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OBJECTIVE: South Asians are diagnosed with type 2 diabetes (T2D) more than a decade earlier in life than seen in European populations. We hypothesized that studying the genomics of age of diagnosis in these populations may give insight into the earlier age diagnosis of T2D among individuals of South Asian descent. RESEARCH DESIGN AND METHODS: We conducted a meta-analysis of genome-wide association studies (GWAS) of age at diagnosis of T2D in 34,001 individuals from four independent cohorts of European and South Asian Indians. RESULTS: We identified two signals near the TCF7L2 and CDKAL1 genes associated with age at the onset of T2D. The strongest genome-wide significant variants at chromosome 10q25.3 in TCF7L2 (rs7903146; P = 2.4 × 10−12, β = −0.436; SE 0.02) and chromosome 6p22.3 in CDKAL1 (rs9368219; P = 2.29 × 10−8; β = −0.053; SE 0.01) were directionally consistent across ethnic groups and present at similar frequencies; however, both loci harbored additional independent signals that were only present in the South Indian cohorts. A genome-wide signal was also obtained at chromosome 10q26.12 in WDR11 (rs3011366; P = 3.255 × 10−8; β = 1.44; SE 0.25), specifically in the South Indian cohorts. Heritability estimates for the age at diagnosis were much stronger in South Indians than Europeans, and a polygenic risk score constructed based on South Indian GWAS explained ∼2% trait variance. CONCLUSIONS: Our findings provide a better understanding of ethnic differences in the age at diagnosis and indicate the potential importance of ethnic differences in the genetic architecture underpinning T2D. [ABSTRACT FROM AUTHOR]

Objective: Diabetes increases the risk of premature mortality and considerably impacts on work productivity. We sought to examine the impact of diabetes in India, in terms of excess premature mortality, years of life lost (YLL), productivity-adjusted life years (PALYs) lost, and its associated economic impact.Research Design and Methods: A life table model was constructed to examine the productivity of the Indian working-age population currently aged 20-59 years with diabetes, followed until death or retirement age (60 years). The same cohort was resimulated, hypothetically assuming that they did not have diabetes. The total difference between the two cohorts, in terms of excess deaths, YLL and PALYs lost reflected the impact of diabetes. Data regarding the prevalence of diabetes, mortality, labor force dropouts, and productivity loss attributable to diabetes were derived from published sources.Results: In 2017, an estimated 54.4 million (7.6%) people of working-age in India had diabetes. With simulated follow-up until death or retirement age, diabetes was predicted to cause 8.5 million excess deaths (62.7% of all deaths), 42.7 million YLL (7.4% of total estimated years of life lived), and 89.0 million PALYs lost (23.3% of total estimated PALYs), equating to an estimated Indian rupee 176.6 trillion (U.S. dollars 2.6 trillion; purchasing power parity 9.8 trillion) in lost gross domestic product.Conclusions: Our study demonstrates the impact of diabetes on productivity loss and highlights the importance of health strategies aimed at the prevention of diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE There are few data on the incidence rates of diabetes and prediabetes (dysglycemia) in Asian Indians. This article presents the incidence of diabetes and prediabetes and the predictors of progression in a population-based Asian Indian cohort. RESEARCH DESIGN AND METHODS Data on progression to diabetes and prediabetes from 1,376 individuals, a subset of 2,207 of the Chennai Urban Rural Epidemiology Study (CURES) cohort (phase 3) with normal glucose tolerance (NGT) or prediabetes at baseline, who were followed for a median of 9.1 years (11,629 person-years), are presented. During follow-up, 534 died and 1,077 with NGT and 299 with prediabetes at baseline were reinvestigated in a 10-year follow-up study. Diabetes and prediabetes were diagnosed based on the American Diabetes Association criteria. Incidence rates were calculated and predictors of progression to prediabetes and/or diabetes were estimated using the Cox proportional hazards model. RESULTS The incidence rates of diabetes, prediabetes, and "any dysglycemia" were 22.2, 29.5, and 51.7 per 1,000 person-years, respectively. Among those with NGT, 19.4% converted to diabetes and 25.7% to prediabetes, giving an overall conversion rate to dysglycemia of 45.1%. Among those with prediabetes, 58.9% converted to diabetes. Predictors of progression to dysglycemia were advancing age, family history of diabetes, 2-h plasma glucose, glycated hemoglobin (HbA1c), low HDL cholesterol, and physical inactivity. CONCLUSIONS Asian Indians have one of the highest incidence rates of diabetes, with rapid conversion from normoglycemia to dysglycemia. Public health interventions should target modifiable risk factors to slow down the diabetes epidemic in this population. [ABSTRACT FROM AUTHOR]

OBJECTIVE Objectives of this ancillary analysis of a prospective, prevention study among Asian Indians with impaired glucose tolerance (IGT) were a) to quantify the reduction in incident diabetes at 24 months in participants who achieved normal glucose tolerance (NGT) at 6 months (NGT-6 m) compared with the other participants, b) the factors influencing the reversal to NGT at the end of the study at 24months (NGT-24 m), and c) to assess changes in cardiometabolic risk factors in different categories of dysglycemia at 24 months. RESEARCH DESIGN AND METHODS Data from a 2-year primary prevention trial were used. Effect of reversion to NGT-6 m on incidence of type 2 diabetes mellitus (T2DM) was analyzed using the Cox proportional hazards model. Predictive variables for reversal to NGT were identified using multiple logistic regression analysis. Changes in cardiometabolic risk factors were estimated according to the final glycemic status using fixed-effect, mixed-linear regression modeling. RESULTS The risk of T2DMin 2 years was lower by 75% in NGT-6 m group (hazard ratio 0.25 [95% CI 0.12-0.52]). Predictive variables for reversal to NGT-24 m were good baseline β-cell function (odds ratio [OR] 2.79 [95% CI 2.30-3.40]) and its further improvement (OR 5.70 [95% CI 4.58-7.08]), and NGT-6 m (OR 2.10 [95% CI 1.14-3.83]). BMI decreased in those who reverted to NGT. Deterioration to T2DM was associated with an increase in the levels of cardiometabolic risk factors. CONCLUSIONS Early reversion to NGT by lifestyle intervention in prediabetic men was associated with a significant reduction in subsequent incidence of diabetes. Good baseline β-cell function and its further improvement and NGT-6 m were associated with reversion to NGT-24 months. Reversion to NGT was associated with modest improvements, whereas conversion to T2DM was associated with significant worsening of the cardiometabolic risk profile. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To examine bβ-cell function across a spectrum of glycemia among Asian Indians, a population experiencing type 2 diabetes development at young ages despite low BMI. RESEARCH DESIGN AND METHODS--One-thousand two-hundred sixty-four individuals without known diabetes in the Diabetes Community Lifestyle Improvement Program in Chennai, India, had a 75-g oral glucose tolerance test, with glucose and insulin measured at 0, 30, and 120 min. Type 2 diabetes, isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT), combined impaired fasting glucose and impaired glucose tolerance, and normal glucose tolerance (NGT) were defined by American Diabetes Association guidelines. Measures included insulin resistance and sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR], modified Matsuda Index, 1/fasting insulin) and bβ-cell function (oral disposition index = [Δinsulin0-30/Δ glucose0-30] x [1/fasting insulin]). RESULTS--Mean age was 44.2 years (SD, 9.3) and BMI 27.4 kg/m² (SD, 3.8); 341 individuals had NGT, 672 had iIFG, IGT, or IFG plus IGT, and 251 had diabetes. Patterns of insulin resistance or sensitivity were similar across glycemic categories. With mild dysglycemia, the absolute differences in age- and sex-adjusted oral disposition index (NGT vs. iIFG, 38%; NGT vs. iIGT, 32%) were greater than the differences in HOMA-IR (NGT vs. iIFG, 25%; NGT vs. iIGT, 23%; each, 0.0001). Compared with NGT and adjusted for age, sex, BMI, waist circumference, and family history, the odds of mild dysglycemia were more significant per SD of oral disposition index (iIFG: odds ratio [OR], 0.36; 95% CI, 0.23-0.55; iIGT: OR, 0.37; 95% CI, 0.24-0.56) than per SD of HOMA-IR (iIFG: OR, 1.69; 95% CI, 1.23-2.33; iIGT: OR, 1.53; 95% CI, 1.11-2.11). CONCLUSIONS--Asian Indians with mild dysglycemia have reduced bβ-cell function, regardless of age, adiposity, insulin sensitivity, or family history. Strategies in diabetes prevention should minimize loss of ββ-cell function. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Risks of diabetes and cardiovascular disease are elevated worldwide in Indian Asians. However, risks of other diabetes-related complications, i.e., foot ulceration and amputation, also with a vascular basis, are substantially lower in Asians than in white Europeans in the U.K., possibly due to less neuropathy. We therefore compared signs, symptoms, and objective quantitative measures of diabetic neuropathy and their risk factors in Indian Asians and Europeans. RESEARCH DESIGN AND METHODS-- This was a cross-sectional study of a population-based sample of age- and sex-matched adults with type 2 diabetes of European (95 male and 85 female) and Asian (96 male and 84 female) descent in the U.K. Patients were assessed for neuropathic symptoms, signs, nerve conduction, autonomic function, and quantitative sensory testing. Peripheral vascular function and other potential risk factors for neuropathy were measured. RESULTS-- Mean nerve conduction velocity Z scores were better in Asians (mean ± SD 0.07 ± 0.62) than in Europeans (-0.11 ± 0.60; P = 0.007) and were explained by the shorter height, fewer pack-years smoked, and higher transcutaneous oxygen levels (TCpO[sub 2]) in Indian Asians (P value for ethnic comparison attenuated to 0.2). Small fiber neuropathy was less prevalent in Indian Asians compared with Europeans (odds ratio 0.58 [95% CI 0.37-0.93]; P = 0.02) and was primarily accounted for by better TCpO[sub 2] (0.70 [0.40-1.21]; P = 0.2). CONCLUSIONS -- Asians with diabetes have substantially less large and small fiber neuropathy than Europeans, despite comparable traditional risk factors. Independent from smoking, the lower risk of neuropathy in Asians is due to better skin microvascularization and may help explain the substantially reduced Asian foot ulcer risk. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To determine A1C cut points for glucose intolerance in Asian Indians. RESEARCH DESIGN AND METHODS -- A total of 2,188 participants without known diabetes were randomly selected from the Chennai Urban Rural Epidemiology Study. All had fasting plasma glucose (FPG) and 2-h postload plasma glucose measurements after a 75-g load and were classified as having impaired fasting glucose (IFG) (American Diabetes Association [ADA] criteria, FPG ≥ 5.5 and <7 mmol/l, and World Health Organization [WHO] criteria, FPG ge;6.1 and <7 mmol/l), impaired glucose tolerance (IGT) (2-h postload plasma glucose ≥7.8 and < 11.1 mmol/l), or diabetes (FPG ≥7 mmol/l and/or 2-h postload plasma glucose ≥11.1 mmol/ l). A1C was measured using the Bio-Rad Variant machine. Based on receiver operating characteristic curves, optimum sensitivity and specificity were derived for defining A1C cut points for diabetes, IGT, and IFG. RESULTS-- Mean ± SD values of A1C among subjects with normal glucose tolerance, IGT, and diabetes were 5.5 ± 0.4, 5.9 ± 0.6, and 8.3 ± 2.0%, respectively (P[sub trend] < 0.001) with considerable overlap. To identify diabetes based on 2-h postload plasma glucose, the A1C cut point of 6.1% had an area under the curve (AUC) of 0.941 with 88.0% sensitivity and 87.9% specificity. When diabetes was defined as FPG ≥7.0 mmol/l, the A1C cut point was 6.4% (AUC = 0.966, sensitivity 93.3%, and specificity 92.3%). For IGT, AUC = 0.708; for IFG, AUC = 0.632 (WHO criteria) and 0.708 (ADA criteria), and the AIC cut point was 5.6%. CONCLUSIONS -- In Asian Indians, A1C cut points of 6.1 and 6.4% defined diabetes by 2-h postload plasma glucose or FPG criteria, respectively. A value of 5.6% optimally identified IGT or IFG but was <70% accurate. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- The objectives of this study were to determine age- and sex-specific concentrations of adiponectin in Asian Indian teenagers and adults and to assess whether its blood levels correlated with insulin resistance and other cardiometabolic parameters. RESEARCH DESIGN AND METHODS-- We studied 196 teenagers (94 boys, 102 girls) 12-18 years of age, selected from a cohort of 2,640 individuals from a cross-sectional school-based survey in Chennai, India. For comparison, adiponectin and plasma insulin were measured in 84 healthy adults. Correlation of adiponectin with plasma levels of insulin, proinsulin, insulin resistance, anthropometry, and family history of diabetes were studied. RESULTS-- Adiponectin showed a sex dimorphism, with girls having higher values (in micro;g/ml) (10.3 ± 5.0) than boys (8.4 ± 3.5) (P < 0.0001), and it showed a positive correlation with HDL cholesterol in boys only and not with other lipid parameters, insulin resistance, proinsulin, anthropometry, and family history of diabetes. In the adults, adiponectin correlated with fasting glucose and inversely with triglycerides. CONCLUSIONS-- In Asian Indian adults and teenagers, adiponectin did not correlate directly with measures of insulin sensitivity, overweight, and other cardiometabolic variables. This was at variance with several reports in other populations showing an inverse association of adiponectin with insulin resistance, proinsulin, and BMI, suggesting ethnic differences in the relationship of adiponectin with insulin sensitivity. The role of adiponectin in relation to action of insulin needs more detailed studies in Asian Indians. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To evaluate the effect of supervised progressive resistance-exercise training (PRT) protocol on insulin sensitivity, glycemia (blood glucose and A1C levels), lipids, and body composition in Asian Indians with type 2 diabetes. RESEARCH DESIGN AND METHODS -- Thirty patients with type 2 diabetes underwent 12 weeks of PRT of six muscle groups (two sets, 10 repetitions each). The subjects were evaluated with detailed anthropometry and with measurements of the disappearance of glucose per unit time (K) during the short insulin tolerance test (K[sub ITT]) for assessment of insulin sensitivity; of fasting blood glucose, A1C, lipids, and high-sensitivity C-reactive protein (hsCRP); of total body fat, regional fat, and lean body mass by dual-energy X-ray absorptiometry; and of cross-sectional skeletal muscle area of upper arm and thigh by computed tomography scan. RESULTS -- Insulin sensitivity improved significantly from mean ± SD K[sub ITT] 1.22 ± 0.73 to 2.13 ± 0.75 (P < 0.0001) after the intervention. Significant decline (mean difference ± SD) from baseline was recorded in levels of the following parameters: A1C (0.54 ± 0.4% P < 0.001), fasting blood glucose (2.7 ± 2.2 mmol/l, P < 0.001), total cholesterol (0.39 ± 0.7 mmol/l, P = 0.003), serum triglycerides (0.39 ± 0.5 mmol/l, P < 0.001), and truncal and peripheral subcutaneous adipose tissue compartments (SCAT) (P < 0.001). However, no significant changes were noticed in BMI or levels of total body fat, truncal fat, lean body mass, cross-sectional skeletal muscle area of the extremities, or hsCRP levels. CONCLUSIONS -- Moderate-intensity PRT for 3 months resulted in significant improvement in insulin sensitivity, glycemia, lipids, and truncal and peripheral SCAT in patients with type 2 diabetes. Resistance training should be an integral part of exercise regimen in Asian Indians with type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Type 2 diabetes has become a global epidemic, and Asian Indians have a higher susceptibility to diabetes than Europeans. We investigated whether Indians had any metabolic differences compared with Northern European Americans that may render them more susceptible to diabetes. RESEARCH DESIGN AND METHODS--We studied 13 diabetic Indians, 13 nondiabetic Indians, and 13 nondiabetic Northern European Americans who were matched for age, BMI, and sex. The primary comparisons were insulin sensitivity by hyper-insulinemic-euglycemic clamp and skeletal muscle mitochondrial capacity for Oxidative phosphorylation (OXPHOS) by measuring mitochondrial DNA copy number (mtDNA), OXPHOS gene transcripts, citrate synthase activity, and maximal mitochondrial ATP production rate (MAPR). Other factors that may cause insulin resistance were also measured. RESULTS--The glucose infusion rates required to maintain identical glucose levels during the similar insulin infusion rates were substantially lower in diabetic Indians than in the nondiabetic participants (P < 0.001), and they were lower in nondiabetic Indians than in nondiabetic Northern European Americans (P < 0.002). mtDNA (P < 0.02), OXPHOS gene transcripts (P < 0.01), citrate synthase, and MAPR (P < 0.03) were higher in Indians irrespective of their diabetic status. Intramuscular triglyceride, C-reactive protein, interleukin-6, and tumor necrosis factor-α concentrations were higher, whereas adiponectin concentrations were lower in diabetic Indians. CONCLUSIONS--Despite being more insulin resistant, diabetic Indians had similar muscle OXPHOS capacity as nondiabetic Indians, demonstrating that diabetes per se does not cause mitochondrial dysfunction. Indians irrespective of their diabetic status had higher OXPHOS capacity than Northern European Americans, although Indians were substantially more insulin resistant, indicating a dissociation between mitochondrial dysfunction and insulin resistance. Diabetes 57:1166-1175, 2008 [ABSTRACT FROM AUTHOR]

OBJECTIVE -- In the Indian Diabetes Prevention Programme (IDPP), a 3-year randomized, controlled trial, lifestyle modification (LSM) and metformin helped to prevent type 2 diabetes in subjects with impaired glucose tolerance (IGT). The direct medical costs and cost-effectiveness of the interventions relative to the control group are reported here. RESEARCH DESIGN AND METHODS -- Relative effectiveness and costs of interventions (LSM, metformin, and LSM and metformin) in the IDPP were estimated from the health care system perspective. Costs of intervention considered were only the direct medical costs. Direct nonmedical, indirect, and research costs were excluded. The cost-effectiveness of interventions was measured as the amount spent to prevent one case of diabetes within the 3-year trial period. RESULTS -- The direct medical cost to identify one subject with IGT was Indian rupees (INR) 5,278 ($117). Direct medical costs of interventions over the 3-year trial period were INR 2,739 ($61) per subject in the control group, INR 10,136 ($225) with LSM, INR 9,881 ($220) with metformin, and INR 12,144 ($270) with LSM and metformin. The number of individuals needed to treat to prevent a case of diabetes was 6.4 with LSM, 6.9 with metformin, and 6.5 with LSM and metformin. Cost-effectiveness to prevent one case of diabetes with LSM was INR 47,341 ($1,052), with metformin INR 49,280 ($1,095), and with LSM and metformin INR 61,133 ($1,359). CONCLUSIONS -- Both LSM and metformin were cost-effective interventions for preventing diabetes among high risk-individuals in India and perhaps may be useful in other developing countries as well. The long-term cost-effectiveness of the interventions needs to be assessed. [ABSTRACT FROM AUTHOR]

