Differences In Insulin Resistance Research Articles

Recommendations for insulin initiation based on ethnicity

Even in a developed country like USA, substantial number of subjects with type 2 diabetes fail to achieve adequate glycemic control despite the availability of several groups of anti-diabetic medications targeting multiple pathophysiological features of type 2 diabetes. Are we treating our type 2 diabetes subjects appropriately? To aid practicing clinicians various professional bodies like American Diabetes Association (ADA), European Association for Study of Diabetes (EASD), Canadian Diabetes Association (CDA), etc. regularly publish clinical practice guidelines and consensus statements. Since racial and ethnic differences in insulin resistance, dietary pattern, glucose metabolism, genetic variation are known phenomena, it would be interesting to evaluate the aptness of these guidelines from ethnopharmacy perspective. We postulate that certain ethnic characteristics of populations will decide the best form of insulin therapy rather than blanket recommendations on starting every patient on basal insulin.

Sex Differences in Energy Metabolism Need to Be Considered with Lifestyle Modifications in Humans

Women have a higher proportion of body fat compared to men. However, women consume fewer kilojoules per kilogram lean mass and burn fat more preferentially during exercise compared with men. During gestation, women store even greater amounts of fat that cannot be solely attributed to increased energy intake. These observations suggest that the relationship between kilojoules consumed and kilojoules utilised is different in men and women. The reason for these sex differences in energy metabolism is not known; however, it may relate to sex steroids, differences in insulin resistance, or metabolic effects of other hormones such as leptin. When considering lifestyle modifications, sex differences in energy metabolism should be considered. Moreover, elucidating the regulatory role of hormones in energy homeostasis is important for understanding the pathogenesis of obesity and perhaps in the future may lead to ways to reduce body fat with less energy restriction.

Differences in Male and Female Adolescents From Various Racial Groups in the Relationship Between Insulin Resistance-Associated Parameters With Sugar-Sweetened Beverage Intake and Physical Activity Levels

To describe racial and gender differences in insulin resistance-associated parameters due to sugar-sweetened beverage (SSB) intake and physical activity (PA) levels in the adolescent population. Data from individuals aged 12 to 19 years from the National Health and Nutrition Examination Survey during the years 1999-2004 were analyzed. SSB intake and PA levels were evaluated in Non-Hispanic whites, Non-Hispanic blacks, and Mexican Americans. Outcome measures included measurements of insulin sensitivity, lipids, blood pressure, waist circumference, and body mass index. Multivariate linear regression analyses showed that anthropometric measurements, metabolic parameters, and indices of insulin resistance differed among the racial groups. Moreover, within each of these racial groups, they differed between the sexes. The differing relationships between insulin resistance-associated parameters and SSB intake and PA levels among racial groups and between the sexes illustrate the importance of race and gender in the investigation of diseases such as obesity and metabolic syndrome.

Differences in Insulin Resistance in Mexican and U.S. Pima Indians with Normal Glucose Tolerance

Insulin resistance is a major risk factor for the development of type 2 diabetes in Pima Indians, a population with the highest prevalence of type 2 diabetes mellitus in the world. Their Mexican counterpart, living a traditional lifestyle in the mountains of Sonora, have at least 5 times less diabetes than the U.S. Pima Indians. We evaluated whether Mexican Pima Indians had lower insulin resistance than U.S. Pima Indians. We compared fasting insulin and homeostasis model assessment for insulin resistance (HOMA-IR) in 194 Mexican Pima Indians (100 females, 94 males) and 449 U.S. Pima Indians (246 females, 203 males) with normal glucose tolerance from a cross-sectional study. Adjusted differences of log-transformed outcomes (fasting insulin and HOMA-IR) between groups were evaluated using multiple linear regression models and paired t test in a matched subset. Unadjusted fasting insulin and HOMA-IR were much lower in the Mexican Pima Indians than in their U.S. counterparts. After adjusting by obesity, age, and sex, mean (95% confidence interval) for fasting insulin was 6.22 (5.34-7.24) vs. 13.56 μU/ml (12.27-14.97) and for HOMA-IR 1.40 (1.20-1.64) vs. 3.07 (2.77-3.40), respectively, for Mexican Pima and U.S. Pima Indians. Results were confirmed in subset matched for age, sex, and body fat. Our results indicate that Mexican Pima Indians have lower insulin resistance in comparison with their genetically related U.S. counterparts, even after controlling for differences in obesity, age, and sex. This finding underscores the importance of lifestyle factors as protecting factors against insulin resistance in individuals with a high propensity to develop diabetes.

