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Plasma mtDNA copy numbers are associated with GSTK1 expression and inflammation in type 2 diabetes
Author(s) -
Deng X.,
Yang G.,
Zheng X.,
Yang Y.,
Qin H.,
Liu ZX.,
Deng H.,
Liu SM.
Publication year - 2020
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.14132
Subject(s) - nefa , medicine , type 2 diabetes , diabetes mellitus , odds ratio , endocrinology , mitochondrial dna , pathogenesis , inflammation , type 1 diabetes , immunology , biology , insulin , genetics , gene
Aims Mitochondrial dysfunction is involved in the pathogenesis of type 2 diabetes. Glutathione S ‐transferase kappa 1 ( GSTK 1) is critical to maintain mitochondrial function and homeostasis. We aimed to investigate whether a potential link exists between mitochondrial DNA (mt DNA ) copy numbers and inflammation, non‐esterified fatty acids ( NEFA ) and GSTK 1 expression in type 2 diabetes. Methods We assessed mt DNA copy numbers in plasma and GSTK 1 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 mt DNA copy numbers ( t = −3.938, P < 0.001) and lower GSTK 1 expression ( Z = −2.985, P = 0.002). mt DNA 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, mt DNA copy number was negatively associated with GSTK 1 expression (β = −0.235, P = 0.036) and positively associated with serum high‐sensitive C‐reactive protein (hs CRP ) (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 , hs CRP , TNF ‐α and IL ‐6 showed significantly elevated mt DNA copy numbers (all P < 0.05). Conclusions mt DNA copy numbers in plasma might have an important role in the progression of diabetic chronic inflammation via inhibition of GSTK 1 and could be a potential biomarker for type 2 diabetes.