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Background & Aims: Accumulation of visceral adipose tissue is associated with insulin resistance and cardio-vascular disease. The aim of this study was to elucidate whether removal of a large amount of visceral fat by omentectomy in conjunction with Roux en-Y gastric bypass operation (RYGB) results in enhanced improvement of insulin sensitivity compared to gastric bypass surgery alone., Methods: Eighty-one obese women scheduled for RYGB were included in the study. They were randomized to RYGB or RYGB in conjunction with omentectomy. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp before operation and sixty-two women were also reexamined 2 years post-operatively. The primary outcome measure was insulin sensitivity and secondary outcome measures included cardio-metabolic risk factors., Results: Two-year weight loss was profound but unaffected by omentectomy. Before intervention, there were no clinical or metabolic differences between the two groups. The difference in primary outcome measure, insulin sensitivity, was not significant between the non-omentectomy (6.7 ± 1.6 mg/kg body weight/minute) and omentectomy groups (6.6 ± 1.5 mg/kg body weight/minute) after 2 years. Nor did any of the cardio-metabolic risk factors that were secondary outcome measures differ significantly., Conclusion: Addition of omentectomy to gastric bypass operation does not give an incremental effect on long term insulin sensitivity or cardio-metabolic risk factors. The clinical usefulness of omentectomy in addition to gastric bypass operation is highly questionable., Clinical Trial Registration Number: NCT01785134., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Introduction: Seasonal variations in hemoglobin-A1c have been reported in diabetic patients, but the underlying mechanisms have not been elucidated., Aims: To study if insulin sensitivity, insulin secretion, and fasting plasma glucose showed seasonal variations in a Swedish population-based cohort of elderly men., Methods: Altogether 1117 men were investigated with a euglycemic insulin clamp and measurements of fasting plasma glucose and insulin secretion after an oral glucose tolerance test. Values were analyzed in linear regression models with an indicator variable for winter/summer season and outdoor temperature as predictors., Results: During winter, insulin sensitivity (M/I, unit = 100 × mg × min(-1) × kg(-1)/(mU × L(-1))) was 11.0% lower (4.84 versus 5.44, P = 0.0003), incremental area under the insulin curve was 16.4% higher (1167 versus 1003 mU/L, P = 0.007). Fasting plasma glucose was, however, not statistically significantly different (5.80 versus 5.71 mmol/L, P = 0.28) compared to the summer season. There was an association between outdoor temperature and M/I (0.57 units increase (95% CI 0.29-0.82, P < 0.0001) per 10°C increase of outdoor temperature) independent of winter/summer season. Adjustment for life-style factors, type 2 diabetes, and medication did not alter these results., Conclusions: Insulin sensitivity showed seasonal variations with lower values during the winter and higher during the summer season. Inverse compensatory variations of insulin secretion resulted in only minor variations of fasting plasma glucose. Insulin sensitivity was associated with outdoor temperature. These phenomena should be further investigated in diabetic patients.

Thirty-four women with polycystic ovary syndrome who previously had participated in studies with intravenous glucose tolerance test and hyperinsulinemic, euglycemic clamp between 1987 and 1995 underwent anthropometric, endocrine (T and sex-hormone binding globulin serum concentration), and metabolic (intravenous glucose tolerance test, hyperinsulinemic, euglycemic clamp, and androgens) measurements. Free androgen levels and β-cell function decreased over time in women with polycystic ovary syndrome, but insulin sensitivity remained unaltered., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The separate roles of inflammation and insulin resistance (IR) in the pathogenesis of cardiovascular disease (CVD) are well recognized. We investigated whether presence of inflammation would modify coronary artery disease (CAD) risk prediction in subjects with or without IR. Insulin, glucose, CRP and fibrinogen levels were determined in 317 Caucasians and 222 African Americans undergoing diagnostic coronary angiography. Extent of CAD was defined by a composite score (0-75). The overall prevalence of IR (HOMA-IR>or=3.0) in Caucasians and African Americans was 32.5% and 22.9%, respectively (P<0.05). The degree of CAD (composite score) was higher in subjects with IR (20.7 vs. 14.5, P=0.014 and 20.1 vs. 13.1, P=0.031 for Caucasians and African Americans, respectively), and in a multiple regression model IR was an independent predictor for CAD in both groups. In both ethnic groups, subjects with a combination of IR and high CRP (>or=3mg/l) had significantly higher composite score compared to those with no IR and low CRP (<3mg/l) (21.2 vs. 13.9, P<0.05 and 20.9 vs. 10.2, P<0.05 for Caucasians and African Americans, respectively). Similarly, the composite score was significantly higher in subjects with IR and high fibrinogen (>or=340 mg/dl) compared to those with no IR and low fibrinogen. In conclusion, elevated levels of inflammatory markers were positively associated with IR. Further, a combination of IR and inflammation resulted in a higher degree of CAD in both Caucasians and African Americans. The results suggest that inflammation may potentiate the cardiovascular risk factor role of IR.

Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle-triglyceride and -cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults.

Background: Impaired acute insulin response (AIR) and insulin resistance (IR) are characteristics of Type 2 diabetes (T2DM). The aim was to develop risk models for T2DM and impaired fasting glucose (IFG), reflecting estimates both of AIR and IR, and of their interaction, as predictors over 20 years of follow-up., Methods: We developed predictive models using hierarchic multiple regression analyses in a population-based cohort of 1227 men with normal fasting blood glucose at baseline (1970-73) and were reinvestigated after 10 and after 20 years. Using IVGTT-variables correlated either to AIR or to IR, separate models were developed. Combined models were also estimated from which prediction scores, representing individual risk, were calculated., Results: In combined models, interaction between prediction scores reflecting AIR and IR predicted T2DM and IFG. Lowest tertile of AIR and the highest tertile of IR showed a relative risk (RR) of 15.3 (95%-CI=5.58-41.84) for T2DM compared to the contrast group (high AIR and low IR). Corresponding RR for IFG was 13.23 (95%-CI=6.53-26.78). C-statistic increased from 0.76 to 0.79 (p=0.018) for T2DM and from 0.77 to 0.80 for IFG (p=0.062) taking interaction into account. Main effects of lowest tertile of AIR and highest tertile of IR versus best were: RR for T2DM, 8.80 (95%-CI=4.25-18.21) and 6.31 (95%-CI=3.26-12.21); for IFG, 9.07, (95%-CI=5.38-15.29) and 4.49 (95%-CI=2.98-6-76)., Conclusion: The interaction between low AIR and high IR revealed a high relative risk for T2DM or IFG reflecting the interplay between these factors over long time on worsening glucose tolerance and development of manifest disease.

Objective: Predictors of insulin resistance have hitherto only been examined in cross-sectional studies without information on lifestyle factors. Few researchers have measured insulin sensitivity directly and compared different metabolic and lifestyle predictors in a large population., Research Design and Methods: Our aim was to investigate independent long-term predictors of insulin sensitivity in a large population-based sample (the Uppsala Longitudinal Study of Adult Men cohort) of 50-year-old men who underwent a euglycemic clamp 20 years later (n = 770). Subjects with diabetes and treatment of cardiovascular disease at baseline were excluded. In linear regression models, metabolic (BMI, triglycerides, HDL cholesterol, glucose, and blood pressure) and lifestyle factors (physical activity, smoking, saturated fat biomarkers, and socioeconomic status) were independent variables at baseline (age 50 years) and insulin sensitivity-dependent variables at follow-up (age 70 years). A subsample of only normal-weight men from the initial population was also examined (n = 440)., Results: BMI was the strongest predictor of insulin sensitivity even after addition of metabolic factors. One SD (+/-2.8) increase in BMI corresponded to a mean 19% decrease in insulin sensitivity. After addition of lifestyle factors, all factors except triglycerides and smoking were significant predictors. BMI remained the strongest predictor (beta = -0.67 [95% CI -0.83 to -0.51], P < 0.0001) followed by physical activity, HDL cholesterol, saturated fat, and socioeconomic status (all P < 0.05). BMI remained the strongest predictor in normal-weight subjects also (P < 0.001). In addition, after adjustment for baseline insulin concentrations, BMI remained the strongest predictor (P < 0.001)., Conclusions: Multiple factors, including novel factors such as saturated fat and socioeconomic status, independently predict insulin sensitivity after 20 years. BMI is, however, the single strongest predictor, even in normal-weight subjects.

