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 environmental factors. Although
the familial aggregation of Type II diabetes is acknowledged, there is little data concerning the prevalence of diabetes in
the relatives of subjects with diabetes in comparison with the general population, and our objective was to address this question
in the defined geographic region of Oxfordshire, England. We studied 139 first degree relatives of 90 probands with Type II
diabetes who attended routine diabetes clinics 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 population data were derived from two large-scale Oxford community studies which documented the prevalences of
known and newly diagnosed diabetes. The prevalences of newly diagnosed and known diabetes were calculated for each group.
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 ≥ 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 prevalence of hyperglycaemia in the first degree relatives
of subjects with Type II diabetes compared with the control population: the prevalence ratio after adjustment for age, sex
and BMI was 4.32 (95 % confidence interval 2.29–8.17). The relatives had a considerably higher fasting plasma glucose concentration
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 statistically significant after adjustment for age, sex and obesity. The relatives
were significantly more obese, had higher fasting plasma insulin concentrations and had lower HDL-cholesterol concentrations.
In conclusion, there is a strong familial aggregation of hyperglycaemia and obesity in the relatives of subjects with Type
II diabetes and these subjects have higher fasting plasma insulin concentrations and lower HDL-cholesterol than the general
population. These data indicate the particular relevance of screening the first degree relatives of subjects with Type II
diabetes, as intervention strategies which aim to improve the metabolic profile are indicated for a large proportion of these
subjects. [Diabetologia (1999) 42: 24–27]
Keywords Type II diabetes - obesity - dyslipidaemia - genetic epidemiology.
Received: 8 May 1998 and in revised form 31 July 1998