCKR, G6PC2 and MTNR1B variants on glucose metabolism and insulin secretion.

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Cheng Hu

Full Text Available BACKGROUND: Single nucleotide polymorphisms (SNPs from GCK, GCKR, G6PC2 and MTNR1B were found to modulate the fasting glucose levels. The current study aimed to replicate this association in the Chinese population and further analyze their effects on biphasic insulin secretion. METHODS/PRINCIPAL FINDINGS: SNPs from GCK, GCKR, G6PC2 and MTNR1B were genotyped in the Shanghai Chinese, including 3,410 type 2 diabetes patients and 3,412 controls. The controls were extensively phenotyped for the traits related to glucose metabolism and insulin secretion. We replicated the association between GCK rs1799884, G6PC2 rs16856187 and MTNR1B rs10830963 and fasting glucose in our samples (p = 0.0003-2.0x10(-8. GCK rs1799884 and G6PC2 rs16856187 showed association to HOMA-beta, insulinogenic index and both first- and second-phases insulin secretion (p = 0.0030-0.0396. MTNR1B rs10830963 was associated to HOMA-beta, insulinogenic index and first-phase insulin secretion (p = 0.0102-0.0426, but not second-phase insulin secretion (p = 0.9933. Combined effect analyses showed individuals carrying more risk allele for high fasting glucose tended to have a higher glucose levels at both fasting and 2 h during OGTTs (p = 1.7x10(-13 and 0.0009, respectively, as well as lower HOMA-beta, insulinogenic index and both first- and second-phases insulin secretion (p = 0.0321-1.1x10(-7. CONCLUSIONS/SIGNIFICANCE: We showed that SNPs from GCK, G6PC2 and MTNR1B modulated the fasting glucose levels in the normoglycaemic population while SNPs from G6PC2 and GCKR was associated with type 2 diabetes. Moreover, we found GCK and G6PC2 genetic variants were associated to both first- and second-phases insulin secretion while MTNR1B genetic variant was associated with first-phase insulin secretion, but not second-phase insulin secretion.

Childhood craniopharyngioma: greater hypothalamic involvement before surgery is associated with higher homeostasis model insulin resistance index

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Trivin, Christine; Busiah, Kanetee; Mahlaoui, Nizar; Recasens, Christophe; Souberbielle, Jean-Claude; Zerah, Michel; Sainte-Rose, Christian; Brauner, Raja

2009-01-01

Background Obesity seems to be linked to the hypothalamic involvement in craniopharyngioma. We evaluated the pre-surgery relationship between the degree of this involvement on magnetic resonance imaging and insulin resistance, as evaluated by the homeostasis model insulin resistance index (HOMA). As insulin-like growth factor 1, leptin, soluble leptin receptor (sOB-R) and ghrelin may also be involved, we compared their plasma concentrations and their link to weight change. Methods 27 children with craniopharyngioma were classified as either grade 0 (n = 7, no hypothalamic involvement), grade 1 (n = 8, compression without involvement), or grade 2 (n = 12, severe involvement). Results Despite having similar body mass indexes (BMI), the grade 2 patients had higher glucose, insulin and HOMA before surgery than the grade 0 (P = 0.02, craniopharyngioma before surgery seems to determine the degree of insulin resistance, regardless of the BMI. The pre-surgery HOMA values were correlated with the post-surgery weight gain. This suggests that obesity should be prevented by reducing inn secretion in those cases with hypothalamic involvement. PMID:19341477

Relationship between tyrosine phosphorylation and protein expression of insulin receptor and insulin resistance in gestational diabetes mellitus.

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Chu, Yong-li; Gong, Yu-dian; Su, Zhi-hui; Yu, Hong-na; Cui, Qing; Jiang, Hai-yang; Qu, Hong-mei

2014-06-01

The relationship between tyrosine phosphorylation (TP) and protein expression of insulin receptor (InsR) and insulin resistance (IR) in patients with gestational diabetes mellitus (GDM) was investigated. The InsR expression and TP in skeleton muscle tissue were determined by Western blotting and immunoprecipitation in women with GDM (GDM group, n=22), normal pregnant women (normal pregnancy group, n=22) and normal non-pregnant women (normal non-pregnant group, n=13). Fasting plasma glucose (FPG) and fasting insulin (FINS) were measured by oxidase assay and immunoradioassay. The results showed that the levels of FPG (5.61±0.78 mmol/L), FINS (15.42±5.13 mU/L) and Homeostasis model assessment-IR (HOMA-IR) (1.21±0.52) in GDM group were significantly higher than those in normal pregnancy group (4.43±0.46 mmol/L, 10.56±3.07 mU/L and 0.80±0.31 respectively) (Ppregnant group (7.56±2.31 mU/L and 0.47±0.26 respectively) (P0.05). TP of InsR with insulin stimulation was significantly decreased in GDM group (0.20±0.05) as compared with normal pregnancy group (0.26±0.06) (Pinsulin stimulation in normal pregnancy group was lower than that in normal non-pregnant group (0.31±0.06) (Pinsulin stimulation was negatively related with HOMA-IR in GDM group (r=-0.525, P0.05). It was suggested that there is no significant correlation between the protein expression of InsR in skeletal muscle and IR in GDM, but changes in TP of InsR are associated with IR in GDM.

Preliminary study on the relationship between insulin resistance and stroke during acute stage

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Wang Xiaorong; Chen Xinghua

2001-01-01

Objective: To explore whether there are insulin resistance (IR) in the patients with stroke and the relationship between IR and the patients' condition and prognosis. Method: Fasting plasma glucose (FPG), fasting serum insulin and cortisol levels were determined in 30 patients with cerebral infarction, 31 patients with cerebral hemorrhage and 28 normal adults. The insulin sensitivity index (ISI) was calculated and the result was analyzed by linear correlation with the score of neurologic impairment and the size of lesions. Results: The study showed that the levels of FPG, FINS and cortisol of the patients with stroke were significantly higher than those of the control group (p < 0.001); ISI in patient was significantly lower than that in control group (p < 0.001). There were als significant deference in FPG, FINS levels and ISI between the mild group and moderate as well as severe groups of stroke (p < 0.001, p < 0.01, p < 0.05). ISI was negatively also correlated with area of infarction and volume of haemorrhage (r = -0.372, r -0.406, p < 0.05). It was also negatively correlated with the score of neurologic impairment (r = -0.321, p < 0.05). The mortality rate and the disability rate in moderate and severe groups were higher than those in mild group. Conclusion: There were presence of IR in the patients with stroke. The insulin level and IR during acute stage were correlated with patients condition and prognosis. It was suggested that insulin should be used to treat the patients with presence of IR (high plasma glucose level and low ISI)

Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes.

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Malin, Steven K; Haus, Jacob M; Solomon, Thomas P J; Blaszczak, Alecia; Kashyap, Sangeeta R; Kirwan, John P

2013-11-15

Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG + IGT is unknown. Twenty-four older (66.7 ± 0.8 yr) obese (34.2 ± 0.9 kg/m(2)) adults were categorized as IFG (n = 8), IGT (n = 8), or IFG + IGT (n = 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ∼85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m(2)·min(-1)) with [6,6-(2)H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG + IGT (P work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training.

Association between insulin resistance and oxidative stress parameters in obese adolescents with non-alcoholic fatty liver disease.

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Pirgon, Özgür; Bilgin, Hüseyin; Çekmez, Ferhat; Kurku, Hüseyin; Dündar, Bumin Nuri

2013-01-01

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in children. The aim of this study was to investigate the associations of oxidative stress with insulin resistance and metabolic risk factors in obese adolescents with NAFLD. Forty-six obese adolescents (23 girls and 23 boys, mean age: 12.8 ± 2.2 years) and 29 control subjects (15 girls and 14 boys, mean age: 12.7 ± 2.7 years) were enrolled in the study. The obese subjects were divided into two groups (NAFLD group and non-NAFLD group) based on the elevated alanine aminotransferase levels (>30 IU/L) and the presence or absence of liver steatosis detected by ultrasonography. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) from fasting samples. Plasma total antioxidant status (TAS) and total oxidant status (TOS) level measurements (REL Assay Diagnostics) were done in all participants. The ratio of TOS to TAS was regarded as an oxidative stress index (OSI), an indicator of the degree of OS. Fasting insulin levels and HOMA-IR values in the NAFLD group were significantly higher than in the non-NAFLD and control groups. TAS measurements were decreased in both obese groups (NAFLD and non-NAFLD) in comparison with the control group. TOS and OSI measurements were higher in the NAFLD group than in the non-NAFLD and control groups. OSI was positively correlated with fasting insulin (r=0.67, p=0.01) and HOMA-IR (r=0.71, p=0.02) in the NAFLD obese group. In this cross-sectional study, elevated OS markers in obese adolescents with NAFLD were associated with insulin resistance. This data suggest that an antioxidant therapy might have a potential for treating NAFLD associated with insulin resistance.

Genetic evidence of a causal effect of insulin resistance on branched-chain amino acid levels

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Mahendran, Yuvaraj; Jonsson, Anna; Have, Christian T

2017-01-01

variable for insulin resistance. A GRS of three variants increasing circulating BCAA levels was used as an instrumental variable for circulating BCAA levels. RESULTS: Fasting plasma BCAA levels were associated with higher HOMA-IR in ADDITION-PRO (β 0.137 [95% CI 0.08, 0.19] p = 6 × 10(-7)). However......, the GRS for circulating BCAA levels was not associated with fasting insulin levels or HOMA-IR in ADDITION-PRO (β -0.011 [95% CI -0.053, 0.032] p = 0.6 and β -0.011 [95% CI -0.054, 0.031] p = 0.6, respectively) or in GWAS results for HOMA-IR from MAGIC (β for valine-increasing GRS -0.012 [95% CI -0.069, 0......(-4), and β 0.67 [95% CI 0.16, 1.18] p = 0.01 for isoleucine, leucine and valine levels, respectively) and instrumental variable analyses in ADDITION-PRO indicated that HOMA-IR is causally related to higher circulating fasting BCAA levels (β 0.73 [95% CI 0.26, 1.19] p = 0.002). CONCLUSIONS/INTERPRETATION: Our...

The influence of the polymorphism in apolipoprotein B codon 2488 on insulin and lipid levels in a Danish twin population

DEFF Research Database (Denmark)

Bentzen, J; Poulsen, P; Vaag, A

2002-01-01

on parameters associated with the insulin resistance syndrome in Danish twins. METHODS: The effect of the polymorphism on lipid, glucose and insulin measures was studied in 548 same sex twins aged 55-74 years. RESULTS: The codon 2488 polymorphism influenced fasting triglyceride levels, as well as insulin......, as measured at 120 min in an oral glucose tolerance test. Subjects with the genotype T2488T had 14% higher triglyceride levels (P = 0.02) and 31% higher insulin levels (P = 0.004) than subjects with genotype C2488C. In twins discordant for genotype, the T-allele was associated with higher levels......AIMS: The apolipoprotein B codon 2488 polymorphism has been associated with the metabolism of lipoproteins in subjects with Type 2 diabetes. However, no data are available on the influence of the polymorphism on insulin or glucose metabolism. This study examines the impact of the polymorphism...

Effects of febuxostat on insulin resistance and expression of high-sensitivity C-reactive protein in patients with primary gout.

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Meng, Juan; Li, Yanchun; Yuan, Xiaoxu; Lu, Yuewu

2017-02-01

We aimed to investigate the effects of febuxostat on IR and the expression of high-sensitivity C-reactive protein (hs-CRP) in patients with primary gout. Forty-two cases of primary gout patients without uric acid-lowering therapy were included in this study. After a physical examination, 20 age- and sex-matched patients were included as normal controls. The levels of fasting insulin (INS), fasting blood glucose (FBG), and hs-CRP were determined. IR was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Gout patients had higher levels of UA, INS, HOMA-IR, and hs-CRP than normal controls (P gout patients and implicate that febuxostat can effectively control the level of serum UA and increase insulin sensitivity in primary gout patients.

Effects of supervised structured aerobic exercise training program on fasting blood glucose level, plasma insulin level, glycemic control, and insulin resistance in type 2 diabetes mellitus.

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Shakil-Ur-Rehman, Syed; Karimi, Hossein; Gillani, Syed Amir

2017-01-01

To determine the effects of supervised structured aerobic exercise training (SSAET) program on fasting blood glucose level (FBGL), plasma insulin level (PIL), glycemic control (GC), and insulin resistance (IR) in type 2 diabetes mellitus (T2DM). Riphah Rehabilitation and Research Centre (RRRC) was the clinical setting for this randomized controlled trial, located at Pakistan Railways General Hospital (PRGH), Rawalpindi, Pakistan. Study duration was 18 months from January 1, 2015 to June 30, 2016. Patients of both genders ranging 40-70 years of age with at least one year of history of T2DM were considered eligible according to WHO criteria, while patients with other chronic diseases, history of smoking, regular exercise and diet plan were excluded. Cohorts of 195 patients were screened out of whom 120 fulfilled the inclusion criteria. Amongst them 102 agreed to participate and were assigned to experimental (n=51) and control (n=51) groups. Experimental group underwent SSAET program, routine medication and dietary plan, whereas the control group received routine medication and dietary plan, while both group received treatment for 25 weeks. The blood samples were taken at baseline and on the completion of 25 weeks. The investigation of fasting blood glucose level, plasma insulin level, and glycemic control was conducted to calculate IR. Patients with T2DM in experimental group (n=51) treated with SSAET program, routine medication and dietary plan significantly improved FBGL (pre-mean= 276.41±25.31, post-mean=250.07±28.23), PIL (pre-mean=13.66±5.31, post-mean=8.91±3.83), GC (pre-mean=8.31±1.79, post-mean 7.28±1.43), and IR (pre-mean=64.95±27.26, post-mean 37.97±15.58), as compared with patients in control group treated with routine medication and dietary plan in whom deteriorations were noted in FBGL (pre-mean=268.19±22.48, post-mean=281.41±31.30), PIL(pre-mean=14.14±5.48, post-mean=14.85±5.27) GC (pre-mean=8.15±1.74, post-mean=8.20±1.44, and IR (pre

Grizzly bears exhibit augmented insulin sensitivity while obese prior to a reversible insulin resistance during hibernation.

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Nelson, O Lynne; Jansen, Heiko T; Galbreath, Elizabeth; Morgenstern, Kurt; Gehring, Jamie Lauren; Rigano, Kimberly Scott; Lee, Jae; Gong, Jianhua; Shaywitz, Adam J; Vella, Chantal A; Robbins, Charles T; Corbit, Kevin C

2014-08-05

The confluence of obesity and diabetes as a worldwide epidemic necessitates the discovery of new therapies. Success in this endeavor requires translatable preclinical studies, which traditionally employ rodent models. As an alternative approach, we explored hibernation where obesity is a natural adaptation to survive months of fasting. Here we report that grizzly bears exhibit seasonal tripartite insulin responsiveness such that obese animals augment insulin sensitivity but only weeks later enter hibernation-specific insulin resistance (IR) and subsequently reinitiate responsiveness upon awakening. Preparation for hibernation is characterized by adiposity coupled to increased insulin sensitivity via modified PTEN/AKT signaling specifically in adipose tissue, suggesting a state of "healthy" obesity analogous to humans with PTEN haploinsufficiency. Collectively, we show that bears reversibly cope with homeostatic perturbations considered detrimental to humans and describe a mechanism whereby IR functions not as a late-stage metabolic adaptation to obesity, but rather a gatekeeper of the fed-fasting transition. Copyright © 2014 Elsevier Inc. All rights reserved.

Plasma lipid fatty acid composition, desaturase activities and insulin sensitivity in Amerindian women.

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Vessby, B; Ahrén, B; Warensjö, E; Lindgärde, F

2012-03-01

Two Amerindian populations--Shuar women living in the Amazonian rain forest under traditional conditions and urbanized women in a suburb of Lima were studied. The fatty acid composition in plasma lipids and the relationships between fatty acid composition and metabolic variables were studied, as well as in a reference group of Swedish women. Fasting plasma was used for analyses of glucose, insulin, leptin and fatty acid composition. Women in Lima had more body fat, higher fasting insulin and leptin and lower insulin sensitivity than the Shuar women, who had insulin sensitivity similar to Swedish women. Shuar women had very high proportions (mean; SD) of palmitoleic (13.2; 3.9%) and oleic (33.9; 3.7%) acids in the plasma cholesteryl esters with very low levels of linoleic acid (29.1; 6.1 3%), as expected on a low fat, high carbohydrate diet. The estimated activity of delta 9 (SCD-1) desaturase was about twice as high in the Shuar compared with Lima women, suggesting neo lipogenesis, while the delta 5 desaturase activity did not differ. The Lima women, as well as the Swedish, showed strong positive correlations between SCD-1 activity on the one hand and fasting insulin and HOMA index on the other. These associations were absent in the Shuar women. The high SCD-1 activity in the Shuar women may reflect increased lipogenesis in adipose tissue. It also illustrates how a low fat diet rich in non-refined carbohydrates can be linked to a good metabolic situation. Copyright © 2010. Published by Elsevier B.V.

Chemical stability of insulin. 2. Formation of higher molecular weight transformation products during storage of pharmaceutical preparations.

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Brange, J; Havelund, S; Hougaard, P

1992-06-01

Formation of covalent, higher molecular weight transformation (HMWT) products during storage of insulin preparations at 4-45 degrees C was studied by size exclusion chromatography. The main products are covalent insulin dimers (CID), but in protamine-containing preparations the concurrent formation of covalent insulin-protamine (CIP) products takes place. At temperatures greater than or equal to 25 degrees C parallel or consecutive formation of covalent oligo- and polymers can also be observed. Rate of HMWT is only slightly influenced by species of insulin but varies with composition and formulation, and for isophane (NPH) preparations, also with the strength of preparation. Temperature has a pronounced effect on CID, CIP, and, especially, covalent oligo- and polymer formation. The CIDs are apparently formed between molecules within the hexameric unit common for all types of preparations and rate of formation is generally faster in glycerol-containing preparations. Compared with insulin hydrolysis reactions (see the preceding paper), HMWT is one order of magnitude slower, except for NPH preparations.

FoxO6 Integrates Insulin Signaling With Gluconeogenesis in the Liver

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Kim, Dae Hyun; Perdomo, German; Zhang, Ting; Slusher, Sandra; Lee, Sojin; Phillips, Brett E.; Fan, Yong; Giannoukakis, Nick; Gramignoli, Roberto; Strom, Stephen; Ringquist, Steven; Dong, H. Henry

2011-01-01

OBJECTIVE Excessive endogenous glucose production contributes to fasting hyperglycemia in diabetes. This effect stems from inept insulin suppression of hepatic gluconeogenesis. To understand the underlying mechanisms, we studied the ability of forkhead box O6 (FoxO6) to mediate insulin action on hepatic gluconeogenesis and its contribution to glucose metabolism. RESEARCH DESIGN AND METHODS We characterized FoxO6 in glucose metabolism in cultured hepatocytes and in rodent models of dietary obesity, insulin resistance, or insulin-deficient diabetes. We determined the effect of FoxO6 on hepatic gluconeogenesis in genetically modified mice with FoxO6 gain- versus loss-of-function and in diabetic db/db mice with selective FoxO6 ablation in the liver. RESULTS FoxO6 integrates insulin signaling to hepatic gluconeogenesis. In mice, elevated FoxO6 activity in the liver augments gluconeogenesis, raising fasting blood glucose levels, and hepatic FoxO6 depletion suppresses gluconeogenesis, resulting in fasting hypoglycemia. FoxO6 stimulates gluconeogenesis, which is counteracted by insulin. Insulin inhibits FoxO6 activity via a distinct mechanism by inducing its phosphorylation and disabling its transcriptional activity, without altering its subcellular distribution in hepatocytes. FoxO6 becomes deregulated in the insulin-resistant liver, accounting for its unbridled activity in promoting gluconeogenesis and correlating with the pathogenesis of fasting hyperglycemia in diabetes. These metabolic abnormalities, along with fasting hyperglycemia, are reversible by selective inhibition of hepatic FoxO6 activity in diabetic mice. CONCLUSIONS Our data uncover a FoxO6-dependent pathway by which the liver orchestrates insulin regulation of gluconeogenesis, providing the proof-of-concept that selective FoxO6 inhibition is beneficial for curbing excessive hepatic glucose production and improving glycemic control in diabetes. PMID:21940782

Correlation between the Plasma Insulin and Glucose Concentration in Normal Korean Adults

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Lee, Jang Kyu; Sung, Ho Kyung; Kim, Jin Eui [Radiological Research Institute, Seoul (Korea, Republic of)

1971-09-15

The correlation between the plasma insulin, and glucose concentration was studied in healthy Korean adults consisting of 20 males and 22 females of 16 to 38 years of age. The blood samples of above subjects were obtained through cubital vein at arbitrary times during their usual working hours. Plasma insulin was assayed by means of double antibody system of radioimmunoassay technics, and blood glucose was determined by means of Van Slyke-Folch method. Results were as follows : 1. There were no differences in the blood sugar levels in relation to the plasma insulin concentration either by sex or age. 2. In the case, when the plasma insulin concentration was within 50 mmuU/ml, the correlation between the insulin, and glucose concentration existed, the ratio of which was expressed as; Plasma glucose concentration (mg/dl)=91.9 + 0.08 X Insulin concentration r=0.62. 3. Insulinogenic index was 12.4%, which was somewhat higher than other reports. 4. It is suggested that the correlation between plasma insulin and glucose concentration could be determined at arbitrary times instead of fasting times.