Objective: It is clinically important to find noninvasive markers of insulin resistance and hyperproinsulinemia because they both predict cardiovascular and diabetes risk. Sagittal abdominal diameter (SAD) or "supine abdominal height" is a simple anthropometric measure previously shown to predict mortality in men, but its association with insulin resistance and hyperproinsulinemia is unknown., Research Design and Methods: In a common high-risk group of 59 moderately obese men (aged 35-65 years, BMI 32.6 +/- 2.3 kg/m(2)), we determined anthropometry (SAD, BMI, waist girth, and waist-to-hip ratio [WHR]); insulin sensitivity (euglycemic-hyperinsulinemic clamp); and plasma concentrations of intact proinsulin, specific insulin, C-peptide, glucose, and serum IGF binding protein-1 (IGFBP-1). To compare SAD with other anthropometric measures, univariate and multiple regression analyses were used to determine correlations between anthropometric and metabolic variables., Results: SAD showed stronger correlations to all measured metabolic variables, including insulin sensitivity, than BMI, waist girth, and WHR. SAD explained the largest degree of variation in insulin sensitivity (R(2) = 0.38, P < 0.0001) compared with other anthropometric measures. In multiple regression analyses, including all anthropometric measures, SAD was the only independent anthropometric predictor of insulin resistance (P < 0.001) and hyperproinsulinemia (P < 0.001)., Conclusions: In obese men, SAD seems to be a better correlate of insulin resistance and hyperproinsulinemia (i.e., cardiovascular risk) than other anthropometric measures. In overweight and obese individuals, SAD could represent a simple, cheap, and noninvasive tool that could identify the most insulin resistant in both the clinic and clinical trials evaluating insulin sensitizers. These results need confirmation in larger studies that also include women and lean subjects.

Variations in the calpain-10 gene (CAPN10) have been identified among Mexican-Americans, and an at-risk haplotype combination (112/121) defined by three polymorphisms, UCSNP-43, -19, and -63, confers increased risk of type 2 diabetes. Here we examine the three polymorphisms in 1,594 Scandinavian subjects, including 409 type 2 diabetic patients, 200 glucose-tolerant control subjects, 322 young healthy subjects, 206 glucose-tolerant offspring of diabetic patients, and 457 glucose-tolerant 70-year-old men. The frequency of the 112/121 combination was not significantly different in 409 type 2 diabetic subjects compared with 200 glucose-tolerant control subjects (0.06 vs. 0.05; odds ratio 1.32 [95% CI 0.58-3.30]). In glucose-tolerant subjects, neither the single-nucleotide polymorphisms individually nor the 112/121 combination were associated with alterations in plasma glucose, serum insulin, or serum C-peptide levels at fasting or during an oral glucose tolerance test, estimates of insulin sensitivity, or glucose-induced insulin secretion. In conclusion, the frequency of the 112/121 at-risk haplotype of CAPN10 is low among Scandinavians and we were unable to demonstrate significant associations between the CAPN10 variants and type 2 diabetes, insulin resistance, or impaired insulin secretion.