Hypovitaminosis D and ethnic differences in insulin resistance

Hypovitaminosis D and ethnic differences in insulin resistance

Higher High-Density Lipoprotein Cholesterol in African-American Women with Polycystic Ovary Syndrome Compared with Caucasian Counterparts

Studies have demonstrated lipid differences among African-Americans and Caucasians and between women with polycystic ovary syndrome (PCOS) and normally ovulating women. However, few studies have examined racial differences in lipoprotein levels in women with PCOS. This study compared lipoprotein levels in African-American and Caucasian women with PCOS. We performed a retrospective chart review of 398 subjects seen as new patients for PCOS at the Duke University Medical Center Endocrinology Clinic in Durham, NC. We identified 126 charts appropriate for review, based on a diagnosis of PCOS (using the 1990 National Institutes of Health criteria), a self-reported race of either Caucasian or African-American, and a body mass index (BMI) higher than 25. We excluded patients taking glucophage, oral contraceptives, or lipid-lowering medications. Age, BMI, total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, random triglycerides (TG), and oral glucose tolerance test measurements were collected and included in the analysis. African-American women with PCOS had higher HDL cholesterol levels (52.6 vs. 47.5 mg/dl, P = 0.019), lower non-HDL cholesterol (134.1 vs. 154.6 mg/dl, P = 0.046), and lower TG levels (97.5 vs. 168.2 mg/dl, P < 0.001) than Caucasian women. These differences could not be attributed to age, BMI, or differences in insulin resistance as determined by homeostasis model assessment of insulin resistance. African-American women with PCOS appear to have a more favorable lipid profile than Caucasian women with PCOS having higher HDL cholesterol, lower non-HDL cholesterol, and lower TG when BMI and insulin resistance are equal.

Resistance to the antilipolytic effect of insulin in adipocytes of African-American compared to Caucasian postmenopausal women

High fatty acid (FA) flux is associated with systemic insulin resistance, and African-American (AA) women tend to be more insulin resistant. We assessed possible depot and race difference in the antilipolytic effect of insulin in adipocytes isolated from abdominal (Abd) and gluteal (Glt) subcutaneous (sc) adipose tissue of overweight, postmenopausal AA and Caucasian (C) women. Percent body fat, fasting insulin, visceral adiposity, and adipocyte size was higher in AA women. Disinhibited lipolysis (presence of adenosine deaminase) per unit adipocyte surface area was similar in Abd and Glt and in AA and C. However, rates of 'basal' [submaximal phenylisopropyl adenosine (PIA)-suppressed] and insulin-suppressed lipolysis were higher in Abd of AA compared with C women even after adjustment for percent fat and visceral fat area. The race difference in rates of PIA- and insulin-suppressed lipolysis in AA were correlated with their hyperinsulinemia, but AA race, independent of fasting insulin, was associated with lower responsiveness (percent suppression) to submaximal insulin concentrations, although sensitivity (ED50) was not affected. Overall, these data are consistent with the hypothesis that decreased responsiveness of Abd adipocytes to antilipolytic effectors may contribute to higher FA availability and thereby to racial differences in insulin resistance.

Mechanisms of genetically-determined diabetes resistance and susceptibility in db/db mice

Aims/Hypothesis: Leptin receptor-deficient db/db mice are a commonly used research model and it is known that the genetic background, on which the mutation is bred, modulates the mice's phenotype. While diabetes-resistant strains exhibit persistent hyperinsulinemia, susceptible backgrounds show progressive hyperglycemia and islet involution. The primary mechanisms of this phenotypic difference however are not known. Differences in insulin resistance, beta cell function, proliferation and apoptosis possibly contribute. We hypothesized that following the phenotypic divergence between two strains of db/db mice with different susceptibility to diabetes would allow us to address this issue.