Studies on insulin receptor, 2

International Nuclear Information System (INIS)

Sakai, Yukio

1979-01-01

The present study is to investigate an influence of starvation and high fat diet on insulin receptor of the plasma membrane by means of radioreceptor assay using 125 I-labelled insulin. Male guinea pigs of Hartley strain were employed for the starvation study, and 125 I-insulin binding capacity on the plasma membrane of the liver and kidney was determined at 24, 48 and 72 hours of the fast after the last meal. Male rats of Wistar strain were employed for the high fat study where the diet containing 35% of butter was fed ad libitum for 38 or 68 days. The animals were killed at the fast of 12 hours, and 125 I-insulin binding capacity on the plasma membrane of the liver was determined. The results obtained are summarized as follows: 1) An increase in 125 I-insulin binding capacity on the plasma membrane of the liver and kidney was observed by the starvation for 24 to 72 hours. 2) The mechanism of the increase by starvation was considered to be different by the organs; it was due to an increase in number of insulin receptor in the liver, and due to an increase in affinity of insulin receptor in the kidney. 3) In non-obese rats fed with high fat diet, the number of insulin receptor on the liver plasma membrane showed a decrease, and this observation clearly indicated that the decrease in number of the receptor did not depend on the obesity. 4) Obese rats also fed with high fat diet presented a decrease in number of insulin receptor without an elevation of insulin levels in the circulating blood. This indicated that at least in the obese rats fed with high fat diet, the decrease in number of the receptor was not due to hyperinsulinemia. (author)

Multilevel Fast Multipole Method for Higher Order Discretizations

DEFF Research Database (Denmark)

Borries, Oscar Peter; Meincke, Peter; Jorgensen, Erik

2014-01-01

The multi-level fast multipole method (MLFMM) for a higher order (HO) discretization is demonstrated on high-frequency (HF) problems, illustrating for the first time how an efficient MLFMM for HO can be achieved even for very large groups. Applying several novel ideas, beneficial to both lower...... order and higher order discretizations, results from a low-memory, high-speed MLFMM implementation of a HO hierarchical discretization are shown. These results challenge the general view that the benefits of HO and HF-MLFMM cannot be combined....

Insulin and leptin levels in overweight and normal-weight Iranian adolescents: The CASPIAN-III study

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Ehsan Bahrami

2014-01-01

Full Text Available Background: In this study, we aim to compare insulin and leptin levels in adolescents with or without excess weight and in those with or without abdominal obesity. Materials and Methods : This case-control study was conducted among 486 samples. We randomly selected 243 overweight and an equal number of normal-weight adolescents from among participants of the third survey of a national surveillance program entitled "Childhood and Adolescence Surveillance and PreventIon of Adult Non-communicable diseases study." Serum insulin and leptin were compared between two groups and their correlation was determined with other variables. Results: The mean age and body mass index (BMI of participants were 14.10 ± 2.82 years and 22.12 ± 6.49 kg/m 2 , respectively. Leptin and insulin levels were higher in overweight than in normal-weight adolescents (P < 0.05. Leptin level was higher in children with abdominal obesity than in their other counterparts (P < 0.001. Leptin level was correlated with age, fasting blood glucose, BMI, and insulin level. Conclusion: Insulin and leptin levels were higher among overweight and obese children, which may reflect insulin and leptin-resistance. Given the complications of excess weight from early life, prevention and controlling childhood obesity should be considered as a health priority.

Insulin resistance in first-trimester pregnant women with pre-pregnant glucose tolerance and history of recurrent spontaneous abortion.

Science.gov (United States)

Hong, Y; Xie, Q X; Chen, C Y; Yang, C; Li, Y Z; Chen, D M; Xie, M Q

2013-01-01

Insulin resistance (IR) has been reported to play an important role in recurrent spontaneous abortion (RSA) among patients with polycystic ovary syndrome (PCOS). However, scanted materials exist regarding the independent effect of IR on RSA. The aim of this study is to investigate the status of IR in first trimester pregnant patients with normal pre-pregnant glucose tolerance and history of RSA. This two-center case-control study enrolled totally 626 first trimester pregnant women including 161 patients with a history of recurrent spontaneous abortion, who were pre-pregnantly glucose-tolerant according to oral glucose tolerance test (OGTT), and 465 women with no history of abnormal pregnancies of any kind. Clinical, biochemical and hormonal parameters were simultaneously measured in all participants. Serum beta-HCG, estradiol, progesterone, fasting plasma glucose and fasting plasma insulin levels, as well, the calculated homeostasis model assessment of insulin resistance index (HOMA-IR), fasting plasma glucose/insulin ratio(G/I) and pregnancy outcome were analyzed and compared. Serum beta-HCG and progesterone were found to be significantly lower in RSA group compared to controls. Subjects in RSA group were found to have higher HOMA-IR and lower G/I ratio than those in control group. Serum beta-HCG and progesterone were negatively correlated with HOMA-IR, and positively with G/I ratio even after adjustment for BMI. The spontaneous abortion rate within first trimester pregnancy of RSA patients was significantly higher than that in controls. In conclusion, woman with recurrent spontaneous abortion and normal pre-pregnant glucose metabolism tends to be more insulin resistant during first trimester pregnancy than healthy controls, no matter whether she has PCOS or not. Insulin resistance might be one of the direct causes that lead to recurrent abortion.

High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity.

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Zhigang Liu

Full Text Available High-fat diet (HFD-induced obesity is associated with insulin resistance, which may affect brain synaptic plasticity through impairment of insulin-sensitive processes underlying neuronal survival, learning, and memory. The experimental model consisted of 3 month-old C57BL/6J mice fed either a normal chow diet (control group or a HFD (60% of calorie from fat; HFD group for 12 weeks. This model was characterized as a function of time in terms of body weight, fasting blood glucose and insulin levels, HOMA-IR values, and plasma triglycerides. IRS-1/Akt pathway was assessed in primary hepatocytes and brain homogenates. The effect of HFD in brain was assessed by electrophysiology, input/output responses and long-term potentiation. HFD-fed mice exhibited a significant increase in body weight, higher fasting glucose- and insulin levels in plasma, lower glucose tolerance, and higher HOMA-IR values. In liver, HFD elicited (a a significant decrease of insulin receptor substrate (IRS-1 phosphorylation on Tyr608 and increase of Ser307 phosphorylation, indicative of IRS-1 inactivation; (b these changes were accompanied by inflammatory responses in terms of increases in the expression of NFκB and iNOS and activation of the MAP kinases p38 and JNK; (c primary hepatocytes from mice fed a HFD showed decreased cellular oxygen consumption rates (indicative of mitochondrial functional impairment; this can be ascribed partly to a decreased expression of PGC1α and mitochondrial biogenesis. In brain, HFD feeding elicited (a an inactivation of the IRS-1 and, consequentially, (b a decreased expression and plasma membrane localization of the insulin-sensitive neuronal glucose transporters GLUT3/GLUT4; (c a suppression of the ERK/CREB pathway, and (d a substantial decrease in long-term potentiation in the CA1 region of hippocampus (indicative of impaired synaptic plasticity. It may be surmised that 12 weeks fed with HFD induce a systemic insulin resistance that impacts

The Higher the Insulin Resistance the Lower the Cardiac Output in Men with Type 1 Diabetes During the Maximal Exercise Test.

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Niedzwiecki, Pawel; Naskret, Dariusz; Pilacinski, Stanislaw; Pempera, Maciej; Uruska, Aleksandra; Adamska, Anna; Zozulinska-Ziolkiewicz, Dorota

2017-06-01

The aim of this study was to assess the hemodynamic parameters analyzed in bioimpedance cardiography during maximal exercise in patients with type 1 diabetes differing in insulin resistance. The study group consisted of 40 men with type 1 diabetes. Tissue sensitivity to insulin was assessed on the basis of the glucose disposal rate (GDR) analyzed during hyperinsulinemic-euglycemic clamp. Patients were divided into groups with GDR insulin sensitivity) and GDR ≥4.5 mg/kg/min (G2 group-higher insulin sensitivity). During the exercise test, the heart rate, systolic volume, cardiac output, cardiac index were measured by the impedance meter (PhysioFlow). Compared with the G2 group, the G1 group had a lower cardiac output (CO): during exercise 8.6 (IQR 7.7-10.0) versus 12.8 (IQR 10.8-13.7) L/min; P insulin resistance is associated with cardiac hemodynamic parameters assessed during and after exercise. The higher the insulin resistance the lower the cardiac output during maximal exercise in men with type 1 diabetes.

Peripheral Insulin Doesn’t Alter Appetite of Broiler Chicks

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Lei Liu

2016-09-01

Full Text Available An experiment was conducted to investigate the effect of peripheral insulin treatment on appetite in chicks. Six-d-age chicks with ad libitum feeding or fasting for 3 h before injection received a subcutaneous injection of 0, 1, 3, 5, 10, or 20 IU of insulin or vehicle (saline. The results showed peripheral insulin treatment (1 to 20 IU did not alter significantly the feed intake in chicks under either ad libitum feeding or fasting conditions within 4 h (p>0.05. Compared with the control, plasma glucose concentration was significantly decreased after insulin treatment of 3, 5, 10, and 20 IU for 4 h in chicks with ad libitum feeding (p0.05. All results suggest peripheral administration of insulin has no effect on appetite in chicks.

Clinical and Genetic Characteristics of Non-Insulin-Requiring Glutamic Acid Decarboxylase (GAD Autoantibody-Positive Diabetes: A Nationwide Survey in Japan.

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Junichi Yasui

Full Text Available Glutamic acid decarboxylase autoantibodies (GADAb differentiate slowly progressive insulin-dependent (type 1 diabetes mellitus (SPIDDM from phenotypic type 2 diabetes, but many GADAb-positive patients with diabetes do not progress to insulin-requiring diabetes. To characterize GADAb-positive patients with adult-onset diabetes who do not require insulin therapy for >5 years (NIR-SPIDDM, we conducted a nationwide cross-sectional survey in Japan.We collected 82 GADAb-positive patients who did not require insulin therapy for >5 years (NIR-SPIDDM and compared them with 63 patients with insulin-requiring SPIDDM (IR-SPIDDM. Clinical and biochemical characteristics, HLA-DRB1-DQB1 haplotypes, and predictive markers for progression to insulin therapy were investigated.Compared with the IR-SPIDDM group, the NIR-SPIDDM patients showed later diabetes onset, higher body mass index, longer duration before diagnosis, and less frequent hyperglycemic symptoms at onset. In addition, C-peptide, LDL-cholesterol, and TG were significantly higher in the NIR-SPIDDM compared to IR-SPIDDM patients. The NIR-SPIDDM group had lower frequency of susceptible HLA-DRB1*04:05-DQB1*04:01 and a higher frequency of resistant HLA-DRB1*15:01-DQB1*06:02 haplotype compared to IR-SPIDDM. A multivariable analysis showed that age at diabetes onset (OR = 0.82, duration before diagnosis of GADAb-positive diabetes (OR = 0.82, higher GADAb level (≥10.0 U/ml (OR = 20.41, and fasting C-peptide at diagnosis (OR = 0.07 were independent predictive markers for progression to insulin-requiring diabetes. An ROC curve analysis showed that the optimal cut-off points for discriminating two groups was the GADAb level of 13.6 U/ml, age of diabetes onset of 47 years, duration before diagnosis of 5 years, and fasting C-peptide of 0.65 ng/ml.Clinical, biochemical and genetic characteristics of patients with NIR-SPIDDM are different from those of IR-SPIDDM patients. Age of diabetes onset, duration before

Plasma resistin, adiponectin and leptin levels in relation to insulin resistance

International Nuclear Information System (INIS)

Shousha, M.A.; Soliman, S.E.T.

2010-01-01

Adipose tissue regulates insulin sensitivity via the circulating adipo cytokines, adiponectin, resistin and leptin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. We examined plasma levels of resistin, adiponectin and leptin in 20 lean subjects with mean body mass index (BMI) of 24, and, 36 nondiabetic obese individuals with mean BMI 34. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 30.4±6.5 vs. 14.4±2.9 mg/l, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P < 0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly reduced in obese compared with lean subjects, P < 0.005 and higher in women, P< 0.001. Adiponectin levels showed significant correlation with HOMA-R and this correlation remained significant after adjustment for gender and BMI. Leptin levels were significantly higher in obese subjects and women and correlated with resistin, but, didn't correlate with HOMA-R. In this small group of patients we demonstrated that insulin resistance correlated most strongly and reciprocally with adiponectin levels. Significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for leptin, the correlation with insulin resistance did not achieve statistical significance

Dietary patterns and the insulin resistance phenotype among non-diabetic adults

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Background: Information on the relation between dietary patterns derived by cluster analysis and insulin resistance is scarce. Objective: To compare insulin resistance phenotypes, including waist circumference, body mass index, fasting and 2-hour post-challenge insulin, insulin sensitivity index (I...

Biomimetic insulin-imprinted polymer nanoparticles as a potential oral drug delivery system

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Paul Pijush Kumar

2017-06-01

Full Text Available In this study, we investigate molecularly imprinted polymers (MIPs, which form a three-dimensional image of the region at and around the active binding sites of pharmaceutically active insulin or are analogous to b cells bound to insulin. This approach was employed to create a welldefined structure within the nanospace cavities that make up functional monomers by cross-linking. The obtained MIPs exhibited a high adsorption capacity for the target insulin, which showed a significantly higher release of insulin in solution at pH 7.4 than at pH 1.2. In vivo studies on diabetic Wistar rats showed that the fast onset within 2 h is similar to subcutaneous injection with a maximum at 4 h, giving an engaged function responsible for the duration of glucose reduction for up to 24 h. These MIPs, prepared as nanosized material, may open a new horizon for oral insulin delivery.

Genetic and phenotypic correlations between surrogate measures of insulin release obtained from OGTT data

DEFF Research Database (Denmark)

Gjesing, Anette Marianne Prior; Ribel-Madsen, Rasmus; Harder, Marie Neergaard

2015-01-01

closely related to fasting insulin with a genetic correlation of 0.85. The effects of 82 selected susceptibility single nucleotide polymorphisms on these insulin secretion indices supported our interpretation of the data and added insight into the biological differences between the examined traits......AIMS/HYPOTHESIS: We examined the extent to which surrogate measures of insulin release have shared genetic causes. METHODS: Genetic and phenotypic correlations were calculated in a family cohort (n = 315) in which beta cell indices were estimated based on fasting and oral glucose-stimulated plasma...... glucose, serum C-peptide and serum insulin levels. Furthermore, we genotyped a large population-based cohort (n = 6,269) for common genetic variants known to associate with type 2 diabetes, fasting plasma glucose levels or fasting serum insulin levels to examine their association with various indices...

Effect of Carthamus tinctorius (Safflower) on fasting blood glucose and insulin levels in alloxan induced diabetic rabbits.

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Qazi, Nasreen; Khan, Rafeeq Alam; Rizwani, Ghazala H; Feroz, Zeeshan

2014-03-01

Diabetes mellitus is a major threat to present and future generations. The role of herbal medication has emerged as a safe alternative to currently available medication due to its decreased potential to produce side effects, hence effect of Carthamus tinctorius was observed on fasting blood glucose and insulin levels in alloxan induced diabetic rabbits. Thirty five healthy male rabbits were divided into 5 groups with 7 rabbits in each (Normal control, diabetic control, diabetic treated with glibenclamide, diabetic treated with Carthamus tinctorius extract at doses of 200 and 300mg/kg of body weight). Drug and extract were given orally for 30 days and the values for blood glucose levels were observed after 15(th) and 30(th) day of treatment by using standard reagent kits provided by Human Germany. While insulin levels were checked at the end of the study by using Architect i1000 by Abbott Diagnostics USA. Animals were also observed for any gross toxicity during the study. Results revealed that Carthamus tinctorius has significant hypoglycemic effect at 200mg/kg and 300mg/kg doses as compared to diabetic control group. Insulin levels were significantly increased in Glibenclamide treated as well as Carthamus tinctorius treated groups as compared to diabetic control.

Genetic variation of fasting glucose and changes in glycemia in response to 2-year weight-loss diet intervention: the POUNDS Lost trial

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Wang, Tiange; Huang, Tao; Zheng, Yan; Rood, Jennifer; Bray, George A.; Sacks, Frank M.; Qi, Lu

2016-01-01

Objective Weight loss intervention through diet modification has been widely used to improve obesity-related hyperglycemia; however, little is known about whether genetic variation modifies the intervention effect. We examined the interaction between weight-loss diets and genetic variation of fasting glucose on changes in glycemic traits in a dietary intervention trial. Research Design and Methods The Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial is a randomized, controlled 2-year weight-loss trial. We assessed overall genetic variation of fasting glucose by calculating a genetic risk score (GRS) based on 14 fasting glucose-associated single nucleotide polymorphisms, and examined the progression in fasting glucose and insulin levels, and insulin resistance and insulin sensitivity in 733 adults from this trial. Results The GRS was associated with 6-month changes in fasting glucose (Pfasting insulin (P=0.042), homeostasis model assessment of insulin resistance (HOMA-IR, P=0.009) and insulin sensitivity (HOMA-S, P=0.043). We observed significant interaction between the GRS and dietary fat on 6-month changes in fasting glucose, HOMA-IR and HOMA-S after multivariable adjustment (P-interaction=0.007, 0.045, and 0.028, respectively). After further adjustment for weight loss, the interaction remained significant on change in fasting glucose (P=0.015). In the high-fat diet group, participants in the highest GRS tertile showed increased fasting glucose, whereas participants in the lowest tertile showed decreased fasting glucose (P-trend<0.001); in contrast, the genetic association was not significant in the low-fat diet group (P-trend=0.087). Conclusions Our data suggest that participants with a higher genetic risk may benefit more by eating a low-fat diet to improve glucose metabolism. PMID:27113490

Improved Multilevel Fast Multipole Method for Higher-Order discretizations

DEFF Research Database (Denmark)

Borries, Oscar Peter; Meincke, Peter; Jorgensen, Erik

2014-01-01

The Multilevel Fast Multipole Method (MLFMM) allows for a reduced computational complexity when solving electromagnetic scattering problems. Combining this with the reduced number of unknowns provided by Higher-Order discretizations has proven to be a difficult task, with the general conclusion b...

Should insulin resistance be screened in lean hirsute women?

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Arduc, Ayse; Sarıcam, Orkun; Dogan, Bercem Aycicek; Tuna, Mazhar Muslum; Tutuncu, Yasemin Ates; Isik, Serhat; Berker, Dilek; Sennaroglu, Engin; Guler, Serdar

2015-04-01

The role of insulin resistance (IR) is well-documented in obese women with polycystic ovary syndrome (PCOS). Controversies exist concerning the presence of IR in idiopathic hirsutism (IH) or if it is a manifestation of high body mass index (BMI). We aimed to investigate the presence/absence of IR in lean hirsute women. One-hundred fifty-one lean women with hirsutism [96 PCOS (group 1) and 55 IH (group 2)] and 58 age-and BMI-matched healthy controls (group 3) were recruited in the study (mean age 25.21 ± 6.1 versus 26.26 ± 4.6years; BMI 21.79 ± 1.7 versus 22.02 ± 2.2 kg/m(2), respectively). Significantly higher insulin and HOMA-IR, and significantly lower fasting glucose insulin ratio (FGIR), quantitative insulin sensitivity check index (QUICKI), reciprocal insulin, and Raynaud index were detected in groups 1 and 2 than in group 3 (p  2, FGIR lean hirsute women regardless of they having PCOS or IH. IR may contribute to aetiopathogenesis of IH, or may cause some metabolic abnormalities in these patients.

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

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

2004-04-01

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

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

International Nuclear Information System (INIS)

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

2004-01-01

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

Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats.

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Yamazaki, Ricardo K; Brito, Gleisson A P; Coelho, Isabela; Pequitto, Danielle C T; Yamaguchi, Adriana A; Borghetti, Gina; Schiessel, Dalton Luiz; Kryczyk, Marcelo; Machado, Juliano; Rocha, Ricelli E R; Aikawa, Julia; Iagher, Fabiola; Naliwaiko, Katya; Tanhoffer, Ricardo A; Nunes, Everson A; Fernandes, Luiz Claudio

2011-04-28

Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Monosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish oil-treated normal weight group (FO), obese control group (Ob), coconut fat-treated obese group (ObCO) and fish oil-treated obese group (ObFO). Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day) for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Obese animals (Ob) presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt) showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO) similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30%) and triacylglycerol (TG; 33%) compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Low dose of fish oil supplementation (1 g/kg/day) was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

Effect of Avocado Soybean Unsaponifiables on Insulin Secretion and Insulin Sensitivity in Patients with Obesity

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Esperanza Martínez-Abundis

2013-10-01

Full Text Available Aim: To evaluate the effect of avocado soybean unsaponifiables (ASU on insulin secretion and insulin sensitivity in patients with obesity. Methods: A randomized, double-blind, placebo-controlled, clinical trial was carried out in 14 obese adult volunteers. After random allocation of the intervention, 7 patients received 300 mg of ASU or placebo during a fasting state for 3 months. A metabolic profile including IL-6 and high-sensitivity C-reactive protein (hs-CRP levels was carried out prior to the intervention. A hyperglycemic-hyperinsulinemic clamp technique was used to assess insulin secretion and insulin sensitivity phases. Mann-Whitney U test and Wilcoxon test were performed for statistical analyses. The study was approved by the local ethics committee of our institution. Results: At baseline, both groups were similar according to clinical and laboratory characteristics. There was no significant difference in insulin secretion and insulin sensitivity with ASU. Conclusions: ASU administration for 3 months did not modify insulin secretion and insulin sensitivity in patients with obesity.

The adipose transcriptional response to insulin is determined by obesity, not insulin sensitivity

DEFF Research Database (Denmark)

Rydén, Mikael; Hrydziuszko, Olga; Mileti, Enrichetta

2016-01-01

Metabolically healthy obese subjects display preserved insulin sensitivity and a beneficial white adipose tissue gene expression pattern. However, this observation stems from fasting studies when insulin levels are low. We investigated adipose gene expression by 5'Cap-mRNA sequencing in 17 healthy...... non-obese (NO), 21 insulin-sensitive severely obese (ISO), and 30 insulin-resistant severely obese (IRO) subjects, before and 2 hr into a hyperinsulinemic euglycemic clamp. ISO and IRO subjects displayed a clear but globally similar transcriptional response to insulin, which differed from the small...... effects observed in NO subjects. In the obese, 231 genes were altered; 71 were enriched in ISO subjects (e.g., phosphorylation processes), and 52 were enriched in IRO subjects (e.g., cellular stimuli). Common cardio-metabolic risk factors and gender do not influence these findings. This study demonstrates...

Decrement of postprandial insulin secretion determines the progressive nature of type-2 diabetes.

