Insulin sensitivity and insulin secretion in monozygotic and dizygotic twins

Aims/hypothesis. To estimate the heritability of insulin sensitivity and in sulin secretion, both of which are considered to contribute to the developm ent of Type II (non-insulin-dependent) diabetes mellitus. Methods. Intraclass correlation coefficients and heritability estimates for insulin sensitivity (euglycaemic clamp) as well as first-phase and late-ph ase insulin secretion (intravenous glucose tolerance test) were calculated in 21 monozygotic and 20 dizygotic twin pairs of the same sex between 54 an d 72 years of age. Results. Intrapair correlations for all traits were consistently higher in monozygotic than in dizygotic pairs. Insulin secretion correlated significa ntly only between monozygotic (first-phase r = 0.55; p = 0.003 and late-pha se r = 0.66; p < 0.001) twins giving heritability estimates of 0.55 and 0.5 8, respectively. Insulin-stimulated glucose uptake showed a more modest cor relation between monozygotic twins (r = 0.46; p = 0.015). The heritability estimate was 0.37. The heritability estimate for waist-to-hip ratio was 0.7 6 in female and 0.70 in male twins. Conclusion/interpretation. Genetic variability seems to contribute to the v ariance of insulin sensitivity as well as of insulin secretion. In the curr ent study, genetic variance accounted almost 60% for the variance in glucos e-stimulated insulin secretion and almost 40% for the variance in insulin-s timulated glucose uptake. Our data is also compatible with findings in mono genic forms of diabetes in which genetic defects in insulin secretion play a predominant part in the pathogenesis of hyperglycaemia.