Decreased mitochondrial DNA content in peripheral blood precedes the development of non-insulin-dependent diabetes mellitus

Qualitative changes in mitochondrial DNA (mtDNA), such as mutations and del etions, have been implicated in the pathogenesis of diabetes mellitus. In a ddition to the qualitative changes, mtDNA is subject to quantitative change s, and is vulnerable to oxidative stress, resulting in both qualitative and quantitative changes. This study was performed to investigate whether quan titative changes in mtDNA occur in non-insulin-dependent diabetes mellitus (NIDDM) patients and also in pre-diabetic subjects. MtDNA content from peri pheral blood was measured by slot-blot analysis in 55 NIDDM patients and 29 age- and sex-matched control subjects. We have also analysed the mtDNA cop ies by quantitative polymerase chain reaction (PCR) method in 23 pre-diabet ic subjects who converted to diabetic in 2 years and 12 age- and sex-matche d control subjects who remained non-diabetic. Mean mtDNA quantity measured by slot blot method was 35% lower in patients with NIDDM than in control su bjects (12.3 +/- 8.1 vs. 19.1 +/- 8.2 AU/mu g DNA; P < 0.05). MtDNA quantit ies did not correlate with age, body mass index, duration of diabetes or Hb A(1c) levels. We have also found that the mtDNA copies in subjects who conv erted to diabetes in 2 years were lower than in controls even before the de velopment of diabetes (102.8 +/- 41.5 vs. 137.8 +/- 67.7 copies/pg template DNA P(0.05). Inverse correlations were noted between mtDNA content and bas eline waist hip circumference ratio (WHR) (r = -0.31, P < 0.05), and fastin g glucose level (r = -0.35, P < 0.05), diastolic blood pressure (r = -0.36, P < 0.05), and WHR (r = -0.40, P < 0.01) after development of diabetes. In conclusion, we demonstrate that the content of mtDNA decreases in peripher al blood of patients with NIDDM and the lower mtDNA levels precede the deve lopment of diabetes. (C) 1998 Published by Elsevier Science Ireland Ltd. Al l rights reserved.