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Shim, Wan Sub; Kim, Soo Kyung; Kim, Hae Jin; Kang, Eun Seok; Ahn, Chul Woo; Lim, Sung Kil; Lee, Hyun Chul; Cha, Bong Soo

2006-10-01

Type-2 diabetes is a progressive disease. However, little is known about whether decreased fasting or postprandial pancreatic beta-cell responsiveness is more prominent with increased duration of diabetes. The aim of this study was to evaluate the relationship between insulin secretion both during fasting and 2 h postprandial, and the duration of diabetes in type-2 diabetic patients. Cross-sectional clinical investigation. We conducted a meal tolerance test in 1466 type-2 diabetic patients and calculated fasting (M0) and postprandial (M1) beta-cell responsiveness. The fasting C-peptide, postprandial C-peptide, M0, and M1 values were lower, but HbA1c values were higher, in patients with diabetes duration > 10 years than those in other groups. There was no difference in the HbA1c levels according to the tertiles of their fasting C-peptide level. However, in a group of patients with highest postprandial C-peptide tertile, the HbA1c values were significantly lower than those in other groups. After adjustment of age, sex, and body mass index (BMI), the duration of diabetes was found to be negatively correlated with fasting C-peptide (gamma = -0.102), postprandial C-peptide (gamma = -0.356), M0 (gamma = -0.263), and M1 (gamma = -0.315; P multiple regression analysis, M0, M1, and homeostasis model assessment for insulin resistance (HOMA-IR) emerged as predictors of HbAlc after adjustment for age, sex, and BMI (R2 = 0.272, 0.080, and 0.056 respectively). With increasing duration of diabetes, the decrease of postprandial insulin secretion is becoming more prominent, and postprandial beta-cell responsiveness may be a more important determinant for glycemic control than fasting beta-cell responsiveness.

Ambient Air Pollutants Have Adverse Effects on Insulin and Glucose Homeostasis in Mexican Americans

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Chen, Zhanghua; Salam, Muhammad T.; Toledo-Corral, Claudia; Watanabe, Richard M.; Xiang, Anny H.; Buchanan, Thomas A.; Habre, Rima; Bastain, Theresa M.; Lurmann, Fred; Wilson, John P.; Trigo, Enrique

2016-01-01

OBJECTIVE Recent studies suggest that air pollution plays a role in type 2 diabetes (T2D) incidence and mortality. The underlying physiological mechanisms have yet to be established. We hypothesized that air pollution adversely affects insulin sensitivity and secretion and serum lipid levels. RESEARCH DESIGN AND METHODS Participants were selected from BetaGene (n = 1,023), a study of insulin resistance and pancreatic β-cell function in Mexican Americans. All participants underwent DXA and oral and intravenous glucose tolerance tests and completed dietary and physical activity questionnaires. Ambient air pollutant concentrations (NO2, O3, and PM2.5) for short- and long-term periods were assigned by spatial interpolation (maximum interpolation radius of 50 km) of data from air quality monitors. Traffic-related air pollution from freeways (TRAP) was estimated using the dispersion model as NOx. Variance component models were used to analyze individual and multiple air pollutant associations with metabolic traits. RESULTS Short-term (up to 58 days cumulative lagged averages) exposure to PM2.5 was associated with lower insulin sensitivity and HDL-to-LDL cholesterol ratio and higher fasting glucose and insulin, HOMA-IR, total cholesterol, and LDL cholesterol (LDL-C) (all P ≤ 0.036). Annual average PM2.5 was associated with higher fasting glucose, HOMA-IR, and LDL-C (P ≤ 0.043). The effects of short-term PM2.5 exposure on insulin sensitivity were largest among obese participants. No statistically significant associations were found between TRAP and metabolic outcomes. CONCLUSIONS Exposure to ambient air pollutants adversely affects glucose tolerance, insulin sensitivity, and blood lipid concentrations. Our findings suggest that ambient air pollutants may contribute to the pathophysiology in the development of T2D and related sequelae. PMID:26868440

Higher protein kinase C ζ in fatty rat liver and its effect on insulin actions in primary hepatocytes.

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Wei Chen

Full Text Available We previously showed the impairment of insulin-regulated gene expression in the primary hepatocytes from Zucker fatty (ZF rats, and its association with alterations of hepatic glucose and lipid metabolism. However, the molecular mechanism is unknown. A preliminary experiment shows that the expression level of protein kinase C ζ (PKCζ, a member of atypical PKC family, is higher in the liver and hepatocytes of ZF rats than that of Zucker lean (ZL rats. Herein, we intend to investigate the roles of atypical protein kinase C in the regulation of hepatic gene expression. The insulin-regulated hepatic gene expression was evaluated in ZL primary hepatocytes treated with atypical PKC recombinant adenoviruses. Recombinant adenovirus-mediated overexpression of PKCζ, or the other atypical PKC member PKCι/λ, alters the basal and impairs the insulin-regulated expressions of glucokinase, sterol regulatory element-binding protein 1c, the cytosolic form of phosphoenolpyruvate carboxykinase, the catalytic subunit of glucose 6-phosphatase, and insulin like growth factor-binding protein 1 in ZL primary hepatocytes. PKCζ or PKCι/λ overexpression also reduces the protein level of insulin receptor substrate 1, and the insulin-induced phosphorylation of AKT at Ser473 and Thr308. Additionally, PKCι/λ overexpression impairs the insulin-induced Prckz expression, indicating the crosstalk between PKCζ and PKCι/λ. We conclude that the PKCζ expression is elevated in hepatocytes of insulin resistant ZF rats. Overexpressions of aPKCs in primary hepatocytes impair insulin signal transduction, and in turn, the down-stream insulin-regulated gene expression. These data suggest that elevation of aPKC expression may contribute to the hepatic insulin resistance at gene expression level.

Correlations between fasting plasma C-peptide, glucagon-stimulated plasma C-peptide, and urinary C-peptide in insulin-treated diabetics

DEFF Research Database (Denmark)

Gjessing, H J; Matzen, L E; Frøland, A

1987-01-01

This study correlated fasting plasma C-peptide (CP), plasma CP 6 min after stimulation with 1 mg glucagon i.v., and the mean of three 24-h urinary excretions of C-peptide (UCP)/creatinine in 132 insulin-treated diabetics. Patients were divided into three groups: group 1, stimulated CP less than 0.......06 nM (n = 51); group 2, stimulated CP 0.06-0.60 nM (n = 48); and group 3, stimulated CP greater than 0.60 nM (n = 33). In all patients fasting CP was closely correlated to stimulated CP (r = .988, P less than .001), whereas the correlations between UCP and both fasting CP (r = .904, P less than .001......) and stimulated CP r = .902, P less than .001) were slightly less pronounced. The associations between UCP and both fasting CP (r = .716, P less than .001) and stimulated CP (r = .731, P less than .001) were modest in group 2, and even more so in group 3 (r = .557, P less than .001 and r = .641, P less than .001...

Peripheral insulin resistance rather than beta cell dysfunction accounts for geographical differences in impaired fasting blood glucose among sub-Saharan African individuals: findings from the RODAM study.

Science.gov (United States)

Meeks, Karlijn A C; Stronks, Karien; Adeyemo, Adebowale; Addo, Juliet; Bahendeka, Silver; Beune, Erik; Owusu-Dabo, Ellis; Danquah, Ina; Galbete, Cecilia; Henneman, Peter; Klipstein-Grobusch, Kerstin; Mockenhaupt, Frank P; Osei, Kwame; Schulze, Matthias B; Spranger, Joachim; Smeeth, Liam; Agyemang, Charles

2017-05-01

The aim of this study was to assess the extent to which insulin resistance and beta cell dysfunction account for differences in impaired fasting blood glucose (IFBG) levels in sub-Saharan African individuals living in different locations in Europe and Africa. We also aimed to identify determinants associated with insulin resistance and beta cell dysfunction among this population. Data from the cross-sectional multicentre Research on Obesity and Diabetes among African Migrants (RODAM) study were analysed. Participants included Ghanaian individuals without diabetes, aged 18-96 years old, who were residing in Amsterdam (n = 1337), Berlin (n = 502), London (n = 961), urban Ghana (n = 1309) and rural Ghana (n = 970). Glucose and insulin were measured in fasting venous blood samples. Anthropometrics were assessed during a physical examination. Questionnaires were used to assess demographics, physical activity, smoking status, alcohol consumption and energy intake. Insulin resistance and beta cell function were determined using homeostatic modelling (HOMA-IR and HOMA-B, respectively). Logistic regression analysis was used to study the contribution of HOMA-IR and inverse HOMA-B (beta cell dysfunction) to geographical differences in IFBG (fasting glucose 5.6-6.9 mmol/l). Multivariate linear regression analysis was used to identify determinants associated with HOMA-IR and inverse HOMA-B. IFBG was more common in individuals residing in urban Ghana (OR 1.41 [95% CI 1.08, 1.84]), Amsterdam (OR 3.44 [95% CI 2.69, 4.39]) and London (OR 1.58 [95% CI 1.20 2.08), but similar in individuals living in Berlin (OR 1.00 [95% CI 0.70, 1.45]), compared with those in rural Ghana (reference population). The attributable risk of IFBG per 1 SD increase in HOMA-IR was 69.3% and in inverse HOMA-B was 11.1%. After adjustment for HOMA-IR, the odds for IFBG reduced to 0.96 (95% CI 0.72, 1.27), 2.52 (95%CI 1.94, 3.26) and 1.02 (95% CI 0.78, 1.38) for individuals in Urban Ghana

Calcium phosphate-PEG-insulin-casein (CAPIC) particles as oral delivery systems for insulin.

Science.gov (United States)

Morçöl, T; Nagappan, P; Nerenbaum, L; Mitchell, A; Bell, S J D

2004-06-11

An oral delivery system for insulin was developed and functional activity was tested in a non-obese diabetic (NOD) mice model. Calcium phosphate particles containing insulin was synthesized in the presence of PEG-3350 and modified by aggregating the particles with caseins to obtain the calcium phosphate-PEG-insulin-casein (CAPIC) oral insulin delivery system. Single doses of CAPIC formulation were tested in NOD mice under fasting or fed conditions to evaluate the glycemic activity. The blood glucose levels were monitored every 1-2h for 12h following the treatments using an ACCU CHECK blood glucose monitoring system. Orally administered and subcutaneously injected free insulin solution served as controls in the study. Based on the results obtained we propose that: (1). the biological activity of insulin is preserved in CAPIC formulation; (2). insulin in CAPIC formulations, but not the free insulin, displays a prolonged hypoglycemic effect after oral administration to diabetic mice; (3). CAPIC formulation protects insulin from degradation while passing through the acidic environment of the GI track until it is released in the less acidic environment of the intestines where it can be absorbed in its biologically active form; (4). CAPIC formulation represents a new and unique oral delivery system for insulin and other macromolecules.

Effect of starvation on human muscle protein metabolism and its response to insulin

International Nuclear Information System (INIS)

Fryburg, D.A.; Barrett, E.J.; Louard, R.J.; Gelfand, R.A.

1990-01-01

To assess the effect of fasting on muscle protein turnover in the basal state and in response to insulin, we measured forearm amino acid kinetics, using [3H]phenylalanine (Phe) and [14C]leucine (Leu) infused systemically, in eight healthy subjects after 12 (postabsorptive) and 60 h of fasting. After a 150-min basal period, forearm local insulin concentration was selectively raised by approximately 25 muU/ml for 150 min by intra-arterial insulin infusion (0.02 mU.kg-1. min-1). The 60-h fast increased urine nitrogen loss and whole body Leu flux and oxidation (by 50-75%, all P less than 0.02). Post-absorptively, forearm muscle exhibited a net release of Phe and Leu, which increased two- to threefold after the 60-h fast (P less than 0.05); this effect was mediated exclusively by accelerated local rates of amino acid appearance (Ra), with no reduction in rates of disposal (Rd). Local hyperinsulinemia in the postabsorptive condition caused a twofold increase in forearm glucose uptake (P less than 0.01) and completely suppressed the net forearm output of Phe and Leu (P less than 0.02). After the 60-h fast, forearm glucose disposal was depressed basally and showed no response to insulin; in contrast, insulin totally abolished the accelerated net forearm release of Phe and Leu. The action of insulin to reverse the augmented net release of Phe and Leu was mediated exclusively by approximately 40% suppression of Ra (P less than 0.02) rather than a stimulation of Rd. We conclude that in short-term fasted humans (1) muscle amino acid output accelerates due to increased proteolysis rather than reduced protein synthesis, and (2) despite its catabolic state and a marked impairment in insulin-mediated glucose disposal, muscle remains sensitive to insulin's antiproteolytic action

Effect of starvation on human muscle protein metabolism and its response to insulin

Energy Technology Data Exchange (ETDEWEB)

Fryburg, D.A.; Barrett, E.J.; Louard, R.J.; Gelfand, R.A. (Yale Univ. School of Medicine, New Haven, CT (USA))

1990-10-01

To assess the effect of fasting on muscle protein turnover in the basal state and in response to insulin, we measured forearm amino acid kinetics, using (3H)phenylalanine (Phe) and (14C)leucine (Leu) infused systemically, in eight healthy subjects after 12 (postabsorptive) and 60 h of fasting. After a 150-min basal period, forearm local insulin concentration was selectively raised by approximately 25 muU/ml for 150 min by intra-arterial insulin infusion (0.02 mU.kg-1. min-1). The 60-h fast increased urine nitrogen loss and whole body Leu flux and oxidation (by 50-75%, all P less than 0.02). Post-absorptively, forearm muscle exhibited a net release of Phe and Leu, which increased two- to threefold after the 60-h fast (P less than 0.05); this effect was mediated exclusively by accelerated local rates of amino acid appearance (Ra), with no reduction in rates of disposal (Rd). Local hyperinsulinemia in the postabsorptive condition caused a twofold increase in forearm glucose uptake (P less than 0.01) and completely suppressed the net forearm output of Phe and Leu (P less than 0.02). After the 60-h fast, forearm glucose disposal was depressed basally and showed no response to insulin; in contrast, insulin totally abolished the accelerated net forearm release of Phe and Leu. The action of insulin to reverse the augmented net release of Phe and Leu was mediated exclusively by approximately 40% suppression of Ra (P less than 0.02) rather than a stimulation of Rd. We conclude that in short-term fasted humans (1) muscle amino acid output accelerates due to increased proteolysis rather than reduced protein synthesis, and (2) despite its catabolic state and a marked impairment in insulin-mediated glucose disposal, muscle remains sensitive to insulin's antiproteolytic action.

Childhood craniopharyngioma: greater hypothalamic involvement before surgery is associated with higher homeostasis model insulin resistance index

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Sainte-Rose Christian

2009-04-01

Full Text Available Abstract Background Obesity seems to be linked to the hypothalamic involvement in craniopharyngioma. We evaluated the pre-surgery relationship between the degree of this involvement on magnetic resonance imaging and insulin resistance, as evaluated by the homeostasis model insulin resistance index (HOMA. As insulin-like growth factor 1, leptin, soluble leptin receptor (sOB-R and ghrelin may also be involved, we compared their plasma concentrations and their link to weight change. Methods 27 children with craniopharyngioma were classified as either grade 0 (n = 7, no hypothalamic involvement, grade 1 (n = 8, compression without involvement, or grade 2 (n = 12, severe involvement. Results Despite having similar body mass indexes (BMI, the grade 2 patients had higher glucose, insulin and HOMA before surgery than the grade 0 (P = 0.02, The data for the whole population before and 6–18 months after surgery showed increases in BMI (P Conclusion The hypothalamic involvement by the craniopharyngioma before surgery seems to determine the degree of insulin resistance, regardless of the BMI. The pre-surgery HOMA values were correlated with the post-surgery weight gain. This suggests that obesity should be prevented by reducing inn secretion in those cases with hypothalamic involvement.

Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance

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Hirvonen, Jussi; Virtanen, Kirsi A.; Nummenmaa, Lauri; Hannukainen, Jarna C.; Honka, Miikka-Juhani; Bucci, Marco; Nesterov, Sergey V.; Parkkola, Riitta; Rinne, Juha; Iozzo, Patricia; Nuutila, Pirjo

2011-01-01

OBJECTIVE Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18F]fluorodeoxyglucose (for brain glucose metabolism) and [15O]H2O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance. PMID:21270256

Icodextrine and insulin resistance in continuous ambulatory peritoneal dialysis patients.

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Canbakan, Mustafa; Sahin, Gülizar Manga

2007-01-01

Insulin resistance is commonly observed in uremic patients. Glucose-based peritoneal dialysis solutions have long-term metabolic complications like hyperinsulinemia, hyperlipidemia, and obesity. The purpose of this study was to examine the insulin resistance in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with standard glucose and icodextrin containing solutions. The entire non diabetic CAPD patients of our center were studied: forty-four patients in all who were on CAPD treatment for 36.2 +/- 23.7 months. Twenty-seven of them (11 male and 16 female) with a mean age of 46 +/- 16 years were treated with standard glucose solutions (glucose group). The other 17 patients (10 male and 7 female) with a mean age of 49 +/- 16 years were treated with standard glucose solutions during the day and icodextrin dwell during the night, for a median of 12 +/- 6.3 months (icodextrin group). Morning fasting serum insulin levels were 20.59 +/- 17.86 in the glucose group and 10.15 +/- 6.87 in the icodextrin group (p = 0.0001). Homeostasis Model Assessment Method scores of the glucose group were significantly higher (4.8+/-4.1 vs 2.3+/- 1.7; p = 0.025) than the icodextrin group. A significant positive correlation of HOMA score with insulin, fasting plasma glucose, and triglyceride levels were found in HOMA (IR+) patients. Twenty patients of the icodextrin group (74%) and 15 patients of the glucose group (88%) were hypertensive, but there was no statistically significant difference between the two groups (p = 0.13). The groups showed no significant differences for body mass index and serum levels of glucose, total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol, triglyceride, intact parathyroid hormone (iPTH), and fibrinogen. In conclusion, the use of icodextrin in the long nighttime dwell can reduce serum insulin levels and increase insulin sensitivity in CAPD patients.

Effect of Postural Change on Plasma Insulin Concentration in Normal Volunteer

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Sung, Ho Kyung; Koh, Joo Whan; Joo, Jong Koo; Kim, Jin Yong; Lee, Jang Kyu [Korea Atomic Research Institute, Seoul (Korea, Republic of)

1974-03-15

The concentrations of some blood constituents are known to be influenced by the postural change. The blood glucose and insulin concentrations were measured, first, in the supine, and then (30 minutes later) in the erect positions under the fasting state. The effects of a duretic, furose-mide, were also studied under the same condition for 5 consecutive days. The materials were 5 healthy volunteers aging 20-29 years old with out any diabetic past, or family histories. The blood glucose was measured by the Nelson's method, and plasma insulin by the radioimmunoassay method. Following are the results; 1) The plasma insulin concentration in the erect position is slightly higher than in the supine position, however, the increase is statistically insignificant because of the notable individual variations in the values of the supine position. 2) Four out of 5 cases show the increase of about 80% of plasma insulin in the erect position, which is statistically significant if analyzed on the basis of frequency distribution. 3) The blood glucose concentration showed no postural changes. 4) The increase of the plasma insulin concentration in the erect position seems to the result of limited extra vasation of insulin in the lower extremities.

Insulin dynamics and biochemical markers for predicting impaired glucose tolerance in obese Thai youth.

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Tirabanchasak, Sirapassorn; Siripunthana, Sukumarn; Supornsilchai, Vichit; Wacharasindhu, Suttipong; Sahakitrungruang, Taninee

2015-09-01

Subjects with impaired glucose tolerance (IGT) are at risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. The predictors of IGT in obese youth are not well described. We studied 115 obese Thai children who underwent an oral glucose tolerance test (OGTT). Plasma glucose and insulin levels were calculated for assessment of β-cell function. Hemoglobin A1c (HbA1c), lipid profile, and clinical parameters were also used to determine predictors of IGT. We found that three patients had T2DM and 30 subjects had IGT. IGT patients had significantly higher fasting glucose (FG), 1-h postload glucose, 2-h postload insulin, and lower whole-body insulin sensitivity indices than in normal glucose tolerance subjects whereas other indices were comparable. By ROC curve analyses, 1-h postload glucose was the best predictor of IGT, but FG or HbA1c represented a poor diagnostic tool for prediabetes screening. Subjects with 1-h OGTT glucose > 155 mg/dL had significantly lower high-density lipoprotein levels, lower insulin sensitivity, and more insulin resistance than those with 1-h postload glucose of ≤ 155 mg/dL. Abnormal glucose tolerance is highly prevalent in obese Thai youth. Several fasting indices and HbA1c fail to predict IGT. An 1-h OGTT glucose of > 155 mg/dL appears to be more associated with adverse insulin dynamics and metabolic profile than 2-h postload glucose.

Association between omentin levels and insulin resistance in pregnancy.

