Peripheral Blood Mitochondrial DNA Content Is Related to Insulin Sensitivity in Offspring of Type 2 Diabetic Patients

Abstract

OBJECTIVE -To investigate whether the peripheral blood mtDNA (pb-mtDNA) content is decreased and linked to insulin resistance in the offspring of type 2 diabetic patients.RESEARCH DESIGN AND METHODS -A total of 82 offspring of type 2 diabetic patients and 52 age-, sex-, and BMI-matched normal subjects from the Mokdong, Korea, population were selected for this study by stratified, randomized sampling. Of the offspring of diabetic patients, 52 had normal glucose tolerance (NGT), 21 had impaired glucose tolerance (IGT), and 9 had newly diagnosed type 2 diabetes. The pb-mtDNA content was measured by real-time polymerase chain reaction with a mitochondria-specific fluorescent probe, normalized by a nuclear DNA, 28S rRNA gene. The associations between pb-mtDNA content and several parameters of insulin resistance were studied.RESULTS -The pb-mtDNA contents tended to be lower in the 82 offspring of type 2 diabetic patients (1,084.7 Ϯ 62.6 vs. 1,304.0 Ϯ 99.2 in the offspring and control subjects, respectively, P ϭ 0.051) and was significantly lower in the combined NGT and IGT offspring group (NGTϩIGT, 1,068.0 Ϯ 67.8, P Ͻ 0.05) than in the control subjects. In NGTϩIGT offspring, the pb-mtDNA content was significantly correlated with logarithmically transformed insulin sensitivity (r ϭ 0.253, P Ͻ 0.05) and was the main predictor of insulin sensitivity.CONCLUSIONS -Quantitative mtDNA status might be a hereditary factor associated with type 2 diabetes and could serve as an indicator for insulin sensitivity. Diabetes Care 24:865-869, 2001T he mitochondria are the major site of intracellular respiration and energy metabolism, and their function is intimately related to insulin secretion and possibly insulin action (1,2). Moreover, the mitochondria contain their own genome, with mtDNA coding for some proteins of the respiratory chain. The mutation of mtDNA was believed to cause ϳ0.5-1% of diabetes (3,4). The content of mtDNA is vital for maintaining the mitochondrial function and the energy demands of the body, but little attention has been paid to the quantitative aspects of mtDNA in diabetes. Several animal and human studies have described variations in mtDNA content. Decreased mtDNA content was found in the pancreatic islets of diabetes-prone Goto-Kakizaki rats (5) and in mitochondrial transcriptional factor A (Tfam)-defective mice (4). Decreased mtDNA content was also found in the skeletal muscle of type 1 and type 2 diabetic patients (6). Although the changes resulting from diabetes might influence the mtDNA content, decreases in peripheral blood mtDNA (pb-mtDNA) were observed before the onset of diabetes (7). Peripheral blood could provide an alternative sample type to skeletal muscle in the diagnosis of mitochondrial pathology because the data on the mitochondrial state in skeletal muscles and peripheral blood lymphocytes were comparable (8). Decreased pb-mtDNA was found to be related to insulin resistance or the development of type 2 diabetes (7).Although maximum oxygen consumption (VO 2max ) was positively related to m...

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