X Deng1, G Yang1, X Zheng2, Y Yang1, H Qin3, Z-X Liu1, H Deng4, S-M Liu1. 1. Department of Clinical Laboratory, Center for Gene Diagnosis & Program of Clinical Laboratory, Wuhan, China. 2. Laboratory of Molecular Cardiology, Wuhan Asia Heart Hospital, Wuhan University, Wuhan, China. 3. Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Hubei Polytechnic University, Guilin, China. 4. Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Abstract
AIMS: Mitochondrial dysfunction is involved in the pathogenesis of type 2 diabetes. Glutathione S-transferase kappa 1 (GSTK1) is critical to maintain mitochondrial function and homeostasis. We aimed to investigate whether a potential link exists between mitochondrial DNA (mtDNA) copy numbers and inflammation, non-esterified fatty acids (NEFA) and GSTK1 expression in type 2 diabetes. METHODS: We assessed mtDNA copy numbers in plasma and GSTK1 expression in white blood cells in 123 people with type 2 diabetes and in 121 healthy controls using a quantitative polymerase chain reaction (qPCR). An automatic chemistry or immunoassay analyser was used to determine serum glucose, lipids and inflammatory markers. Multiple linear regression and multivariable logistic regression models were used to evaluate associations and risks. RESULTS: Compared with healthy controls, individuals with diabetes showed higher mtDNA copy numbers (t = -3.938, P < 0.001) and lower GSTK1 expression (Z = -2.985, P = 0.002). mtDNA copy number was associated with type 2 diabetes risk [odds ratio (OR) = 1.80, 95% confidence intervals (CI) 1.25-2.58, P = 0.001] after controlling for confounding factors. In individuals with diabetes, mtDNA copy number was negatively associated with GSTK1 expression (β = -0.235, P = 0.036) and positively associated with serum high-sensitive C-reactive protein (hsCRP) (β = 0.839, P < 0.001), tumour necrosis factor alpha (TNF-α) (β = 0.549, P < 0.001), interleukin-6 (IL-6) (β = 0.589, P = 0.006) and NEFA (β = 0.001, P = 0.020). In the diabetic group, individuals with an abnormal increase in NEFA, hsCRP, TNF-α and IL-6 showed significantly elevated mtDNA copy numbers (all P < 0.05). CONCLUSIONS: mtDNA copy numbers in plasma might have an important role in the progression of diabetic chronic inflammation via inhibition of GSTK1 and could be a potential biomarker for type 2 diabetes.
AIMS: Mitochondrial dysfunction is involved in the pathogenesis of type 2 diabetes. Glutathione S-transferase kappa 1 (GSTK1) is critical to maintain mitochondrial function and homeostasis. We aimed to investigate whether a potential link exists between mitochondrial DNA (mtDNA) copy numbers and inflammation, non-esterified fatty acids (NEFA) and GSTK1 expression in type 2 diabetes. METHODS: We assessed mtDNA copy numbers in plasma and GSTK1 expression in white blood cells in 123 people with type 2 diabetes and in 121 healthy controls using a quantitative polymerase chain reaction (qPCR). An automatic chemistry or immunoassay analyser was used to determine serum glucose, lipids and inflammatory markers. Multiple linear regression and multivariable logistic regression models were used to evaluate associations and risks. RESULTS: Compared with healthy controls, individuals with diabetes showed higher mtDNA copy numbers (t = -3.938, P < 0.001) and lower GSTK1 expression (Z = -2.985, P = 0.002). mtDNA copy number was associated with type 2 diabetes risk [odds ratio (OR) = 1.80, 95% confidence intervals (CI) 1.25-2.58, P = 0.001] after controlling for confounding factors. In individuals with diabetes, mtDNA copy number was negatively associated with GSTK1 expression (β = -0.235, P = 0.036) and positively associated with serum high-sensitive C-reactive protein (hsCRP) (β = 0.839, P < 0.001), tumour necrosis factor alpha (TNF-α) (β = 0.549, P < 0.001), interleukin-6 (IL-6) (β = 0.589, P = 0.006) and NEFA (β = 0.001, P = 0.020). In the diabetic group, individuals with an abnormal increase in NEFA, hsCRP, TNF-α and IL-6 showed significantly elevated mtDNA copy numbers (all P < 0.05). CONCLUSIONS: mtDNA copy numbers in plasma might have an important role in the progression of diabetic chronic inflammation via inhibition of GSTK1 and could be a potential biomarker for type 2 diabetes.