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Aktas, G; Alcelik, A; Ozlu, T; Tosun, M; Tekce, B K; Savli, H; Tekce, H; Dikbas, O

2014-03-01

Omentin is a new adipokine secreted mainly from visceral adipose tissue. Serum omentin is found to be reduced in patients with impaired glucose tolerance, type 2 diabetes mellitus, obesity and insulin resistant states. Despite the fact that pregnancy is also characterized with hyperinsulinemia, literature is lacking about data of omentin levels and its association with insulin resistance in pregnant women. We aimed to evaluate the association of omentin levels and insulin resistance in pregnant women and to compare these levels with those of non-pregnant, non-diabetic women. Uncomplicated pregnant women who admit to our outpatient clinics for routine follow-up were included in the study group. Non-pregnant women without diabetes mellitus were served as control group. Fasting glucose, insulin, omentin levels and HOMA IR were recorded. SPSS 15.0 for Windows was used for statistical analysis. There were 36 pregnant women in the study group and 37 healthy, non-pregnant women in the control group. Serum omentin and fasting glucose levels were significantly decreased and fasting insulin was significantly increased in the study group compared to control group. Omentin might be an indicator of insulin resistance in pregnant women. Larger prospective studies are needed to claim whether omentin can have a clinical use for diagnosis of gestational diabetes mellitus. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

The dipeptidyl peptidase-4 inhibitor vildagliptin improves beta-cell function and insulin sensitivity in subjects with impaired fasting glucose

DEFF Research Database (Denmark)

Utzschneider, Kristina M; Tong, Jenny; Montgomery, Brenda

2007-01-01

OBJECTIVE: To evaluate the effect of treatment with the dipeptidyl peptidase (DPP)-4 inhibitor vildagliptin on insulin sensitivity and beta-cell function in subjects with impaired fasting glucose (IFG). RESEARCH DESIGN AND METHODS: A total of 22 subjects with IFG (11 female and 11 male, mean +/- SD...... age 59.6 +/- 11.5 years) were treated orally with 100 mg vildagliptin once daily in a single-blind study. Subjects received placebo for 2 weeks (run-in) followed by vildagliptin for 6 weeks (treatment) and then placebo for 2 weeks (washout). A frequently sampled intravenous glucose tolerance test....... RESULTS: Fasting plasma glucose did not change after 6 weeks of vildagliptin treatment. With treatment, mean +/- SEM AIR(g) increased from 224 +/- 44 to 286 +/- 52 pmol/l (P

Specific insulin and proinsulin secretion in glucokinase-deficient individuals

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V.C. Pardini

1999-04-01

Full Text Available Glucokinase (GCK is an enzyme that regulates insulin secretion, keeping glucose levels within a narrow range. Mutations in the glucokinase gene cause a rare form of diabetes called maturity-onset diabetes of the young (MODY. An early onset (less than 25 years, autosomal dominant inheritance and low insulin secretion stimulated by glucose characterize MODY patients. Specific insulin and proinsulin were measured in serum by immunofluorimetric assays (IFMA during a 75-g oral glucose tolerance test (OGTT. Two kindreds (SA and LZ were studied and compared to non-diabetic unrelated individuals (control group 1 matched for age and body mass index (BMI. In one kindred, some of these subjects were also obese (BMI >26 kg/m2, and other family members also presented with obesity and/or late-onset NIDDM. The MODY patients were also compared to a group of five of their first-degree relatives with obesity and/or late-onset NIDDM. The proinsulin profile was different in members of the two MODY kindreds. Fasting proinsulin and the proinsulin/insulin ratio were similar in MODY members of kindred LZ and subjects from control group 1, but were significantly lower than in MODY members of kindred SA (P<0.02 and P<0.01, for proinsulin and proinsulin/insulin ratio, respectively. Moreover, MODY members of family SA had higher levels of proinsulin and proinsulin/insulin ratio, although not significantly different, when compared to their first-degree relatives and to subjects from control group 2. In conclusion, we observed variable degrees of proinsulin levels and proinsulin/insulin ratio in MODY members of two different kindreds. The higher values of these parameters found in MODY and non-MODY members of kindred SA is probably related to the obesity and late-onset NIDDM background present in this family.

Obese Japanese adults with type 2 diabetes have higher basal metabolic rates than non-diabetic adults.

Science.gov (United States)

Miyake, Rieko; Ohkawara, Kazunori; Ishikawa-Takata, Kazuko; Morita, Akemi; Watanabe, Shaw; Tanaka, Shigeho

2011-01-01

Several cross-sectional studies in Pima Indians and Caucasians have indicated that obese individuals with type 2 diabetes have a higher basal metabolic rate (BMR) than healthy, obese individuals. However, no study has investigated this comparison in Japanese subjects, who are known to be susceptible to type 2 diabetes due to genetic characteristics. Thirty obese Japanese adults with pre-type 2 diabetes (n=7) or type 2 diabetes (n=13) or without diabetes (n=10) participated in this study. BMR was measured using indirect calorimetry. The relationships between residual BMR (calculated as measured BMR minus BMR adjusted for fat-free mass, fat mass, age, and sex) and biomarkers including fasting glucose, glycosylated hemoglobin (HbA(1c)), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-R), triglycerides, and free fatty acids were examined using Pearson's correlation. BMR in diabetic subjects adjusted for fat-free mass, fat mass, age, and sex was 7.1% higher than in non-diabetic subjects. BMR in diabetic subjects was also significantly (pBMR and fasting glucose (r=0.391, p=0.032). These results indicate that in the Japanese population, obese subjects with type 2 diabetes have higher BMR compared with obese non-diabetic subjects. The fasting glucose level may contribute to these differences.

Epigenome-wide association study of fasting measures of glucose, insulin, and HOMA-IR in the Genetics of Lipid Lowering Drugs and Diet Network study.

Science.gov (United States)

Hidalgo, Bertha; Irvin, M Ryan; Sha, Jin; Zhi, Degui; Aslibekyan, Stella; Absher, Devin; Tiwari, Hemant K; Kabagambe, Edmond K; Ordovas, Jose M; Arnett, Donna K

2014-02-01

Known genetic susceptibility loci for type 2 diabetes (T2D) explain only a small proportion of heritable T2D risk. We hypothesize that DNA methylation patterns may contribute to variation in diabetes-related risk factors, and this epigenetic variation across the genome can contribute to the missing heritability in T2D and related metabolic traits. We conducted an epigenome-wide association study for fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) among 837 nondiabetic participants in the Genetics of Lipid Lowering Drugs and Diet Network study, divided into discovery (N = 544) and replication (N = 293) stages. Cytosine guanine dinucleotide (CpG) methylation at ∼470,000 CpG sites was assayed in CD4(+) T cells using the Illumina Infinium HumanMethylation 450 Beadchip. We fit a mixed model with the methylation status of each CpG as the dependent variable, adjusting for age, sex, study site, and T-cell purity as fixed-effects and family structure as a random-effect. A Bonferroni corrected P value of 1.1 × 10(-7) was considered significant in the discovery stage. Significant associations were tested in the replication stage using identical models. Methylation of a CpG site in ABCG1 on chromosome 21 was significantly associated with insulin (P = 1.83 × 10(-7)) and HOMA-IR (P = 1.60 × 10(-9)). Another site in the same gene was significant for HOMA-IR and of borderline significance for insulin (P = 1.29 × 10(-7) and P = 3.36 × 10(-6), respectively). Associations with the top two signals replicated for insulin and HOMA-IR (P = 5.75 × 10(-3) and P = 3.35 × 10(-2), respectively). Our findings suggest that methylation of a CpG site within ABCG1 is associated with fasting insulin and merits further evaluation as a novel disease risk marker.

Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats

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Iagher Fabiola

2011-04-01

Full Text Available Abstract Background Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Methods Monosodium glutamate (MSG (4 mg/g body weight was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C, coconut fat-treated normal weight group (CO, fish oil-treated normal weight group (FO, obese control group (Ob, coconut fat-treated obese group (ObCO and fish oil-treated obese group (ObFO. Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Results Obese animals (Ob presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30% and triacylglycerol (TG; 33% compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Conclusions Low dose of fish oil supplementation (1 g/kg/day was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

Reversal of diet-induced obesity increases insulin transport into cerebrospinal fluid and restores sensitivity to the anorexic action of central insulin in male rats.

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Begg, Denovan P; Mul, Joram D; Liu, Min; Reedy, Brianne M; D'Alessio, David A; Seeley, Randy J; Woods, Stephen C

2013-03-01

Diet-induced obesity (DIO) reduces the ability of centrally administered insulin to reduce feeding behavior and also reduces the transport of insulin from the periphery to the central nervous system (CNS). The current study was designed to determine whether reversal of high-fat DIO restores the anorexic efficacy of central insulin and whether this is accompanied by restoration of the compromised insulin transport. Adult male Long-Evans rats were initially maintained on either a low-fat chow diet (LFD) or a high-fat diet (HFD). After 22 weeks, half of the animals on the HFD were changed to the LFD, whereas the other half continued on the HFD for an additional 8 weeks, such that there were 3 groups: 1) a LFD control group (Con; n = 18), 2) a HFD-fed, DIO group (n = 17), and 3) a HFD to LFD, DIO-reversal group (DIO-rev; n = 18). The DIO reversal resulted in a significant reduction of body weight and epididymal fat weight relative to the DIO group. Acute central insulin administration (8 mU) reduced food intake and caused weight loss in Con and DIO-rev but not DIO rats. Fasting cerebrospinal fluid insulin was higher in DIO than Con animals. However, after a peripheral bolus injection of insulin, cerebrospinal fluid insulin increased in Con and DIO-rev rats but not in the DIO group. These data provide support for previous reports that DIO inhibits both the central effects of insulin and insulin's transport to the CNS. Importantly, DIO-rev restored sensitivity to the effects of central insulin on food intake and insulin transport into the CNS.

Lower dietary vitamin E intake during the second trimester is associated with insulin resistance and hyperglycemia later in pregnancy.

Science.gov (United States)

Ley, S H; Hanley, A J; Sermer, M; Zinman, B; O'Connor, D L

2013-11-01

Beneficial effects of vitamin E on insulin sensitivity have been reported in observational and short-term intervention studies in non-pregnant populations. We aimed to investigate whether dietary vitamin E intake during the second trimester would be associated with glucose metabolism later in pregnancy and whether this association would be influenced by an insulin-sensitizing hormone adiponectin. Women with singleton pregnancies (n=205) underwent a 3-h oral glucose tolerance test at 30 weeks gestation and were asked to recall second trimester dietary intake. Higher dietary vitamin E intake was associated with lower fasting glucose, lower HOMA insulin resistance, and higher Matsuda insulin sensitivity index after covariate adjustment including serum adiponectin among women consuming daily multivitamin supplements (all P≤0.03). Lower dietary vitamin E intake during the second trimester is associated with hyperglycemia and insulin resistance later in pregnancy among women consuming daily multivitamin supplementations. Further, these associations are not influenced by adiponectin.

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

Vitamin D Supplementation Does Not Impact Insulin Resistance in Black and White Children.

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Ferira, Ashley J; Laing, Emma M; Hausman, Dorothy B; Hall, Daniel B; McCabe, George P; Martin, Berdine R; Hill Gallant, Kathleen M; Warden, Stuart J; Weaver, Connie M; Peacock, Munro; Lewis, Richard D

2016-04-01

Vitamin D supplementation trials with diabetes-related outcomes have been conducted almost exclusively in adults and provide equivocal findings. The objective of this study was to determine the dose-response of vitamin D supplementation on fasting glucose, insulin, and a surrogate measure of insulin resistance in white and black children aged 9–13 years, who participated in the Georgia, Purdue, and Indiana University (or GAPI) trial: a 12-week multisite, randomized, triple-masked, dose-response, placebo-controlled vitamin D trial. Black and white children in the early stages of puberty (N = 323, 50% male, 51% black) were equally randomized to receive vitamin D3 (0, 400, 1000, 2000, or 4000 IU/day) for 12 weeks. Fasting serum 25-hydroxyvitamin D (25(OH)D), glucose and insulin were assessed at baseline and weeks 6 and 12. Homeostasis model assessment of insulin resistance was used as a surrogate measure of insulin resistance. Statistical analyses were conducted as intent-to-treat using a mixed effects model. Baseline serum 25(OH)D was inversely associated with insulin (r = −0.140, P = 0.017) and homeostasis model assessment of insulin resistance (r = −0.146, P = 0.012) after adjusting for race, sex, age, pubertal maturation, fat mass, and body mass index. Glucose, insulin, and insulin resistance increased (F > 5.79, P insulin resistance, vitamin D supplementation had no impact on fasting glucose, insulin, or a surrogate measure of insulin resistance over 12 weeks in apparently healthy children.

An uncommon cause of hypoglycemia: insulin autoimmune syndrome.

Science.gov (United States)

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

2014-01-01

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

Insulin binding to erythrocytes after acute 16-methyleneprednisolone ingestion.

Science.gov (United States)

Dwenger, A; Holle, W; Zick, R; Trautschold, I

1982-10-01

The binding of [125I]insulin to erythrocytes, glucose and insulin were determined before and 1, 7 and 35 days after ingestion of 2 X 60-methyleneprednisolone. None of two groups of volunteers (7 males, 4 females showed clear alterations of the insulin binding parameters (Ka and R0), or of the fasting cortisol, glucose and insulin concentrations. These results exclude the possibility that the diabetogenic effect of glucocorticoides is accompanied by an alteration of the insulin receptor characteristics of erythrocytes.

Plasma insulin levels are increased by sertraline in rats under oral glucose overload

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Gomez R.

2001-01-01

Full Text Available Recognition and control of depression symptoms are important to increase patient compliance with treatment and to improve the quality of life of diabetic patients. Clinical studies indicate that selective serotonin reuptake inhibitors (SSRI are better antidepressants for diabetic patients than other drugs. However, preclinical trials have demonstrated that not all SSRI reduce plasma glucose levels. In fact, fluoxetine increases and sertraline decreases glycemia in diabetic and non-diabetic rats. In the present study we evaluated plasma insulin levels during fasting and after glucose overload after treatment with sertraline. Adult male Wistar rats were fasted and treated with saline or 30 mg/kg sertraline and submitted or not to glucose overload (N = 10. Blood was collected and plasma insulin was measured. The mean insulin levels were: fasting group: 25.9 ± 3.86, sertraline + fasting group: 31.10 ± 2.48, overload group: 34.1 ± 3.40, and overload + sertraline group: 43.73 ± 5.14 µU/ml. Insulinemia was significantly increased in the overload + sertraline group. There were no differences between the other groups. No difference in glucose/insulin ratios could be detected between groups. The overload + sertraline group was the only one in which a significant number of individuals exceeded the upper confidence limit of insulin levels. This study demonstrates that sertraline increases glucose-stimulated insulin secretion without any change in peripheral insulin sensitivity.

Effects of exposure to electromagnetic field radiation (EMFR generated by activated mobile phones on fasting blood glucose

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Sultan Ayoub Meo

2013-04-01

Full Text Available Objective: Extensive use of mobile phones has been accompanied by a common public debate about possible adverse effects on human health. No study has been published so far to establish any association between the fastest growing innovation of mobile phone and fasting blood glucose. The aim was to determine the effects of exposure to electromagnetic field radiation generated by mobile phones on fasting blood glucose in Wistar Albino rats. Materials and Methods: 40 Male Albino rats (Wistar Strain were divided into 5 equally numerous groups. Group A served as the control one, group B received mobile phone radiation for less than 15 min/day, group C: 15-30 min/day, group D: 31-45 min/day, and group E: 46-60 min/day for a total period of 3 months. Fasting blood glucose was determined by using Spectrophotometer and serum insulin by Enzyme-linked Immunosorbent Assay (ELISA. The Homeostatic Model (HOMA-B was applied for the assessment of β-cell function and (HOMA-IR for resistance to insulin. Results: Wister Albino rats exposed to mobile phone radiation for longer than 15 min a day for a total period of 3 months had significantly higher fasting blood glucose (p < 0.015 and serum insulin (p < 0.01 compared to the control group. HOMA-IR for insulin resistance was significantly increased (p < 0.003 in the groups that were exposed for 15-30 and 46-60 min/day compared to the control rats. Conclusion: The results of the present study show an association between long-term exposure to activated mobile phones and increase in fasting blood glucose and serum insulin in Albino rats.

Effect of chloroquine on insulin and glucose homoeostasis in normal subjects and patients with non-insulin-dependent diabetes mellitus.

OpenAIRE

Smith, G D; Amos, T A; Mahler, R; Peters, T J

1987-01-01

Plasma glucose, insulin, and C peptide concentrations were determined after an oral glucose load in normal subjects and in a group of patients with non-insulin-dependent diabetes mellitus before and during a short course of treatment with chloroquine. In the control group there was a small but significant reduction in fasting blood glucose concentration but overall glucose tolerance and hormone concentrations were unaffected. In contrast, the patients with non-insulin-dependent diabetes melli...

Modification and Validation of the Triglyceride-to-HDL Cholesterol Ratio as a Surrogate of Insulin Sensitivity in White Juveniles and Adults without Diabetes Mellitus: The Single Point Insulin Sensitivity Estimator (SPISE).

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Paulmichl, Katharina; Hatunic, Mensud; Højlund, Kurt; Jotic, Aleksandra; Krebs, Michael; Mitrakou, Asimina; Porcellati, Francesca; Tura, Andrea; Bergsten, Peter; Forslund, Anders; Manell, Hannes; Widhalm, Kurt; Weghuber, Daniel; Anderwald, Christian-Heinz

2016-09-01

The triglyceride-to-HDL cholesterol (TG/HDL-C) ratio was introduced as a tool to estimate insulin resistance, because circulating lipid measurements are available in routine settings. Insulin, C-peptide, and free fatty acids are components of other insulin-sensitivity indices but their measurement is expensive. Easier and more affordable tools are of interest for both pediatric and adult patients. Study participants from the Relationship Between Insulin Sensitivity and Cardiovascular Disease [43.9 (8.3) years, n = 1260] as well as the Beta-Cell Function in Juvenile Diabetes and Obesity study cohorts [15 (1.9) years, n = 29] underwent oral-glucose-tolerance tests and euglycemic clamp tests for estimation of whole-body insulin sensitivity and calculation of insulin sensitivity indices. To refine the TG/HDL ratio, mathematical modeling was applied including body mass index (BMI), fasting TG, and HDL cholesterol and compared to the clamp-derived M-value as an estimate of insulin sensitivity. Each modeling result was scored by identifying insulin resistance and correlation coefficient. The Single Point Insulin Sensitivity Estimator (SPISE) was compared to traditional insulin sensitivity indices using area under the ROC curve (aROC) analysis and χ(2) test. The novel formula for SPISE was computed as follows: SPISE = 600 × HDL-C(0.185)/(TG(0.2) × BMI(1.338)), with fasting HDL-C (mg/dL), fasting TG concentrations (mg/dL), and BMI (kg/m(2)). A cutoff value of 6.61 corresponds to an M-value smaller than 4.7 mg · kg(-1) · min(-1) (aROC, M:0.797). SPISE showed a significantly better aROC than the TG/HDL-C ratio. SPISE aROC was comparable to the Matsuda ISI (insulin sensitivity index) and equal to the QUICKI (quantitative insulin sensitivity check index) and HOMA-IR (homeostasis model assessment-insulin resistance) when calculated with M-values. The SPISE seems well suited to surrogate whole-body insulin sensitivity from inexpensive fasting single-point blood draw and BMI

Studies on insulin receptor, 2. Studies on the influence of starvation and high fat diet on insulin receptor

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Sakai, Y [Hiroshima Univ. (Japan). School of Medicine

1979-08-01

The present study is to investigate an influence of starvation and high fat diet on insulin receptor of the plasma membrane by means of radioreceptor assay using /sup 125/I-labelled insulin. Male guinea pigs of Hartley strain were employed for the starvation study, and /sup 125/I-insulin binding capacity on the plasma membrane of the liver and kidney was determined at 24, 48 and 72 hours of the fast after the last meal. Male rats of Wistar strain were employed for the high fat study where the diet containing 35% of butter was fed ad libitum for 38 or 68 days. The animals were killed at the fast of 12 hours, and /sup 125/I-insulin binding capacity on the plasma membrane of the liver was determined. The results obtained are summarized as follows: 1) An increase in /sup 125/I-insulin binding capacity on the plasma membrane of the liver and kidney was observed by the starvation for 24 to 72 hours. 2) The mechanism of the increase by starvation was considered to be different by the organs; it was due to an increase in number of insulin receptor in the liver, and due to an increase in affinity of insulin receptor in the kidney. 3) In non-obese rats fed with high fat diet, the number of insulin receptor on the liver plasma membrane showed a decrease, and this observation clearly indicated that the decrease in number of the receptor did not depend on the obesity. 4) Obese rats also fed with high fat diet presented a decrease in number of insulin receptor without an elevation of insulin levels in the circulating blood. This indicated that at least in the obese rats fed with high fat diet, the decrease in number of the receptor was not due to hyperinsulinemia.

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

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

2017-05-30

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

An adult-based insulin resistance genetic risk score associates with insulin resistance, metabolic traits and altered fat distribution in Danish children and adolescents who are overweight or obese

DEFF Research Database (Denmark)

Graae, Anne-Sofie; Hollensted, Mette; Kloppenborg, Julie T

2018-01-01

and adolescents from a population-based study. Anthropometric data, dual-energy x-ray absorptiometry scans, BP, fasting plasma glucose, fasting serum insulin and fasting plasma lipid measurements were obtained, and HOMA-IR was calculated. The GRS53 was examined for association with metabolic traits in children...... by linear regressions using an additive genetic model. In overweight/obese children and adolescents, the GRS53 associated with higher HOMA-IR (β = 0.109 ± 0.050 (SE); p = 2.73 × 10-2), fasting plasma glucose (β = 0.010 ± 0.005 mmol/l; p = 2.51 × 10-2) and systolic BP SD score (β = 0.026 ± 0.012; p = 3...

Lower adiponectin levels at first trimester of pregnancy are associated with increased insulin resistance and higher risk of developing gestational diabetes mellitus.

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Lacroix, Marilyn; Battista, Marie-Claude; Doyon, Myriam; Ménard, Julie; Ardilouze, Jean-Luc; Perron, Patrice; Hivert, Marie-France

2013-06-01

To evaluate the associations between adiponectin levels and 1) the risk of developing gestational diabetes mellitus (GDM), and 2) insulin resistance/sensitivity, β-cell function, and compensation indices in a prospective cohort representative of the general population of pregnant women. We performed anthropometric measurements and collected blood samples at 1st (6-13 weeks) and 2nd (24-28 weeks) trimesters. Diagnosis of GDM was made at 2nd trimester based on a 75-g oral glucose tolerance test (International Association of the Diabetes and Pregnancy Study Groups criteria). Insulin was measured (ELISA; Luminex) to estimate homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUC(insulin/glucose)), and β-cell compensation (insulin secretion sensitivity index-2). Adiponectin was measured by radioimmunoassay. Among the 445 participants included in this study, 38 women developed GDM. Women who developed GDM had lower 1st-trimester adiponectin levels (9.67 ± 3.84 vs. 11.92 ± 4.59 µg/mL in women with normal glucose tolerance). Lower adiponectin levels were associated with higher risk of developing GDM (OR, 1.12 per 1 µg/mL decrease of adiponectin levels; P = 0.02, adjusted for BMI and HbA1c at 1st trimester). Adiponectin levels at 1st and 2nd trimesters were associated with HOMA-IR (both: r = -0.22, P insulin/glucose). Pregnant women with lower adiponectin levels at 1st trimester have higher levels of insulin resistance and are more likely to develop GDM independently of adiposity or glycemic measurements.

