Reduced peripheral blood mtDNA content is associated with impaired glucose‐stimulated islet <i>β</i> cell function in a Chinese population with different degrees of glucose tolerance

Zhou, Meicen; Zhu, Lixin; Cui, Xiangli; Feng, Linbo; Zhao, Xuefeng; He, Song; Ping, Fan; Li, Wei; Li, Yuxiu

doi:10.1002/dmrr.2814

Cited by 22 publications

(22 citation statements)

References 25 publications

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“…These results indicate that the mtDNA-CN has a huge potential as a biomarker of future diabetes. We also found in the two-group comparison tests that 1-h glucose had the highest significance of the glucose metabolism-related variables, which is consistent with previous findings 16 . In univariate analysis, some variables maintained their significance throughout the follow-up, while the significance of others varied according to the follow-up time.…”

Section: Discussionsupporting

confidence: 92%

Mitochondrial DNA copy number augments performance of A1C and oral glucose tolerance testing in the prediction of type 2 diabetes

Cho

Koh

Nam

et al. 2017

Sci Rep

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Here, we tested the performance of the mitochondrial DNA copy number (mtDNA-CN) in predicting future type 2 diabetes (n = 1108). We used the baseline clinical data (age, sex, body mass index, waist-to-hip ratio, systolic and diastolic blood pressure) and the mtDNA-CN, hemoglobin A1c (A1C) levels and results of oral glucose tolerance test (OGTT) including fasting plasma glucose, 1-hour glucose, and 2-hour glucose levels, to predict future diabetes. We built a prediction model using the baseline data and the diabetes status at biannual follow-up of 8 years. The mean area under curve (AUC) for all follow-ups of the full model including all variables was 0.92 ± 0.04 (mean ± standard deviation), while that of the model excluding the mtDNA-CN was 0.90 ± 0.03. The sensitivity of the f4ull model was much greater than that of the model not including mtDNA-CN: the mean sensitivities of the model with and without mtDNA-CN were 0.60 ± 0.06 and 0.53 ± 0.04, respectively. We found that the mtDNA-CN of peripheral leukocytes is a biomarker that augments the predictive power for future diabetes of A1C and OGTT. We believe that these results could provide invaluable information for developing strategies for the management of diabetes.

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Section: Discussionsupporting

confidence: 92%

Mitochondrial DNA copy number augments performance of A1C and oral glucose tolerance testing in the prediction of type 2 diabetes

Cho

Koh

Nam

et al. 2017

Sci Rep

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“…In support of this notion, previous studies have indicated that diabetic patients with DN have higher oxidative stress than non-diabetic individuals (36,37). Furthermore, a study by Zhou et al (38) reported that reduced peripheral blood mtDNA-CN as a result of hyperglycemia-induced oxidative stress is closely associated with glucose-stimulated insulin secretion in diabetic patients. In recent years, activation of the immune system and chronic inflammation have been proposed as novel pathways involved in DN.…”

Section: Discussionmentioning

confidence: 80%

Peripheral blood mitochondrial DNA copy number as a novel potential biomarker for diabetic nephropathy in type�2 diabetes patients

