The insulin gene VNTR, type 2 diabetes and birth weight

We recently reported an association between common allelic variation (class I or class III) at the variable number of tandem repeat (VNTR) locus in the promoter region of the insulin gene (INS) and birthweight. In a contemporary, wellnourished group of 758 children, the Children in Focus sub-cohort of the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC), the frequency of the III/III genotype was 9% and associated with an increase of 200 g in birth weight. The class III allele and III/III genotype have also been associated with insulin resistance, diabetic hypertriglyceridaemia, atherosclerosis, cardiovascular disease and central obesity, anovulatory polycystic ovary syndrome and, in some studies, type 2 diabetes. These results, however, conflict with data showing strong associations between low birth weight and a raised prevalence of impaired glucose tolerance (IGT) and type 2 diabetes in adult life. To address this paradox, we analysed the INS VNTR in 218 men born in Hertfordshire between 1920 and 1930 in whom the link between low birth weight and IGT/type 2 diabetes was first described. IGT or type 2 diabetes was found in 52 of 218 men, as determined by blood glucose levels 2 hours after a 75-g glucose drink (IGT, glucose 7.8-11.0 mmol/l; type 2 diabetes, glucose>11.1).