Involvement of mitochondrial gene abnormalities in the pathogenesis of diabetes mellitus

An A to G mutation at nucleotide position 3243 of the mitochondrial genome has been shown to be associated with insulin-dependent diabetes mellitus (IDDM) and with noninsulin-dependent diabetes mellitus (NIDDM) with deafness. We investigated the prevalence of this mutation in Japanese patients with IDDM, NIDDM, and impaired glucose tolerance (IGT) and in nondiabetic control individuals and identified it in three of 300 patients with NIDDM or IGT (1.0%). None of these individuals had significant sensorineural hearing loss. None of the 94 IDDM or the 115 nondiabetic control subjects was positive for this mutation. Oral glucose tolerance test revealed that a 57-year-old male with this mutation was rather hyperinsulinemic in the fasting state. The insulin secretion in this patient decreased with age; he did not complain of any hearing disorder, although audiometry revealed a slight elevation of hearing threshold at high frequencies. In conclusion, we found that a mitochondrial gene mutation at np 3243 was present in about 1% of NIDDM patients including IGT, and the subtype of diabetes mellitus with this mutation may have a similar clinical profile to that found in patients with NIDDM commonly seen in outpatient clinics. Screening of 116 patients with type 1 diabetes mellitus and 149 patients with autoimmune thyroid diseases revealed that this mutation rarely exists in patients with autoimmune diseases.