Association of mitochondrial DNA copy number with metabolic syndrome and type 2 diabetes in 14 176 individuals

Fazzini, Federica; Lamina, Claudia; Raftopoulou, Athina; Koller, Arnold; Fuchsberger, Christian; Pattaro, Cristian; Greco, Fabiola M. Del; Döttelmayer, P.; Fendt, Liane; Fritz, Josef; Meiselbach, Heike; Schönherr, Sebastian; Forer, Lukas; Weißensteiner, Hansi; Pramstaller, Peter P.; Eckardt, Kai‐Uwe; Hicks, Andrew A.; Kronenberg, Florian

doi:10.1111/joim.13242

Cited by 62 publications

(56 citation statements)

References 53 publications

(79 reference statements)

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“…In the present issue of J Int Med, Fazzini et al [7] contribute with important information to the literature when reporting that lower mtDNA-CN associates with metabolic syndrome and type-2 diabetes in both patients with CKD and in the general population. They observed that a major part of the effects of mtDNA-CN is mediated by obesity parameters.…”

Section: Mitochondrial Dysfunction As Part Of An Inflammatory Intermediate Phenotype That Drives Premature Ageingmentioning

confidence: 87%

“…The results reported by Fazzini et al [7] This phenotype (i.e. inflammageing) is related to cellular senescence, depression of the cytoprotective transcription factor nuclear factor erythroid 2related factor 2 (Nrf2), metabolic imbalances, tissue hypoxia, telomere attrition and oxidative stress; dysregulations that together drive a prematurely aged phenotype (Fig.…”

Section: Mitochondrial Dysfunction As Part Of An Inflammatory Intermediate Phenotype That Drives Premature Ageingmentioning

confidence: 90%

“…Thus, to defend the functionality of telomeres and mitochondria, lifetime weight management seems important. Whilst the study by Fazzini et al [7] benefits from two large patient populations and robust statistics, analyses of mtDNA-CN only in peripheral blood cells limit the interpretation of mtDNA-CN status. The number of mtDNA-CN per cells varies by several orders of magnitude between different organs [2].…”

Section: Mitochondrial Dysfunction As Part Of An Inflammatory Intermediate Phenotype That Drives Premature Ageingmentioning

confidence: 99%

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Mitochondrial dysfunction as part of an inflammatory intermediate phenotype that drives premature ageing

Stenvinkel

2021

J Intern Med

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Section: Mitochondrial Dysfunction As Part Of An Inflammatory Intermediate Phenotype That Drives Premature Ageingmentioning

confidence: 87%

Section: Mitochondrial Dysfunction As Part Of An Inflammatory Intermediate Phenotype That Drives Premature Ageingmentioning

confidence: 90%

Section: Mitochondrial Dysfunction As Part Of An Inflammatory Intermediate Phenotype That Drives Premature Ageingmentioning

confidence: 99%

See 1 more Smart Citation

Mitochondrial dysfunction as part of an inflammatory intermediate phenotype that drives premature ageing

Stenvinkel

2021

J Intern Med

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“…A cohort study in Korean population also reported decreased mtDNA copy number ( Lee et al., 1998 ; Song et al., 2001 ). Decreased mtDNA was found to be associated with metabolic syndrome and T2D in Italian and German populations ( Fazzini et al., 2021 ). Mitochondrial dysfunctions in T2D were reported to be linked with mtDNA copy number reduction ( Rolo and Palmeira, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

“…MtDNA copy number, indirect marker of mitochondrial dysfunction ( Malik and Czajka, 2013 ), alterations have been found in several diseases ( Filograna et al, 2020 ). Reduced mtDNA copy number in patients with type 2 diabetes is now well evident ( Al-Kafaji et al, 2018 ; Fazzini et al, 2021 ; Latini et al, 2020 ; Xu et al, 2012 ). Busnelli et al (2019) ) demonstrated indirect relation between reduced mtDNA copy number and oxidative stress along with inflammation.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of D-loop hypervariable region I variations, haplogroups and copy number of mitochondrial DNA in Bangladeshi population with type 2 diabetes

