Mitochondrial DNA copy number in adults with and without Type 1 diabetes
•First report of circulating mtDNA-cn in people with Type 1 diabetes and non-diabetic subjects.•Lower mtDNA-cn in adults with vs. without Type 1 diabetes.•Lower mtDNA-cn in adults with Type 1 diabetes with vs. without chronic kidney disease.•mtDNA-cn levels associated negatively with smoking, inflam...
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| Published in | Diabetes research and clinical practice Vol. 203; p. 110877 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Ireland
Elsevier B.V
01.09.2023
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0168-8227 1872-8227 1872-8227 |
| DOI | 10.1016/j.diabres.2023.110877 |
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| Abstract | •First report of circulating mtDNA-cn in people with Type 1 diabetes and non-diabetic subjects.•Lower mtDNA-cn in adults with vs. without Type 1 diabetes.•Lower mtDNA-cn in adults with Type 1 diabetes with vs. without chronic kidney disease.•mtDNA-cn levels associated negatively with smoking, inflammation and blood pressure.
Mitochondrial damage is implicated in diabetes pathogenesis and complications. Mitochondrial DNA copy number (mtDNA-cn) in human Type 1 diabetes (T1D) studies are lacking. We related mtDNA-cn in T1D and non-diabetic adults (CON) with diabetes complications and risk factors.
Cross-sectional study: 178 T1D, 132 non-diabetic controls. Associations of whole blood mtDNA-cn (qPCR) with complications, inflammation, and C-peptide.
mtDNA-cn (median (LQ, UQ)) was lower in: T1D vs. CON (271 (189, 348) vs. 320 (264, 410); p < 0.0001); T1D with vs. without kidney disease (238 (180, 309) vs. 294 (198, 364); p = 0.02); and insulin injection vs. pump-users (251 (180, 340) vs. 322 (263, 406); p = 0.008). Significant univariate correlates of mtDNA-cn: T1D: (positive) HDL-C; (negative) fasting glucose, white cell count (WCC), sVCAM-1, sICAM-1; CON: (negative) WHR (waist-hip-ratio). Detectable C-peptide in T1D increased with lowest-highest mtDNA-cn tertiles (54%, 69%, 79%, p = 0.02). Independent determinants of mtDNA-cn: T1D: (positive) HDL-C; (negative) age, sICAM-1; AUROC 0.71; CON: WCC (negative), never smoking, (positive) female, pulse pressure; AUROC 0.74.
mtDNA-cn is lower in T1D vs. CON, and in T1D kidney disease. In T1D, mtDNA-cn correlates inversely with age and inflammation, and positively with HDL-C, detectable C-peptide and pump use. Further clinical and basic science studies are merited. |
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| AbstractList | Mitochondrial damage is implicated in diabetes pathogenesis and complications. Mitochondrial DNA copy number (mtDNA-cn) in human Type 1 diabetes (T1D) studies are lacking. We related mtDNA-cn in T1D and non-diabetic adults (CON) with diabetes complications and risk factors.
Cross-sectional study: 178 T1D, 132 non-diabetic controls. Associations of whole blood mtDNA-cn (qPCR) with complications, inflammation, and C-peptide.
mtDNA-cn (median (LQ, UQ)) was lower in: T1D vs. CON (271 (189, 348) vs. 320 (264, 410); p<0.0001); T1D with vs. without kidney disease (238 (180, 309) vs. 294 (198, 364); p=0.02); and insulin injection vs. pump-users (251 (180, 340) vs. 322 (263, 406); p=0.008). Significant univariate correlates of mtDNA-cn: T1D: (positive) HDL-C; (negative) fasting glucose, white cell count (WCC), sVCAM-1, sICAM-1; CON: (negative) WHR (waist-hip-ratio). Detectable C-peptide in T1D increased with lowest-highest mtDNA-cn tertiles (54%, 69%, 79%, p=0.02). Independent determinants of mtDNA-cn: T1D: (positive) HDL-C; (negative) age, sICAM-1; AUROC 0.71; CON: WCC (negative), never smoking, (positive) female, pulse pressure; AUROC 0.74.