OBJECTIVE-- This study examines the association of A1C with cardiovascular disease (CVD) risk factors, coronary artery disease (CAD), and metabolic syndrome in Asian Indians with normal glucose tolerance (NGT). RESEARCH DESIGN AND METHODS -- This cross-sectional study recruited subjects from phase III of the Chennai Urban Rural Epidemiology Study (CURES), an epidemiological study in a representative population of Chennai (formerly Madras) in South India, conducted between January 2003 and June 2004. Included were 1,644 subjects with NGT, i.e., fasting plasma glucose <100 mg/dl (5.6 mmol/l) and 2-h postload plasma glucose <140 mg/dl (7.8 mmol/l). A1C was measured using the Biorad Variant machine. Metabolic syndrome was defined based on modified Adult Treatment Panel III guidelines. RESULTS -- The mean ± SD A1C value in the study cohort was 5.5 ± 0.4%. A1C showed a significant association with BMI (β = 0.017, P < 0.001), systolic (β = 0.002, P = 0.028) and diastolic (β = 0.202, P = 0.017) blood pressure, waist circumference (β = 0.007, P < 0.001), serum cholesterol (β = 0.002, P < 0.001), triglycerides (β = 0.001, P < 0.001), LDL cholesterol (β = 0.002, P < 0.001), fasting insulin (β = 0.009, P < 0.001), and homeostasis model assessment of insulin resistance (β = 0.047, P < 0.001) after adjusting for age and sex. Regression analysis showed that A1C had a strong association with metabolic syndrome that persisted after adjusting for age and sex (odds ratio [OR] 2.9 [95% CI 2.08-4.00]; P < 0.001). A1C also had a strong association with CAD (2.6 [1.23-5.63]; P = 0.01), but the significance was lost when adjusted for age and sex. CONCLUSIONS -- There is a strong association of A1C with prevalent CVD risk factors in Asian-Indian subjects with NGT. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- The risk of diabetes and coronary heart disease is high in Asian Indians. In this study, we aim to assess 1) the prevalence of hyperglycemia in incident acute coronary syndrome (ACS), 2) the effect of glycemia on the outcome, and 3) the association of plasma levels of insulin and proinsulin with ACS. RESEARCH DESIGN AND METHODS -- A total of 146 nondiabetic subjects (121 men, 25 women) with ACS admitted to two hospitals in 1 year were enrolled. Random blood glucose at admission and a standard oral glucose tolerance test within 3 days were done. Glucose tolerance was categorized as normal glucose tolerance, impaired glucose tolerance (IGT) or impaired fasting glucose, and diabetes. Diabetes was arbitrarily classified further as undiagnosed (HbA1c [A1C] >6.0%) or possibly stress diabetes (A1C <6.0%). Subjects not on antidiabetic treatment were reassessed with a glucose tolerance test between 1 and 2 months. Fasting plasma specific insulin, proinsulin, their molar ratios, and insulin resistance (homeostasis model assessment) were estimated at baseline. RESULTS -- Mean age of the cohort was 55 ± 10.6 (SD) years. At baseline, 24 (16.4%) had normal glucose tolerance, 67 (45.9%) had IGT or impaired fasting glucose, and 55 (37%) had diabetes (35 [24%] were undiagnosed and 20 [13.7%] had stress diabetes). At follow-up, 53 of 92 responders (57.6%) continued to have IGT or diabetes. Mean baseline plasma insulin, pro-insulin and its ratios, and insulin resistance were higher than normal in all subgroups. CONCLUSIONS -- Nondiabetic Asian Indians showed a high prevalence of hyperglycemia following ACS. ACS was associated with insulin resistance and increased levels of specific insulin, proinsulin, and high proinsulin-to-insulin ratios. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Among Europeans, mutations in the hepatocyte nuclear factor-1α (HNF1α) gene are associated with the most common form of maturity-onset diabetes of the young (MODY)3. In Asian Indians, type 2 diabetes occurs earlier and often overlaps with MODY, but the genetics of the latter are unknown. The aim of this study was to estimate the prevalence of Ala98Val polymorphism of the: HNF1α gene in different types of diabetes in Asian Indians. RESEARCH DESIGN AND METHODS -- Genotyping of Ala98Val was done by the PCR-restriction fragment-length polymorphism method in the following groups: 1) MODY, defined as non-insulin-dependent diabetes (age at onset <25 years) and vertical transmission of diabetes through at least three generations (n = 122); 2) very-early-onset type 2 diabetes (age at onset <25 years) without family history (n = 23); 3) early-onset type 2 diabetes (age at onset between 26 and 40 years, n = 171); 4) late-onset type 2 diabetes (age at onset >40 years, n = 133); 5) type 1 diabetes (n = 130); and 6) normal glucose tolerance (n = 130). The frequency of the Val genotypes was compared in the diabetic and control groups. RESULTS -- The frequency of the Val allele was significantly higher in MODY patients (P = 0.0013) compared with control groups. Furthermore, in the total group of patients with type 2-like diabetes (groups 1-4), the Val allele was associated with an earlier diagnosis of diabetes (P = 0.0002). CONCLUSIONS -- Among Asian Indians, the Ala98Val polymorphism of HNF1α gene is associated with MODY and with earlier age at onset of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Asian Indians have a high risk of developing glucose intolerance with small increments in their BMI. They generally have high upper-body adiposity, despite having a lean BMI. Therefore, this analysis was performed to find out the normal cutoff values for BMI and upper-body adiposity (waist circumference [WC] or waist-to-hip ratio [WHR]) by computing their risk associations with diabetes.Research Design and Methods: The risk of diabetes with stratified BMI, WC, or WHR was computed in 10,025 adults aged > or =20 years without a history of diabetes, and they were tested by oral glucose tolerance tests, using World Health Organization criteria. The calculations were performed separately in men and women using diabetes as the dependent variable versus normoglycemia (normal glucose tolerance) in multiple logistic regression analyses. Age-adjusted and stratified BMI, WC, or WHR were used as the independent variables, using the first stratum as the reference category. The upper limit of the stratum above which the risk association became statistically significant (P < 0.05) was considered to be the cutoff for normal values.Results: Normal cutoff values for BMI was 23 kg/m(2) for both sexes. Cutoff values for WC were 85 and 80 cm for men and women, respectively; the corresponding WHRs were 0.88 and 0.81, respectively. Optimum sensitivity and specificity obtained from the receiver operator characteristic curve corresponded to these cutoff values.Conclusions: The cutoff value for normal BMI for men and women was 23 kg/m(2). The cutoff values for WC and WHR were lower in women than in men. The values were significantly lower compared with the corresponding values in white populations. [ABSTRACT FROM AUTHOR]

