Heritability of Type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance - a population-based twin study

Abstract

To elucidate the relative importance of genetic and environmental factors on the development of Type II (non-insulin dependent) diabetes mellitus, we examined a sample of twins (n = 606) ascertained from the population-based Danish Twin Register. Based on a standard 75 g oral glucose tolerance test and current WHO criteria we identified 62 pairs in which one or both had Type II diabetes. The probandwise concordance (monozygotic: 0.50; dizygotic: 0.37) for Type II diabetes per se was not very different. When including the twins with impaired glucose tolerance (IGT), however, the probandwise concordance for abnormal glucose tolerance was significantly different between monozygotic (0.63) and dizygotic (0.43) twin pairs, (p < 0.01). These findings were supported by the heritability estimates for Type II diabetes per se (26%) and for abnormal glucose tolerance (61%). The metabolic variables, insulin resistance and insulin secretion, and anthropometric variables, body mass index and waist to hip ratio, known to be associated with the development of glucose intolerance had a heritability of 26, 50, 80 and 6% respectively. This study confirms the notion of a multifactorial aetiology of Type II diabetes. It supports the contribution of non-genetic aetiological components in the development of Type II diabetes per se. The study also indicates a role for genes in the aetiology of abnormal glucose tolerance. We therefore propose that genetic predisposition is important for the development of abnormal glucose tolerance. Non-genetic factors, however, might play a predominant role in controlling whether a genetically predisposed individual progresses to overt Type II diabetes.