A Common Mitochondrial DNA Variant and Increased Body Mass Index as Associated Factors for Development of Type 2 Diabetes: Additive Effects of Genetic and Environmental Factors

Objective: The suggested correlation between a T-to-C transition at the nucleotide 16189 in mitochondrial DNA (mtDNA) with increasing insulin resistance and adult-onset diabetes mellitus (DM) is debatable. Methods: Our study examined mtDNA from 462 subjects with type 2 diabetes (T2DM) and 592 normoglycemic controls (non-DM). Each participant’s body mass index (BMI), fasting plasma glucose, fasting insulin concentration, insulin resistance index, and β-cell function were measured. Sequencing for mtDNA, focusing on exploration of the hypervariable polycytosine tract within the control region, was also conducted in all subjects. Results: Prevalence of the mtDNA 16189 variant was significantly different between DM and non-DM subjects (39.2% vs. 30.7% respectively; P = 0.004). Increased incidence of DM was noted in those harboring the 16189 variant compared with those lacking the variant (multivariate odds ratio, 1.38; 95% confidence interval, 1.07–1.80). Moreover, increased BMI was identified as an aggravatin...