Reduced peripheral blood mtDNA content is associated with impaired glucose-stimulated islet β cell function in a Chinese population with different degrees of glucose tolerance.

AIMS: Our aim is to explore the associations between mitochondrial DNA (mtDNA) content and basal plasma glucose, plasma glucose after oral glucose administration and oxidative stress in a Chinese population with different levels of glucose tolerance. We also aimed to investigate the effect of mtDNA content on basal and oral glucose-stimulated insulin secretion.

METHODS: Five hundred and fifty-six Chinese subjects underwent a 75-g, 2-h oral glucose tolerance test. Subjects with diabetes (n = 159), pre-diabetes (n = 197) and normal glucose tolerance (n = 200) were screened. Blood lipid profile was assessed, and levels of the oxidative stress indicators superoxide dismutase, glutathione reductase (GR) and 8-oxo-2'-deoxyguanosine (8-oxo-dG) were measured. Levels of HbA1c , plasma glucose, insulin and C-peptide were also determined. Measurements were taken at 0, 30, 60 and 120 min after 75 g oral glucose tolerance test. Peripheral blood mtDNA content was assessed using a real-time polymerase chain reaction assay. Insulin sensitivity was evaluated by homeostatic model assessment of insulin resistance and Matsuda index (ISIM ). Basal insulin secretion index (HOMA-β), early phase disposition index (DI30 ) and total phase disposition index (DI120 ) indicate insulin levels at different phases of insulin secretion.

RESULTS: Peripheral blood mtDNA content was positively associated with DI30 and DI120 and was negatively associated with plasma glucose measured 30, 60 and 120 min after oral glucose administration. However, there was no correlation between mtDNA content and basal insulin secretion (HOMA-β), serum lipid or oxidative stress indicators (8-oxo-dG, superoxide dismutase, GR). HbA1c was negatively associated with GR (r = -0.136, p = 0.001). Multiple linear regression analysis showed that reduced peripheral blood mtDNA content increased the risk of impaired glucose-stimulated β cell function (DI30 : β = 0.104, p = 0.019; DI120 : β = 0.116, p = 0.009).

CONCLUSIONS: Decreased peripheral blood mtDNA content was more closely associated with glucose-stimulated insulin secretion than with basal secretion. Reduction in glucose-stimulated insulin secretion causes postprandial hyperglycaemia. The oxidative stress was probably largely influenced by hyperglycaemia; it was probably that the decreased mt DNA content led to hyperglycaemia, which caused elevated oxidative stress. © 2016 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd.