Insulin Resistance In South Asians Research Articles

Adipose Tissue Insulin Resistance in South Asian and Nordic Women after Gestational Diabetes Mellitus

South Asians (SAs) have a higher risk of developing type 2 diabetes (T2D) than white Europeans, especially following gestational diabetes mellitus (GDM). Despite similar blood glucose levels post-GDM, SAs exhibit more insulin resistance (IR) than Nordics, though the underlying mechanisms are unclear. This study aimed to assess markers of adipose tissue (AT) IR and liver fat in SA and Nordic women post-GDM. A total of 179 SA and 108 Nordic women in Norway underwent oral glucose tolerance tests 1–3 years post-GDM. We measured metabolic markers and calculated the AT IR index and non-alcoholic fatty liver disease liver fat (NAFLD-LFS) scores. Results showed that normoglycaemic SAs had less non-esterified fatty acid (NEFA) suppression during the test, resembling prediabetes/T2D responses, and higher levels of plasma fetuin-A, CRP, and IL-6 but lower adiponectin, indicating AT inflammation. Furthermore, normoglycaemic SAs had higher NAFLD-LFS scores, lower insulin clearance, and higher peripheral insulin than Nordics, indicating increased AT IR, inflammation, and liver fat in SAs. Higher liver fat markers significantly contributed to the ethnic disparities in glucose metabolism, suggesting a key area for intervention to reduce T2D risk post-GDM in SAs.

Lipoprotein Insulin Resistance Index: A Simple, Accurate Method for Assessing Insulin Resistance in South Asians.

Identification of insulin resistance (IR) in South Asians, who are at a higher risk for type 2 diabetes, is important. Lack of standardization of insulin assays limits the clinical use of insulin-based surrogate indices. The lipoprotein insulin resistance index (LP-IR), a metabolomic marker, reflects the lipoprotein abnormalities observed in IR. The reliability of the LP-IR index in South Asians is unknown. We evaluated the predictive accuracy of LP-IR compared with other IR surrogate indices in South Asians. In a cross-sectional study (n = 55), we used calibration model analysis to assess the ability of the LP-IR score and other simple surrogate indices (Homeostatic Model Assessment of Insulin Resistance, Quantitative insulin sensitivity check index, Adipose insulin resistance index, and Matsuda Index) to predict insulin sensitivity (SI) derived from the reference frequently sampled intravenous glucose tolerance test. LP-IR index was derived from lipoprotein particle concentrations and sizes measured by nuclear magnetic resonance spectroscopy. Predictive accuracy was determined by root mean squared error (RMSE) of prediction and leave-one-out cross-validation type RMSE of prediction (CVPE). The optimal cut-off of the LP-IR index was determined by the area under the receiver operating characteristic curve (AUROC) and the Youden index. The simple surrogate indices showed moderate correlations with SI (r = 0.53-0.69, P < .0001). CVPE and RMSE were not different in any of the surrogate indices when compared with LP-IR. The AUROC was 0.77 (95% CI 0.64-0.89). The optimal cut-off for IR in South Asians was LP-IR >48 (sensitivity: 75%, specificity: 70%). The LP-IR index is a simple, accurate, and clinically useful test to assess IR in South Asians.

Epidemiology of diabetes among South Asians in the United States: lessons from the MASALA study.

South Asian individuals in the United States are at an increased risk of type 2 diabetes (T2DM); however, the mechanisms behind this are not well understood. The Mediators of Atherosclerosis in South Asians Living in America (MASALA) study is the only longitudinal cohort of South Asians in the United States and provides key insights as to the epidemiology of T2DM in South Asians. Evidence from the MASALA study suggests that South Asians experience a disproportionately high burden of prevalent and incident T2DM compared with members of other race/ethnic groups. Higher insulin resistance in South Asians, even with low body mass index (BMI), more impairment in insulin secretion, and greater deposition of ectopic fat likely play a role in T2DM etiology. Furthermore, South Asian migrants to the United States experience a range of factors related to acculturation, social networks, and religious beliefs, which may impact physical activity and dietary practices. Interventions to prevent T2DM in South Asians should include a focus on cultural factors related to health and should consider the complete mechanistic pathway and the relative contributions of insulin resistance, β cell dysfunction, and ectopic fat deposition on T2DM development in South Asians, particularly in those with lower BMI.