Ethnic Variation in Adiponectin and Leptin Levels and Their Association With Adiposity and Insulin Resistance

OBJECTIVETo investigate ethnic differences in adiponectin and leptin concentration and to determine whether these adipokines and a high–glycemic index diet account for ethnic variation in insulin resistance.RESEARCH DESIGN AND METHODSIn 1,176 South Asian, Chinese, Aboriginal, and European Canadians, fasting blood samples were drawn, and clinical history and dietary habits including glycemic index/glycemic load were recorded using standardized questionnaires. Insulin resistance was defined using homeostasis model assessment–insulin resistance (HOMA-IR).RESULTSAdiponectin concentrations were significantly higher in Europeans (adjusted mean 12.94 [95% CI 2.27–13.64]) and Aboriginal people (11.87 [11.19–12.59]) than in South Asians (9.35 [8.82–9.92]) and Chinese (8.52 [8.03–9.03]) (overall P < 0.001). Serum leptin was significantly higher in South Asians (11.82 [10.72–13.04]) and Aboriginal people (11.13 [10.13–12.23]) than in Europeans (9.21 [8.38–10.12]) and Chinese (8.25 [7.48–9.10]). BMI and waist circumference were inversely associated with adiponectin in every group except the South Asians (P < 0.001 for interaction). Adiponectin was inversely and leptin was positively associated with HOMA-IR (P < 0.001). The increase in HOMA-IR for each given decrease in adiponectin was larger among South Asians (P = 0.01) and Aboriginal people (P < 0.001) than among Europeans. A high glycemic index was associated with a larger decrease in adiponectin among South Asians (P = 0.03) and Aboriginal people (P < 0.001) and a larger increase in HOMA-IR among South Asians (P < 0.05) relative to that in other groups.CONCLUSIONSSouth Asians have the least favorable adipokine profile and, like the Aboriginal people, display a greater increase in insulin resistance with decreasing levels of adiponectin. Differences in adipokines and responses to glycemic foods parallel the ethnic differences in insulin resistance.

Coping style predicts the (in)sensitivity for developing hyperinsulinemia on a high fat diet in rats

The aim of this study was to explore interactions between coping style and diet as risk factors for developing insulin resistance in rats. We hypothesized that rats characterized by a passive coping strategy are more susceptible for developing insulin resistance and visceral obesity than proactively coping rats, particularly on a high (45%) fat diet. This hypothesis was tested by comparing 1) insulin and glucose responses to an intravenous glucose tolerance test (IVGTT), and 2) body fat distribution, in two rat models for passive and proactive coping styles. We found that the most extremely passive rats are characterized by elevated insulin levels during a IVGTT, even on chow. Moderately passive rats display normal insulin responses under chow conditions, but develop insulin resistance on a high fat diet. Proactive rats are remarkably resistant to insulin resistance and visceral obesity, even when overfeeding on a high fat diet. Carcass analysis revealed that passive rats are characterized by increased epididymal fat deposition, which is in line with the observed differences in insulin resistance. We conclude that a passive personality is prone to develop insulin resistance and visceral obesity on a palatable fat diet and a proactive personality might be protected against the development of diet-induced insulin resistance.

Racial and Ethnic Differences in an Estimated Measure of Insulin Resistance Among Individuals With Type 1 Diabetes

