Exaggerated glucagon responses to hypoglycemia in women with polycystic ovary syndrome

ContextPremenopausal women have blunted counter-regulatory hormone responses (CRR) to hypoglycemia compared to men. Postmenopausal women have CRR similar to men; the premenopausal pattern can be restored by estrogen. However, glucagon and pancreatic polypeptide (PP) responses remain lower in postmenopausal women than in men. Since hyperandrogenemia contributes to the metabolic phenotype of polycystic ovary syndrome (PCOS), we hypothesize that CRR to hypoglycemia especially of glucagon and PP is exaggerated in premenopausal women with PCOS compared to premenopausal control women.Study Subjects and MethodsTen obese women with PCOS and 9 control women of similar ethnicity, age and BMI underwent determination of CRR in response to hypoglycemia during 180-min 60 mU/m²/min insulin dose hypoglycemic clamp with isotopic assessment of endogenous glucose production (EGP). To assess CRR to hypoglycemia, glucagon, cortisol, growth hormone (GH), epinephrine, norepinephrine, PP, lactate, free fatty acid (FFA), β-hydroxybutyrate, and glycerol levels were sampled at 15-min intervals throughout the clamp.Main FindingsIncremental glucagon levels were ~ 3-fold higher during hypoglycemia (P = 0.03) in PCOS. Postabsorptive, steady-state and incremental GH, cortisol, epinephrine, norepinephrine, PP, FFA, glycerol and β-hydroxybutyrate did not differ. At target glucose levels of ~ 52 mg/dL, insulin mediated glucose disposal (IMGD) was decreased by ~ 40% (P = 0.02) in PCOS, compared to control women, despite ~ 20% higher steady-state insulin levels (P = 0.03). Neither postabsorptive nor steady-state EGP differed. However, postabsorptive lactate levels were ~ 50% higher (P = 0.02). PCOS status (P = 0.04) and IMGD (P = 0.02) predicted the differential glucagon response to hypoglycemia in separate regression models, however, neither parameter remained an independent predictor in a combined model.Principal ConclusionsGlucagon responses were increased in PCOS, whereas other CRR did not differ. Women with PCOS were insulin resistant under hypoglycemic conditions and higher postabsorptive lactate levels in PCOS were consistent with this finding. Insulin resistance may have contributed to exaggerated glucagon response to hypoglycemia in PCOS.     

Impact of age and menopausal status on the postprandial triacylglycerol response in healthy women

ObjectiveTo examine the impact of age and the natural menopause on the postprandial triacylglycerol (TAG) response in healthy women.Methods and resultsThirty-seven premenopausal and sixty-one postmenopausal women underwent a sequential meal postprandial investigation, in which blood samples were taken at regular intervals after a test breakfast and lunch given at 0 and 330 min respectively. Lipids and glucose were measured in the fasting sample, with TAG analysed in the postprandial samples. Postmenopausal women were shown to have higher fasting total cholesterol, low density lipoprotein cholesterol (LDL-C) and glucose (P < 0.02). Marked differences in the postprandial TAG response were evident between the groups, with a greater incremental area under the curve (IAUC) and maximum TAG concentration in the postmenopausal women (P < 0.04). Multivariate regression analysis revealed both age and fasting TAG to be independently associated with the summary measures of the postprandial TAG response in the premenopausal women only. Interestingly, sub-division of the women into both younger and older pre- and postmenopausal subgroups, showed the most marked difference in TAG-IAUC to be between the younger and the older premenopausal women, whereas differences in fasting LDL-C were most evident between the older premenopausal and the younger postmenopausal women.ConclusionsOur results suggest a divergence in the relationship of age and menopausal status with fasting LDL-C and postprandial TAG which may reflect differences in the metabolic effects of age and the menopause on these lipid risk markers or a greater impact of early oestrogen decline on pathways of TAG rather than LDL metabolism.     