Methods for quantifying adipose tissue insulin resistance in overweight/obese humans.

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Ter Horst, K W; van Galen, K A; Gilijamse, P W; Hartstra, A V; de Groot, P F; van der Valk, F M; Ackermans, M T; Nieuwdorp, M; Romijn, J A; Serlie, M J

2017-08-01

Insulin resistance of adipose tissue is an important feature of obesity-related metabolic disease. However, assessment of lipolysis in humans requires labor-intensive and expensive methods, and there is limited validation of simplified measurement methods. We aimed to validate simplified methods for the quantification of adipose tissue insulin resistance against the assessment of insulin sensitivity of lipolysis suppression during hyperinsulinemic-euglycemic clamp studies. We assessed the insulin-mediated suppression of lipolysis by tracer-dilution of [1,1,2,3,3- 2 H 5 ]glycerol during hyperinsulinemic-euglycemic clamp studies in 125 overweight or obese adults (85 men, 40 women; age 50±11 years; body mass index 38±7 kg m -2 ). Seven indices of adipose tissue insulin resistance were validated against the reference measurement method. Low-dose insulin infusion resulted in suppression of the glycerol rate of appearance ranging from 4% (most resistant) to 85% (most sensitive), indicating a good range of adipose tissue insulin sensitivity in the study population. The reference method correlated with (1) insulin-mediated suppression of plasma glycerol concentrations (r=0.960, PInsulin Resistance (Adipo-IR) index (fasting plasma insulin-NEFA product; r=-0.526, Pinsulin-glycerol product (r=-0.467, PInsulin Resistance Index (fasting plasma insulin-basal lipolysis product; r=0.460, PInsulin Sensitivity Check Index (QUICKI)-NEFA index (r=0.621, Pinsulin resistance (area under the curve ⩾0.801, Pinsulin sensitivity (that is, the antilipolytic action of insulin) can be reliably quantified in overweight and obese humans by simplified index methods. The sensitivity and specificity of the Adipo-IR index and the fasting plasma insulin-glycerol product, combined with their simplicity and acceptable agreement, suggest that these may be most useful in clinical practice.

Anti-inflammatory effects of insulin.

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Dandona, Paresh; Chaudhuri, Ajay; Mohanty, Priya; Ghanim, Husam

2007-07-01

This review deals with the recent observations on the pro-inflammatory effects of glucose and the anti-inflammatory actions of insulin. Apart from being novel, they are central to our understanding of why hyperglycemia is a prognosticator of bad clinical outcomes including patients with acute coronary syndromes, stroke and in patients in the intensive care unit. The pro-inflammatory effect of glucose as well as that of other macronutrients including fast food meals provides the basis of chronic oxidative stress and inflammation in the obese and their propensity to atherosclerotic disease. The anti-inflammatory action of insulin provides a neutralizing effect to balance macronutrient induced inflammation on the one hand and the possibility of using insulin as an anti-inflammatory drug on the other. The actions of macronutrients and insulin described above explain why insulin resistant states like obesity and type 2 diabetes are associated with oxidative stress, inflammation and atherosclerosis. They also suggest that insulin may be antiatherogenic.

Anti-Mullerian hormone and insulin resistance in classic phenotype lean PCOS.

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Caglar, Gamze Sinem; Kahyaoglu, Inci; Pabuccu, Recai; Demirtas, Selda; Seker, Rabia

2013-10-01

This study is designed to explore the correlation between AMH levels and IR in normal weight PCOS women. This prospective study was conducted on 55 patients, who were admitted to obstetrics and gynecology department of a university clinic. Study group was consisted of 34 patients diagnosed as polycystic ovary syndrome (PCOS) according to the Rotterdam Criteria, whereas control group was consisted of 21 healthy volunteers without any features of clinical or biochemical hyperandrogenism, who had regular menstrual cycles. BMI ≥ 25 kg/m(2) were considered overweight and obese and excluded. Blood samples were obtained during days 2-3 after spontaneous menses or progesterone-induced withdrawal bleeding after overnight fasting for at least 12 h. The weight, height, hip and waist circumferences of the patients were measured. Fasting insulin and glucose (FPG) levels were used for calculating different insulin resistance indexes (Homeostatic Model Assessment (HOMA-IR), Quantitative Insulin Sensitivity Check Index (QUICKI)). No significant difference was found between PCOS and control groups regarding the mean age, BMI, waist to hip ratio (WHR), mean values of FPG, FPG/insulin ratio and HOMA B (p > 0.05). AMH values were significantly higher in PCOS cases when compared with controls (4.7 vs. 3.4 ng/mL) (p PCOS cases when compared with controls. E2 levels were significantly lower and Total-T were significantly higher in PCOS patients. When PCOS cases are categorized according to the existence of IR, no difference in Total-T and AMH levels between both groups. Although not statistically significant, a negative correlation of AMH with HOMA-IR and a positive correlation with QUICKI index were found. Among the hormone parameters, AMH was found to be positively correlated with Total-T (r = 0.332, p = 0.013). Although the relation between AMH and androgen production is supported by current evidence, the mechanism underlying the relation between AMH and insulin

Effect of vitamin K supplementation on insulin sensitivity: a meta-analysis

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Suksomboon N

2017-05-01

Full Text Available Naeti Suksomboon,1 Nalinee Poolsup,2 Htoo Darli Ko Ko1 1Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; 2Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon-Pathom, Thailand Objective: To perform a systematic review and meta-analysis of randomized, placebo-controlled trials to assess the effect of vitamin K supplementation on insulin sensitivity.Data sources: MEDLINE, the Cochrane Library, CINAHL, Web of Science, Scopus, clinicaltrials.gov, and clinicaltrialresults.org were searched up to January 2017. Reference lists of related papers were also scanned.Study selection: Randomized controlled trials were selected if they compared vitamin K supplementation with placebo or no treatment and reported homeostasis model assessment of insulin resistance, fasting plasma glucose, fasting plasma insulin, C-reactive protein, adiponectin, leptin, or interleukin-6 levels.Data extraction: Data extraction and study quality assessment were performed independently by two investigators using a standardized data extraction form. Any inconsistencies were resolved by a third reviewer. Effect estimates were pooled using inverse-variance weighted method. Heterogeneity was assessed by the I2 and Q statistic.Results: A total of eight trials involving 1,077 participants met the inclusion criteria. A wide variety of participants were enrolled, including older men, postmenopausal women, prediabetic premenopausal women, and participants with a history of diabetes, hypertension, or vascular disease. Vitamin K1 and vitamin K2 (MK-4 and MK-7 subtypes were assessed. Supplementation period ranged from 4 weeks to 3 years. Vitamin K supplementation did not affect insulin sensitivity as measured by homeostasis model assessment of insulin resistance, fasting plasma glucose, fasting plasma insulin, C-reactive protein, adiponectin, leptin, and interleukin-6 levels.Conclusion: Our analysis suggests no effect of vitamin K

Mid-gestational serum uric acid concentration effect on neonate birth weight and insulin resistance in pregnant women.

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Nasri, Khadijeh; Razavi, Maryamsadat; Rezvanfar, Mohammad Reza; Mashhadi, Esmat; Chehrei, Ali; Mohammadbeigi, Abolfazl

2015-01-01

To investigate the relationship between mid-gestational serum uric acid and birth weight in diabetic pregnant women with or without insulin resistance. In a prospective cohort study, fasting uric acid, blood glucose, and serum insulin were measured in 247 pregnant women between 20-22 weeks of gestational period. Insulin resistance was estimated using the homeostasis model assessment-insulin resistance (HOMA-IR). Stratification analysis and independent t-test was used to assess the association between uric acid and birth weights regarding to insulin resistance. The means of the mid-gestational serum uric acid concentrations were not significantly different in women with and without insulin resistance. But stratification analysis showed that there was a significant difference between uric acid concentration and macrosomic birth in diabetic women without insulin resistance. Higher mid - gestation serum uric acid concentration, even if it does not exceed the normal range, is accompanied by lower birth weight only in non-insulin resistance women. Insulin resistance could have a negative confounding effect on hyperuriemia and birth weight.

Chemical stability of insulin. 3. Influence of excipients, formulation, and pH.

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Brange, J; Langkjaer, L

1992-01-01

The influence of auxiliary substances and pH on the chemical transformations of insulin in pharmaceutical formulation, including various hydrolytic and intermolecular cross-linking reactions, was studied. Bacteriostatic agents had a profound stabilizing effect--phenol > m-cresol > methylparaben--on deamidation as well as on insulin intermolecular cross-linking reactions. Of the isotonicity substances, NaCl generally had a stabilizing effect whereas glycerol and glucose led to increased chemical deterioration. Phenol and sodium chloride exerted their stabilizing effect through independent mechanisms. Zinc ions, in concentrations that promote association of insulin into hexamers, increase the stability, whereas higher zinc content had no further influence. Protamine gave rise to additional formation of covalent protamine-insulin products which increased with increasing protamine concentration. The impact of excipients on the chemical processes seems to be dictated mainly via an influence on the three-dimensional insulin structure. The effect of the physical state of the insulin on the chemical stability was also complex, suggesting an intricate dependence of intermolecular proximity of involved functional groups. At pH values below five and above eight, insulin degrades relatively fast. At acid pH, deamidation at residue A21 and covalent insulin dimerization dominates, whereas disulfide reactions leading to covalent polymerization and formation of A- and B-chains prevailed in alkaline medium. Structure-reactivity relationship is proposed to be a main determinant for the chemical transformation of insulin.

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

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

2010-06-07

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

Increased CD19+CD24+CD27+ B regulatory cells are associated with insulin resistance in patients with type I Hashimoto's thyroiditis.

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Yang, Min; Du, Changji; Wang, Yinping; Liu, Jun

2017-06-01

Hashimoto's thyroiditis (HT) is characterized by dysregulated immune responses and is commonly associated with insulin resistance. However, the mechanism of insulin resistance in HT remains to be fully elucidated. The aim of the present study was to investigate the correlation between the percentage of B regulatory lymphocytes (Bregs) and insulin resistance in patients with HT but with normal thyroid function (type I). A total of 59 patients with type I HT and 38 healthy volunteers were enrolled in the study. An oral glucose tolerance test was performed to measure insulin secretion and assess β‑cell functions. Flow cytometry was performed to examine the percentages of lymphocyte populations. The patients with HT exhibited normal fasting and postprandial glucose and fasting insulin secretion, but increased secretion of early‑phase and total insulin. The patients with HT also had insufficient β‑cell compensation for insulin resistance, indicated by a reduced disposition index, in the fasting state. An elevation in the percentage of CD19+CD24+CD27+ Bregs was also observed, which correlated positively with insulin secretion and insulin resistance in the fasting state. The patients with type I HT had postprandial insulin resistance and insufficient β‑cell compensation for fasting insulin resistance. Therefore, the increase in CD19+CD24+CD27+ Bregs was closely associated with fasting insulin secretion. These results provide novel insight into the mechanism of insulin resistance in HT.

Association of leptin and insulin resistance in PCOS: A case-controlled study.

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Namavar Jahromi, Bahia; Dabaghmanesh, Mohammad Hassan; Parsanezhad, Mohammad Ebrahim; Fatehpoor, Faranak

2017-07-01

Endocrine abnormalities related to polycystic ovary Syndrome (PCOS) are important problems. To compare serum leptin levels between infertile women with and without PCOS. To rank sensitivity of six indirect methods for detection of insulin resistance (IR) and to evaluate the association between leptin and IR in PCOS group. This Case-controlled study performed on 189 infertile women referred to Shiraz Mother and Child Hospital during 2012-2015. Ninety-nine PCOS cases according to Rotterdam criteria were compared to 90 cases without PCOS. Serum leptin, body mass index (BMI), several hormones, and their correlation coefficients with leptin were compared. IR in PCOS women was measured by indirect methods, including fasting blood sugar (FBS), fasting insulin (FI), glucose/insulin, homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and MacAuley index. Association between IR and leptin was evaluated. Independent sample t-test and Pearson's test were used. Infertile women with PCOS had higher BMI (26.47±3.62 vs. 24.82±5.18 kg/m 2 ) and serum leptin levels (41.79±187.89 vs. 19.38±12.57 ng/mL). Leptin showed significant association with weight and BMI in both groups (pPCOS group. HOMA-IR showed the highest rate of IR followed by FI and QUICKI methods. The mean leptin levels had positive association with IR assessed by HOMA-IR (pPCOS infertile women. HOMA-IR followed by FI and QUICKI is the most sensitive test for detection of IR.

No Weight Catch-Up Growth of SGA Infants Is Associated with Impaired Insulin Sensitivity during the Early Postnatal Period

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Tong-yan Han

2010-01-01

Full Text Available Objective. To investigate the relationship between weight catch-up growth and insulin sensitivity in small for gestational age (SGA infants. Methods. Forty-four singleton SGA subjects met the inclusion criteria and finished-3-month followup. Body weight, length, fasting glucose, and fasting insulin (FI levels were measured at 3 days and 3 months. Insulin sensitivity was evaluated by FI and homeostasis model assessment (HOMA. Results. According to the change of weight Z-score, forty-four subjects were divided into two groups: noncatch-up growth (NCUG and catch-up growth (CUG. By 3 months of age, the body weight, body length and BMI of NCUG group were significantly lower than those of CUG group. The FI and HOMA were significantly higher in NCUG group. The change of weight Z-score during 3 months was inversely related to the HOMA at 3 months. Conclusion. Our data exemplified that no weight catch-up growth during the first 3 months was associated with impaired insulin sensitivity in SGA infants.

Chronic fructose substitution for glucose or sucrose in food or beverages has little effect on fasting blood glucose, insulin, or triglycerides: a systematic review and meta-analysis.

Science.gov (United States)

Evans, Rebecca A; Frese, Michael; Romero, Julio; Cunningham, Judy H; Mills, Kerry E

2017-08-01

Background: Conflicting evidence exists on the role of long-term fructose consumption on health. No systematic review has addressed the effect of isoenergetic fructose replacement of other sugars and its effect on glycated hemoglobin (HbA1c), fasting blood glucose, insulin, and triglycerides. Objective: The objective of this study was to review the evidence for a reduction in fasting glycemic and insulinemic markers after chronic, isoenergetic replacement of glucose or sucrose in foods or beverages by fructose. The target populations were persons without diabetes, those with impaired glucose tolerance, and those with type 2 diabetes. Design: We searched the Cochrane Library, MEDLINE, EMBASE, the WHO International Clinical Trials Registry Platform Search Portal, and clinicaltrials.gov The date of the last search was 26 April 2016. We included randomized controlled trials of isoenergetic replacement of glucose, sucrose, or both by fructose in adults or children with or without diabetes of ≥2 wk duration that measured fasting blood glucose. The main outcomes analyzed were fasting blood glucose and insulin as well as fasting triglycerides, blood lipoproteins, HbA1c, and body weight. Results: We included 14 comparison arms from 11 trials, including 277 patients. The studies varied in length from 2 to 10 wk (mean: 28 d) and included doses of fructose between 40 and 150 g/d (mean: 68 g/d). Fructose substitution in some subgroups resulted in significantly but only slightly lowered fasting blood glucose (-0.14 mmol/L; 95% CI: -0.24, -0.036 mmol/L), HbA1c [-10 g/L (95% CI: -12.90, -7.10 g/L; impaired glucose tolerance) and -6 g/L (95% CI: -8.47, -3.53 g/L; normoglycemia)], triglycerides (-0.08 mmol/L; 95% CI: -0.14, -0.02 mmol/L), and body weight (-1.40 kg; 95% CI: -2.07, -0.74 kg). There was no effect on fasting blood insulin or blood lipids. Conclusions: The evidence suggests that the substitution of fructose for glucose or sucrose in food or beverages may be of benefit

Association Between Insulin Resistance and Bone Structure in Nondiabetic Postmenopausal Women

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Finkelstein, Joel S.; Bouxsein, Mary L.; Yu, Elaine W.

2016-01-01

Context: The clinical consequences of insulin resistance and hyperinsulinemia on bone remain largely unknown. Objective: The objective of the study was to evaluate the effect of insulin resistance on peripheral bone geometry, volumetric bone mineral density (vBMD), bone microarchitecture, and estimated bone strength. Design, Setting, and Participants: This cross-sectional study included 146 postmenopausal, nondiabetic Caucasian women (mean age 60.3 ± 2.7 y) who were participating in the Study of Women's Health Across the Nation. Interventions: There were no interventions. Main Outcome Measures: High-resolution peripheral quantitative computed tomography was used to assess bone density and microstructure at the distal radius and tibia. Fasting insulin and glucose were measured and insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR), with higher values indicating greater insulin resistance. Results: There was a negative association between HOMA-IR and bone size and a positive association between HOMA-IR and total vBMD, trabecular vBMD, trabecular thickness, and cortical thickness at the radius and tibia. These relationships remained, even after adjusting for body weight and other potential covariates (eg, time since menopause, cigarette smoking, physical activity, prior use of osteoporosis medications or glucocorticoids). Conclusions: In nondiabetic, postmenopausal women, insulin resistance was associated with smaller bone size, greater volumetric bone mineral density, and generally favorable bone microarchitecture at weight-bearing and nonweight-bearing skeletal sites. These associations were independent of body weight and other potential covariates, suggesting that hyperinsulinemia directly affects bone structure independent of obesity and may explain, in part, the higher trabecular bone density and favorable trabecular microarchitecture seen in individuals with type 2 diabetes mellitus. PMID:27243136

Fasting as possible complementary approach for polycystic ovary syndrome: Hope or hype?

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Chiofalo, Benito; Laganà, Antonio Simone; Palmara, Vittorio; Granese, Roberta; Corrado, Giacomo; Mancini, Emanuela; Vitale, Salvatore Giovanni; Ban Frangež, Helena; Vrtačnik-Bokal, Eda; Triolo, Onofrio

2017-08-01

Polycystic ovary syndrome (PCOS) is a common endocrine system disorder among women of reproductive age. In several cases, PCOS women show infertility or subfertility and other metabolic alteration, such as insulin resistance (InsR), dyslipidaemia, hyperinsulinemia and obesity. Despite the aetiology of the syndrome is still far from be elucidated, it could be considered the result of concurrent endocrine modifications, lifestyle factors and genetic background. In particular, accumulating evidence suggests that InsR and compensatory hyperinsulinemia play a pivotal pathogenic role in the hyperandrogenism of many PCOS phenotypes, which in turn have a clear detrimental effect on chronic anovulation. Different forms of fasting, such as intermittent fasting (IF, including alternate day fasting, or twice weekly fasting, for example) and periodic fasting (PF, lasting several days or longer every 2 or more weeks) are currently being tested in several in vitro and in vivo studies. Changes in the circulating levels of Insulin Growth Factor-1 (IGF-1), Insulin-like Growth Factor-Binding Protein 1 (IGFBP1), glucose and insulin are typical effects of fasting which may play a key role on aging and metabolic homeostasis. Considering the paramount importance of InsR and compensatory hyperinsulinemia, different fasting regimens can reduce IGF-1, IGFBP1, glucose and insulin levels and consequently have beneficial effects on ovarian function, androgen excess and infertility in PCOS women. Copyright © 2017 Elsevier Ltd. All rights reserved.

Medium-chain triglyceride ameliorates insulin resistance and inflammation in high fat diet-induced obese mice.

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Geng, Shanshan; Zhu, Weiwei; Xie, Chunfeng; Li, Xiaoting; Wu, Jieshu; Liang, Zhaofeng; Xie, Wei; Zhu, Jianyun; Huang, Cong; Zhu, Mingming; Wu, Rui; Zhong, Caiyun

2016-04-01

The aim of the present study was to investigate the in vivo effects of dietary medium-chain triglyceride (MCT) on inflammation and insulin resistance as well as the underlying potential molecular mechanisms in high fat diet-induced obese mice. Male C57BL/6J mice (n = 24) were fed one of the following three diets for a period of 12 weeks: (1) a modified AIN-76 diet with 5 % corn oil (normal diet); (2) a high-fat control diet (17 % w/w lard and 3 % w/w corn oil, HFC); (3) an isocaloric high-fat diet supplemented with MCT (17 % w/w MCT and 3 % w/w corn oil, HF-MCT). Glucose metabolism was evaluated by fasting blood glucose levels and intraperitoneal glucose tolerance test. Insulin sensitivity was evaluated by fasting serum insulin levels and the index of homeostasis model assessment-insulin resistance. The levels of serum interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α were measured by ELISA, and hepatic activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways was determined using western blot analysis. Compared to HFC diet, consumption of HF-MCT did not induce body weight gain and white adipose tissue accumulation in mice. HFC-induced increases in serum fasting glucose and insulin levels as well as glucose intolerance were prevented by HF-MCT diet. Meanwhile, HF-MCT resulted in significantly lower serum IL-6 level and higher IL-10 level, and lower expression levels of inducible nitric oxide synthase and cyclooxygenase-2 protein in liver tissues when compared to HFC. In addition, HF-MCT attenuated HFC-triggered hepatic activation of NF-κB and p38 MAPK. Our study demonstrated that MCT was efficacious in suppressing body fat accumulation, insulin resistance, inflammatory response, and NF-κB and p38 MAPK activation in high fat diet-fed mice. These data suggest that MCT may exert beneficial effects against high fat diet-induced insulin resistance and inflammation.

Hyperleptinaemia rather than fasting hyperinsulinaemia is associated with obesity following hypothalamic damage in children.

