Insulin secretion and insulin sensitivity are normal in non-diabetic subjects from maternal inheritance diabetes and deafness families

Background The pathophysiological mechanism of diabetes mellitus in the pre sence of the 3243 A-G tRNA(LEU(UR)) mitochondrial DNA mutation is thought t o result from deficient insulin secretion. However, few subjects with norma l glucose tolerance have been studied to determine the sequence of events r esulting in the development of diabetes mellitus. Aim To determine whether abnormalities of insulin sensitivity, insulin secr etion or glucose effectiveness are present in non-diabetic subjects with th e 3243 A-G tRNA(LEU(UUR)) mitochondrial DNA mutation. Methods Twelve non-diabetic subjects with the mutation were compared with 1 2 controls, matched for age and anthropometric parameters, using both oral and intravenous glucose tolerance tests, the latter with Minimal Model anal ysis. Results Following an oral glucose load we found significantly higher blood glucose levels at 90 min and 120 min and significantly higher insulin level s at 120 min and 180 min in non-diabetic subjects with the mutation but no difference in the insulinogenic indices at 30 min and 180 min. From the int ravenous glucose tolerance test there was no difference in overall glucose tolerance, insulin sensitivity, first- or second-phase insulin secretion, p roinsulin secretion or glucose effectiveness. Insulin-independent glucose d isposal was increased in subjects with lower insulin sensitivity and declin ed with increasing age in subjects with the mutation but not in controls. Conclusions While there appear to be subtle defects of glucose handling in non-diabetic subjects with the 3243 mutation, these could not be explained by differences in insulin sensitivity or secretion.