It has been shown that an
adenine (A) to
guanine (G) transition at position 3243 of the mitochondrial
transfer RNA(
tRNA)leu(UUR) gene is associated with a subgroup of
diabetes mellitus. Therefore, we screened for this transition in 86 patients with
non-insulin-dependent diabetes mellitus (
NIDDM) in which two or three generations were affected with diabetes, in 14 patients with
insulin-dependent diabetes mellitus, and in 9 families with
diabetes mellitus and/or associated disorders suggesting mitochondrial gene abnormalities. We failed to identify the mutation in 100 diabetic patients, 86
NIDDM and 14
insulin-dependent diabetes mellitus (
IDDM). Out of the latter 9 families, we identified an A to G transition in 14 individuals in 5 families.
Diabetes mellitus was shown to be maternally inherited in one family. In 9 of 14 patients with the mutation,
insulin was required to treat
diabetes mellitus, indicating impaired insulin secretion. A hyperglycemic clamp test performed in one subject revealed significant impairment of insulin secretion, whereas euglycemic clamp test showed normal
insulin sensitivity in this patient. The heteroplasmy of the mutant
mitochondrial DNA (
mtDNA) in leukocytes does not appear to correlate with the severity of diabetes in terms of the
insulin therapy required. Body mass index of the affected individuals was less than 23.3. In one family, in addition to
diabetes mellitus and
hearing loss,
hypoparathyroidism was associated with the mutation, suggesting that
hypoparathyroidism is caused by the impaired processing and/or secretion of
proparathyroid hormone due to the mutation. In addition, the affected subjects presented with
proteinuria at the time of diagnosis of
diabetes mellitus which appeared not to be related with
diabetic nephropathy.