Science.gov (United States)

Shaikh, M Guftar; Grundy, Richard G; Kirk, Jeremy M W

2008-12-01

Obesity following hypothalamic damage is often severe and resistant to lifestyle changes. Disruption of hypothalamic feedback mechanisms that maintain energy homeostasis may be responsible for this intractable obesity. Adipocytokines including insulin and leptin are also known to be important regulators of appetite and weight. To investigate the role of insulin, leptin, adiponectin and resistin in the aetiology of hypothalamic obesity (HO). This was a cross-sectional study of three groups of children, those with HO, congenital hypopituitarism (CH) and simple obesity (SO). A total of 69 children (HO=28, CH=18, SO=23) had leptin, resistin, adiponectin and insulin measured. Although fasting hyperinsulinaemia and insulin resistance were demonstrated, no differences in insulin or insulin resistance were seen between the groups. The HO group, however, had higher levels of leptin, adiponectin and resistin, which persisted even after adjusting for fat mass, compared with the other groups (Pfasting hyperinsulinaemia or insulin resistance were seen between the groups; however, leptin levels are elevated, even after adjusting for fat mass, suggesting that an element of leptin resistance is associated with HO. This is consistent with the inability of leptin to act on the hypothalamus, either due to transport across the blood-brain barrier or dysfunctional receptors. The lack of response to leptin may be more important in the development of obesity in these individuals, and the fasting hyperinsulinaemia is a result of the increased adipose tissue rather than the cause of the weight gain.

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

Science.gov (United States)

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

2014-06-01

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

Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies

Directory of Open Access Journals (Sweden)

Suk Chon

2011-02-01

Full Text Available BackgroundType B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans.MethodsTo evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patient's dialyzed serum before and after immunosuppressive therapy.ResultsIn the patient's pre-treatment serum IgG, the binding of 125I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%.ConclusionWe treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patient's insulin receptor antibodies by measuring the inhibition of insulin binding.

Ratiometric measurements of adiponectin by mass spectrometry in bottlenose dolphins (Tursiops truncatus with iron overload reveal an association with insulin resistance and glucagon

Directory of Open Access Journals (Sweden)

Benjamin A Neely

2013-09-01

Full Text Available High molecular weight (HMW adiponectin levels are reduced in humans with type 2 diabetes and insulin resistance. Similar to humans with insulin resistance, managed bottlenose dolphins (Tursiops truncatus diagnosed with hemochromatosis (iron overload have higher levels of 2 h post-prandial plasma insulin than healthy controls. A parallel reaction monitoring assay for dolphin serum adiponectin was developed based on tryptic peptides identified by mass spectrometry. Using identified post-translational modifications, a differential measurement was constructed. Total and unmodified adiponectin levels were measured in sera from dolphins with (n=4 and without (n=5 iron overload. This measurement yielded total adiponectin levels as well as site specific percent unmodified adiponectin that may inversely correlate with HMW adiponectin. Differences in insulin levels between iron overload cases and controls were observed 2 h post-prandial, but not during the fasting state. Thus, post-prandial as well as fasting serum adiponectin levels were measured to determine whether adiponectin and insulin would follow similar patterns. There was no difference in total adiponectin or percent unmodified adiponectin from case or control fasting animals. There was no difference in post-prandial total adiponectin levels between case and control dolphins (mean ± S.D. at 763 ± 298 and 727 ± 291 pmol/ml, respectively (p = 0.91; however, percent unmodified adiponectin was significantly higher in post-prandial cases compared controls (30.0 ± 6.3 versus 17.0 ± 6.6%, respectively; p = 0.016. Interestingly, both total and percent unmodified adiponectin were correlated with glucagon levels in controls (r = 0.999, p < 0.001, but not in cases, which is possibly a reflection of insulin resistance. Although total adiponectin levels were not significantly different, the elevated percent unmodified adiponectin follows a trend similar to HMW adiponectin reported for humans with

Is insulin the most effective injectable antihyperglycaemic therapy?

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Buse, J B; Peters, A; Russell-Jones, D; Furber, S; Donsmark, M; Han, J; MacConell, L; Maggs, D; Diamant, M

2015-02-01

The recent type 2 diabetes American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) position statement suggested insulin is the most effective glucose-lowering therapy, especially when glycated haemoglobin (HbA1c) is very high. However, randomized studies comparing glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide once-weekly [OW; DURATION-3 (Diabetes therapy Utilization: Researching changes in A1c, weight, and other factors Through Intervention with exenatide ONce-Weekly)] and liraglutide once-daily [OD; LEAD-5 (Liraglutide Effect and Action in Diabetes)] with insulin glargine documented greater HbA1c reduction with GLP-1RAs, from baseline HbA1c ∼8.3% (67 mmol/mol). This post hoc analysis of DURATION-3 and LEAD-5 examined changes in HbA1c, fasting glucose and weight with exenatide OW or liraglutide and glargine, by baseline HbA1c quartile. Descriptive statistics were provided for change in HbA1c, fasting glucose, weight, and insulin dose, and subjects (%) achieving HbA1c <7.0%, by baseline HbA1c quartile. Inferential statistical analysis on the effect of baseline HbA1c quartile was performed for change in HbA1c. An analysis of covariance (ANCOVA) model was used to evaluate similarity in change in HbA1c across HbA1c quartiles. At 26 weeks, in both studies, HbA1c reduction, and proportion of subjects reaching HbA1c <7.0%, were similar or numerically greater with the GLP-1RAs than glargine for all baseline HbA1c quartiles. Fasting glucose reduction was similar or numerically greater with glargine. Weight decreased with both GLP-1RAs across all quartiles; subjects taking glargine gained weight, more at higher baseline HbA1c. Adverse events were uncommon although gastrointestinal events occurred more frequently with GLP-1RAs. HbA1c reduction with the GLP-1RAs appears at least equivalent to that with basal insulin, irrespective of baseline HbA1c. This suggests that liraglutide and exenatide OW may be appropriate

Impact of intermittent fasting on glucose homeostasis.

Science.gov (United States)

Varady, Krista A

2016-07-01

This article provides an overview of the most recent human trials that have examined the impact of intermittent fasting on glucose homeostasis. Our literature search retrieved one human trial of alternate day fasting, and three trials of Ramadan fasting published in the past 12 months. Current evidence suggests that 8 weeks of alternate day fasting that produces mild weight loss (4% from baseline) has no effect on glucose homeostasis. As for Ramadan fasting, decreases in fasting glucose, insulin, and insulin resistance have been noted after 4 weeks in healthy normal weight individuals with mild weight loss (1-2% from baseline). However, Ramadan fasting may have little impact on glucoregulatory parameters in women with polycystic ovarian syndrome who failed to observe weight loss. Whether intermittent fasting is an effective means of regulating glucose homeostasis remains unclear because of the scarcity of studies in this area. Large-scale, longer-term randomized controlled trials will be required before the use of fasting can be recommended for the prevention and treatment of metabolic diseases.

Effects of mealtime insulin aspart and bedtime NPH insulin on postprandial coagulation and fibrinolysis in patients with type 2 diabetes

DEFF Research Database (Denmark)

Bladbjerg, Else-Marie; Henriksen, Je; Akram, S

2012-01-01

and Methods: This was tested in a parallel controlled study in well-controlled patients with type 2 diabetes assigned to bedtime NPH insulin (n=41) or mealtime insulin aspart (n=37). They were served standard diabetic meals for breakfast (8:00) and lunch (12:00). Blood samples were collected at 7:40 (fasting...

An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance.

OpenAIRE

Baier, L J; Sacchettini, J C; Knowler, W C; Eads, J; Paolisso, G; Tataranni, P A; Mochizuki, H; Bennett, P H; Bogardus, C; Prochazka, M

1995-01-01

The intestinal fatty acid binding protein locus (FABP2) was investigated as a possible genetic factor in determining insulin action in the Pima Indian population. A polymorphism at codon 54 of FABP2 was identified that results in an alanine-encoding allele (frequency 0.71) and a threonine-encoding allele (frequency 0.29). Pimas who were homozygous or heterozygous for the threonine-encoding allele were found to have a higher mean fasting plasma insulin concentration, a lower mean insulin-stimu...

Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance

Science.gov (United States)

Peripheral insulin resistance shifts metabolic fuel use away from carbohydrates, and towards lipids, and is most commonly associated with Type 2 diabetes mellitus. However, regulated insulin resistance is an evolved mechanism to preserve glucose for the brain in conditions of high demand or carbohy...

Assessing the association of nativity and acculturation to fast food restaurant use and its relationship to metabolic risk factors among US blacks with Afro-Caribbean ethnicity.

Science.gov (United States)

Tull, Eugene S; Taylor, Jerome

2014-01-01

This investigation among Afro-Caribbean adults in the United States Virgin Islands (USVI) examined whether acculturation and preference for dining out accounted for variation by nativity in the frequency of fast food restaurant use, and assessed the relationship of fast food restaurant use to body weight and insulin resistance. A randomly selected sample of 679 Afro-Caribbean adults (aged ≥ 20 years), including 436 who were foreign-born and 243 who were native-born, were recruited on the island of St. Croix, USVI. Information on demographic characteristics, level of acculturation and dietary practices were obtained from participants by questionnaire. Fasting blood samples, which were measured for glucose and insulin, and anthropometric measurements were also collected from participants. Insulin resistance was estimated by the homeostasis model assessment (HOMA). Relationships between variables were assessed with analysis of variance and logistic regression analyses. In bivariate analyses, birth in the USVI, younger age, being single, greater preference for dining out and higher levels of education and acculturation were significantly (P restaurant use. In multivariate logistic regression analyses, birth in the USVI, younger age and preference for dining out were independently associated with frequent (≥ 2 days/week) fast food restaurant use. The mean level of HOMA insulin resistance among participants increased significantly with more frequent use of fast food restaurants. Among Afro-Caribbean adults in the USVI, fast food restaurant use is positively associated with insulin resistance and varies by nativity, but acculturation does not account for this variation.

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

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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.

A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes

DEFF Research Database (Denmark)

Moltke, Ida; Grarup, Niels; Jørgensen, Marit Eika

2014-01-01

carriers of this variant have markedly higher concentrations of plasma glucose (β = 3.8 mmol l(-1), P = 2.5 × 10(-35)) and serum insulin (β = 165 pmol l(-1), P = 1.5 × 10(-20)) 2 hours after an oral glucose load compared with individuals with other genotypes (both non-carriers and heterozygous carriers......). Furthermore, homozygous carriers have marginally lower concentrations of fasting plasma glucose (β = -0.18 mmol l(-1), P = 1.1 × 10(-6)) and fasting serum insulin (β = -8.3 pmol l(-1), P = 0.0014), and their T2D risk is markedly increased (odds ratio (OR) = 10.3, P = 1.6 × 10(-24)). Heterozygous carriers have...... transporter GLUT4, with increasing number of p.Arg684Ter alleles. These findings are concomitant with a severely decreased insulin-stimulated glucose uptake in muscle, leading to postprandial hyperglycaemia, impaired glucose tolerance and T2D. The observed effect sizes are several times larger than any...

Chronic hepatitis B associated with hepatic steatosis, insulin ...

African Journals Online (AJOL)

Objectives: The aim of this study was to investigate the viral and host causes of ... Homeostasis Model Assessment- Insulin Resistance (HOMA-IR), viral load, ... those diagnosed with diabetes and cirrhosis, patients ... insulin (µU/ml) × fasting glucose (mmol/L))/22.514. ..... ic steatosis B virus infected patients: meta-analysis of.

Acacia nilotica leave extract and glyburide: comparison of fasting flood glucose, serum insulin, b-thromboglubulin levels and platelet aggregation in treptozotocin induced diabetic rats

International Nuclear Information System (INIS)

Asad, M.; Munir, T.A.; Afzal, N.

2011-01-01

Objectives: To evaluate the hypoglycaemic and anti-platelet aggregation effect of aqueous methanol extract of Acacia Nilotica (AN) leaves compared with glyburide on streptozotocin induced diabetic rats. Methods: Diabetes mellitus was induced in 90 out of 120 albino rats by administering 50 mg/kg body weight (b.w) streptozotocin and was confirmed by measuring fasting blood glucose level >200 mg/dL on fourth post-induction day. The rats were equally divided into 4 groups, A (normal control), B (diabetic control), C (diabetic rats treated with AN extract) and group D (diabetic rats treated with glyburide). The rats of group C and D were given 300 mg/kg b.w AN extract and 900 mu gm/kg b.w glyburide respectively for 3 weeks. Blood glucose was measured by gluco meter, platelet aggregation by Dia-Med method and insulin and b-thrombo globulin by ELISA technique. Results: A significant increase (p<0.05) in fasting blood glucose, b-thrombo globulin and platelet aggregation and a significant decrease (p<0.05) in insulin levels was observed in streptozotocin induced diabetic rats than the normal controls. The rats treated with AN extract and glyburide showed a significant decrease (p<0.05) in fasting blood glucose and increase (p<0.05) in insulin levels than the diabetic control rats. However, the levels in both the treatment groups remained significantly different than the normal controls. A significant decrease (p<0.05) in b-thrombo globulin levels was seen in diabetic rats treated with glyburide than the diabetic control rats and diabetic rats treated with AN extract. Conclusions: AN leaves extract result into hypoglycaemic and anti-platelet aggregation activity in diabetic rats as that of glyburide. (author)

Ceramide content is higher in type I compared to type II fibers in obesity and type 2 diabetes mellitus

DEFF Research Database (Denmark)

Kristensen, Ditte Bech; Prats Gavalda, Clara; Larsen, Steen

2012-01-01

This study investigated fiber-type-specific muscle ceramide content in obese subjects and type 2 diabetes patients. Two substudies, one which compared type 2 diabetes patients to both lean- and obese BMI-matched subjects and the other study which compared lean body-matched post-obese, obese......, and control subjects, were performed. A fasting blood sample was obtained and plasma insulin and glucose determined. A muscle biopsy was obtained from deltoideus and vastus lateralis, and fiber-type ceramide content was determined by fluorescence immunohistochemistry. Insulin sensitivity estimated by Quicki...... index was higher in lean compared to type 2 diabetes patients and obese controls. Also in control and post-obese subjects, a higher insulin sensitivity was observed compared to obese subjects. Ceramide content was consistently higher in type I than in type II muscle fibers and higher in deltoideus than...

Plasma HDL-cholesterol and triglycerides, but not LDL-cholesterol, are associated with insulin secretion in non-diabetic subjects.

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Natali, Andrea; Baldi, Simona; Bonnet, Fabrice; Petrie, John; Trifirò, Silvia; Tricò, Domenico; Mari, Andrea

2017-04-01

Experimental data support the notion that lipoproteins might directly affect beta cell function, however clinical data are sparse and inconsistent. We aimed at verifying whether, independently of major confounders, serum lipids are associated with alterations in insulin secretion or clearance non-diabetic subjects. Cross sectional and observational prospective (3.5yrs), multicentre study in which 1016 non-diabetic volunteers aged 30-60yrs. and with a wide range of BMI (20.0-39.9kg/m 2 ) were recruited in a setting of University hospital ambulatory care (RISC study). baseline fasting lipids, fasting and OGTT-induced insulin secretion and clearance (measured by glucose and C-peptide modeling), peripheral insulin sensitivity (by the euglycemic clamp). Lipids and OGTT were repeated in 980 subjects after 3.5years. LDL-cholesterol did not show independent associations with fasting or stimulated insulin secretion or clearance. After accounting for potential confounders, HDL-cholesterol displayed negative and triglycerides positive independent associations with fasting and OGTT insulin secretion; neither with insulin clearance. Low HDL-cholesterol and high triglycerides were associated with an increase in glucose-dependent and a decrease in non-glucose-dependent insulin secretion. Over 3.5years both an HDL-cholesterol decline and a triglycerides rise were associated with an increase in fasting insulin secretion independent of changes in body weight or plasma glucose. LDL-cholesterol does not seem to influence any major determinant of insulin bioavailability while low HDL-cholesterol and high triglycerides might contribute to sustain the abnormalities in insulin secretion that characterize the pre-diabetic state. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of Fasting Status and Sample Preparation on Metabolic Biomarker Measurements in Postmenopausal Women.

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Murphy, Neil; Falk, Roni T; Messinger, Diana B; Pollak, Michael; Xue, Xiaonan; Lin, Juan; Sgueglia, Robin; Strickler, Howard D; Gaudet, Mia M; Gunter, Marc J

2016-01-01

Epidemiologic data linking metabolic markers-such as insulin, insulin-like growth factors (IGFs)-and adipose tissue-derived factors with cancer are inconsistent. Between-study differences in blood collection protocols, in particular participant's fasting status, may influence measurements. We investigated the impact of fasting status and blood sample processing time on components of the insulin/IGF axis and in adipokines in a controlled feeding study of 45 healthy postmenopausal-women aged 50-75 years. Fasting blood samples were drawn (T0), after which subjects ate a standardized breakfast; subsequent blood draws were made at 1 hour (T1), 3 hours (T3), and 6 hours (T6) after breakfast. Serum samples were assayed for insulin, C-peptide, total- and free-IGF-I, IGF-binding protein [BP]-1 and -3, total and high molecular weight (HMW)-adiponectin, retinol binding protein-4, plasminogen activator inhibitor (PAI)-1, and resistin. Insulin and C-peptide levels followed similar postprandial trajectories; intra-class correlation coefficients [ICC] for insulin = 0.75, (95%CI:0.64-0.97) and C-peptide (ICC = 0.66, 95%CI:0.54-0.77) were similarly correlated in fasting (Spearman correlation, r = 0.78, 95%CI:0.64-0.88) and postprandial states (T1, r = 0.77 (95%CI: 0.62-0.87); T3,r = 0.78 (95%CI: 0.63-0.87); T6,r = 0.77 (95%CI: 0.61-0.87)). Free-IGF-I and IGFBP-1 levels were also affected by fasting status, whereas total-IGF-I and IGFBP-3 levels remained unchanged. Levels of adipokines were largely insensitive to fasting status and blood sample processing delays. Several components of the insulin/IGF axis were significantly impacted by fasting state and in particular, C-peptide levels were substantially altered postprandially and in a similar manner to insulin.

Differences in cardiovascular risk profile based on relationship between post-load plasma glucose and fasting plasma levels.

Science.gov (United States)

Succurro, Elena; Marini, Maria Adelaide; Grembiale, Alessandro; Lugarà, Marina; Andreozzi, Francesco; Sciacqua, Angela; Hribal, Marta Letizia; Lauro, Renato; Perticone, Francesco; Sesti, Giorgio

2009-05-01

It has been shown that subjects with normal glucose tolerance (NGT), whose plasma glucose (PG) levels do not return to their fasting PG level within 2 h during an oral glucose tolerance test (OGTT) (Group I), have a significantly higher risk to develop type 2 diabetes than NGT subjects whose 2-h glucose returns to, or drops below, the fasting level (Group I). However, it is still unsettled whether individuals in Group II have a more atherogenic profile than Group I subjects. To address this issue, we examined 266 non-diabetic offspring of type 2 diabetic patients, recruited in the context of EUGENE2 cross-sectional study. All subjects underwent an euglycaemic-hyperinsulinemic clamp to assess glucose tolerance and insulin sensitivity. Furthermore, cardiovascular risk factors and ultrasound measurement of carotid intima-media thickness (IMT) were evaluated. Individuals in Group II exhibited significantly higher waist circumference, blood pressure, triglycerides, 2-h post-load PG, hsC-reactive protein, interleukin-6, insulin-like growth factor-1 (IGF-1), IMT, and lower insulin sensitivity than subjects in Group I. Subjects with NGT, whose PG concentration does not return to their fasting PG level within 2 h during OGTT, have an atherogenic profile, suggesting that performing OGTT with measurement of PG every 30 min may be useful to assess the risk for cardiovascular disease in glucose-tolerant subjects.

Effects of subcutaneous, low-dose glucagon on insulin-induced mild hypoglycaemia in patients with insulin pump treated type 1 diabetes

DEFF Research Database (Denmark)

Ranjan, Ajenthen; Schmidt, S; Madsbad, Sten

2016-01-01

AIM: To investigate the dose-response relationship of subcutaneous glucagon administration on plasma glucose and on counterregulatory hormone responses during subcutaneous insulin induced mild hypoglycaemia in patients with type 1 diabetes treated with insulin pumps. MATERIALS AND METHODS: Eight...... hypoglycaemia in patients with type 1 diabetes....... insulin pump treated patients completed a blinded, randomized, placebo-controlled study. Hypoglycaemia was induced in the fasting state by a subcutaneous insulin bolus and when plasma glucose reached 3.4 mmol/l (95%CI 3.2-3.5), a subcutaneous bolus of either 100, 200, 300 µg glucagon or saline...

Comparison of two methods using plasma triglyceride concentration as a surrogate estimate of insulin action in nondiabetic subjects: triglycerides × glucose versus triglyceride/high-density lipoprotein cholesterol.

Science.gov (United States)

Abbasi, Fahim; Reaven, Gerald M

2011-12-01

The objective was to compare relationships between insulin-mediated glucose uptake and surrogate estimates of insulin action, particularly those using fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations. Insulin-mediated glucose uptake was quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test in 455 nondiabetic subjects. Fasting TG, HDL-C, glucose, and insulin concentrations were measured; and calculations were made of the following: (1) plasma concentration ratio of TG/HDL-C, (2) TG × fasting glucose (TyG index), (3) homeostasis model assessment of insulin resistance, and (4) insulin area under the curve (insulin-AUC) during a glucose tolerance test. Insulin-AUC correlated most closely with SSPG (r ∼ 0.75, P index, homeostasis model assessment of insulin resistance, and fasting TG and insulin (r ∼ 0.60, P index correlated with SSPG concentration to a similar degree, and the relationships were comparable to estimates using fasting insulin. The strongest relationship was between SSPG and insulin-AUC. Copyright © 2011 Elsevier Inc. All rights reserved.

Subcutaneous insulin absorption explained by insulin's physicochemical properties. Evidence from absorption studies of soluble human insulin and insulin analogues in humans.