Saha

Saba

Hasib

et al. 2021

Heliyon

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The profound impact of mitochondrion in cellular metabolism has been well documented. Since type 2 diabetes (T2D) is a metabolic disorder, mitochondrial dysfunction is intricately linked with the disease pathogenesis. Mitochondrial DNA (mtDNA) variants are involved with functional dysfunction of mitochondrion and play a pivotal role in the susceptibility to T2D. In this study, we opted to find the association of mtDNA variants within the D-loop hypervariable region I (HVI), haplogroups and mtDNA copy number with T2D in Bangladeshi population. A total of 300 unrelated Bangladeshi individuals (150 healthy and 150 patients with T2D) were recruited in the present study, their HVI regions were amplified and sequenced using Sanger chemistry. Haplogrep2 and Phylotree17 tools were employed to determine the haplogroups. MtDNA copy number was measured using primers of mitochondrial tRNA Leu (UUR) gene and nuclear β2-microglobulin gene. Variants G16048A (OR:0.12, p = 0.04) and G16129A (OR: 0.42, p = 0.007) were found to confer protective role against T2D according to logistic regression analysis. However along with G16129A, two new variants C16294T and T16325C demonstrated protective role against T2D when age and gender were adjusted. Haplogroups A and H showed significant association with the risk of T2D after adjustments out of total 19 major haplogroups identified. The mtDNA copy numbers were stratified into 4 groups according to the quartiles (groups with lower, medium, upper and higher mtDNA copy numbers were respectively designated as LCN, MCN, UCN and HCN). Patients with T2D had significantly lower mtDNA copy number compared to their healthy counterparts in HCN group. Moreover, six mtDNA variants were significantly associated with mtDNA copy number in the participants. Thus, our study confers that certain haplogroups and novel variants of mtDNA are significantly associated with T2D while decreased mtDNA copy number (though not significant) has been observed in patients with T2D. However, largescale studies are warranted to establish association of novel variants and haplogroup with type 2 diabetes.

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Mitochondrial DNA Copy Number Is a Potential Biomarker for Treatment Choice Between Metformin and Acarbose

Wang

Liang

Wang

et al. 2023

Clin Pharma and Therapeutics

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Metformin is the first-line drug for type 2 diabetes (T2D) while acarbose is suggested as a viable alternative in Chinese patients with newly diagnosed T2D. However, few biomarkers have been established to guide the choice between these two agents. Mitochondrial DNA (mtDNA) copy number (mtDNA-CN) is a biomarker of mitochondrial function, which is associated with various metabolic outcomes. Using data from the trial of Metformin and Acarbose in Chinese as the Initial Hypoglycaemic Treatment (MARCH) (metformin n = 214; acarbose n = 198), we examined whether mtDNA-CN was associated with response to the drugs in terms of glycemic response and β-cell function protection response. The glycemic response is defined as the maximum glucose reduction of glycated hemoglobin A 1c , fasting plasma glucose, or postprandial blood glucose during 48 weeks. β-cell function protection response is defined as the maximum increment of insulinogenic index (IGI) or disposition index (DI). For all three glycemic responses, mtDNA-CN was not significantly associated with either metformin or acarbose. Importantly, for β-cell function protection response, we found the increased mtDNA-CN was significantly associated with more IGI increment (beta: 0.84; 95% confidence interval (CI), 0.02 to 1.66) in the metformin group, but less IGI increment (beta: −1.38; 95% CI, −2.52 to −0.23) in the acarbose group. A significant interaction (P = 0.008) between mtDNA-CN and the treatment group was observed. Consistent results were also obtained when DI increment was used as a measure of β-cell function response. This study demonstrated the potential application of mtDNA-CN in guiding the treatment choice between metformin and acarbose based on β-cell protection.

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Association of mitochondrial DNA copy number with metabolic syndrome and type 2 diabetes in 14 176 individuals

Abstract: Association of mitochondrial DNA copy number with metabolic syndrome and type 2 diabetes in 14 176 individuals (Original Article).

Cited by 62 publications

References 53 publications

Mitochondrial dysfunction as part of an inflammatory intermediate phenotype that drives premature ageing

Mitochondrial dysfunction as part of an inflammatory intermediate phenotype that drives premature ageing

Evaluation of D-loop hypervariable region I variations, haplogroups and copy number of mitochondrial DNA in Bangladeshi population with type 2 diabetes

Mitochondrial DNA Copy Number Is a Potential Biomarker for Treatment Choice Between Metformin and Acarbose

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