SAT-624 Predictive Ability of Lipoprotein Insulin Resistance (LPIR) Score in South Asians: A Comparison of Surrogate Indices of Insulin Sensitivity/Resistance

South Asians (SA) are at higher risk for developing insulin resistance (IR) and type 2 diabetes. Consequently, identifying IR in this population is important. Lack of standardization and harmonization of insulin assays limit the clinical use of insulin-based surrogate indexes of insulin resistance. The lipoprotein insulin resistance (LPIR) score, a metabolomic marker, reflects the lipoprotein abnormalities observed in insulin-resistant states. The reliability of the LPIR score to predict IR in South Asians is currently unknown. In this study, we aimed to evaluate the predictive accuracy of LPIR compared to other fasting-based surrogate indices in SA.In a cross-sectional study of 59 non-diabetic SA subjects (age 36 ± 8 years, BMI 26.5 ± 5.2 kg/m2), we used calibration model analysis to assess the ability of the LPIR score and other simple surrogate indices [homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and Adipose tissue insulin sensitivity (Adipo-SI)] to predict insulin sensitivity derived from the reference frequently sampled intravenous glucose tolerance test (FSIVGTT) and Minimal Model analysis (SiMM). LPIR scores were calculated using six lipoprotein particle concentrations and sizes measured by nuclear magnetic resonance (NMR) spectroscopy. Further, quantitative predictive accuracy and index comparisons were determined by root mean squared error (RMSE) of prediction and leave-one-out cross-validation-type RMSE of prediction (CVPE). Receiver operating characteristic (ROC) curve analysis was performed to determine how well LPIR distinguished insulin resistant individuals, categorized as an SiMM < 3.As determined by calibration model analysis, Adipo-SI, HOMA-IR, and QUICKI showed moderate correlations with for SiMM (Adipo-SI: r = 0.66; HOMA-IR: r = 0.60; QUICKI: r = 0.57, p = <0.0001). No significant differences were noted among CVPE or RMSE from any of the routinely used surrogate indices when compared with LPIR. The ROC area under the curve was 0.76 (95% CI 0.64–0.87) suggesting that LPIR performed well in identifying insulin resistant subjects. The optimal cut-off in IR individuals was LPIR >46 (sensitivity: 75.9 %, specificity: 70.0%). We conclude that NMR-derived LPIR may be an appropriate index to assess insulin resistance in South Asians.

Abstract 402: Adiponectin Receptor 3 is Associated With Endothelial Nitric Oxide Synthase Dysfunction and Predicts Insulin Resistance in South Asians

Type 2 diabetes (T2DM) is a global epidemic affecting over 400 million people and causes significant morbidity and mortality. T2DM has a strong association with cardiovascular disease (CVD), the number one cause of death globally with 17.5 million deaths per year. A precursor of T2DM, insulin resistance is central to the development of T2DM and is a risk factor for CVD. Insulin resistance is difficult to diagnose and individuals are often untreated prior to the onset of T2DM or CVD. South Asians are more likely to have insulin resistance, diabetes and cardiovascular disease when compared to age matched European cohorts. The molecular mechanisms of why South Asians are predisposed to insulin resistance and consequently cardiovascular disease were investigated using induced pluripotent stem cells (iPSCs) derived endothelial cells (iPSC-EC). Endothelial cells line blood vessels of the cardiovascular system. Unlike previous models, iPSC-EC are unique because they contain the individual's genetic information and the environmental influences retained in epigenetic marks are removed via reprogramming and differentiation. iPSC-ECs from insulin resistant South Asians show evidence of impaired insulin signaling as evidenced by decreased Akt phosphorylation, and paradoxically overexpression of eNOS and adiponectin receptor 3. In the cellular milieu of prediabetes, insulin resistance iPSC-ECs show impaired tubule formation and nitric oxide release. When adiponectin receptor 3 expression is suppressed using siRNA, eNOS expression decreases and expression of components of the insulin signaling cascade are improved to levels observed in control iPSC-ECs. Multiple linear regression modeling of clinical characteristics and gene and cellular phenotype was used to develop a scoring system that predicts a patient’s risk of developing insulin resistance and hence subsequently diabetes and cardiovascular complications. To our knowledge, this is the first iPSC-derived endothelial cell risk calculator with the potential to identify South Asian patients at risk for developing insulin resistance and cardiovascular disease before disease onset, which would allow for the early implementation of interventions that prevent morbidity and mortality.