OBJECTIVEInsulin resistance is greater in racial/ethnic minorities than in non-Hispanic whites (NHWs) for those with and without type 2 diabetes. Because previous research on insulin resistance in type 1 diabetes was limited to NHWs, racial/ethnic variation in an estimated measure of insulin resistance in type 1 diabetes was determined.RESEARCH DESIGN AND METHODSThe sample included 79 individuals with type 1 diabetes diagnosed at age <18 years (32.9% NHWs, 46.8% non-Hispanic black [NHB], 7.6% other/mixed, and 12.7% Hispanic) and their families. Estimated glucose disposal rate (eGDR) (milligrams per kilogram per minute; a lower eGDR indicates greater insulin resistance) was calculated using A1C, waist circumference, and hypertension status.RESULTSMean current age was 13.5 years (range 3.2–32.5) and diabetes duration was 5.7 years (0.1–19.9). eGDR was inversely associated with age. Compared with that in NHWs, age-adjusted eGDR was significantly lower among nonwhites (NHB, other/mixed, and Hispanic: Δ = −1.83, P = 0.0006). Age-adjusted eGDR was negatively associated with body fat, triglycerides, urinary albumin/creatinine, acanthosis nigricans, parental obesity, and parental insulin resistance and positively related to HDL and sex hormone–binding globulin. In multivariable analysis, lower eGDR was significantly associated with older age, nonwhite race/ethnicity, acanthosis, and lower HDL.CONCLUSIONSMinorities with type 1 diabetes are significantly more insulin resistant, as measured by eGDR, than NHWs. Exploring potential mechanisms, including disparities in care and/or physiological variation, may contribute to preventing racial/ethnic differences in insulin resistance–associated outcomes.

Ethnic Variation in Fat and Lean Body Mass and the Association with Insulin Resistance

Body fat distribution varies among different ethnic groups, yet less is known regarding differences in lean mass and how this may affect insulin resistance. Our objective was to compare total body fat to lean mass ratio (F:LM) in Aboriginal, Chinese, European, and South Asian individuals with differences in insulin resistance. Aboriginal (196), Chinese (222), European (202), and South Asian (208) individuals were recruited across a range of body mass index to participate in this cross-sectional community study. Total body fat, lean mass, and insulin resistance were assessed using homeostasis model assessment (HOMA). After adjustment for confounders and at a given body fat, South Asian men had less lean mass than Aboriginal [3.42 kg less; 95% confidence interval (CI) = 1.55-5.29], Chinese (3.01 kg less; 95% CI = 1.33-4.70), and European (3.57 kg less; 95% CI = 1.82-5.33) men, whereas South Asian women had less lean mass than Aboriginal (1.98 kg less; 95% CI = 0.45-3.50), Chinese (2.24 kg less; 95% CI = 0.81-3.68), and European (2.97 kg less; 95% CI = 1.67-4.27) women. In adjusted models, F:LM was higher in South Asian compared with Chinese and European men and higher in South Asian compared with Aboriginal, Chinese, and European women (P < 0.01 for all). Insulin and HOMA were greatest in South Asians after adjustment; however, these differences were no longer apparent when F:LM was considered. South Asians have a phenotype of high fat mass and low lean mass, which may account for greater levels of insulin and HOMA compared with other ethnic groups.

Different pathophysiology of impaired glucose tolerance in first-degree relatives of individuals with type 2 diabetes mellitus

To assess whether an increased genetic predisposition for type 2 diabetes mellitus (T2DM) influences the contributions of insulin resistance and impaired insulin secretion to impaired glucose tolerance (IGT), 437 subjects not known to have T2DM underwent an oral glucose tolerance test and a 3-hour hyperglycemic clamp. Plasma insulin responses and insulin sensitivity were compared between all subjects (unselected for demographic or anthropometric characteristics) who had normal glucose homeostasis and no first-degree T2DM relative (n = 133), IGT with a first-degree T2DM relative (IGT/FH+, n = 74), or IGT without a first-degree T2DM relative (IGT/FH−, n = 50). Compared with those with normal glucose homeostasis, first- and second-phase plasma insulin responses were reduced approximately 45% and 30%, respectively (both P < .001), in IGT/FH+, whereas insulin sensitivity was only approximately 20% reduced ( P = .011). In contrast, in IGT/FH−, first-phase plasma insulin responses were only approximately 20% reduced ( P = .016), second-phase plasma insulin responses were not reduced, but insulin sensitivity was approximately 40% reduced ( P < .001). The IGT/FH+ group differed significantly from the IGT/FH− group by having 25% to 30% lower first-phase plasma insulin responses ( P = .026) and 25% to 30% greater insulin sensitivity ( P = .027). Adjustment for obesity abolished the differences in insulin resistance but not plasma insulin responses. However, when the IGT groups were stratified into subgroups based on body mass index (BMI), first-phase plasma insulin responses were approximately 30% lower in IGT/FH+ with a BMI of at least 27 kg/m 2 ( P = .018) but similar in IGT/FH+ with a BMI less than 27 kg/m 2 compared with the corresponding IGT/FH− subgroups. We conclude that, in IGT, an increased genetic predisposition for T2DM increases the contribution of impaired insulin secretion to its pathophysiology. This effect is enhanced by obesity.