Predictors of insulin resistance in the obese with metabolic syndrome

BackgroundIn the obese, the metabolic syndrome (MetS) is assumed to reflect insulin resistance.ObjectiveTo determine the predictors of insulin resistance in obese subjects with MetS.DesignWe used the 90th percentile of the homeostasis model assessment (HOMA) to define insulin resistance in 4958 nondiabetic adults evaluated in the National Health and Nutrition Examination Surveys, 1999–2004, and compared the 373 obese subjects who were insulin-resistant (HOMA 9.52 ± 5.73) to a control group of 373 obese who had the highest sensitivity to insulin (HOMA 1.79 ± 0.44).MeasurementsMetS was present in 312 (83.6%) obese with insulin resistance and in 156 (41.8%) obese from the insulin-sensitive control group. Demographic, metabolic, and lifestyle variables were analyzed with logistic regression.ResultsIn a logistic model of insulin resistance given the presence of MetS, the significant predictors were triglycerides (P = 0.0021), body mass index (P = 0.0096), HDL-cholesterol (P = 0.0098), age (P = 0.0242) and smoking (P = 0.0366).LimitationsCross-sectional design prevents elucidation of causality for the association between insulin resistance and MetS.ConclusionsInsulin resistance is not an obligatory correlate of MetS in the obese. Its likelihood can be predicted by cigarette smoking and by the severity of obesity and dyslipidemia.     

Association of vitamin D deficiency and insulin resistance with breast cancer in premenopausal Algerian women: A cross-sectional study

BackgroundLow 25(OH)D levels are mainly related to breast cancer (BC) risk in postmenopausal women, while the impact of insulin resistance (IR) on BC prognosis is controversial.ObjectiveConsidering the high prevalence of BC in younger Algerian women, this cross-sectional study analyzed whether vitamin D status and IR are biomarkers for breast tumor status in premenopausal women.MethodsIn 96 women (mean age, 40.96 ± 0.65years) newly diagnosed with BC, tumor status was determined immunohistochemically, classified by molecular subtype, then correlated with body-mass index, total plasma 25(OH)D, insulin and glucose levels and HOMA-IR, using Chi², Student t, Spearman and ANOVA tests and multivariate logistic regression.ResultsA total of 66 of the 96 patients (68.75%) showed vitamin D deficiency (9.74 ng/mL). Overweight and obese patients with HOMA-IR > 2.5, positive for HER2 and with high Ki-67 index had the most severe vitamin D deficiency. There was a significant association between vitamin D deficiency, high Ki-67 index (OR, 14.55; 95% CI: 3.43–82.59; P = 0.00078) and IR (OR, 4.99; 95% CI: 1.27–24.47; P = 0.03), and between IR and HER2-positivity (OR, 3.23; 95% CI: 1.05–10.56; P = 0.04).ConclusionsVitamin D deficiency and IR are potential biomarkers for poorer prognosis in BC patients, independently of and/or synergically with high Ki-67 index and HER2-positivity in premenopausal overweight or obese women. The potential relationship of vitamin D receptor gene expression with breast cancer survival in Algerian patients will be investigated in a large cohort.     

Combining a nontargeted and targeted metabolomics approach to identify metabolic pathways significantly altered in polycystic ovary syndrome

ObjectivePolycystic ovary syndrome (PCOS) is a condition of androgen excess and chronic anovulation frequently associated with insulin resistance. We combined a nontargeted and targeted metabolomics approach to identify pathways and metabolites that distinguished PCOS from metabolic syndrome (MetS).MethodsTwenty obese women with PCOS were compared with 18 obese women without PCOS. Both groups met criteria for MetS but could not have diabetes mellitus or take medications that treat PCOS or affect lipids or insulin sensitivity. Insulin sensitivity was derived from the frequently sampled intravenous glucose tolerance test. A nontargeted metabolomics approach was performed on fasting plasma samples to identify differentially expressed metabolites, which were further evaluated by principal component and pathway enrichment analysis. Quantitative targeted metabolomics was then applied on candidate metabolites. Measured metabolites were tested for associations with PCOS and clinical variables by logistic and linear regression analyses.ResultsThis multiethnic, obese sample was matched by age (PCOS, 37 ± 6; MetS, 40 ± 6 years) and body mass index (BMI) (PCOS, 34.6 ± 5.1; MetS, 33.7 ± 5.2 kg/m²). Principal component analysis of the nontargeted metabolomics data showed distinct group separation of PCOS from MetS controls. From the subset of 385 differentially expressed metabolites, 22% were identified by accurate mass, resulting in 19 canonical pathways significantly altered in PCOS, including amino acid, lipid, steroid, carbohydrate, and vitamin D metabolism. Targeted metabolomics identified many essential amino acids, including branched-chain amino acids (BCAA) that were elevated in PCOS compared with MetS. PCOS was most associated with BCAA (P = .02), essential amino acids (P = .03), the essential amino acid lysine (P = .02), and the lysine metabolite α-aminoadipic acid (P = .02) in models adjusted for surrogate variables representing technical variation in metabolites. No significant differences between groups were observed in concentrations of free fatty acids or vitamin D metabolites. Evaluation of the relationship of metabolites with clinical characteristics showed 1) negative associations of essential and BCAA with insulin sensitivity and sex hormone-binding globulin and 2) positive associations with homeostasis model of insulin resistance and free testosterone; metabolites were not associated with BMI or percent body fat.ConclusionsPCOS was associated with significant metabolic alterations not attributed exclusively to androgen-related pathways, obesity, or MetS. Concentrations of essential amino acids and BCAA are increased in PCOS, which might result from or contribute to their insulin resistance.     