Science.gov (United States)

Kang, S; Brange, J; Burch, A; Vølund, A; Owens, D R

1991-11-01

To study the influence of molecular aggregation on rates of subcutaneous insulin absorption and to attempt to elucidate the mechanism of absorption of conventional soluble human insulin in humans. Seven healthy male volunteers aged 22-43 yr and not receiving any drugs comprised the study. This study consisted of a single-blind randomized comparison of equimolar dosages of 125I-labeled forms of soluble hexameric 2 Zn2+ human insulin and human insulin analogues with differing association states at pharmaceutical concentrations (AspB10, dimeric; AspB28, mixture of monomers and dimers; AspB9, GluB27, monomeric). After an overnight fast and a basal period of 1 h, 0.6 nmol/kg of either 125I-labeled human soluble insulin (Actrapid HM U-100) or 125I-labeled analogue was injected subcutaneously on 4 separate days 1 wk apart. Absorption was assessed by measurement of residual radioactivity at the injection site by external gamma-counting. The mean +/- SE initial fractional disappearance rates for the four preparations were 20.7 +/- 1.9 (hexameric soluble human insulin), 44.4 +/- 2.5 (dimeric analogue AspB10), 50.6 +/- 3.9 (analogue AspB28), and 67.4 +/- 7.4%/h (monomeric analogue AspB9, GluB27). Absorption of the dimeric analogue was significantly faster than that of hexameric human insulin (P less than 0.001); absorption of monomeric insulin analogue AspB9, GluB27 was significantly faster than that of dimeric analogue AspB10 (P less than 0.01). There was an inverse linear correlation between association state and the initial fractional disappearance rates (r = -0.98, P less than 0.02). Analysis of the disappearance data on a log linear scale showed that only the monomeric analogue had a monoexponential course throughout. Two phases in the rates of absorption were identified for the dimer and three for hexameric human insulin. The fractional disappearance rates (%/h) calculated by log linear regression analysis were monomer 73.3 +/- 6.8; dimer 44.4 +/- 2.5 from 0 to 2 h and

Treatment of spontaneously hypertensive rats with rosiglitazone and/or enalapril restores balance between vasodilator and vasoconstrictor actions of insulin with simultaneous improvement in hypertension and insulin resistance.

Science.gov (United States)

Potenza, Maria A; Marasciulo, Flora L; Tarquinio, Mariela; Quon, Michael J; Montagnani, Monica

2006-12-01

Spontaneously hypertensive rats (SHRs) exhibit endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance may contribute to hypertension by causing imbalanced regulation of endothelial-derived vasodilators (e.g., nitric oxide) and vasoconstrictors (e.g., endothelin-1 [ET-1]). Treatment of SHRs with rosiglitazone (insulin sensitizer) and/or enalapril (ACE inhibitor) may simultaneously improve hypertension, insulin resistance, and endothelial dysfunction by rebalancing insulin-stimulated production of vasoactive mediators. When compared with WKY control rats, 12-week-old vehicle-treated SHRs were hypertensive, overweight, and insulin resistant, with elevated fasting levels of insulin and ET-1 and reduced serum adiponectin levels. In mesenteric vascular beds (MVBs) isolated from vehicle-treated SHRs and preconstricted with norepinephrine (NE) ex vivo, vasodilator responses to insulin were significantly impaired, whereas the ability of insulin to oppose vasoconstrictor actions of NE was absent (versus WKY controls). Three-week treatment of SHRs with rosiglitazone and/or enalapril significantly reduced blood pressure, insulin resistance, fasting insulin, and ET-1 levels and increased adiponectin levels to values comparable with those observed in vehicle-treated WKY controls. By restoring phosphatidylinositol 3-kinase-dependent effects, rosiglitazone and/or enalapril therapy of SHRs also significantly improved vasodilator responses to insulin in MVB preconstricted with NE ex vivo. Taken together, our data provide strong support for the existence of reciprocal relationships between endothelial dysfunction and insulin resistance that may be relevant for developing novel therapeutic strategies for the metabolic syndrome.

Erythrocytes 125I-Insulin Binding Studies in Viral Hepatitis and Schistosomiasis Patients

International Nuclear Information System (INIS)

Ahmed, A.M.

2003-01-01

The present study aims to evaluate the alterations of insulin binding sites in human erythrocytes in patients with chronic viral B and C hepatitis and in schistosomiasis. Fifty men with ages ranged from 20-45 years were diagnosed into five groups; hepatitis B virus, hepatitis C virus, mixed hepatitis B and C, schistosomiasis and normal healthy volunteers as a control group. Biochemical analyses as erythrocyte insulin radioreceptor, plasma insulin estimation, fasting and post prandial blood glucose levels and liver function tests were performed. The results revealed significant decrease in insulin binding sites/cell in patients with hepatitis C virus, mixed B and C viruses and in schistosomiasis compared to the control group. There were significant increase in fasting plasma glucose levels in groups of hepatitis C virus mixed B and C viruses, while there were highly significant increase in post prandial plasma glucose levels in patients with mixed B and C viruses and in schistosomiasis groups compared to the normal control. Also, fasting plasma insulin levels were significantly elevated in groups of hepatitis C mixed B and C viruses and in schistosomiasis group. The obtained results revealed the importance of laboratory follow up of glucose and insulin levels in patients with chronic liver diseases

The Relationship between 25-hydroxyvitamin D Levels, Insulin Sensitivity and Insulin Secretion in Women 3 Years after Delivery.

Science.gov (United States)

Tänczer, Tímea; Magenheim, Rita; Fürst, Ágnes; Domján, Beatrix; Janicsek, Zsófia; Szabó, Eszter; Ferencz, Viktória; Tabák, Ádám G

2017-12-01

There is a direct correlation between 25-hydroxyvitamin D (25[OH]D) levels and insulin sensitivity. Furthermore, women with gestational diabetes (GDM) may have lower levels of 25(OH)D compared to controls. The present study intended to investigate 25(OH)D levels and their association with insulin sensitivity and insulin secretion in women with prior GDM and in controls 3.2 years after delivery. A total of 87 patients with prior GDM and 45 randomly selected controls (age range, 22 to 44 years) with normal glucose tolerance during pregnancy nested within a cohort of all deliveries at Saint Margit Hospital, Budapest, between January 1 2005, and December 31 2006, were examined. Their 25(OH) D levels were measured by radioimmunoassay. Insulin sensitivity and fasting insulin secretion were estimated using the homeostasis model asssessment (HOMA) calculator and early insulin secretion by the insulinogenic index based on a 75 g oral glucose tolerance test. There was no significant difference in 25(OH)D levels between cases and controls (27.2±13.1 [±SD] vs. 26.9±9.8 ng/L). There was a positive association between HOMA insulin sensitivity and 25(OH)D levels (beta = 0.017; 95% CI 0.001 to 0.034/1 ng/mL) that was robust to adjustment for age and body mass index. There was a nonsignificant association between HOMA insulin secretion and 25(OH)D (p=0.099), while no association was found with the insulinogenic index. Prior GDM status was not associated with 25(OH)D levels; however, 25(OH) D levels were associated with HOMA insulin sensitivity. It is hypothesized that the association between HOMA insulin secretion and 25(OH)D levels is related to the autoregulation of fasting glucose levels because no association between 25(OH)D and insulinogenic index was found. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Mass-Díaz Eliezer

2010-06-01

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

Maternal Fructose Intake Induces Insulin Resistance and Oxidative Stress in Male, but Not Female, Offspring

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Lourdes Rodríguez

2015-01-01

Full Text Available Objective. Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and cardiovascular diseases. However, consumption of beverages containing fructose is allowed during gestation. Recently, we found that an intake of fructose (10% wt/vol throughout gestation produces an impaired fetal leptin signalling. Therefore, we have investigated whether maternal fructose intake produces subsequent changes in their progeny. Methods. Blood samples from fed and 24 h fasted female and male 90-day-old rats born from fructose-fed, glucose-fed, or control mothers were used. Results. After fasting, HOMA-IR and ISI (estimates of insulin sensitivity were worse in male descendents from fructose-fed mothers in comparison to the other two groups, and these findings were also accompanied by a higher leptinemia. Interestingly, plasma AOPP and uricemia (oxidative stress markers were augmented in male rats from fructose-fed mothers compared to the animals from control or glucose-fed mothers. In contrast, female rats did not show any differences in leptinemia between the three groups. Further, insulin sensitivity was significantly improved in fasted female rats from carbohydrate-fed mothers. In addition, plasma AOPP levels tended to be diminished in female rats from carbohydrate-fed mothers. Conclusion. Maternal fructose intake induces insulin resistance, hyperleptinemia, and plasma oxidative stress in male, but not female, progeny.

The degree of coronary atherosclerosis as a marker of insulin resistance in non-diabetics

Directory of Open Access Journals (Sweden)

Parapid Biljana

2010-01-01

Full Text Available Introduction. The metabolic syndrome and its influence on coronary artery disease development and progression remains in focus of international research debates, while insulin resistance, which represents its core, is the key component of hypertension, dyslipidaemias, glucose intolerance and obesity. Objective. The aim of this study was to establish relationship between basal glucose and insulin levels, insulin sensitivity and lipid panel and the degree of coronary atherosclerosis in nondiabetic patients. Methods. The coronary angiograms were evaluated for the presence of significant stenosis, insulin sensitivity was assessed using the intravenous glucose tolerance test with a minimal model according to Bergman, while baseline glucose (G0, insulin (I0 and lipid panel measurements (TC, HDL, LDL, TG were taken after a 12-hour fasting. Results. The protocol encompassed 40 patients (19 men and 21 women treated at the Institute for Cardiovascular Diseases of the Clinical Centre of Serbia, Belgrade. All were non-diabetics who were divided into 3 groups based on their angios: Group A (6 patients, 15%, with no significant stenosis, Group B (18 patients, 45%, with a single-vessel disease and Group C (16 patients, 40%, with multi-vessel disease. Presence of lower insulin sensitivity, higher I0 and TC in the group of patients with a more severe degree of coronary atherosclerosis (insulin sensitivity: F=4.279, p=0.023, A vs. C p=0.012, B vs. C p=0.038; I0: F=3.461 p=0.042, A vs. B p=0.045, A vs. C p=0.013; TC: F=2.572, p=0.09, while no significant difference was found for G0, LDL, HDL and TG. Conclusion. Baseline insulinaemia, more precisely, fasting hyperinsulinaemia could be a good predictor of significant coronary atherosclerosis in non-diabetic patients, which enables a more elegant cardiometabolic risk assessment in the setting of everyday clinical practice.

Association between haptoglobin gene and insulin resistance in Arab-Americans.

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Burghardt, Kyle J; Masri, Dana El; Dass, Sabrina E; Shikwana, Sara S; Jaber, Linda A

2017-11-01

To analyze associations between variation in the HP gene and lipid and glucose-related measures in Arab-Americans. Secondary analyses were performed based on sex. Genomic DNA was extracted from samples obtained from a previous epidemiological study of diabetes in Arab-Americans. The HP 1 and 2 alleles were analyzed by polymerase chain reaction and gel electrophoresis. Associations were analyzed by linear regression. Associations were identified between the heterozygous haptoglobin 2-1 genotype and insulin resistance, fasting insulin and fasting c-peptide. The effect of sex did not remain significant after adjustment for relevant variables. HP genetic variation may have utility as a biomarker of insulin resistance and diabetes risk in Arab-Americans, however, future prospective studies are needed.

Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance.

Science.gov (United States)

Moreno-Navarrete, José María; Sabater, Mònica; Ortega, Francisco; Ricart, Wifredo; Fernández-Real, José Manuel

2012-01-01

Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA) was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity). Circulating zonulin increased with body mass index (BMI), waist to hip ratio (WHR), fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002) contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01) contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase.

Dietary phytochemical index and the risk of insulin resistance and β-cell dysfunction: a prospective approach in Tehran lipid and glucose study.

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Bahadoran, Zahra; Mirmiran, Parvin; Tohidi, Maryam; Azizi, Fereidoun

2015-01-01

In this study, we aimed to investigate the association of dietary phytochemical index (DPI) with insulin resistance, β-cell dysfunction, and insulin sensitivity. This longitudinal study was conducted on 1141 participants of the Tehran Lipid and Glucose Study. Dietary data were collected using a validated semi-quantitative FFQ with 168 food items at baseline and DPI was calculated. Fasting serum insulin and glucose were measured at baseline and again after a 3-year of follow-up. After 3-years of follow-up, the risk of hyperinsulinemia significantly decreased by 65 (OR = 0.35, 95% CI = 0.21-0.60) and 86% (OR = 0.14, 0.07-0.29), in the third and fourth quartile categories of DPI, respectively. The occurrence of insulin resistance and insulin insensitivity in participants with higher DPI was significantly lower than the others (OR = 0.48, 95% CI = 0.25-0.93 and OR = 0.11, 95% CI = 0.05-0.24, respectively). Higher consumption of phytochemical-rich foods may have protective effects against development of insulin resistance.

The GCKR rs780094 polymorphism is associated with elevated fasting serum triacylglycerol, reduced fasting and OGTT-related insulinaemia, and reduced risk of type 2 diabetes

DEFF Research Database (Denmark)

Sparsø, T; Andersen, G; Nielsen, T

2007-01-01

to metabolic traits (mainly fasting hypertriacylglycerolaemia) and traits related to pancreatic beta cell function. METHODS: The polymorphism was genotyped in 16,853 Danes using Taqman allelic discrimination. Association was analysed in case-control studies and quantitative trait analyses. We also analysed...... the possible interactive effect between the GCK -30G>A polymorphism and the GCKR rs780094 variant on metabolic traits. RESULTS: The minor GCKR A-allele of rs780094 is associated with an increased level of fasting serum triacylglycerol (p = 6 x 10(-14)), impaired fasting (p = 0.001) and OGTT-related insulin...... release (p = 3 x 10(-6)), reduced homeostasis model assessment of insulin resistance (p = 0.0004), WHO-defined dyslipidaemia (p = 6 x 10(-9)) and a modestly decreased risk of type 2 diabetes (p = 0.01). Significantly increased fasting serum insulin concentrations were demonstrated when analysing the GCK...

Effectiveness of insulin glargine in type 2 diabetes mellitus patients failing glycaemic control with premixed insulin: Adriatic countries data meta-analysis.

Science.gov (United States)

Cigrovski Berkovic, Maja; Petrovski, Goran; Grulovic, Natasa

2016-10-01

Type 2 diabetes mellitus (T2DM) is a progressive disease, often requiring exogenous insulin therapy and treatment intensification. Despite new therapies, most patients do not reach the recommended HbA1c targets, among them a significant proportion of patients on premixed insulins. The aim was to summarize published data in Adriatic countries on effectiveness of insulin glargine based therapy in type 2 diabetic patients suboptimally controlled on premix insulin. A meta-analysis was carried out in major medical databases up to April 2014, focusing on Adriatic region. We searched observational studies with duration of at least 6 months, evaluating effectiveness and safety of insulin glargine (IGlar), in combination with OAD or bolus insulin in patients with T2 failing premixed insulin therapy. Outcomes included values of HbA1c, fasting blood glucose and two hours post-prandial glucose concentration as well as changes in body mass index after at least 6 months of study duration. Three prospective, observational, multicentric trials (698 patients in total) were included. The basal bolus regimen with glargine significantly reduced HbA1c (Mean Difference, MD=2.27, CI [1.76, 2.78]), fasting glucose (MD=5.15, CI [4.86, 5.44]) and 2-hours postprandial glucose concentration (MD=6.94, CI [6.53, 7.34]). No significant changes were found in BMI after switching from premixes to IGlar based treatment. Insulin glargine based therapy following premix failure is efficacious and safe option of type 2 diabetes treatment intensification.

The Fast-Casual Conundrum: Fast-Casual Restaurant Entrées Are Higher in Calories than Fast Food.

Science.gov (United States)

Schoffman, Danielle E; Davidson, Charis R; Hales, Sarah B; Crimarco, Anthony E; Dahl, Alicia A; Turner-McGrievy, Gabrielle M

2016-10-01

Frequently eating fast food has been associated with consuming a diet high in calories, and there is a public perception that fast-casual restaurants (eg, Chipotle) are healthier than traditional fast food (eg, McDonald's). However, research has not examined whether fast-food entrées and fast-casual entrées differ in calorie content. The purpose of this study was to determine whether the caloric content of entrées at fast-food restaurants differed from that found at fast-casual restaurants. This study was a cross-sectional analysis of secondary data. Calorie information from 2014 for lunch and dinner entrées for fast-food and fast-casual restaurants was downloaded from the MenuStat database. Mean calories per entrée between fast-food restaurants and fast-casual restaurants and the proportion of restaurant entrées that fell into different calorie ranges were assessed. A t test was conducted to test the hypothesis that there was no difference between the average calories per entrée at fast-food and fast-casual restaurants. To examine the difference in distribution of entrées in different calorie ranges between fast-food and fast-casual restaurants, χ(2) tests were used. There were 34 fast-food and 28 fast-casual restaurants included in the analysis (n=3,193 entrées). Fast-casual entrées had significantly more calories per entrée (760±301 kcal) than fast-food entrées (561±268; Prestaurants to determine whether the energy content or nutrient density of full meals (ie, entrées with sides and drinks) differs between fast-casual restaurants and fast-food restaurants. Calorie-conscious consumers should consider the calorie content of entrée items before purchase, regardless of restaurant type. Copyright © 2016 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Association of insulin resistance with obesity in children

International Nuclear Information System (INIS)

Siddiqui, S.A.; Bashir, S.; Shabbir, I.; Sherwani, M.K.; Aasim, M.

2011-01-01

Background: Insulin resistance is the primary metabolic disorder associated with obesity. Little is known about its role as a determinant of the metabolic syndrome in obese children. Objectives: To assess the association of insulin resistance with metabolic syndrome in obese and non obese children. Study type and settings: Cross sectional analytical study conducted among children of ten Municipal Corporation high schools of Data Ganj Buksh Town Lahore. Subjects and Methods: A total of 46 obese and 49 non obese children with consent were recruited for the study. Fasting blood glucose, serum insulin, high density lipoprotein in cholesterol, triglycerides, cholesterol, non HDL-cholesterol LDL-cholesterol were measured using standard methods. Data were analyzed by using statistical software SPSS-Version 15. Results: A total of 95 children 49 obese and 46 non obese were recruited for the study. A significant association of serum triglyceride(p<0.001), high density lipoprotein cholesterol(p<0.001), fasting blood glucose(p<0.001), and insulin levels (p<0.001) , was seen between the two groups. For each component of metabolic syndrome, when insulin resistance increased so did odds ratios for cardio metabolic risk factors. Conclusions: Insulin resistance was seen in 34.7% children. Metabolic syndrome was found in 31.6% children reflecting that obese children are at high risk for metabolic syndrome and have low HDL-cholesterol and high triglycerides levels. (author)

Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study

DEFF Research Database (Denmark)

Tabák, A.G.; Jokela, M.; Akbaraly, T.N.

2009-01-01

BACKGROUND: Little is known about the timing of changes in glucose metabolism before occurrence of type 2 diabetes. We aimed to characterise trajectories of fasting and postload glucose, insulin sensitivity, and insulin secretion in individuals who develop type 2 diabetes. METHODS: We analysed data...... from our prospective occupational cohort study (Whitehall II study) of 6538 (71% male and 91% white) British civil servants without diabetes mellitus at baseline. During a median follow-up period of 9.7 years, 505 diabetes cases were diagnosed (49.1% on the basis of oral glucose tolerance test). We...... assessed retrospective trajectories of fasting and 2-h postload glucose, homoeostasis model assessment (HOMA) insulin sensitivity, and HOMA beta-cell function from up to 13 years before diabetes diagnosis (diabetic group) or at the end of follow-up (non-diabetics). FINDINGS: Multilevel models adjusted...

Plasma insulin pattern in a Hausa-Fulani ethnic group in northern ...

African Journals Online (AJOL)

Plasma insulin pattern in a Hausa-Fulani ethnic group in northern Nigeria. ... Results: Although there were marked individual variations with 16.7% of individuals demonstrating fasting ... Key Words: Plasma Insulin, northern Nigeria Annals of ...

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

Science.gov (United States)

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

2018-05-01

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

Serum progranulin levels in relation to insulin resistance in childhood obesity.

Science.gov (United States)

Alissa, Eman M; Sutaih, Rima H; Kamfar, Hayat Z; Alagha, Abdulmoeen E; Marzouki, Zuhair M

2017-11-27

Progranulin is an adipokine that is involved in the inflammatory response, glucose metabolism, insulin resistance, and may therefore be involved in chronic subclinical inflammation associated with the pathogenesis of childhood obesity. We aimed to investigate the association of circulating progranulin levels with metabolic parameters in children and to assess the importance of progranulin as a biomarker for metabolic diseases. A total of 150 children were consecutively recruited from the Pediatric Nutrition Clinics at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Children were classified into four groups based on quartile for serum progranulin. Anthropometric variables were measured in all study subjects. Fasting blood samples were collected for measurement of blood glucose, insulin and lipid profile. Children within the upper quartile for serum progranulin concentration were heavier, more insulin resistant and had higher concentrations of serum total cholesterol, triglycerides, insulin and high sensitivity C reactive protein compared to those in the lower quartile. On correlation analysis, serum progranulin concentrations were significantly related to general and central adiposity, metabolic parameters, markers of inflammation and insulin resistance. Stepwise multiple regression showed that 26.6% of the variability in serum progranulin could be explained by measures of adiposity. The increased serum progranulin concentrations were closely related to measures of adiposity, metabolic parameters, inflammatory marker and insulin resistance indices, suggesting that progranulin may be an excellent biomarker for obesity in childhood.

Limitations of insulin resistance assessment in polycystic ovary syndrome

Science.gov (United States)

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

2018-01-01

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

Nesfatin-1 in childhood and adolescent obesity and its association with food intake, body composition and insulin resistance.

Science.gov (United States)

Anwar, Ghada M; Yamamah, Gamal; Ibrahim, Amani; El-Lebedy, Dalia; Farid, Tarek M; Mahmoud, Rasha

2014-01-10

Nesfatin-1 is an anorexigenic peptide that controls feeding behavior and glucose homeostasis. However, there is little data that exists regarding nesfatin-1 secretion in obese children and young adolescents. The aim of this study is to investigate serum nesfatin-1 in childhood and adolescent obesity and to study potential correlations with food intake, anthropometric indices, body composition and insulin resistance. Forty obese children and adolescents and 40 healthy control subjects were studied. Anthropometric measurements were assessed, dietary food intake was evaluated based on 3-days food record and body composition indices were evaluated using bioelectrical impedance analysis. Lipid profile, fasting blood sugar, fasting insulin and HOMA-IR were measured. Fasting serum nesfatin-1 was quantitatively assayed by ELISA. Serum nesfatin-1 was significantly higher in obese group (2.49±1.96 ng/ml) than in control group (0.70±0.81 ng/ml), P=0.001. Positive correlations with serum insulin (P=0.001), HOMA-IR (P=0.000), BMI-SDS (P=0.04), body fat % (P=0.000), fat mass (P=0.000), fat free mass (P=0.03), CHO % (P=0.000), and saturated fat % (P=0.01) were found. While significant negative correlation with protein % (P=0.000) was observed. In conclusion, our results denote that nesfatin-1 might have an important role in regulation of food intake and pathogenesis of insulin resistance in obese children and young adolescents. Copyright © 2014 Elsevier B.V. All rights reserved.