Gender differences in insulin resistance, body composition, and energy balance

Men and women differ substantially in regard to degrees of insulin resistance, body composition, and energy balance. Adipose tissue distribution, in particular the presence of elevated visceral and hepatic adiposity, plays a central role in the development of insulin resistance and obesity-related complications. This review summarizes published data on gender differences in insulin resistance, body composition, and energy balance, to provide insight into novel gender-specific avenues of research as well as gender-tailored treatments of insulin resistance, visceral adiposity, and obesity. English-language articles were identified from searches of the PubMed database through November 2008, and by reviewing the references cited in these reports. Searches included combinations of the following terms: gender, sex, insulin resistance, body composition, energy balance, and hepatic adipose tissue. For a given body mass index, men were reported to have more lean mass, women to have higher adiposity. Men were also found to have more visceral and hepatic adipose tissue, whereas women had more peripheral or subcutaneous adipose tissue. These differences, as well as differences in sex hormones and adipokines, may contribute to a more insulin-sensitive environment in women than in men. When normalized to kilograms of lean body mass, men and women had similar resting energy expenditure, but physical energy expenditure was more closely related to percent body fat in men than in women. Greater amounts of visceral and hepatic adipose tissue, in conjunction with the lack of a possible protective effect of estrogen, may be related to higher insulin resistance in men compared with women.

Polycystic Ovary Syndrome Is Associated with Tissue-Specific Differences in Insulin Resistance

The potential differential contributions of skeletal muscle and adipose tissue to whole body insulin resistance were evaluated in subjects with polycystic ovary syndrome (PCOS). Forty-two PCOS subjects and 15 body mass index-matched control subjects were studied. Insulin action was evaluated by the hyperinsulinemic/euglycemic clamp procedure. Isolated adipocytes and cultured muscle cells were analyzed for glucose transport activity; adipocytes, muscle tissue, and myotubes were analyzed for the expression and phosphorylation of insulin-signaling proteins. Fifty-seven per cent of the PCOS subjects had impaired glucose tolerance and the lowest rate of maximal insulin-stimulated whole body glucose disposal compared to controls (P < 0.01). PCOS subjects with normal glucose tolerance had intermediate reduction in glucose disposal rate (P < 0.05 vs. both control and impaired glucose tolerance subjects). However, rates of maximal insulin-stimulated glucose transport (insulin responsiveness) into isolated adipocytes were comparable between all three groups, whereas PCOS subjects displayed impaired insulin sensitivity. In contrast, myotubes from PCOS subjects displayed reduced insulin responsiveness for glucose uptake and normal sensitivity. There were no differences between groups in the expression of glucose transporter 4 or insulin-signaling proteins or maximal insulin stimulation of phosphorylation of Akt in skeletal muscle, myotubes, or adipocytes. Individuals with PCOS display impaired insulin responsiveness in skeletal muscle and myotubes, whereas isolated adipocytes display impaired insulin sensitivity but normal responsiveness. Skeletal muscle and adipose tissue contribute differently to insulin resistance in PCOS. Insulin resistance in PCOS cannot be accounted for by differences in the expression of selected signaling molecules or maximal phosphorylation of Akt.

