RESUMO
The insertion/deletion, I/D polymorphism, in the gene encoding Angiotensin Converting Enzyme, ACE is a popular genetic marker for cardiovascular disease, CVD. With alarming rise in diabetes, the risk of CVD among Indian subjects is further enhanced. The present study explored the role of ACE I/D polymorphism, rs4340 as a genetic marker and its association with diabetes. Genomic DNA, isolated from a cohort of 410 urban subjects attending our hospital, was genotyped using polymerase chain reaction followed by electrophoresis. Among the subjects, 84 had type-2 diabetes and 68 had hypertension while 258 were free from these risk factors. Majority (57/84) of diabetic subjects were also suffering from hypertension. Genotype frequencies of ACE I/D polymorphism, of diabetic (84) patients were not different from that of non-diabetic subjects (258). In sharp contrast, we found significant differences, in genotype frequencies of women with diabetes (n = 38) compared to non-diabetic women (70). Diabetic women had significantly higher prevalence of the high risk 'D' allele. Analysis of odds ratio, OR revealed that women with 'D/D' genotype, exhibited threefold risk (OR 3.12, 95% CI 1.21-8.05; p = 0.018) of diabetes, in the recessive model (D/D vs I/I + I/D). Further when we analysed Odds ratio of diabetic women (8) who were free from hypertension, the results revealed even a greater, 6- fold (OR 6.0, 95% CI 1.29-27.96, p = 0.027) risk of diabetes for D/D homozygous women (D/D vs I/I + I/D). These results suggest 'sex-specific' association of ACE 'I/D' polymorphism, with type-2 diabetes, affecting women while there was no influence observed among men. In view of the increased cardiovascular mortality among Indians, data from our pilot study if confirmed in a larger cohort, could add value to our future intervention efforts.
RESUMO
OBJECTIVE: Asian Indian subjects have a high tendency to develop Type 2 diabetes even though obesity is relatively uncommon. We evaluated the serum leptin levels in a group of non-obese Type 2 diabetic patients from Mumbai, Western India. DESIGN: Cross sectional study. METHODS: A total of 104 subjects consisting of 28 with Type 2 diabetes, 16 with impaired glucose tolerance and 60 age and sex-matched control subjects were given 75 g oral glucose tolerance test. Fasting serum leptin (IRMA), insulin and C-peptide were measured along with fasting and 2 h plasma glucose. The relation between these variables was studied by univariate and multiple regression analysis. RESULTS: Type 2 diabetes was associated with marked (50-60%) reduction in serum leptin levels, in both men and women. Women, but not men, with impaired glucose tolerance exhibited 60% lower leptin. Serum leptin levels were positively correlated to body mass index (BMI; r = 0.501, p = 0.001) and calculated body fat percent (r = 0.525, p = 0.001) in all the study subjects with a better correlation in the normal subjects (r = 0.562 for BMI and 0.735 for body fat). On the other hand, serum leptin showed significant correlation to serum insulin (r = 0.362, p = 0.008) only in subjects with diabetes or IGT. In the multiple regression model, BMI was the only independent predictor of leptin, in all the subjects. However, in subjects with diabetes or impaired glucose tolerance, waist circumference (p = 0.003), gender (p = 0.007) and body fat (p = 0.009) were significant predictors of leptin, besides BMI. Gender-specific multiple regression revealed serum insulin as an independent predictor of leptin in men (p = 0.026). Therefore, lower serum leptin levels in diabetes is partly due to increased waist circumference, decreased BMI and male sex. These observations are consistent with the view that leptin levels in this cohort of non-obese Indians from Mumbai exhibit gender-specific relationship partly attributed to changes in serum insulin and waist circumference in men and to changes in BMI, in women.