Insulin Gene Variable Number of Tandem Repeat Genotype, Early Growth and Glucose Metabolism in Adult Life

he predisposition to type 2 diabetes is programmed early in life and genotypes promoting survival during nutritional adversity could increase the risk of type 2 diabetes. The insulin gene and variation in the insulin gene variable number of tandem repeats (VNTR) polymorphism has been suggested to modify birth size and diabetes susceptibility. Materials and Methods: We assessed the association between the insulin gene VNTR genotypes, early growth and glucose and insulin metabolism in adult life in 488 subjects participating in the Helsinki Birth Cohort Study. Results: Body size at birth did not differ significantly between the INS VNTR genotypes. One additional type III allele was associated with a 13 g decrease (95% CI -55 to 81 g; p=0.7) in birth weight. Fasting glucose concentration was highest in the carriers of the III/III genotype. The cumulative incidence of type 2 diabetes did not differ between the genotypes. Interactions between birth size and insulin VNTR genotype in relation to fasting glucose (p for interaction = 0.08 for birth weight, p=0.05 for birth length) and 2-hour insulin (p for interaction =0.04) were observed. Conclusions: These interactions between body size at birth and genotype reflect interactions between the insulin VNTR gene and the intrauterine environment. Our findings are consistent with the hypothesis of developmental plasticity, where one genotype can give rise to different phenotypes dependent on the early environment.