Serum sex steroids and steroidogenesis-related enzyme expression in skeletal muscle during experimental weight gain in men

ObjectivesLow-circulating testosterone is associated with development of type 2 diabetes in obese men. In this study, we examined the effects of experimental overfeeding and weight gain on serum levels of sex hormones and skeletal muscle expression of steroidogenic enzymes in healthy men with (FH+) and without (FH–) a family history of type 2 diabetes.MethodsFollowing a 3-day lead in energy balanced diet, FH+ (n = 9) and FH– men (n = 11) were overfed by 5200 kJ/day (45% fat) for 28 days. Body weight, fasting glucose, insulin, sex steroid, sex hormone binding globulin (SHBG) levels, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) and body fat (DXA) were assessed in all individuals at baseline and day 28, and sex steroidogenesis-related enzyme expression in vastus lateralis biopsies was examined in a subset (n = 11).ResultsBody weight, fat mass and fasting insulin levels were increased by overfeeding (P < 0.01) and insulin was increased significantly more in FH+ men (P < 0.01). Serum sex hormone binding globulin (SHBG) and 5α-dihydrotestosterone (DHT) were reduced with overfeeding (P < 0.05), and serum testosterone and DHT were reduced to a greater extent in FH+ men (P < 0.05). Overfeeding reduced mRNA expression of 3β-hydroxysteroid dehydrogenase (HSD) and 17βHSD (P ≤ 0.007), independently of group. 5α-Reductase (SRD5A1) mRNA expression was not changed overall, but a time by group interaction was observed (P = 0.04).ConclusionOverfeeding reduced SHBG and muscle expression of enzymes involved in the formation of testosterone in skeletal muscle. Men with a family history of T2DM were more susceptible to deleterious outcomes of overfeeding with greater reductions in serum testosterone and DHT and greater increases in markers of insulin resistance, which may contribute to increased risk of developing type 2 diabetes.     

Efficacy of genistein aglycone on some cardiovascular risk factors and homocysteine levels: A follow-up study

Background and AimRecent evidence suggests that genistein aglycone may act beneficially on surrogate cardiovascular risk markers in postmenopausal women.We assessed the effects of genistein aglycone on some cardiovascular risk factors and homocysteine levels after 3-years of continued therapy in a cohort of osteopenic, postmenopausal women.Methods and ResultsThe parent study was a randomized, double-blind, placebo-controlled trial involving 389 postmenopausal women with low bone mass for 24 months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Participants received 54 mg of genistein aglycone (n = 71) or placebo (n = 67), daily. Both arms received calcium and vitamin D₃ in therapeutic doses. Moreover, 4 weeks before randomization procedures and during our follow-up study, all patients received dietary instructions in an isocaloric fat-restricted diet. Blood lipid profiles, fasting glucose and insulin, insulin resistance (HOMA-IR), fibrinogen, osteoprotegerin (OPG) and homocysteine at baseline and after 24 and 36 months of treatment were measured.Compared to placebo, genistein significantly decreased fasting glucose and insulin, HOMA-IR, fibrinogen and homocysteine after 24 and 36 months of treatment. By contrast, isoflavone administration did not affect high-density lipoprotein cholesterol and triglycerides though serum OPG was higher in the genistein recipients. There were no differences in adverse events or discomfort between groups. Results on routine biochemical, liver function, and hematologic testing did not change over time in placebo or genistein group.ConclusionsAfter 3-years of treatment, genistein aglycone plus calcium, vitamin D₃ and a healthy diet showed positive effects on some cardiovascular risk factors and homocysteine levels in a cohort of postmenopausal women with low bone mass.     

