The relative risks of hyperglycaemia, obesity and dyslipidaemia in the relatives of patients with Type II diabetes mellitus

Type II (non-insulin-dependent) diabetes mellitus has a substantial genetic component; however, its molecular basis remains largely unknown. The mode of inheritance is likely to be polygenic, with penetrance influenced by env ironmental factors. Although the familial aggregation of Type II diabetes i s acknowledged, there is little data concerning the prevalence of diabetes in the relatives of subjects with diabetes in comparison with the general p opulation, and our objective was to address this question in the defined ge ographic region of Oxfordshire, England. We studied 139 first degree relati ves of 90 probands with Type II diabetes who attended routine diabetes clin ics in Oxfordshire and documented the fasting plasma glucose, triglyceride and HDL-cholesterol concentrations and BMI of these subjects. The probands were selected without regard to family history of diabetes. The control pop ulation data were derived from two large-scale Oxford community studies whi ch documented the prevalences of known and newly diagnosed diabetes. The pr evalences of newly diagnosed and known diabetes were calculated for each gr oup. The mean BMI, and concentrations of fasting glucose, triglyceride and HDL-cholesterol were compared and prevalence ratios for obesity (defined as BMI >30 kg/m(2)), hyperglycaemia (defined as fasting plasma glucose greate r than or equal to 6.1 mmol/l), and dyslipidaemia (defined as triglyceride >2.0 mmol/l, HDL<1.0 mmol/l) were calculated There was a fourfold higher pr evalence of hyperglycaemia in the first degree relatives of subjects with T ype II diabetes compared with the control population: the prevalence ratio after adjustment for age, sex and BMI was 4.32 (95% confidence interval 2.2 9-8.17). The relatives had a considerably higher fasting plasma glucose con centration than the control population (5.18 +/- 0.67 mmol/l (mean +/- 1 SD ) vs 4.76 +/- 1.59 mmol/l, p = 0.0001), and this difference remained statis tically significant after adjustment for age, sex and obesity. The relative s were significantly more obese, had higher fasting plasma insulin concentr ations and had lower HDL-cholesterol concentrations. In conclusion, there i s a strong familial aggregation of hyperglycaemia and obesity in the relati ves of subjects with Type II diabetes and these subjects have higher fastin g plasma insulin concentrations and lower HDL-cholesterol than the general population. These data indicate the particular relevance of screening the f irst degree relatives of subjects with Type II diabetes, as intervention st rategies which aim to improve the metabolic profile are indicated for a lar ge proportion of these subjects.