Differential effects of insulin sensitivity on androgens in obese women with polycystic ovary syndrome or normal ovulation

The differential effects of insulin sensitivity and adiposity on androgen concentrations in women with polycystic ovary syndrome (PCOS) are unclear. To address this issue, we divided 43 overweight women into 4 groups based on both their clinical classification (PCOS or normal) and whether they were insulin resistant (IR) or insulin sensitive (IS) by their steady-state plasma glucose concentrations. Total testosterone concentrations were significantly increased as a function of both clinical classification (PCOS vs normal, P < .0001) and steady-state plasma glucose concentration (IR vs IS, P = .002). Mean testosterone concentrations were higher in PCOS-IR compared with PCOS-IS, normal-IR, or normal-IS women ( P < .005). In addition, there was a statistically significant interaction ( P = .03) between clinical classification (PCOS vs normal) and insulin sensitivity (IR vs IS) for testosterone concentrations. In contrast, androstenedione concentrations were higher in women with PCOS ( P = .001), irrespective of whether they were IR or IS ( P = .31); and no interaction between clinical classification and insulin sensitivity was discerned ( P = .34). These results indicate that both PCOS and insulin resistance independently contributed to increased total testosterone concentrations within a group of overweight/obese women. These findings are consistent with the hypothesis that the ovaries of women with PCOS are hypersensitive to the ability of insulin to increase testosterone production and that the more insulin resistant the patient, the higher the testosterone concentration. In contrast, androstenedione concentrations seem to be independent of differences in insulin resistance. Our findings emphasize the need to increase understanding of the factors that modulate ovarian androgen secretion.

Exercise training has greater effects on insulin sensitivity in daughters of patients with type 2 diabetes than in women with no family history of diabetes

Aims/hypothesisSedentary offspring of patients with type 2 diabetes are often more insulin-resistant than persons with no family history of diabetes, but when active or fit offspring of type 2 diabetic patients are compared with non-diabetic persons, differences in insulin resistance are less evident. This study aimed to determine the effects of an exercise training intervention on insulin sensitivity in both groups.MethodsWomen offspring (n = 34) of type 2 diabetic patients (offspring age 35.6 ± 7.0 years, BMI 28.1 ± 5.1 kg/m2) and 36 matched female controls (age 33.6 ± 6.1 years, BMI 27.3 ± 4.7 kg/m2) participated. Body composition, fitness and metabolic measurements were made at baseline and after a controlled 7 week exercise intervention.ResultsAt baseline, insulin sensitivity index (ISI) was 22% lower in offspring than controls (p < 0.05), despite similar body fat and maximal oxygen uptake left( {dot VO_{2max } } right) values in the two groups. ISI increased by 23% (p < 0.05) in offspring following the exercise intervention, compared with 7% (NS) in the controls. Increases in dot VO_{2max } were similar in both groups (controls 12%, offspring 15%, p < 0.05 for both). Plasma leptin concentrations decreased significantly in the offspring (−24%, p < 0.01) but not in controls (0%, NS). Change in ISI correlated significantly with baseline ISI (r = −0.47, p < 0.0005) and change in leptin (r = −0.43, p < 0.0005). The latter relationship was not attenuated by adjustment for changes in body fat.Conclusions/interpretationOffspring, but not controls, significantly increased ISI in response to an exercise intervention, indicating that insulin sensitivity is more highly modulated by physical activity in daughters of patients with type 2 diabetes than in women with no family history of the disease. Trial registration: NCT00268541 Funding: British Heart Foundation (PG/03/145).Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-008-1097-6) contains supplementary material, which is available to authorised users.

Differences in insulin resistance and pancreatic B‐cell function in obese subjects with isolated impaired glucose tolerance and isolated impaired fasting glucose

To investigate changes in insulin action and insulin secretion in obese subjects with different categories of impaired glucose regulation (IGR): impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and combined IFG/IGT (CGI). A total of 222 subjects underwent an oral glucose tolerance test and a frequently sampled intravenous glucose tolerance test (FSIGTT); 100 had normal glucose tolerance (subdivided into 32 lean NGT, 68 obese NGT), and 122 were obese with IGR (82 IGT, 14 IFG and 26 CGI). The insulin sensitivity index (S(I)) was assessed by Bergman's minimal model method with FSIGTT; insulin secretion was determined by acute insulin response to glucose (AIRg). The disposition index (DI), the product of AIRg and S(I), was used to determine whether AIRg was adequate to compensate for insulin resistance. S(I) was similar in NGT and IGR obese subgroups. AIRg was significantly increased in obese NGT as compared with lean NGT, significantly reduced in IGT, and further reduced in IFG and CGI subjects as compared with obese NGT subgroups. DI was reduced in NGT obese individuals. Within the obese IGR subgroups, IFG and CGI subjects had even lower DI value than IGT subjects. Obese Chinese subjects with IGR have a similar degree of insulin resistance but differ in insulin secretion. Subjects with IFG and CGI have a more prominent deficiency in insulin secretion than subjects with IGT.