Presents information on several regarding primary prevention of type 2 diabetes to be discussed at the 65th Scientific Sessions of the American Diabetes Association at the San Diego Convention Center in California from June 10 to 14, 2005. Contribution of psychological risk factors to glucose metabolism in children; Effectiveness of lifestyle modification in preventing diabetes in non-obese Asian Indian prediabetic subjects; Prediction rule for incident type 2 diabetes in Framingham Offspring.

Examines the ethnic and regional food practices of the U.S. population. Nutrition considerations for African Americans; Health issues being faced by Asian Indian immigrant population in the U.S.; Actions that should be taken by health care teams when working with Mexican-American patients

A letter to the editor is presented in response to a study by R. M. Anjana and colleagues regarding predictors of diabetes and prediabetes progression among Asian Indians, which appeared within the issue.

A letter to the editor is presented in response to the article "Comment on Anjana et al. Incidence of diabetes and prediabetes and predictors of progression among Asian Indians:10-year follow-up of the Chennai Urban Rural Epidemiology Study (CURES)" by D. Dutta and S. Mukhopadhyay in a 2015 issue.

A letter to the editor is presented in response to the article "Incidence of diabetes and prediabetes and predictors of progression among Asian Indians: 10-year follow-up of the Chennai Urban Rural Epidemiology Study (CURES)" by Anjana R.M. and colleagues in a 2015 issue.