et al. 2018

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The mitochondrial DNA copy number (mtDNA-CN) is a surrogate measure of mitochondrial function and altered mtDNA-CN reflects the oxidant-induced cell damage. A previous study by our group demonstrated that a reduction in the renal mtDNA-CN is implicated in the pathogenesis of diabetic nephropathy (DN), a leading cause of end-stage renal disease in diabetic patients. In the present study, it was investigated whether the mtDNA-CN in the peripheral blood may be utilized as a biomarker for DN in type 2 diabetes (T2D) patients. The study included 50 non-diabetic and 100 diabetic subjects. The diabetic subjects were sub-divided based on their albumin-to-creatinine ratio (ACR) into T2D patients with normoalbuminuria (n=50), DN patients with microalbuminuria (n=29) and DN patients with macroalbuminuria (n=21). The mtDNA-CN was measured in the peripheral blood by real-time polymerase chain reaction analysis. Patients with DN had a lower mtDNA-CN than patients with T2D and healthy controls (P<0.05). A sub-group analysis with stratification by the ACR indicated that a decreased mtDNA-CN was associated with the severity and the presence of DN, as it was lower in DN patients with macroalbuminuria than in DN patients with microalbuminuria and T2D patients with normoalbuminuria (P<0.01). The area under the receiver operating characteristic curve (AUC) for mtDNA-CN was 0.916 (sensitivity, 86% and specificity, 74%) and 0.961 (sensitivity, 96% and specificity, 88%) for differentiating DN patients from T2D patients without DN and from healthy controls, respectively. Furthermore, the AUC of mtDNA-CN for differentiating DN patients with microalbuminuria from those with macroalbuminuria was 0.895 (sensitivity, 83% and specificity, 85%). Multivariate analysis revealed that the mtDNA-CN was significantly associated with the occurrence and progression of DN, even after adjustment for age, mean blood pressure, glycated haemoglobin A1c and total cholesterol (P<0.05). In patients with DN, a decreased mtDNA-CN was negatively correlated with albuminuria and conventional risk factors for DN, and was positively correlated with the estimated glomerular filtration rate. The present results therefore suggest the utilization of circulating mtDNA-CN as a novel biomarker for the early diagnosis of DN and indicate the significance of decreased mtDNA-CN as another independent risk factor for DN.

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“…The characteristic of study subjects is shown in Table 1. The median (min-max) age of the study subjects was 20 (19)(20)(21)(22)(23)(24) years while mtDNA copy number was 9.56 (8.07-12.34). The correlation between mtDNA copy number with other variables is shown in Table 2.…”

Section: Resultsmentioning

confidence: 99%

“…Several diseases have been linked to mitochondrial dysfunction shown by the change of mtDNA copy number [19]. It has been reported that reduced mtDNA copy number is associated with various conditions such as visceral adiposity [11], impaired glucosestimulated islet β cell function [20], diabetic nephropathy [12], chronic kidney disease [13], Parkinson's disease [14], and prostate cancer [15]. Instead, various mixed results have been reported.…”

Section: Discussionmentioning

confidence: 99%

BMI and Waist Circumference Have Positive Correlation With Mitochondrial DNA Copy Number in Young Adult Male

Kurniawan¹,

Bahrun²,

Hatta³

et al. 2018

TOOBESJ

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Background:Abdominal obesity is associated with metabolic and cardiovascular diseases. Mitochondrial dysfunction is often related to metabolic disorder commonly found in abdominal obesity. Mitochondrial DNA (mtDNA) copy number is a biomarker which can be used to reflect the activity of mitochondria. Abdominal obesity is more commonly found in males compared to females and the incidence is growing in young adult male, therefore we investigated the relationship of mtDNA copy number and anthropometric and metabolic biomarkers in young adult male.Methods:A total of 25 healthy young adult males of age 19 to 24 years old were recruited in the study. Metabolic biomarkers were evaluated along with body mass index, waist circumference and total body fat, visceral fat by bioelectrical impedance analysis. mtDNA copy number was measured in peripheral blood leukocytes by using real-time polymerase chain reaction method.Results:After adjusting for ages, mtDNA copy number correlated with body mass index (r= 0.45,P= 0.03) and waist circumference (r= 0.43,P= 0.04) but had no significant correlation with fasting plasma glucose, insulin, HOMA-IR, testosterone, total body fat and visceral fat.Conclusion:mtDNA copy number has a positive correlation with BMI and waist circumference. Even though it is still controversial over other studies, further studies are needed to explain the causality and significance of our findings.

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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

Cited by 22 publications

References 25 publications

Mitochondrial DNA copy number augments performance of A1C and oral glucose tolerance testing in the prediction of type 2 diabetes

Mitochondrial DNA copy number augments performance of A1C and oral glucose tolerance testing in the prediction of type 2 diabetes

Peripheral blood mitochondrial DNA copy number as a novel potential biomarker for diabetic nephropathy in type�2 diabetes patients

BMI and Waist Circumference Have Positive Correlation With Mitochondrial DNA Copy Number in Young Adult Male

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