Interleukin-20 circulating levels in obese women: Effect of weight loss

Background and aimsObesity is associated with an increased risk of developing atherosclerosis. Interleukin-20 (IL-20) is a pleiotropic cytokine thought to be involved in the onset and progression of atherosclerosis. The aim of this study was to determine whether circulating levels of IL-20 are elevated in obese women and whether they could be affected by a substantial decrease in body weight.Methods and resultsFifty obese and 50 age-matched, normal weight, premenopausal women participated in the study. Obese women entered into a medically supervised weight loss program aimed at reducing body weight to 90% of baseline. We measured anthropometric, glucose and lipid parameters, and IL-20, C-Reactive Protein (CRP) and interleukin-10 (IL-10) circulating levels. Circulating IL-20 and CRP levels were significantly higher in obese than control women (P = 0.01), while IL-10 levels were significantly lower; IL-20 levels were positively associated with body weight (r = 0.35; P = 0.02) and visceral fat (waist–hip ratio; r = 0.32; P = 0.025). Caloric restriction-induced weight loss (>10% of original weight) over 6 months reduced IL-20 levels from 152 (112/184) to 134 (125/153) pg/ml (median and 25%/75%; P = 0.03), and it was positively associated with changes in body mass index and waist–hip ratio.ConclusionIn premenopausal obese women, IL-20 levels are higher than matched normal weight control women, are associated with body weight and waist–hip ratio, and are reduced by weight loss.     

Plasma adiponectin levels in women with polycystic ovary syndrome: Impact of Metformin treatment in a case–control study

ObjectiveAn interaction between adiponectin, steroid synthesis or action and measures of insulin resistance (IR) have been reported in the pathogenesis of polycystic ovary syndrome (PCOS). The present study was done to determine plasma adiponectin concentration (PAC) in women with and without PCOS and to assess its correlation to the hormonal and metabolic parameters including measures of IR. The effect of Metformin for 6 months in PCOS was also evaluated.PatientsIn total, 72 selected women were classified as follows: 17 obese (body mass index (BMI)) > 25 kg/m² with PCOS; 19 normal weight (BMI) 18–22.9 kg/m² with PCOS; 17 obese (BMI) > 25 kg/m² without PCOS and 19 normal weight (BMI) 18–22.9 kg/m² without PCOS.InterventionsBlood samples were collected from all women with PCOS between 0800 and 1100 h, after an overnight fast.Main outcome measuresSerum level of LH, FSH, TSH, total T4, testerosterone, 17-α-hydroxyprogesterone (17OHP), DHEAS, insulin, adiponectin and glucose. Measures of IR included fasting serum insulin (FSI), glucose-to-insulin ratio, and homeostasis model assessment (HOMA).Result and conclusionWaist–hip ratio (WHR), insulin, and HOMA index were significantly higher in the lower adiponectin group than in the higher adiponectin group. By using stepwise multiple regression analysis, in model 1 (including BMI, FSI, fasting plasma glucose (FPG) with other variables such serum as testerosterone and DHEAS), the weight and contributions from other variables, namely FSI and FPG were significant independent determinants of fasting PAC (adjusted r² = 0.66); and in model 2 (including BMI, HOMA, FPG only as an index of IR with other variables such as serum testerosterone and DHEAS), BMI, and HOMA were significant independent determinants of fasting PAC (adjusted r² = 0.59). FPG, HOMA index and FSI were significantly lower after Metformin treatment in both obese and non-obese PCOS while adiponectin levels increased significantly.     

Association of circulating irisin levels with metabolic and metabolite profiles of Korean adolescents

ContextIrisin, a novel exercise-induced myokine, has been suggested to regulate energy metabolism.ObjectiveWe studied the relationship between circulating irisin and metabolic and metabolite profiles of Korean adolescents, and investigated the effects of physical activity, obesity, and metabolic syndrome (MetS) on irisin levels.Materials and MethodsData were obtained from the Korean Children–Adolescents Study. Our cross-sectional study included 618 adolescents (370 normal-weight and 248 obese adolescents; 316 boys and 302 girls) aged 12–15 years. Body composition was determined using an impedance body composition analyzer and general participant characteristics and lifestyle information were obtained from questionnaires. Serum irisin levels were measured using a commercial kit.ResultsMean body mass index (BMI) was 19.4 kg/m² in normal-weight adolescents and 31.4 kg/m² in obese adolescents. Circulating irisin was positively correlated with adiposity indices, including BMI z-score, waist circumference, percent body fat, fat mass, fat-free mass, fat mass to fat-free mass ratio, and lipid and glucose metabolism markers, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, glucose, insulin, and homeostasis model assessment-estimated insulin resistance (all p ≤ 0.006). Of these, increased body fat mass [standardized (Std) ß, 0.23; p < 0.0001], LDL-C (Std ß, 0.14; p = 0.0005) and fasting glucose (Std ß, 0.08; p = 0.0383) were the main independent factors associated with higher irisin levels. Moreover, elevated serum irisin was associated with the risk of obesity [odds ratio (OR], 2.2; confidence interval (CI), 1.19–3.87] and MetS (OR, 2.0; CI, 1.15–3.47). Furthermore, irisin and branched-chain amino acids were positively associated (p < 4 × 10^− 4 for Bonferroni correction). Additionally, in the normal-weight group, girls had higher irisin levels than boys (p = 0.006) and adolescents who engaged in regular physical activity had higher levels of irisin than sedentary adolescents (p = 0.0388). The relationship between physical activity and irisin levels was not observed in obese adolescents.ConclusionsElevated serum irisin was independently associated with the risk of obesity and positively correlated with unhealthy metabolic parameters and metabolites. Moreover, irisin levels were higher in active versus sedentary adolescents in the normal-weight group, but not in the obese group. Our findings suggest that irisin plays an important role in metabolic disorders and may be affected by physiopathological status.     