The aim of this study was to test our hypothesis that insulin resistance determines systemic atherosclerosis in type 2 diabetic patients. The design of the study was cross-sectional and included 28 type 2 patients with 48 type 1 patients as controls. The total daily insulin dose required to maintain glycosylated hemoglobin, HbA(1c), at 6.0% for 1 year was used as a measure of long-term insulin resistance. Systemic atherosclerosis was estimated by the toe systolic blood pressure index (TSPI). The results showed that total daily insulin dose was closely and independently associated with TSPI (r =.4652, partial P =.0064) in type 2 diabetic patients with secondary failure, even when adjusted for serum C-peptide (r =.4443, partial P =.00123). The association was absent in type 1 patients. Established risk factors were not associated with TSPI, but the products between individual risk factors and insulin dose were closely associated with TSPI. In conclusion, the daily insulin dose is associated with peripheral atherosclerosis in type 2 diabetic patients with high insulin resistance, but not in type 1 diabetes. The effect is additive to a lesser, underlying effect of established risk factors on atherosclerosis. Longstanding insulin resistance, as estimated by the daily insulin dose, is a determinant of atherogenesis., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Aims/hypothesis: We examined whether the Pro12-Ala polymorphism of the human peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) gene was related to altered insulin sensitivity among glucose-tolerant subjects or a lower accumulated incidence or prevalence of IGT and Type II (non-insulin-dependent) diabetes mellitus among Scandinavian Caucasians., Methods: The Pro12Ala polymorphism was examined using PCR-RFLP Whole-body insulin sensitivity measured under hyperinsulinaemic-euglycaemic conditions was estimated in a population-based sample of 616 glucose tolerant Swedish Caucasian men at age 70. In addition, insulin sensitivity index was measured using IVGTT and Bergman minimal modelling in a population-based sample of 364 young healthy Danish Caucasians. Finally, we evaluated whether the polymorphism predicted Type II diabetes and IGT in 841 seventy-year-old Swedish men. A case-control study was carried out in 654 unrelated Danish Type II diabetic patients and 742 Danish glucose tolerant subjects matched for age and sex., Results: Whole-body insulin sensitivity was significantly improved in carriers compared with non-carriers of the Ala-allele of the codon 12 polymorphism in Swedish Caucasian men (6.0+/-2.5 vs 5.6+/-2.5 mg kg(-1) x min(-1) x mU/l](-1) x 100, p = 0.044). The same tendency, but not significant, was observed in the insulin sensitivity index among the group of young healthy Danish Caucasians. The incidence of Type II diabetes and IGT among the Swedish subjects at the age of 70 was similar in the three genotype-groups of the Pro12Ala variant and the Ala-allele was not related to a lower prevalence of Type II diabetes in Danish Caucasians., Conclusion/interpretation: The Ala-allele of the PPAR-gamma2 polymorphism is associated with improved whole body insulin sensitivity among Swedish Caucasians.

In humans, the Met326Ile missense variant of the p85alpha regulatory subunit of the phosphoinositide 3-kinase (PI3K) has been associated with either significant reductions in glucose effectiveness and intravenous glucose tolerance in Caucasians or a significantly higher insulin secretory response in Pima Indians. In the present study, we genotyped 1,190 Caucasian males to evaluate the impact in vivo of the Met326Ile variant of the p85alpha subunit of PI3K on the acute insulin response, intravenous glucose tolerance, insulin-mediated glucose uptake, and the prevalence of type 2 diabetes after 20 years of follow-up. We also expressed the variant in vitro to evaluate the impact on insulin-stimulated activation of protein kinase B (PKB). The Met326Ile variant of p85alpha was not associated with type 2 diabetes or with alterations in insulin secretion, insulin sensitivity, or intravenous glucose tolerance in vivo. Expressed in vitro, the Ile326 and the Met326 variant acted equally as a dominant-negative and prevented (60-70% inhibition) insulin-mediated activation of PKB by inhibiting the phosphorylation of PKB at Thr308. We conclude that the Met326Ile variant of the p85alpha regulatory subunit of PI3K is likely to be as functionally normal in vivo as in vitro.

Women with the polycystic ovary syndrome (PCOS) have a high prevalence of insulin resistance, with consequent increased risk of metabolic diseases later in life. An early metabolic screening would therefore be of clinical relevance. By using stepwise regression analysis on several variables obtained in 72 women with PCOS, we constructed simple and reliable mathematical models predicting insulin sensitivity, as measured by the euglycaemic hyperinsulinaemic clamp. The normal ranges of insulin sensitivity were calculated from 81 non-hirsute, normally menstruating women with normal ovaries, and similar body mass index (BMI) and age as the women with PCOS. Measured variables included BMI, waist and hip circumferences, truncal-abdominal skin folds, circulating concentrations of gonadotrophins, androgens, sex hormone-binding globulin (SHBG), triglycerides, total cholesterol and cholesterol subfractions, fasting insulin, C-peptide and free fatty acids. The three best prediction models included waist circumference, together with insulin (model I: R(2) = 0.77), serum triglycerides (model II: R(2) = 0.65), and the subscapularis skin fold (model III: R(2) = 0. 64). Using reference limits for insulin sensitivity obtained in the 81 normal pre-menopausal women, the models identify insulin resistant women with PCOS. These simple and inexpensive models are potentially useful in clinical practice as an early screening in women with PCOS.