Peripheral insulin resistance rather than beta cell dysfunction accounts for geographical differences in impaired fasting blood glucose among sub-Saharan African individuals : findings from the RODAM study

NARCIS (Netherlands)

Meeks, Karlijn A C; Stronks, Karien; Adeyemo, Adebowale; Addo, Juliet; Bahendeka, Silver; Beune, Erik; Owusu-Dabo, Ellis; Danquah, Ina; Galbete, Cecilia; Henneman, Peter; Klipstein-Grobusch, Kerstin; Mockenhaupt, Frank P; Osei, Kwame; Schulze, Matthias B; Spranger, Joachim; Smeeth, Liam; Agyemang, Charles

2017-01-01

AIMS/HYPOTHESIS: The aim of this study was to assess the extent to which insulin resistance and beta cell dysfunction account for differences in impaired fasting blood glucose (IFBG) levels in sub-Saharan African individuals living in different locations in Europe and Africa. We also aimed to

Peripheral insulin resistance rather than beta cell dysfunction accounts for geographical differences in impaired fasting blood glucose among sub-Saharan African individuals: findings from the RODAM study

NARCIS (Netherlands)

Meeks, Karlijn A. C.; Stronks, Karien; Adeyemo, Adebowale; Addo, Juliet; Bahendeka, Silver; Beune, Erik; Owusu-Dabo, Ellis; Danquah, Ina; Galbete, Cecilia; Henneman, Peter; Klipstein-Grobusch, Kerstin; Mockenhaupt, Frank P.; Osei, Kwame; Schulze, Matthias B.; Spranger, Joachim; Smeeth, Liam; Agyemang, Charles

2017-01-01

The aim of this study was to assess the extent to which insulin resistance and beta cell dysfunction account for differences in impaired fasting blood glucose (IFBG) levels in sub-Saharan African individuals living in different locations in Europe and Africa. We also aimed to identify determinants

Dimethylarginine Dimethylaminohydrolase Overexpression enhances Insulin Sensitivity

Science.gov (United States)

Sydow, Karsten; Mondon, Carl E.; Schrader, Joerg; Konishi, Hakuoh; Cooke, John P.

2011-01-01

Objective Previous studies suggest that nitric oxide (NO) may modulate insulin-induced uptake of glucose in insulin-sensitive tissues. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase (NOS). We hypothesized that a reduction in endogenous ADMA would increase NO synthesis and thereby enhance insulin sensitivity. Methods and Results To test this hypothesis we employed a transgenic mouse in which we overexpressed human dimethylarginine dimethylaminohydrolase (DDAH-I). The DDAH-I mice had lower plasma ADMA at all ages (22–70 weeks) by comparison to wild-type (WT) littermates. With a glucose challenge, WT mice showed a prompt increase in ADMA, whereas DDAH-I mice had a blunted response. Furthermore, DDAH-I mice had a blunted increase in plasma insulin and glucose levels after glucose challenge, with a 50% reduction in the insulin resistence index, consistent with enhanced sensitivity to insulin. In liver, we observed an increased Akt phosphorylation in the DDAH-I mice after i.p. glucose challenge. Incubation of skeletal muscle from WT mice ex vivo with ADMA (2μM) markedly suppressed insulin-induced glycogen synthesis in fast-twitch but not slow-twitch muscle. Conclusions These findings suggest that the endogenous NOS inhibitor ADMA reduces insulin sensitivity, consistent with previous observations that NO plays a role in insulin sensitivity. PMID:18239148

Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased activation by glargine but not by its metabolites M1 and M2.

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Cécile Pierre-Eugene

Full Text Available BACKGROUND: In diabetic patients, the pharmacokinetics of injected human insulin does not permit optimal control of glycemia. Fast and slow acting insulin analogues have been developed, but they may have adverse properties, such as increased mitogenic or anti-apoptotic signaling. Insulin/IGF1 hybrid receptors (IR/IGF1R, present in most tissues, have been proposed to transmit biological effects close to those of IGF1R. However, the study of hybrid receptors is difficult because of the presence of IR and IGF1R homodimers. Our objective was to perform the first study on the pharmacological properties of the five marketed insulin analogues towards IR/IGF1R hybrids. METHODOLOGY: To study the effect of insulin analogues on IR/IGF1R hybrids, we used our previously developed Bioluminescence Resonance Energy Transfer (BRET assay that permits specific analysis of the pharmacological properties of hybrid receptors. Moreover, we have developed a new, highly sensitive BRET-based assay to monitor phophatidylinositol-3 phosphate (PIP(3 production in living cells. Using this assay, we performed a detailed pharmacological analysis of PIP(3 production induced by IGF1, insulin and insulin analogues in living breast cancer-derived MCF-7 and MDA-MB231 cells. RESULTS: Among the five insulin analogues tested, only glargine stimulated IR/IGF1R hybrids with an EC50 that was significantly lower than insulin and close to that of IGF1. Glargine more efficiently stimulated PIP(3 production in MCF-7 cells but not in MDA-MB231 cells as compared to insulin. In contrast, glargine metabolites M1 and M2 showed lower potency for hybrid receptors stimulation, PIP(3 production, Akt and Erk1/2 phosphorylation and DNA synthesis in MCF-7 cells, compared to insulin. CONCLUSION: Glargine, possibly acting through IR/IGF1R hybrids, displays higher potency, whereas its metabolites M1 and M2 display lower potency than insulin for the stimulation of proliferative/anti-apoptotic pathways in

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

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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.

The Impact of Intra-articular Depot Betamethasone Injection on Insulin Resistance Among Diabetic Patients With Osteoarthritis of the Knee: A Case-Control Study.

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Habib, George; Chernin, Mark; Sakas, Fahed; Artul, Suheil; Jabbour, Adel; Jabaly-Habib, Haneen

2018-06-01

The aim of this study was to evaluate the impact of intra-articular corticosteroid injection (IACI) of depot betamethasone at the knee joint on insulin resistance (IR). Patients with type 2 diabetes, non-insulin treated, with painful osteoarthritis of the knee were requested to participate in our study. After consent, demographic, clinical, and laboratory parameters were documented in addition to fasting blood glucose (FBG) and fasting blood insulin levels just prior to IACI of 1 mL of depot betamethasone. Fasting blood glucose and fasting blood insulin levels were repeated the next day following the IACI and 8 days later. Age- and sex-matched group of patients with type 2 diabetes from the same clinic were recruited as a control group (case-control study). Insulin resistance was calculated using Homeostasis Model Assessment-Insulin Resistance. Mann-Whitney U test, χ test, and Wilcoxon signed rank tests were used for statistical analysis. Eleven patients were recruited in the patients' group and 10 patients in the control group. Median FBG in the patients' group at baseline was 148 ± 51 mg/dL, and median IR was 5.12 ± 2.46. One day following the IACI, median FBG level was 247 ± 104 mg/dL (P = 0.004, compared with baseline), with median IR of 20.8 ± 7.01 (P = 0.0039). The median ratios of blood glucose and IR 1 day following the IACI compared with baseline were 1.7 and 4.1, respectively. Eight days following the IACI, mean FBG and IR levels were not significantly different from baseline. Intra-articular corticosteroid injection of betamethasone at the knee joint among patients with diabetes was associated with a significant increase in IR levels compared with baseline levels, 1 day following the injection. The mean percentage of increase in IR was higher than that for FBG levels.

Moderate alcohol consumption is associated with improved insulin sensitivity, reduced basal insulin secretion rate and lower fasting glucagon concentration in healthy women

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Bonnet, F; Disse, E; Laville, M

2012-01-01

Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes with a stronger effect in women. As the underlying mechanisms remain poorly characterised, we investigated its relationship with insulin resistance, insulin secretion, clearance of insulin and glucagon concentration....

Diet Quality Is Linked to Insulin Resistance among Adults in China.

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Wang, Zhihong; Adair, Linda S; Cai, Jianwen; Gordon-Larsen, Penny; Siega-Riz, Anna Maria; Zhang, Bing; Popkin, Barry M

2017-11-01

Background: Little is known about the impact of Chinese diet quality changes on diabetes-related markers. Objective: The present study examined the association of changes in overall diet quality with various biomarkers of diabetes among adults in China. Methods: The current analysis used longitudinal diet data from 1991 to 2006 and fasting blood samples from 2009 for 4734 adults aged 18-65 y from the China Health and Nutrition Survey. Dietary intake was assessed by using 3 consecutive 24-h recalls and household food weighing. The tailored Alternative Healthy Eating Index (tAHEI) was adapted from the 2010 Harvard Alternative Healthy Eating Index to measure overall diet quality. We categorized baseline tAHEI scores into tertiles and annual changes in the scores into 5 levels (high decrease, low decrease, maintain, low increase, and high increase). We performed mixed-effects regressions to assess the associations between baseline scores and changes in the tAHEI scores and diabetes or insulin markers. Results: Adults with high baseline tAHEI scores tended to be male, older, of lower socioeconomic status, and with higher physical activity levels. After adjustment for all of the covariates, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) values were 5.1% (95% CI: -0.100, -0.002) and 5.7% (95% CI: -0.113, -0.001) lower, respectively, for adults with high compared with low baseline tAHEI scores and 8.6% (95% CI: -0.155, -0.017) and 9.8% (95% CI: -0.177, -0.018) lower, respectively, for adults with a high increase in score compared with the "maintain" category. Null associations were observed between baseline scores and changes in the scores and fasting blood glucose, glycated hemoglobin (HbA1c), and diabetes prevalence. Conclusions: Baseline and changes in diet quality were independently associated with lower HOMA-IR and plasma insulin but not with fasting blood glucose and HbA1c in Chinese adults. Prospective studies on overall diet quality in

Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.

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Scheen, A J; Schmitt, H; Jiang, H H; Ivanyi, T

2017-02-01

To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA 1c ) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. This post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA 1c of <7.0% (<53mmol/mol) per baseline HbA 1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia. Patients had comparable demographic characteristics and similar HbA 1c and FHG values at baseline in each HbA 1c quartile regardless of whether they reached the target HbA 1c . The higher the HbA 1c quartile, the greater was the decrease in HbA 1c , but also the smaller the percentage of patients achieving the target HbA 1c . HbA 1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA 1c quartiles with either insulin treatment. Patients not achieving the target HbA 1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA 1c , suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Metabolic and fibrinolytic response to changed insulin sensitivity in users of oral contraceptives

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Petersen, Kresten R.; Christiansen, Erik; Madsbad, Sten

1999-01-01

systems, are relevant in the evaluation of the risk of developing vascular disorders or diabetes in OC users. We studied insulin sensitivity index (S(I)), glucose effectiveness (S(g)), and insulin response in young, healthy women by frequently sampled intravenous glucose tolerance tests before and after...... randomization to 6 months of treatment with ethinyl estradiol in triphasic combination with norgestimate (n = 17) or gestodene (n = 20). Measurements of fasting triglycerides and antigen concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were also...... included. Both compounds increased fasting plasma insulin and reduced S(i) but did not affect S(g). The relationships between S(i) and insulin response were unchanged. No consistent correlation between insulin sensitivity and triglycerides, t-PA, or PAI-1 were demonstrated before or during treatment. We...

Obesity modifies the association between serum 25-hydroxyvitamin D and insulin resistance in Korean general population without increased fasting glucose levels.

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Lee, Sung Woo; Kim, Myounghee; Kim, Ho; Han, Seung Seok; Lee, Hajeong; Lee, Jung Pyo; Kim, Dong Ki; Lim, Chun Soo; Kim, Yon Su; Park, Ae Kyung; Joo, Kwon Wook

2014-10-01

The inverse relationship between 25-hydroxyvitamin D [25(OH)D] status and insulin resistance (IR) has been reported, but many interventional studies failed to reduce IR with 25(OH)D supplementation. In addition, there has been a paucity of literature on the interaction between 25(OH)D status and IR according to the degree of obesity in Asian subjects. We therefore evaluated the association between 25(OH)D status and IR according to the degree of obesity. Data from the Korea National Health and Nutrition Examination Survey in 2008-2010 were analyzed. The study subjects comprised 10,629 participants aged ≥20 years with fasting glucoseobesity in an adult Korean population without increased fasting glucose levels. We suggest that proper supplementation of vitamin D might be beneficial in obese Korean adults.

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

DEFF Research Database (Denmark)

Dupuis, Josée; Langenberg, Claudia; Prokopenko, Inga

2010-01-01

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up...... to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA......2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell...

New measure of insulin sensitivity predicts cardiovascular disease better than HOMA estimated insulin resistance.

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Kavita Venkataraman

Full Text Available CONTEXT: Accurate assessment of insulin sensitivity may better identify individuals at increased risk of cardio-metabolic diseases. OBJECTIVES: To examine whether a combination of anthropometric, biochemical and imaging measures can better estimate insulin sensitivity index (ISI and provide improved prediction of cardio-metabolic risk, in comparison to HOMA-IR. DESIGN AND PARTICIPANTS: Healthy male volunteers (96 Chinese, 80 Malay, 77 Indian, 21 to 40 years, body mass index 18-30 kg/m(2. Predicted ISI (ISI-cal was generated using 45 randomly selected Chinese through stepwise multiple linear regression, and validated in the rest using non-parametric correlation (Kendall's tau τ. In an independent longitudinal cohort, ISI-cal and HOMA-IR were compared for prediction of diabetes and cardiovascular disease (CVD, using ROC curves. SETTING: The study was conducted in a university academic medical centre. OUTCOME MEASURES: ISI measured by hyperinsulinemic euglycemic glucose clamp, along with anthropometric measurements, biochemical assessment and imaging; incident diabetes and CVD. RESULTS: A combination of fasting insulin, serum triglycerides and waist-to-hip ratio (WHR provided the best estimate of clamp-derived ISI (adjusted R(2 0.58 versus 0.32 HOMA-IR. In an independent cohort, ROC areas under the curve were 0.77±0.02 ISI-cal versus 0.76±0.02 HOMA-IR (p>0.05 for incident diabetes, and 0.74±0.03 ISI-cal versus 0.61±0.03 HOMA-IR (p<0.001 for incident CVD. ISI-cal also had greater sensitivity than defined metabolic syndrome in predicting CVD, with a four-fold increase in the risk of CVD independent of metabolic syndrome. CONCLUSIONS: Triglycerides and WHR, combined with fasting insulin levels, provide a better estimate of current insulin resistance state and improved identification of individuals with future risk of CVD, compared to HOMA-IR. This may be useful for estimating insulin sensitivity and cardio-metabolic risk in clinical and

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

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Diego Real de Asua

2014-12-01

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

One-Hour Postload Hyperglycemia Confers Higher Risk of Hepatic Steatosis to HbA1c-Defined Prediabetic Subjects.

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Fiorentino, Teresa Vanessa; Andreozzi, Francesco; Mannino, Gaia Chiara; Pedace, Elisabetta; Perticone, Maria; Sciacqua, Angela; Perticone, Francesco; Sesti, Giorgio

2016-11-01

Individuals with glycated hemoglobin (HbA1c)-defined prediabetes (HbA1c value of 5.7-6.4%) and 1-hour plasma glucose ≥155 mg/dL during an oral glucose tolerance test have an increased risk of developing type 2 diabetes. To evaluate the degree to which HbA1c-defined prediabetes and 1-hour postload glucose ≥155 mg/dL individually and jointly associate with hepatic steatosis and related biomarkers. A cross-sectional analysis was performed on 1108 White individuals. Ambulatory care. Anthropometric and metabolic characteristics including hepatic steatosis assessed by ultrasonography. Compared with the normal group (HbA1c prediabetic and diabetic individuals exhibit higher values of fasting, 1-hour, and 2-hour postload glucose; fasting and 2-hour postload insulin; triglycerides; uric acid; homeostasis model of assessment for insulin resistance; liver insulin resistance index; liver enzymes; and inflammatory biomarkers; and lower levels of high-density lipoprotein cholesterol and IGF-1. Prediabetic and diabetic subjects have increased risk of hepatic steatosis (1.5- and 2.46-fold, respectively). Stratifying participants according to HbA1c and 1-hour postload glucose, we found that individuals with HbA1c-defined prediabetes and 1-hour postload glucose ≥155 mg/dL have significantly higher risk of hepatic steatosis as compared with individuals with HbA1c-defined prediabetes but 1-hour postload glucose prediabetes and 1-hour postload glucose ≥155 mg/dL exhibit higher values of liver enzymes; fasting, 1-hour, and 2-hour postload glucose; insulin; triglycerides; uric acid; and inflammatory biomarkers; and lower levels of high-density lipoprotein and IGF-1. These data suggest that a value of 1-hour postload glucose ≥155 mg/dL may be helpful to identify a subset of individuals within HbA1c-defined glycemic categories at higher risk of hepatic steatosis.

Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance.

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José María Moreno-Navarrete

Full Text Available Zonulin is the only physiological mediator known to regulate intestinal permeability reversibly by modulating intercellular tight junctions. To investigate the relationship between intestinal permeability and obesity-associated metabolic disturbances in humans, we aimed to study circulating zonulin according to obesity and insulin resistance. Circulating zonulin (ELISA was measured in 123 caucasian men in association with inflammatory and metabolic parameters (including minimal model-measured insulin sensitivity. Circulating zonulin increased with body mass index (BMI, waist to hip ratio (WHR, fasting insulin, fasting triglycerides, uric acid and IL-6, and negatively correlated with HDL-cholesterol and insulin sensitivity. In multiple regression analysis, insulin sensitivity (p = 0.002 contributed independently to circulating zonulin variance, after controlling for the effects of BMI, fasting triglycerides and age. When circulating IL-6 was added to this model, only BMI (p = 0.01 contributed independently to circulating zonulin variance. In conclusion, the relationship between insulin sensitivity and circulating zonulin might be mediated through the obesity-related circulating IL-6 increase.

Plasma Ascorbic Acid in Insulin and Non-insulin Dependent Diabetes

African Journals Online (AJOL)

Blood glucose, plasma ascorbic acid and haemoglobin levels were estimated in insulin dependent diabetics, non-insulin dependent diabetics and controls matched for number, sex and age. Significantly higher levels of these parameters were found in control group than in the other two groups. Statistically differences were ...

Bariatric surgery in morbidly obese insulin resistant humans normalises insulin signalling but not insulin-stimulated glucose disposal.

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Mimi Z Chen

Full Text Available Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB, and compared this to lean volunteers.The hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR in eight morbidly obese (body mass index, BMI=47.3 ± 2.2 kg/m(2 patients, before and after RYGB, and in eight lean volunteers (BMI=20.7 ± 0.7 kg/m2. Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50 and maximal (GDR100 GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity.Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001. Weight-loss of 29.9 ± 4 kg after surgery significantly improved GDR50 (P=0.004 but not GDR100 (P=0.3. These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001. Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA, and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA, and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively.Our data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss.

Major Pathophysiology in Prediabetes and Type 2 Diabetes: Decreased Insulin in Lean and Insulin Resistance in Obese.

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Kabadi, Udaya M

2017-06-01

Lowering of body mass index (BMI) to ≥25 kg/m 2 as obesity by ADA suggests insulin resistance as a major mechanism of impaired glucose metabolism (IGM) in Asians. However, glimepiride, an insulin secretagogue, delayed onset of type 2 diabetes (DM2) from prediabetes (PreDM), indicating decreased insulin secretion (IS) as a major factor in lean (L; BMI DM2. Seventy-five men and 45 women ages 36 to 75 years were divided into six groups: LN, LPreDM, LDM2, ObN, ObPreDM, and ObDM2. Determination of IS by insulinogenic indices (I/G) at fasting (FI/FG), first phase (∆I/∆G), and cumulative responses over 2 hours of OGTT (CRI/CRG), and IR by FIXFG, ∆IX∆G, and CRIXCRG. Changes in IS and IR for PreDM and DM2 were calculated as % fall and % rise, respectively, from levels in N. All indices of IS and IR were lower ( P DM2 ( P < 0.05) in both groups. However, the declines in IS were greater ( P < 0.05) than rises in IR in LPreDM and LDM2. Whereas, the rises in IR were higher ( P < 0.05) than declines in IS in ObPreDM and ObDM2. In L, major mechanism of IGM is declining IS and not rising IR documented among Ob.

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...

Does cardiorespiratory fitness modify the association between birth weight and insulin resistance in adult life?

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Tomoko Aoyama

Full Text Available OBJECTIVE: Lower birth weight is associated with higher insulin resistance in later life. The aim of this study was to determine whether cardiorespiratory fitness modifies the association of birth weight with insulin resistance in adults. METHODS: The subjects were 379 Japanese individuals (137 males, 242 females aged 20-64 years born after 1943. Insulin resistance was assessed using a homeostasis model assessment of insulin resistance (HOMA-IR, which is calculated from fasting blood glucose and insulin levels. Cardiorespiratory fitness (maximal oxygen uptake, VO2max was assessed by a maximal graded exercise test on a cycle ergometer. Birth weight was reported according to the Maternal and Child Health Handbook records or the subject's or his/her mother's memory. RESULTS: The multiple linear regression analysis revealed that birth weight was inversely associated with HOMA-IR (β = -0.141, p = 0.003, even after adjustment for gender, age, current body mass index, mean blood pressure, triglycerides, HDL cholesterol, and smoking status. Further adjustments for VO2max made little difference in the relationship between birth weight and HOMA-IR (β = -0.148, p = 0.001, although VO2max (β = -0.376, p<0.001 was a stronger predictor of HOMA-IR than birth weight. CONCLUSIONS: The results showed that the association of lower birth weight with higher insulin resistance was little modified by cardiorespiratory fitness in adult life. However, cardiorespiratory fitness was found to be a stronger predictor of insulin resistance than was birth weight, suggesting that increasing cardiorespiratory fitness may have a much more important role in preventing insulin resistance than an individual's low birth weight.