Impaired glucose tolerance precedes but does not predict insulin-dependent diabetes mellitus: a study of identical twins

Summary Non-diabetic identical twins of insulin-dependent diabetic patients were studied within five years of the diagnosis of their index twin in order to determine whether changes in intermediary metabolism precede the onset of insulin-dependent diabetes mellitus. Two studies were performed: a cross-sectional study of 12 non-diabetic twins and a prospective study of a separate group of 41 non-diabetic twins. Ofthe 12 twins tested in the cross-sectional study six developed insulin-dependent diabetes and six did not; the six who developed diabetes were given an oral glucose load a mean of 10 months before diagnosis; they then had normal fasting blood glucose levels but worse glucose tolerance than control subjects (120 min post-load (mean±SD) blood glucose 8.5±3.5 vs 4.9±0.9 mmol/l respectively, p<0.05). However, blood lactate, pyruvate, alanine, glycerol, 3-hydroxybutyrate and serum insulin levels were similar. In contrast, the six twins in this cross-sectional study who did not develop diabetes and are now unlikely to do so, as a group, had no significant changes compared with the control subjects though one had impaired glucose tolerance. To determine the predictive value of impaired glucose tolerance a separate group of 41 non-diabetic twins was studied prospectively for 8 to 22 years having a total of 147 glucose tolerance tests in this period; in this group six developed diabetes. Eight of the 41 had impaired glucose tolerance; impaired glucose tolerance was found in four of the six who developed diabetes as compared with only four of the 35 who did not (p<0.01). Impaired glucose tolerance in these non-diabetic identical twins had a positive predictive value of33% for developing diabetes. The four twins with impaired glucose tolerance who remain nondiabetic now have normal glucose tolerance. We conclude that impaired glucose tolerance may precede the onset of insulin-dependent diabetes mellitus by many months but the change does not specifically predict the disease even in identical twins of diabetic patients. These observations are consistent with the possibility that in some twins the disease process can occur yet remit without leading to diabetes.