The purpose of this investigation was to examine to what extent variability in the muscle morphology and insulin sensitivity influence the correlation between them. Reproducibility of muscle characteristics was estimated in duplicate biopsies from the same thigh of 23 subjects from a cohort of 70-year-old men. The coefficient of variation (CV) for different characteristics of muscle morphology was between 11 and 42% in duplicate biopsies. Coefficient of variation for markers of insulin sensitivity ranged between 12 and 39%. The variability reflected by intra-class correlation ranged from 0.23 to 0.60 for muscle morphology and from 0.68 to 0.96 for estimates of insulin sensitivity. The correlation analysis between muscle morphology and insulin resistance was performed in a sample of 515 men from the cohort, correlation coefficients were calculated with (rtrue) and without (r) adjustment for intra-individual variation. Insulin sensitivity showed a positive relationship with percentage of type I fibres (rtrue=0.33, r=0.21; P < 0.0001) and capillary density (rtrue=0.43, r=0.21; P < 0. 0001) and negative correlations with percentage of type IIB fibres (rtrue=-0.35, r=-0.24; P < 0.0001). Capillary density was inversely correlated to insulin. Thus, an obvious improvement of the correlation was seen after correcting intra-individual variation. In conclusion, owing to the low degree of reproducibility of muscle morphology variables and insulin sensitivity, implying a noticeable underestimation of correlations, the r-values should be adjusted for within-subject variation in order to demonstrate a more accurate estimate of the strength of the relationships studied.

A polymorphism (PP1ARE) in the 3'-untranslated region of the gene encoding the glycogen-associated regulatory subunit of type 1 protein phosphatase PPP1R3 is associated with insulin resistance in Pima Indians. The aim of this study was to investigate whether two common variants in the PPP1R3 gene, Asp905Tyr and PP1ARE, are associated with reduced insulin sensitivity or can predict the development of impaired glucose tolerance (IGT) or type 2 diabetes during a 20-year follow-up period in 696 50-year-old Caucasian men. The allelic frequency of Tyr905 was 0.11 (95% CI 0.09-0.13) and of PP1ARE 0.34 (0.31-0.37) and the two polymorphisms were in linkage disequilibrium (chi2 = 46, P < 0.0001, Fisher's exact test). None of the polymorphisms was associated with the development of IGT or type 2 diabetes, but the PP1ARE polymorphism was weakly correlated to whole-body insulin sensitivity (r = -0.08, P = 0.04). In conclusion, we found no evidence in Swedish men that the PP1ARE or the Asp905Tyr variants over a 20-year period predict the development of IGT or type 2 diabetes, but the PP1ARE polymorphism could have a higher penetrance in other populations.

Objectives: To investigate candidate predictors for insulin sensitivity in healthy elderly males, with special reference to the influence of insulin-mediated skeletal muscle blood flow and serum nonesterified fatty acids (NEFA)., Subjects: From the participants in a health survey of 70-year-old males, focusing on cardiovascular risk factors, a subgroup of 46 men was sampled. Only men who declared themselves healthy and without medication were included., Interventions: Insulin sensitivity was measured with the euglycaemic hyperinsulinaemic clamp. Leg blood flow was measured before and during the clamp, using the Doppler ultrasound technique., Results: Hyperinsulinaemia [steady-state plasma insulin 105(15) mU L-1] increased leg blood flow by 10% (P < 0.004). When tested in bivariate analysis incremental leg blood flow was only significantly related to the serum NEFA concentration (r = - 0.38, P < 0.01) amongst a number of measured variables. Insulin-mediated glucose disposal was related to body mass index (BMI) (r = -0.49, P = 0. 0006), waist/hip ratio (r = - 0.31, P = 0.036), NEFA (r = - 0.50, P = 0.0004) and heart rate (r = - 0.34, P = 0.02). In multivariate analysis only BMI and NEFA remained significantly related to whole-body glucose uptake., Conclusions: The study demonstrates that in elderly men BMI and fasting serum NEFA but not insulin-induced vasodilation are related to insulin sensitivity. High fasting levels of NEFA relate to both impaired insulin-mediated vasodilation and impaired glucose disposal, respectively. These two insulin actions were not interrelated, however, a finding which may indicate dissociated mechanisms.

Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been discussed as a part of the insulin resistance syndrome. However, it is not clear whether the relationship between PAI-1 and insulin resistance is independent of or mediated by increased triglycerides levels. The aim of this study was to investigate whether PAI-1 activity is associated with insulin sensitivity independently of serum triglycerides (sTG) and of other potential confounders. Seventy-year-old men (n=871), participating in a cohort study undergoing extensive metabolic investigations, had blood samples taken for determination of PAI-1 activity. Insulin sensitivity was determined by the euglycemic hyperinsulinemic clamp. In multivariate correlation and regression analyses, insulin sensitivity was a statistically significant determinant of PAI-1 activity (partial r=-.12; P<.001), independent of sTG, body mass index, waist-hip ratio, and other potential confounders. The levels of sTG were also independently related to PAI-1 activity (partial r=.18; P<.001). The relationships between PAI-1 and insulin sensitivity and sTG were independent of fasting glucose levels. Aggregation of risk factors of the insulin resistance syndrome was associated with increased activity of PAI-1 in men with normal glucose tolerance. We conclude that PAI-1 activity is related to insulin sensitivity and sTG, independently of each other and of other potential confounders, and that increased levels of PAI-1 should be regarded as a component of the insulin resistance syndrome.

A prediction model for estimating insulin resistance in hypertensive patients is presented. Body-mass index, serum triglyceride concentrations and liver enzyme activity in plasma correlate to insulin resistance determined with the euglycaemic, hyperinsulinaemic clamp technique. Prediction models using body-mass index and either triglycerides or serum alanine-amino transferase were equally good in predicting insulin resistance and gave results that were as reliable as those obtained in a model using fasting-insulin concentrations. The hyperinsulinaemic clamp had a reproducibility error of 14%, and body-mass index and serum triglycerides had a multiple correlation of 0.57 to the insulin-sensitivity results. The model predicts insulin resistance with acceptable statistical power, whereas the power to predict high values of insulin sensitivity is less good.

Insulin secretion in response to iv glucose and insulin sensitivity (euglycemic hyperinsulinemic clamp) were evaluated in 49 women with polycystic ovary syndrome (PCOS) [body mass index (BMI), 17.6-37.2 kg/m2] and 42 control subjects (BMI, 18.8-38.1 kg/m2). Seven women with PCOS exhibited glucose intolerance with subnormal insulin secretion. Compared with control subjects, women with PCOS and normal glucose tolerance had an increased (36-56%) insulin increment, not explained by insulin resistance, and over the whole range of BMI. In contrast, insulin sensitivity was similar in women with PCOS and control subjects at BMI 21 kg/m2, but showed a more pronounced decline with increasing BMI in women with PCOS, who had 35% and 70% lower insulin sensitivities at BMI 28 and 35 kg/m2, respectively. After adjusting for truncal-abdominal sc fat distribution, which was more pronounced in the women with PCOS, the two groups had similar insulin sensitivity over the entire range of BMI (P = 0.9), whereas the difference in insulin increment was insignificant after adjusting for the free androgen index (testosterone x 100/sex hormone binding globulin; P = 0.16). Hemoglobin A1C levels were lower in women with PCOS than in the control subjects. It is concluded that the early insulin response to glucose was increased in women with PCOS, not accounted for by insulin resistance, closely associated to the increased androgenicity, and present also at low-normal BMI. In contrast, insulin resistance was seen only at higher BMI levels and was largely determined by the increased truncal-abdominal fat mass in PCOS.

Aims/hypothesis. The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. Methods. The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. Results. Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10 %, p = 0.03) but did not change on the monounsaturated fatty acid diet ( + 2 %, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E %). Here, insulin sensitivity was 12.5 % lower and 8.8 % higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet ( + 4.1 %, p < 0.01) but decreased on the monounsaturated fatty acid diet (MUFA) (–5.2, p < 0.001), whereas lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12 % (p < 0.001). Conclusions/interpretation. A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake ( > 37E %). [Diabetologia (2001) 44: 312–319] [ABSTRACT FROM AUTHOR]