Asian Indians are highly susceptible to Type 2 Diabetes (T2D) and constitute the largest diabetic population in the world. The underlying etiology for this increased susceptibility for T2D among Asian Indians remains to be defined. To determine whether Asian Indians are more insulin resistant and whether their insulin resistance is associated with any differences in muscle gene transcript levels, we studied 13 non-diabetic (fasting glucose < 100 mg/dl) Asian Indians (Age=47.2±2.4 y, BMI=23.8±0.5 kg/m²) and 13 gender-matched Americans of North European origin (European Americans; Age=46.6±2.2 y, BMI=24.5±0.8 kg/m2). Insulin sensitivity was measured by hyperinsulinemic (1.5 mU/kg FFM/min) euglycemic clamp. To maintain identical plasma glucose levels, Asian Indians required a substantially lower glucose infusion rate than European American controls (42.3 ± 4.0 vs. 68.3 ± 4.2 µmol/Kg FFM/min,p<0.001). Percutaneous needle biopsy samples were collected for gene array analysis. Total RNA was extracted from snap frozen muscle biopsy samples, amplified, labeled with fluorescent probe, fragmented and hybridized to the U133 Pins 2.0 Affymetrix genechip and GCRMA software was used to analyze microarray data. Out of about 47,000 transcripts surveyed, 58 genes transcript levels were altered (52 increased and 6 decreased) in Asian Indians compared to European Americans. Examples are as follows: Lipid metabolism: Fatty acid binding protein 7 (↑3.7); Glucose metabolism: GAPDH (↑1.03), Lactate dehydrogenase A (↑1.3); Chaperone: heat shock proteins 70 (↓0.65); and Energy metabolism: NADH1 (↑1.07), ATP synthase (↑1.1), Cytochrome C oxidase Va (↑1.20), Cytochrome C oxidase VLLc (↑1.1). In conclusion, nondiabetic Asian Indians are significantly more insulin resistant and have altered skeletal muscle gene transcript levels involving multiple metabolic pathways including mitochondrial bioenergetics. The results indicate potential mechanisms for higher susceptibility of Asian Indians to become diabetic. [ABSTRACT FROM AUTHOR]

Provides information on several studies about insulin action to be presented at the 65th Scientific Sessions of the American Diabetes Association at the San Diego Convention Center in California from June 10 to 14, 2005. Correlation of low birth weight with adult insulin resistance in Asian Indian children; Effect of high-fat feed to induced insulin resistance on male and female rats; Background on the mechanism of pancreatic islet cell insulin resistance in high-fat-diet obese rats.

Deals with a study which estimated GAD65 antibody in a group of Asian Indian subjects with diagnosis of diabetes made between twenty and forty years of age. Research design and methods; Results; Discussion.

The article discusses a study which examined diabetes prevalence rates and risk factors among three of the largest Asian American subgroups in New York City (NYC). Involved in the study were 2,246 Chinese, 408 Koreans, and 277 Asian Indians. To predict a diabetes diagnosis outcome, the researchers performed logistic regression.

Corrections to articles published in previous issues are presented, including "AIC cut points to define various glucose intolerance groups in Asian Indians" and "Effects of long-term fenobibrate treatment on markers of renal function in type 2 diabetes: the FIELD Helsinski substudy.

Corrections to the articles "Intracellular Angiotensin II Production in Diabetic Rats is Correlated With Cardiomyocyte Apoptosis, Oxidative Stress and Cardiac Fibrosis," by V. P. Singh, B. Le and K. M. Baker and "Asian Indians Have Enhanced Skeletal Muscle Mitochondrial Capacity to Produce ATP in Association With Severe Insulin Resistance," by K. S. Nair, Y. W. Asmann and B. A. Irving is presented.

Asian Indians have high prevalence of diabetes and premature coronary artery disease (CAD). The aim of this study was to determine the association of CAD in Asian Indian type 2 diabetic subjects with normo, micro and macroalbuminuria. Type 2 diabetic subjects [n= 1736], inclusive of self reported diabetic subjects [1382/1529, response rate 90.4%] and randomly selected newly diagnosed diabetic subjects [n=354] were recruited from the Chennai Urban Rural Epidemiology Study [CURES], a population based study in Chennai in Southern India. Microalbuminuria, estimated by immunoturbidimetric assay, was diagnosed if albumin excretion was between 30 - 299 µg/mg of creatinine and macroalbuminuria, if ≥300 µg/mg of creatinine. Coronary artery disease [CAD] was diagnosed based on a past history of documented myocardial infarction and/or electrocardiographic [ECG] evidence of Q wave and/or ST segment changes. Analysis was restricted to 1596 individuals on whom data on albumin excretion and CAD were available [1596/1736, response rate 91.9%]. The overall prevalence of micoalbuminuria was 26.8% [427 / 1596], macroalbuminuria, 5.5% [87/1596] and CAD, 13.0% [208/1596]. Subjects with macroalbuminuria had the highest prevalence of CAD [34.5%], followed by microalbuminuric subjects [14.8%] and normoalbuminuria [10.6%, p for trend: <0.0001]. Univariate regression showed both microalbuminuria [Odds ratio [OR]: 1.46, 95% confidence interval [CI]: 1.05 - 2.02, p<0.001] and macroalbuminuria [OR: 4.46, 95% CI: 2.7 - 7.1, p<0.001] to be significantly associated with CAD. After adjusting for age, glycated hemoglobin, smoking, triglycerides and LDL cholesterol, the association remained significant only for macroalbuminuria [OR:3.73, 95% CI: 2.2 - 6.4, p< 0.001]. In conclusion, there is an association between albumin excretion and CAD in Asian Indian type 2 diabetic subjects and this is stronger in those with macroalbuminuria. [ABSTRACT FROM AUTHOR]