Supervised home-based exercise may attenuate the decline of glucose tolerance in obese pregnant women

AimThe significant deterioration of insulin sensitivity and glucose tolerance during pregnancy can have serious health implications for both the pregnant woman and her baby. Although it is well established that regular exercise benefits insulin sensitivity in the nonpregnant population, the effect on glucose tolerance in obese pregnant women is not known. The purpose of this study was to investigate the effect of a supervised 10-week, home-based, exercise programme, beginning at week 18 of gestation, on glucose tolerance and aerobic fitness in previously sedentary obese women.MethodsTwelve sedentary obese women were randomized into an exercise (EX; n = 6) or control (CON; n = 6) group at 18 weeks of gestation. Those randomized to EX engaged in 10 weeks of supervised home-based exercise (three sessions a week of stationary cycling), while those in the CON group maintained their usual daily activity. Their glucose and insulin responses to an oral glucose tolerance test (OGTT), as well as their aerobic fitness, were assessed both pre- and postintervention.ResultsReduced glucose tolerance in the CON, but not EX, group was indicated by a tendency postintervention towards higher blood glucose levels at 1 h of the OGTT (P = 0.072). Furthermore, at 2 h of the postintervention OGTT, blood glucose tended to remain elevated from baseline in the CON (P = 0.077). There was also a trend towards increased fitness in the EX (P = 0.064), but not the CON group.ConclusionRegular aerobic exercise begun during pregnancy may have favourable effects on glucose tolerance and fitness in obese women, and warrants further investigation in a larger sample population.     

Effects of acute hyperinsulinaemia on total and high-molecular-weight adiponectin concentration in metabolically healthy but obese postmenopausal women: A Montreal–Ottawa New Emerging Team (MONET) study

AimThe aim of this study was to determine the differences and changes in total and high-molecular-weight (HMW) adiponectin levels among metabolically healthy but obese (MHO) postmenopausal women in response to acute hyperinsulinaemia.MethodIn this cross-sectional study, 55 non-diabetic overweight and obese postmenopausal women underwent a hyperinsulinaemic–euglycaemic clamp test to evaluate insulin sensitivity. Subjects within the upper tertile of insulin sensitivity were described as ‘MHO’ (n = 18), whereas those within the lowest tertile were considered ‘at risk’ (n = 18). Plasma total and HMW adiponectin levels were measured by ELISA at 0 (baseline), 90, 160 and 180 min during the clamp.ResultsAt baseline and at all time points during the clamp, MHO individuals had significantly higher total and HMW adiponectin levels than at-risk subjects (AUC: total adiponectin = 2506 ± 1010 vs 1616 ± 830; HMW adiponectin = 909 ± 307 vs 604 ± 349; P < 0.05). In addition, a significant reduction in total adiponectin was observed at 160 min and 180 min in at-risk and MHO subjects, respectively, while HMW adiponectin significantly decreased at 160 min in at-risk subjects, and at 90 min as well as 160 min in MHO women.ConclusionMHO postmenopausal women had higher levels of plasma total and HMW adiponectin than at-risk subjects at baseline and during the clamp. Furthermore, significant decreases in total and HMW adiponectin were observed at certain time points in both the MHO and at-risk subjects.     