Association between serum and adipose tissue resistin with dysglycemia in South Asian women

Background/ObjectivesMechanisms of obesity-associated insulin resistance and dysglycemia in South Asians remain relatively unknown. The objective of this study was to detect subcutaneous (SAT) vs. visceral (VAT) adipose tissue characteristics and adipocytokines associated with obesity, insulin resistance, and dysglycemia in South Asian women.Subjects/MethodsThis was a hospital-based cross-sectional study conducted in Sri Lanka. Subjects comprised of 58 adult women who underwent routine abdominal surgeries. SAT and VAT were obtained from anterior abdominal wall and omentum, respectively. Measures of adiposity, serum insulin and glucose, SAT and VAT crown-like structures (CLS), macrophages, resistin by immunohistochemistry, mean adipocyte area (MAA), and serum adipocytokines were examined.ResultsThe homeostatic model assessment for insulin resistance (HOMA-IR) score significantly correlated with age and waist circumference (WC), but not with body mass index (BMI). Although the number of CLS positively correlated with BMI, there were no significant differences between the number of CLS in women with normal fasting glucose (NFG) vs. those with impaired fasting glucose (IFG), indicating that adipose tissue macrophage infiltration is unlikely to be related to dysglycemia. In contrast, serum resistin level was on average 60% higher in women with IFG compared to ones with NFG (p < 0.05). Serum resistin levels correlated with age (r = 0.36, p < 0.05) and WC (r = 0.27, p < 0.05). There were no associations in serum levels of other adipocytokines with IFG. Adipose immunohistochemistry showed that women with IFG had a higher percentage of resistin positive adipocytes in SAT compared to ones with NFG. MAA of VAT, but not SAT, correlated with both BMI and WC.ConclusionsResistin may be an important adipokine linking central adiposity and insulin resistance in South Asian women. Both systemic and adipose tissue resistin are linked to dysglycemia in these individuals and may be a potential biomarker for diabetes in this population.

Abstract #241: High Prevalence of Diabetes, Prediabetes and Insulin Resistance in South Asians: Implications for Public Health Prevention Based on a Novel Community Registry

Abstract #241: High Prevalence of Diabetes, Prediabetes and Insulin Resistance in South Asians: Implications for Public Health Prevention Based on a Novel Community Registry

Abstract 410: Link Between Hypertension and Insulin Resistance in South Asians: Implications for Prevention of Cardiovascular Complications

Background: The coexistence of hypertension (HTN) and insulin resistance (IR) substantially increases cardiovascular risk (CVR) and diabetes (DM) perhaps by endothelial dysfunction from low-grade chronic inflammation and oxidative stress. South Asian immigrants in United States (SA-USA) have a high salt consumption, IR, and salt sensitivity. The triglyceride (TG)/ HDL ratio is a known correlate of IR with ratios ≥3.5 associated with high risk. It is unknown whether SA-USA have a coexistence of HTN, IR, and DM resulting in high CVR. Methods: We reviewed the clinical history and Vertical Auto Profile technology (VAP) + lipid panel utilizing ultracentrifugation to directly measure lipid sub-fractions, for 348 participants (42% women) of the South Asian Cardiovascular Registry. Prevalent DM and Pre-DM were defined as HbA1c ≥ 6.5 and 5.7-6.4, respectively. Results: Of the 348 participants, mean age 55.3 years, 128 had HTN and were stratified into clinical risk groups based on fasting TG (mg/dL) levels: TG&lt;150 (n=69), TG 150-199 (n=24), TG 200-499 (n=32), TG&gt;500 (n=3). The corresponding TG/HDL ratios were: 1.7, 3.5, 6.2, and 20.4, respectively; the median TG (mg/dL) levels were: 100, 182, 268, and 572, respectively; the median LDL (mg/dL) levels were: 113, 144, 133, 102, respectively; the rates of DM were: 13%, 17%, 38%, and 67%; and the rates of Pre-DM/DM were: 62%, 63%, 78%, and 67%, respectively. Relative Risk for DM with TG/HDL≥ 3.5 was 3.6 (46 % had TG/HDL ≥ 3.5). Conclusions: South Asian immigrants participating in a community registry have: 1) A high rate of coexistence of HTN and IR portending a very high relative risk of diabetes. 2) A discordance of LDL levels and IR in patients with HTN. As IR gets higher, the relative risk of diabetes goes up but LDL levels decline. Clinical Implications: South Asian immigrants in the United States have a diet that is very high in salt, simple carbohydrates, and saturated fat. Many are vegetarian with no consumption of fish. Public health efforts to help reduce risk of CVD in South Asian immigrants should focus on low salt diet, with consumption of multigrain complex carbohydrates, poly-unsaturated fatty acids, omega-3 fatty acids, and lifestyle changes to reduce metabolic syndrome, diabetes, and hypertension.