Asian Indians (AI) are insulin resistant and have a higher risk of diabetes compared to Caucasians (C). However, potential abnormalities in insulin secretion and their relationship to the severity of insulin resistance in AI have not been carefully studied. To address this question we examined l) first (0-10 min) and second (l0-120 min) phase insulin secretion during a 2-hr hyperglycemic clamp at +90 mg/dl, 2) insulin secretion in response to a non-glucose secretagogue (arginine, 5 gm IV) at euglycemia and at the end of the hyperglycemic clamp, and 3) insulin sensitivity (M) during a 1 mU/kg⋅min hyperinsulinemic euglycemic clamp. Four healthy AI and 6 C of similar age (29±2 vs 38±6 yrs) and BMI (25.3±2.3 vs 24.7±1.3 kg/msup2;) were studied. AI and C had similar FPG (94±2 vs 90±2. mg/dl), but AI had higher fasting insulin levels (9.1±2.2 vs 3.4±0.6 µU/ml, p<0.05) and were very insulin resistant during the euglycemic clamp (M = 4.0±0.5 vs 9.7±0.6 mg/kg/min, p<0.001). During the hyperglycemic clamp, first phase (321±106 vs 102±22 µU/ml⋅0 min, p<0.05) and second phase (4920±959 vs 1340±174 pU/ml. 110 min, p<0.01) insulin secretion were significantly increased in AI vs C. The insulin responses to arginine at euglycemia (314±43 vs 145±9 µU/ml. l0 min, p<0.01) and hyperglycemia (2399±415 vs 1203±235 #U/ml. 10 min, p<0.05) also were significantly higher in AI. All measures of insulin secretion were inversely correlated with M (r = -0.69 to -0.82, p<0.05 to 0.005). The glucose disposition index (M x first phase insulin secretion) was increased moderately (by 29%), but not significantly, in AI vs C. Conclusion: Non-diabetic AI are characterized by l) marked insulin resistance, 2) enhanced first- and second-phase insulin responses to hyperglycemia, 3) increased insulin response to arginine at euglycemia and hyperglycemia, and 4) a moderate increase in the glucose disposition index. These data suggest that beta cell function remains intact in non-diabetic AI despite the presence of significant insulin resistance. [ABSTRACT FROM AUTHOR]

Transcription factor 7-like2 (TCF7L2) gene has been associated with type 2 diabetes in different ethnic groups. As TCF7L2 gene is involved in regulation of insulin secretion, we hypothesized that TCF7L2 gene variants may be associated with MODY. We examined the role of rs12255372(G/T) and rs7903146(C/T) polymorphisms of TCF7L2 gene in MODY, early-onset type 2 diabetes (EO-T2DM), late-onset type 2 diabetes (LO-T2DM), type 1 diabetes (T1DM) and normal glucose tolerant (NGT) Asian Indians. Subjects were selected from the Chennai Urban Rural Epidemiology Study, a population based study in south India (EO-T2DM, LO-T2DM and NGT) and a tertiary diabetes centre (MODY and TIDM). 136 MODY subjects with autosomal dominant inheritance (age at onset(AAO) <25years), 397 EO-T2DM (AAO:25-40years), 738 LO-T2DM (AAO:>40years), 174 T1DM and 996 NGT subjects were studied. Genotyping of the two polymorphisms was carried out using PCR-RFLP and confirmed by direct sequencing. Frequency of the 'T' allele of rs12255372 and rs7903146 was significantly higher in MODY (30%,p=0.00001 and 45%,p<0.00001 respectively) and EO-T2DM (25%,p=0.0004; 37%,p<0.00001) compared to NGT (19%;28%). Odds ratios (OR) for GT and TT genotypes of the rs12255372 were higher in the MODY (OR:l.53,p=0.032 and 3.77,p=0.00002 respectively) and EO-T2DM (OR:1.48,p=0.002 and 1.75,p=0.034) compared to GG. The OR for CT and TT genotypes of rs7903146 were higher in MODY (OR:2.73,p<0.00001 and 4.10,p<0.00001 respectively) and EO-T2DM (OR: 1.71,p=0.00002 and 1.94,p=0.001) compared to CC. The CT genotype of rs7903146 showed association with LO-T2DM (OR: 1.26,p=0.022 compared to CC) but the TT genotype did not show any association. There was no association of rs12255372 with LO-T2DM and both polymorphisms were not associated with T1DM. Among Asian Indians, rs12255372(G/T) and rs7903146(C/T) polymorphisms of TCF7L2 gene are more strongly associated with MODY and EOT2DM and rs7903146 less strongly with LO-T2DM, while both polymorphisms are not associated with T1DM. [ABSTRACT FROM AUTHOR]

Type 2 diabetes [T2D] and the metabolic syndrome are far more common and presents at a younger age in people of South Asian origin. The aim of the study was to determine the heritability of common traits associated with diabetes in South Indian families and compare them to those obtained in British white Caucasians. 1094 subjects from 296 families were studied from a community-based cross-sectional study in Chennai, India. Clinical details, anthropometric measures and fasting bloods were taken from all available family members. Heritabilities [h²] were calculated for individual waits using SOLAR v4.0.3. corrected for age, sex and BMI. h² [SE] for waist was 0.50 [0.06], WHR 0.33 [0.06], body fat 0.39 [0.07], BMR 0.57 [0.06], systolic (s)BP 0.30 [0.06], triglycerides (tg) 0.53 [0.06] and fasting glucose (FBG) 0.37 [0.06]. All p values were <0.0001. The h² values using a similar model implemented in SOLAR were generally higher than for a healthy white population in the UK (Freeman et al 2002: WHR 0.15 [0.11], sBP 0.14 [0.07], Tg 0.20 [0.08] and FBG 0.20 [0.08]) whereas they were similar apart from FBG to non diabetic relatives of patients with T2D ascertained for the Diabetes UK Warren2 family collection (Mills et al 2004: WHR 0.22 [0.08], sBP 0.30 [0.1], Tg 0.51 [0.1] and FBG 0.81 [0.09]). These studies suggest that risk variables for diabetes which are strongly influenced by lifestyle have an increased genetic component in south Asians compared healthy white Europeans. [ABSTRACT FROM AUTHOR]