Relationship between uric acid and hepatic steatosis among Koreans

AimThe relationship between high uric-acid levels and hepatic steatosis, according to body mass index (BMI) categories, and their coexistence with the metabolic syndrome (MetS) were examined in the present study.MethodsThe study involved a cross-sectional sample of 13,621 Koreans (7221 men and 6400 women) who visited a health checkup centre between 2005 and 2006. Hepatic steatosis was diagnosed using ultrasonography. Hyperuricaemia was defined as > 7 mg/dL for men and > 6 mg/dL for women. The MetS was defined as the presence of three or more MetS components—obesity (BMI ≥ 25.0 kg/m²), high blood pressure, elevated levels of triglycerides and glucose, and low levels of high-density lipoprotein (HDL)-cholesterol.ResultsIn total, 26.2% were diagnosed with hepatic steatosis, of whom 11.9% were non-obese (BMI < 25 kg/m²) and 52.5% were obese. Hyperuricaemia was associated with hepatic steatosis in non-obese (adjusted odds ratio [AOR] of 1.4 in men and 2.2 in women) as well as in obese individuals (AOR of 1.8 in men and 2.3 in women) after adjusting for age, other MetS components and liver function tests. The AOR (95% CI) for hepatic steatosis in obese individuals with hyperuricaemia compared with non-obese individuals with normal uric-acid levels was 7.7 (6.4–9.3) in men and 12.4 (7.8–19.5) in women. The adjusted age and liver-function test ORs (95% CI) for hepatic steatosis in those with hyperuricaemia and no MetS compared with those who had normal uric acid levels and no MetS were 2.0 (1.7–2.4) in men and 3.2 (2.1–4.9) in women. The ORs (95% CI) in those with hyperuricaemia and the MetS increased to 6.9 (5.5–8.8) and 15.2 (8.4–27.4) in men and women, respectively.ConclusionHyperuricaemia is independently associated with hepatic steatosis regardless of BMI category or the presence of the MetS in Korean adults. Further research into the causal relationship is needed.     

Habitual shortened sleep and insulin resistance: An independent relationship in obese individuals

ObjectiveShort sleep duration has been reported to be associated with obesity, type 2 diabetes, and pre-diabetes. Since excess weight, glucose abnormalities, and insulin resistance tend to cluster, the individual role insulin resistance may have in habitual shortened sleep is unclear. The study purpose was to assess whether habitual sleep curtailment is independently related to insulin resistance in obese individuals.Materials/MethodsNon-diabetic, overweight/obese individuals from the community were stratified as insulin-resistant (n = 35) or insulin-sensitive (n = 21) based on steady-state plasma glucose concentrations (SSPG) during the insulin suppression test. Seventy-five gram oral glucose tolerance tests were performed. Participants were asked, “On average, how many hours of sleep do you get per night?” Shortened sleep duration was defined as less than 7 h of sleep per night.ResultsSSPG concentrations differed 2.5-fold (P < 0.001) between insulin-resistant and insulin-sensitive individuals. Impaired fasting glucose and glucose intolerance were prevalent in both groups (> 40%); however, body mass index, waist circumference, mean fasting or 2-h post-glucola glucose concentrations were not significantly different. Insulin-resistant individuals reported (mean ± SD) fewer hours of sleep than did insulin-sensitive individuals (6.53 ± 1.1 vs 7.24 ± 0.9 h, P < 0.05). Shortened sleep duration was more prevalent among insulin-resistant as compared with insulin-sensitive individuals (60% vs 24%, P < 0.05).ConclusionsNon-diabetic, insulin-resistant individuals averaged fewer hours of sleep and were more likely to report shortened sleep duration as compared with similarly obese insulin-sensitive individuals. There appears to be an independent association between habitual shortened sleep and insulin resistance among obese, dysglycemic adults without diabetes.     

Comparison between several insulin sensitivity indices and metabolic risk factors in overweight and obese postmenopausal women: A MONET study

