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Aims: Recent genome-wide association studies have identified several Type 2 diabetes-related loci. We investigated the effect of susceptibility genetic variants, individually, together and in combination with conventional risk factors, on Type 2 diabetes and diabetes-related traits in Indians., Methods: We genotyped 33 variants in 1808 Indian patients and 1549 control subjects and performed association analyses with Type 2 diabetes and related traits using an additive model for individual variant and for genetic risk score based on 32 polymorphisms. The discriminatory value of genetic risk over conventional risk factors was analysed using receiver-operating characteristics curve analysis., Results: The allelic odds ratio ranged from 1.01 (95% CI 0.85-1.19) to 1.66 (95% CI 1.32-2.01) for single-variant analyses. Although, only 16 variants had significant odds ratios, the direction of association for others was similar to earlier reports. The odds ratio for Type 2 diabetes at each genetic risk score point was 1.11 (95% CI 1.09-1.14; P = 5.6 × 10(-17)) and individuals with extremes of genetic risk score (≥ 29.0 and ≤ 17.0) had a 7.5-fold difference in risk of Type 2 diabetes. The discrimination rate between control subjects and patients improved marginally on addition of genetic risk score to conventional risk factors (area under curve = 0.959 and 0.963, respectively; P = 0.001). Of all the quantitative traits analysed, MC4R variants showed strong association with BMI (P = 4.1 × 10(-4)), fat mass per cent (P = 2.4 × 10(-4)) and other obesity-related traits, including waist circumference and hip circumference (P = 2.0 × 10(-3) for both), as well as insulin resistance (P =0.02)., Conclusions: We replicated the association of well-established common variants with Type 2 diabetes in Indians and observed a similar association as reported in Western populations. Combined analysis of 32 variants aids identification of subgroups at increased risk of Type 2 diabetes, but adds only a minor advantage over conventional risk factors., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

Circulating concentrations of total cholesterol, triglycerides, non-esterified fatty acids (NEFA), glycerol, and 3-hydroxybutyrate (3-HB) were measured in 133 subjects with normal glucose tolerance (NGT), 78 with impaired-glucose-tolerance (IGT) and 189 non-insulin dependent (Type 2) diabetic (NIDDM) patients. Plasma cholesterol concentration was similar in the three groups; NGT (4.2 (2.3-7.5) mmol l-1, median (range)), IGT (4.7 (2.7-6.3)) and NIDDM (4.3 (2.3-6.9)). Plasma triglycerides (NGT 0.88 (0.37-2.80), IGT 1.26 (0.43-3.82) and NIDDM 1.38 (0.62-3.91) mmol l-1) and NEFA (NGT 0.81 (0.29-1.58), IGT 1.02 (0.33-1.87) and NIDDM 1.02 (0.48-2.77) mmol l-1) were higher in the two hyperglycaemic groups, but blood 3-HB concentration was similar in the three groups. Plasma cholesterol concentration in these subjects is lower than that reported in white Caucasians in the UK and USA and migrant Indian NIDDM patients in the UK. In NIDDM patients plasma cholesterol concentration was related to age, body mass index (BMI), and plasma glucose concentration while plasma triglyceride concentration was related to plasma NEFA and insulin (IRI) concentration. Evidence of ischaemia on electrocardiography in patients with diabetes was associated with higher age, blood pressure, plasma triglyceride, glucose, and IRI concentrations.