Ethnic Differences in the Role of Adipocytokines Linking Abdominal Adiposity and Insulin Sensitivity Among Asians.

Among Asian ethnic groups, Chinese or Malays are more insulin sensitive than South Asians, in particular in lean individuals. We have further reported that body fat partitioning did not explain this ethnic difference in insulin sensitivity. We examined whether adipocytokines might explain the ethnic differences in the relationship between obesity and insulin resistance among the three major ethnic groups in Singapore. This was a cross-sectional study of 101 Chinese, 82 Malays, and 81 South Asian men. Insulin sensitivity index (ISI) was measured using hyperinsulinemic euglycemic clamp. Visceral (VAT) and subcutaneous adipose tissue (SAT) volumes were quantified using magnetic resonance imaging. Plasma total and high-molecular-weight adiponectin, leptin, visfatin, apelin, IL-6, fibroblast growth factor 21 (FGF21), retinol binding protein-4 (RBP 4), and resistin were measured using enzyme-linked immunoassays. Principle component (PC) analysis on the adipocytokines identified three PCs, which explained 49.5% of the total variance. Adiponectin loaded negatively, and leptin and FGF21 loaded positively onto PC1. Visfatin, resistin, and apelin all loaded positively onto PC2. IL-6 loaded positively and RBP-4 negatively onto PC3. Only PC1 was negatively associated with ISI in all ethnic groups. In the path analysis, SAT and VAT were negatively associated with ISI in Chinese and Malays without significant mediatory role of PC1. In South Asians, the relationship between VAT and ISI was mediated partly through PC1, whereas the relationship between SAT and ISI was mediated mainly through PC1. The relationships between abdominal obesity, adipocytokines and insulin sensitivity differ between ethnic groups. Adiponectin, leptin, and FGF21 play a mediating role in the relationship between abdominal adiposity and insulin resistance in South Asians, but not in Malays or Chinese.

Anthropometric Measures and Insulin Resistance in Rural Indian Adolescents

Aims: To evaluate the relationship of anthropometric measures with insulin resistance (IR) in 1162 Indian adolescents from the follow-up survey of the Hyderabad Nutrition trial. Methods: Analysis was done on data collected from 1162 adolescent participants of the Hyderabad Nutrition trial follow up survey. Participation included an interview, physical examinations and blood draws. Associations of body mass index (BMI), fat mass index (FMI), fat free mass index (FFMI), central to peripheral skinfold ratio (CPR), percent of body fat, waist circumference (WC) and waist-hip ratio (WHR) with IR were studied using linear regression models accounting for village clustering and adjusting for age and pubertal stage. Anthropometric indices were calculated from height, weight, skinfold thickness, waist and hip circumferences and IR was calculated by the homoeostasis model assessment (HOMA). Results: We observed strong associations of BMI, FMI and FFMI with HOMA. Interestingly, FFMI (β (95% confidence interval) -0.03 (0.01, 0.06); P=0.007 (girls) and 0.06 (0.03, 0.09); P<0.0001 (boys)) was as strongly associated with IR as BMI (0.03 (0.01, 0.06); P=0.006 (girls) and 0.06 (0.03, 0.09); P<0.0001(boys)) and FMI (0.03 (0.01, 0.05); P=0.02 (girls) and 0.05 (0.02, 0.07); P=0.001 (boys)) We explored the relationship of lean mass with IR relative to fat mass and the associations remained strong. Conclusions: We conclude that lean mass is as strongly associated with IR as fat mass in rural Indian adolescents. These findings appear contrary to the belief that higher rates of IR in South Asians reflect greater central adiposity. Future research needs to increase our understanding of the underlying mechanisms that lead to these associations in both obese and lean populations.

