Decreased peripheral blood mitochondrial DNA content is related to HbA1c, fasting plasma glucose level and age of onset in type 2 diabetes mellitus

Abstract

Aims: Mitochondrial DNA (mtDNA) content is essential for maintaining normal mitochondrial function, and the mitochondrial function is critical for the production and the release of insulin in Type 2 diabetes mellitus. We investigated whether peripheral blood mtDNA content was reduced in Type 2 diabetes, and what were the major factors?

Methods: The mtDNA content of peripheral blood in a sample of 147 Type 2 diabetes and 170 normal Chinese subjects was determined by amplification of the mitochondrial gene CYT-B and normalized by a nuclear DNA β-globin gene. Fasting plasma glucose, HbA(1c) , fasting plasma insulin and lipid profile (HDL-cholesterol, LDL-cholesterol, total cholesterol, triglyceride) were analysed with commercial kits on an automatic analyser.

Results: In Type 2 diabetes group, the mean HbA(1c) was 62 mmol/mol (7.8%). Moreover, BMI, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, LDL-cholesterol, triglyceride, fasting plasma insulin and homeostasis model assessment for insulin resistance were significantly higher in Type 2 diabetes group than that in control group. Peripheral blood mtDNA content was 24% lower than that in the controls (1.4 ± 0.5 vs. 1.8 ± 0.7, P < 0.001). The mtDNA content was negatively correlated with BMI, fasting plasma glucose, fasting plasma insulin, homeostasis model assessment for insulin resistance (P < 0.01), and age, triglyceride and LDL-cholesterol levels (P < 0.05); while positively correlated with HDL-cholesterol level (P < 0.05) in both groups. Stepwise regression analysis indicated that HbA(1c), fasting plasma glucose and age of onset were the major factors affecting the mtDNA content in the Type 2 diabetes group; however, BMI was the only variable associated with lower mtDNA content in control group.

Conclusion: Our results demonstrate that lower peripheral blood mtDNA content is associated with Type 2 diabetes in Chinese individuals, and HbA(1c), fasting plasma glucose and age of onset are the major factors affecting the mtDNA content.