Background and aimsThe purpose of this study was to compare the relationship of several insulin sensitivity indices with cardiometabolic risk factors in overweight and obese postmenopausal women.Methods and resultsThis was a cross-sectional study involving 137 overweight and obese postmenopausal women (age: 57.7 ± 4.8 yrs; body mass index: 32.4 ± 4.6 kg/m²; body fat: 38.6 ± 9.2 kg). Insulin sensitivity was determined by the euglycaemic–hyperinsulinemic (EH) clamp technique as well as by oral glucose tolerance test (OGTT) derived indices (Stumvoll, Matsuda and SI_is) and fasting surrogate indices (HOMA, QUICKI). Cardiometabolic risk factors included: body composition and visceral fat that were measured using dual energy X-ray absorptiometry and computed tomography, respectively. Peak oxygen consumption, lower body muscle strength (using weight training equipment), physical activity energy expenditure (doubly labeled water), plasma lipids and C-reactive protein were also measured. Correlations of insulin sensitivity indices with metabolic risk factors showed some similarities, however, a wide range of variations were also observed. Furthermore, our results showed that visceral fat was the primary predictor for surrogate and OGTT indices, explaining 15–28% of the variance and the triglycerides/HDL-C ratio was the primary predictor for the EH clamp indices, explaining 15–17% of the variance.ConclusionThe present study indicates that the different methods of measuring and/or expressing insulin sensitivity display variations for associations with cardiometabolic risk factors. Therefore, interpretations of relationships between insulin sensitivity indices and cardiometabolic risk factors should take into account the method used to estimate and express insulin sensitivity.     

Association of the FTO gene with obesity and the metabolic syndrome is independent of the IRS-2 gene in the female population of Southern France

AimThe objective of the present study was to investigate the genetic association of the fat-mass-and-obesity-associated (FTO) gene in obese women in the presence of the known influential role of the insulin receptor substrate 2 (IRS-2) gene.MethodsThis case-control study was carried out in the Languedoc-Roussillon region of France, and included lean control women (n = 128), and women (n = 119) of various degrees of obesity (body mass index [BMI] mean ± S.D.: 39.3 ± 7.4 kg/m²) and a prevalence of 26.9% of the metabolic syndrome (MetS). For the FTO gene, genotyping was performed by sequence-specific oligonucleotide–polymerase chain reaction (SSO–PCR) on the single nucleotide polymorphism (SNP) rs1421085 (C/T) while, for IRS-2, the rs1805097 (G/A) corresponding to variant Gly1057Asp was genotyped by direct sequencing.ResultsThe FTO gene (homozygous C/C) was significantly associated to both simple and morbid obesity (P < 0.026 and P < 0.0034, respectively), with odds-ratios (ORs) of 2.58 (95% CI: 1.1–6.0) and 4.1 (95% CI: 1.6–10.5), respectively, independent of IRS-2. MetS was also associated with FTO (P < 0.032, OR: 3.1, 95% CI: 1.1–8.5), but not with IRS-2. Genotypes of FTO were correlated with insulin resistance, and homozygous C/C was positively correlated with an increase in insulin resistance over the value predicted by the increase in BMI.ConclusionThese data confirm the influential role of the FTO gene in obesity in the French female population and, in addition, revealed the role of FTO in insulin resistance and MetS. These effects appeared to be independent of IRS-2, which is directly involved in insulin action. This study may offer new insights into the genetic determinants of obesity and MetS in women.     

Irisin and leptin concentrations in relation to obesity,and developing type 2 diabetes: A cross sectional and a prospective case-control study nested in the Normative Aging Study

ObjectiveTo investigate the associations between irisin and leptin levels in obesity and insulin resistance in a cross sectional study. To assess the potential role of irisin and leptin as a predictive marker of T2DM using a nested case-control study.MethodsBoth studies were designed within the longitudinal VA NAS cohort. The cross sectional study involved 111 non obese and 105 obese subjects who were subdivided into two groups based on their fasting glucose tolerance. In the nested 1:3 case-control study, 47 subjects with T2DM and 140 non-diabetic controls were selected. Serum samples collected 3-5 years before the diagnosis of T2DM were analyzed. Irisin and leptin concentrations were measured using a validated ELISA and radioimmunoassay respectively.ResultsIn the cross-sectional study, irisin did not differ between groups based on their fasting glucose tolerance. When subjects were grouped based on obesity status, both irisin and leptin concentrations were significantly higher in obese compared to the non-obese group (p = 0.03 and < 0.001, respectively). Irisin concentrations positively correlated with leptin concentrations (r = 0.392, P < 0.001). In the nested case control study, leptin concentrations were a significant predictor of developing diabetes (p = 0.005) in unadjusted models, but not after correcting for BMI, whereas irisin concentrations did not play a role of comparable significance.ConclusionsLeptin concentrations are higher in the obese group irrespective of their glucose tolerance. Obese individuals with impaired fasting glucose have higher concentrations of circulating irisin compared to non-obese subjects with normal glucose tolerance. Irisin concentrations do not predict risk of developing diabetes prospectively.     