We and others in a variety of ethnic groups have previously described associations of various SNPs of the uncoupling protein genes UCP2 and UCP3 (located within 17 kb of each other on chromosome 11q13) with both central fat disposition and BMI. The aim of this study was to do a replication study in South Indian subjects using a family based approach and selecting SNP's by' a priori hypothesis' defined by a previous association with obesity/waits in other studies and/or functional data. Five SNPs were studied; 1 by Ampliflour (UCP2-866 rs659366), 1 by SNAPSHOT (UCP3Y210Y rs2075577), 2 by TaqMan (UCP3-55 rs1800849, UCP2 A55V rs660339) and one by PCR-RFLP (UCP2 exon 8 INDEL) in 882 South Indian participants from 236 families ascertained from community based study of healthy families living in Chennai, India. Statistical analysis was performed using SOLAR and anthropometric variables were corrected for age and sex. The QTLD analysis showed the BMI was associated to the UCP3 rs1800849 (AA 23.9±0.29, AB 23.5±0.32, BB 23.0±0.5, p=0.027) and UCP3 rs2075577 (AA 24.6±0.37, AB 24.0±0.30, BB 23.4±0.39, p=0.022). Waist circumference to the UCP2 rs660339 (AA 84.3±0A8, AB 85.1±0.41, BB 85.9±0.65, p=0.028). Body fat percentage to UCP2 rs660339 (AA 22.9±0.31, AB 23.2±0.27, BB 23.5±0.42, p=0.048) and UCP2 rs659366 (AA 22.7±0.31, AB 22.9±0.26, BB 23.27±0.41, p=0.076). This detailed analysis confirms associations between anthropometric traits and the UCP2/UCP3 locus but that separate SNPs are associated with either BMI or fat distribution. [ABSTRACT FROM AUTHOR]

Asian Indians particularly those with type 2 diabetes have accelerated atherosclerosis at younger age. The aim of the present study was to assess the association of hsCRP, TNF-α with carotid IMT in individuals with different grades of glucose intolerance among Asian Indians. Three groups were randomly recruited from the Chennai Urban Rural Epidemiology Study [CURES], a population based study in Chennai in South India, Group 1: normal glucose tolerance (NGT) (n=150); Group 2: impaired glucose tolerance (IGT) (n=150) and Group 3: type 2 diabetes (DM) (n = 150). hs-CRP [Nephelometry, DadeBehring], TNF-α [enzyme linked immunosorbent assay] and carotid IMT [high resolution B-mode ultrasonography] were assessed. Subjects with diabetes had higher IMT values [0.85 ± 0.30 mm] compared to IGT [0.79 ± 0.16 mm; p<0.05] and NGT subjects [0.71 ± 0.12 mm; p<0.001]. HsCRP levels were higher in those with DM and IGT [DM: 2.8 mg/L, IGT: 2.1 mg/L] compared to NGT [1.2 mg/L, p for trend 0.003]. TNF-α levels were also higher in IGT and DM groups compared to NGT subjects [NGT: 3.5 ± 2.2, IGT: 4.6 ± 2.1, DM: 6.1 ± 2.4 pg / ml, p for trend <0.001]. HsCRP [r = 0.104, p=0.02] and TNF-α [r = 0.265, p<0.001] showed a positive correlation with IMT in the total study population and in subjects with NGT [hsCRP: r = 0.253, p = 0.002, TNF-α: r = 0.265, p = 0.001]. In multiple linear regression analysis, hsCRP [β =0.006, p<0.034] and TNF-α [β =0.015, p<0.001] showed an association with IMT among NGT subjects even after adjusting for age and gender. We conclude that among Asian Indians (1) levels of hsCRP and TNF-α increase with increasing degrees of glucose intolerance (2) among NGT subjects, both hsCRP and TNF-α are associated with increase in carotid IMT and this is independent of age and gender. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the prevalence of, and risk factors for, diabetic neuropathy among Asian Indian type 2 diabetic subjects. Subjects were recruited from CURES, a population-based study conducted on a representative population of Chennai city in south India. Of the 1529 known diabetic [KD] subjects, 1382 participated in the study [response rate: 90.4%]; in addition, 354 newly detected diabetic [NDD] subjects were also randomly selected. Neuropathy was diagnosed if the vibratory perception threshold of the right great toe measured by biothesiometry (Biomedical Instrument Co., Newbury, Ohio, USA) was ≥25. Of the total of 1736 individuals, biothesiometry studies were performed in 1632 subjects (94.0% response rate). The overall prevalence of neuropathy was 11% [age-standardized-5.8%], while it was 12.2% [age-standardized-6.5%] and 10% [age-standardized-5.2%] in male and female subjects respectively. The prevalence of neuropathy was significantly higher among KD subjects compared to NDD subjects [12.1% vs 6.8%, p=0.006]. It was also higher among subjects with diabetic retinopathy [26.9% vs 16.9%, p=0.001] and proteinuria [9.6% vs 5.3%, p=0.019] compared to those without. There was a linear increase in the prevalence of neuropathy with increasing age among both genders [p<0.0001]. The odds ratio (OR) for neuropathy in subjects having duration of diabetes >15 years was 5.51 [95% confidence interval (CI): 3.04-10.01, p<0.0001]. Multivariate logistic regression analysis showed age [OR: 1.16, 95% CI: 1.13-1.19, p<0.001], height [OR: 1.04, 95% CI: 1.01 -1.07, p=0.016] and fasting plasma glucose [OR: 1.00, 95% CI: 1.00 -1.01, p=0.001] to be significantly associated with neuropathy. Duration of diabetes showed an association with neuropathy but significance was lost when age was introduced into the model. This is the first population-based data on prevalence of diabetic neuropathy from India, which has the largest number of diabetic patients in the world. [ABSTRACT FROM AUTHOR]