Insulin Resistance and Body Fat Distribution in South Asian Men Compared to Caucasian Men

ObjectiveSouth Asians are susceptible to insulin resistance even without obesity. We examined the characteristics of body fat content, distribution and function in South Asian men and their relationships to insulin resistance compared to Caucasians.Research Design and MethodsTwenty-nine South Asian and 18 Caucasian non-diabetic men (age 27±3 and 27±3 years, respectively) underwent euglycemic-hyperinsulinemic clamp for insulin sensitivity, underwater weighing for total body fat, MRI of entire abdomen for intraperitoneal (IP) and subcutaneous abdominal (SA) fat and biopsy of SA fat for adipocyte size.ResultsCompared to Caucasians, in spite of similar BMI, South Asians had higher total body fat (22±6 and 15±4% of body weight; p-value<0.0001), higher SA fat (3.5±1.9 and 2.2±1.3 kg, respectively; p-value = 0.004), but no differences in IP fat (1.0±0.5 and 1.0±0.7 kg, respectively; p-value = 0.4). SA adipocyte cell size was significantly higher in South Asians (3491±1393 and 1648±864 µm2; p-value = 0.0001) and was inversely correlated with both glucose disposal rate (r-value = −0.57; p-value = 0.0008) and plasma adiponectin concentrations (r-value = −0.71; p-value<0.0001). Adipocyte size differences persisted even when SA was matched between South Asians and Caucasians.ConclusionsInsulin resistance in young South Asian men can be observed even without increase in IP fat mass and is related to large SA adipocytes size. Hence ethnic excess in insulin resistance in South Asians appears to be related more to excess truncal fat and dysfunctional adipose tissue than to excess visceral fat.

South Asians and Cardiovascular Risk

Case presentation: A 36-year-old nonsmoking, normotensive South Asian man presented to the emergency department of a community hospital with retrosternal chest pain of &60 minutes’ duration. His 12-lead ECG demonstrated 10 mm of ST-segment elevation in leads V2 through V6, and he received fibrinolytic therapy within 90 minutes of symptom onset. His pain resolved, but his ST segments only partially normalized; he had a peak creatine kinase of 4564 IU/L, and he showed signs of early heart failure. LDL cholesterol was 135 mg/dL, HDL 32 mg/dL, triglycerides 20 mg/dL, and total cholesterol 206 mg/dL; his body mass index (BMI) was 24 kg/m2. Cardiac catheterization demonstrated severe and diffuse triple-vessel disease, including occlusion of the proximal left anterior descending artery, as well as moderate left ventricular dysfunction. While in the hospital, he was diagnosed with new-onset type 2 diabetes mellitus and subsequently underwent uncomplicated coronary bypass surgery. South Asians are individuals whose ethnic roots originate from the Indian subcontinent, a large geographic area that includes India, Pakistan, Sri Lanka, Nepal, and Bangladesh. Collectively, South Asians represent one fifth of the global population. In North America, more than 2 million South Asians reside in the United States and almost 1 million in Canada. It is important to recognize that the term “South Asian” refers to a heterogeneous population, with important differences in diet, culture, and lifestyle among different South Asian populations and religions. Multiple studies of migrant South Asian populations have, however, confirmed a 3- to 5-fold increase in the risk for myocardial infarction and cardiovascular death as compared with other ethnic groups.1–3 In an analysis of age-standardized coronary heart disease (CHD) mortality in Canada over a 15-year period, South Asians had the highest CHD mortality compared with individuals of Chinese and European descent.4 In …