Global Adiposity Rather Than Abnormal Regional Fat Distribution Characterizes Women with Polycystic Ovary Syndrome

Obesity-related predisposition to polycystic ovary syndrome (PCOS) could reflect overall adiposity and/or regional accumulation of abdominal visceral fat. The objective of the study was to compare distributions of visceral, abdominal sc, and gluteofemoral sc adipose tissue in PCOS cases vs. control women. This was a cross-sectional study. Fat depot measurements from axial magnetic resonance imaging scans taken at anatomically predefined sites were compared between 22 body mass index (BMI)/fat mass-matched pairs of PCOS cases and controls; whole-group comparisons included 50 PCOS cases vs. 28 female controls. All subjects were of UK British/Irish origin. We measured cross-sectional areas of adipose tissue within visceral (mid-L4), abdominal (mid-L4) sc, and gluteofemoral (greater trochanteric and midfemoral) sc fat depots. Other measurements included fat mass, BMI, testosterone, SHBG, and homeostasis model assessment of insulin resistance (a measure of insulin sensitivity). Whole-group analyses were adjusted for fat mass and age. There were no significant differences in fat-depot measurements between BMI/fat mass-matched pairs of PCOS cases and controls: mid-L4 visceral (P=0.40), abdominal sc (P=0.22), gluteal sc (P=0.67), and midfemoral sc (P=0.37) depots. Whole-group comparisons gave similar results after adjustments for fat mass and age. Fasting serum insulin concentrations (P=0.03) and homeostasis model assessment of insulin resistance (P=0.03) were significantly higher in the PCOS group than BMI/fat mass-matched controls. PCOS cases and BMI/fat mass-matched control women are indistinguishable with respect to distribution of fat within visceral, abdominal sc, and gluteofemoral sc depots, despite significant differences in insulin resistance between these two groups.

Lipoprotein abnormalities are associated with insulin resistance in South Asian Indian women

South Asian Indians are at increased risk of coronary heart disease (CHD), possibly related to dyslipidemia characterized by high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentrations. The importance of differences in insulin resistance as compared to abdominal obesity in the development of this atherogenic lipoprotein profile is not clear, and the current cross-sectional study was initiated to examine this issue. Consequently, we defined the relationship between differences in insulin-mediated glucose uptake (IMGU), abdominal obesity, and various measures of lipoprotein metabolism known to increase CHD risk in 52 apparently healthy women of South Asian Indian ancestry. IMGU was quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test and abdominal obesity was assessed by measurement of waist circumference (WC), and the population was divided into tertiles on the basis of their SSPG results. Results indicated that although there were significant differences in SSPG, TG, and HDL-C values, there were no differences in age, blood pressure, total cholesterol, low-density lipoprotein cholesterol, body mass index, or WC between the highest and lowest tertiles. SSPG concentrations were significantly correlated with both log TG ( r = 0.44, P = .001) and HDL-C ( r = −0.44, P < .001) concentration, whereas TG and HDL-C concentrations were not significantly related to WC. Furthermore, the relationships between SSPG concentration and TG and HDL-C remained significant when adjusted for age and WC. Finally, a more extensive lipoprotein analysis indicated that the most insulin resistant tertile had higher TG concentrations, lower concentrations of HDL-C and HDL-C subclasses, and smaller and denser low-density lipoprotein particles than the most insulin sensitive tertile, despite the 2 groups not being different in age, BMI, or WC. These results indicate that a highly atherogenic lipoprotein profile seen in South Asian Indian women is significantly associated with insulin resistance independent of differences in WC.