Insulin resistance in patients with the mitochondrial tRNA(Leu(UUR)) gene mutation at position 3243

• Published in: Experimental and clinical endocrinology & diabetes Vol. 110; no. 6; p. 291
• Main Authors: Becker, Regine, Laube, Heiner, Linn, Thomas, Damian, Maxwell S
• Format: Journal Article
• Language: English
• Published: Germany 01.09.2002
• Subjects: Female; Humans; Insulin Resistance - genetics; Male; MELAS Syndrome - genetics; Mitochondria - chemistry; Pedigree; Point Mutation; RNA, Transfer, Leu - genetics
• ISSN: 0947-7349
• DOI: 10.1055/s-2002-34592

The point mutation at position 3243 of the tRNA Leu(UUR) of the mitochondrial DNA is associated with mitochondrial encephalomyopathy, lactic acidosis and strokes (MELAS) as well as with mitochondrial diabetes and deafness (MIDD). A defect in insulin secretion has been found in most of these patients. However, there have been controversial findings to which extent insulin resistance contributes to pathogenesis. The aim of the present investigation was to study the insulin sensitivity index (SI), insulin secretion (AIR(Glucose)) and glucose effectiveness (Sg) in patients with the 3243-mutation. 7 patients of a large pedigree (some of the members who were not investigated had MELAS) and 3 siblings of another family in whom the 3243-mutation had been detected, as well as 23 non-related, healthy control subjects underwent a modified intravenous glucose tolerance test (Bergman's minimal model). In addition, a screening of islet cell antibodies (ICA) was performed. All patients except for one with known diabetes mellitus revealed normal glucose tolerance. There was no difference between patients and controls for SI, AIR(Glucose) or Sg. However, when looking at the individual results, there were 4 closely related members of the large family with very poor insulin sensitivity. The other 2 patients of this pedigree were more distantly related and extremely insulin sensitive. The siblings of the other family revealed normal or even a very good insulin sensitivity. In one patient, ICA were detected. The 3243-mutation does not seem to be causative for insulin resistance in our patients. Whether nuclear genes are involved and indirectly influence the expression of the 3243-mutation or, more likely, directly lead to impaired insulin sensitivity in some of our patients cannot be answered by our data. It remains open whether there is a difference in the pathogenesis of diabetes between patients with MIDD and those with MELAS.