Comparison of metabolic syndrome with glucose measurement for prediction of type 2 diabetes: The Isfahan Diabetes Prevention Study

AimsThe aim of this study was to compare the ability of the metabolic syndrome (MetS) and fasting and 2-h glucose to predict progression to diabetes in non-diabetic first-degree relatives (FDRs) of patients with type 2 diabetes.MethodsA total of 706 non-diabetics FDR 20–70 years old in 2003–2005 were followed through 2008 for the occurrence of type 2 diabetes mellitus. At baseline and through follow-ups, participants undergo a standard 75 g 2-h oral glucose tolerance test. MetS was defined by NCEP-ATP III.ResultsThe fasting and 2-h glucose values were better predictors of progression to diabetes than MetS. Compared to participants without MetS, the age-adjusted relative risk (RRs) of diabetes was similar for participants with MetS (1.09 (95% CI 0.92, 1.29)). The age-adjusted relative risk of diabetes among those with impaired glucose tolerance (IGT) and MetS was 1.89 (95% CI 1.47, 2.42) and among those with IGT but without MetS was 1.59 (95% CI 1.32, 1.91). Areas under the receiver operating characteristic curves were 0.789 for fasting and 0.760 for 2-h glucose versus 0.595 for number of metabolic abnormalities (P < 0.001).ConclusionsThese data indicate that fasting or 2-h glucose during the OGTT may be more effective and efficient than MetS in predicting progression to diabetes.     

Women with normal glucose tolerance and a history of gestational diabetes show significant impairment of β-cell function at normal insulin sensitivity

ObjectiveAlthough the nature of gestational diabetes mellitus (GDM) remains unclear, the condition is thought to be related primarily to insulin resistance, overweight and obesity. Most studies include women with a history of GDM and later carbohydrate metabolism abnormalities, while reports of women with previous GDM and subsequent normoglycaemia are scarce. The aim of this study was to assess insulin resistance and β-cell function in normoglycaemic women with a history of GDM.Materials and methodsThe study group included 199 women, aged 38.4 ± 6.6 years, diagnosed with GDM within the last 5–12 years [GDM(+)] and a control group of 50 comparable women in whom GDM was excluded [GDM(−)], according to WHO criteria. Blood glucose and insulin levels were measured at the beginning (fasting) and at 60 and 120 min of oral glucose tolerance tests. Indices of insulin resistance (HOMA-IR), insulin sensitivity (HOMA-S%) and β-cell function (HOMA-B%) were calculated.ResultsNormoglycaemia was observed in 57% of GDM(+) and 88% of GDM(−) women (P = 0.0003). Diabetes was diagnosed in 13 (6.5%) GDM(+) women and in none of the GDM(−) women. Comparison of 113 normoglycaemic GDM(+) and 44 normoglycaemic GDM(−) women revealed significantly impaired β−cell function (HOMA-B%: 131.1 ± 51.1 vs 144.7 ± 47.1, respectively; P = 0.038) with similar normal body mass index (BMI) and no differences in HOMA-IR and HOMA-S%.ConclusionIn this study, more than half of the GDM(+) women were presented with normal glucose tolerance. However, despite normoglycaemia, women with a history of GDM were characterized by significantly impaired insulin secretion, but no signs of increased insulin resistance.     

The relationship between left ventricular mass and insulin resistance in obese patients

ObjectiveIn this study, we investigated the relationship between left ventricular mass and insulin resistance in obese patients.MethodsA total of 90 subjects, 66 women, and 24 men, with an age range from 24 to 56 years, were enrolled in the study. Forty-nine patients were in the obesity group whose body mass index (BMI) was >29.9 kg/m² and 41 subjects were in the control group with a BMI <25 kg/m². All of them were normotensive, nondiabetic, and did not have any cardiovascular disease. They were not taking any medication. Weight, height, and waist circumference were measured and BMI was calculated. Plasma glucose, insulin, serum total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and triglyceride levels were measured, and insulin resistance was calculated via homeostasis model of assessment-estimated insulin resistance (HOMA-IR). Subjects were examined by echocardiography and left ventricular mass (LVM) and index (LVMI) were calculated with Devereux formula.ResultsInsulin levels, HOMA-IR, LVM, and LVMI were significantly higher in obesity group (p < 0.01). Fasting glucose, triglyceride, fasting insulin levels, and waist circumference did not correlate with LVMI.ConclusionIn conclusion, though findings of the present study suggest increased left ventricular hypertrophy (LVH) in obese subjects compared to controls, it appears that the increased LVM or LVH is not linked to BMI and insulin resistance in this study population.