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

Abstract

The pathophysiological mechanism of diabetes mellitus in the presence of the 3243 A-G tRNALEU(UR) mitochondrial DNA mutation is thought to result from deficient insulin secretion. However, few subjects with normal glucose tolerance have been studied to determine the sequence of events resulting in the development of diabetes mellitus. To determine whether abnormalities of insulin sensitivity, insulin secretion or glucose effectiveness are present in non-diabetic subjects with the 3243 A-G tRNALEU(UUR) mitochondrial DNA mutation. Twelve non-diabetic subjects with the mutation were compared with 12 controls, matched for age and anthropometric parameters, using both oral and intravenous glucose tolerance tests, the latter with Minimal Model analysis. Following an oral glucose load we found significantly higher blood glucose levels at 90 min and 120 min and significantly higher insulin levels 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 intravenous glucose tolerance test there was no difference in overall glucose tolerance, insulin sensitivity, first- or second-phase insulin secretion, proinsulin secretion or glucose effectiveness. Insulin-independent glucose disposal was increased in subjects with lower insulin sensitivity and declined with increasing age in subjects with the mutation but not in controls. 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.