mtDNA-cn is lower in T1D vs. CON, and in T1D kidney disease. In T1D, mtDNA-cn correlates inversely with age and inflammation, and positively with HDL-C, detectable C-peptide and pump use. Further clinical and basic science studies are merited. •First report of circulating mtDNA-cn in people with Type 1 diabetes and non-diabetic subjects.•Lower mtDNA-cn in adults with vs. without Type 1 diabetes.•Lower mtDNA-cn in adults with Type 1 diabetes with vs. without chronic kidney disease.•mtDNA-cn levels associated negatively with smoking, inflammation and blood pressure. Mitochondrial damage is implicated in diabetes pathogenesis and complications. Mitochondrial DNA copy number (mtDNA-cn) in human Type 1 diabetes (T1D) studies are lacking. We related mtDNA-cn in T1D and non-diabetic adults (CON) with diabetes complications and risk factors. Cross-sectional study: 178 T1D, 132 non-diabetic controls. Associations of whole blood mtDNA-cn (qPCR) with complications, inflammation, and C-peptide. mtDNA-cn (median (LQ, UQ)) was lower in: T1D vs. CON (271 (189, 348) vs. 320 (264, 410); p < 0.0001); T1D with vs. without kidney disease (238 (180, 309) vs. 294 (198, 364); p = 0.02); and insulin injection vs. pump-users (251 (180, 340) vs. 322 (263, 406); p = 0.008). Significant univariate correlates of mtDNA-cn: T1D: (positive) HDL-C; (negative) fasting glucose, white cell count (WCC), sVCAM-1, sICAM-1; CON: (negative) WHR (waist-hip-ratio). Detectable C-peptide in T1D increased with lowest-highest mtDNA-cn tertiles (54%, 69%, 79%, p = 0.02). Independent determinants of mtDNA-cn: T1D: (positive) HDL-C; (negative) age, sICAM-1; AUROC 0.71; CON: WCC (negative), never smoking, (positive) female, pulse pressure; AUROC 0.74. mtDNA-cn is lower in T1D vs. CON, and in T1D kidney disease. In T1D, mtDNA-cn correlates inversely with age and inflammation, and positively with HDL-C, detectable C-peptide and pump use. Further clinical and basic science studies are merited. Mitochondrial damage is implicated in diabetes pathogenesis and complications. Mitochondrial DNA copy number (mtDNA-cn) in human Type 1 diabetes (T1D) studies are lacking. We related mtDNA-cn in T1D and non-diabetic adults (CON) with diabetes complications and risk factors.AIMSMitochondrial damage is implicated in diabetes pathogenesis and complications. Mitochondrial DNA copy number (mtDNA-cn) in human Type 1 diabetes (T1D) studies are lacking. We related mtDNA-cn in T1D and non-diabetic adults (CON) with diabetes complications and risk factors.Cross-sectional study: 178 T1D, 132 non-diabetic controls. Associations of whole blood mtDNA-cn (qPCR) with complications, inflammation, and C-peptide.METHODSCross-sectional study: 178 T1D, 132 non-diabetic controls. Associations of whole blood mtDNA-cn (qPCR) with complications, inflammation, and C-peptide.mtDNA-cn (median (LQ, UQ)) was lower in: T1D vs. CON (271 (189, 348) vs. 320 (264, 410); p < 0.0001); T1D with vs. without kidney disease (238 (180, 309) vs. 294 (198, 364); p = 0.02); and insulin injection vs. pump-users (251 (180, 340) vs. 322 (263, 406); p = 0.008). Significant univariate correlates of mtDNA-cn: T1D: (positive) HDL-C; (negative) fasting glucose, white cell count (WCC), sVCAM-1, sICAM-1; CON: (negative) WHR (waist-hip-ratio). Detectable C-peptide in T1D increased with lowest-highest mtDNA-cn tertiles (54%, 69%, 79%, p = 0.02). Independent determinants of mtDNA-cn: T1D: (positive) HDL-C; (negative) age, sICAM-1; AUROC 0.71; CON: WCC (negative), never smoking, (positive) female, pulse pressure; AUROC 0.74.RESULTSmtDNA-cn (median (LQ, UQ)) was lower in: T1D vs. CON (271 (189, 348) vs. 320 (264, 410); p < 0.0001); T1D with vs. without kidney disease (238 (180, 309) vs. 294 (198, 364); p = 0.02); and insulin injection vs. pump-users (251 (180, 340) vs. 322 (263, 406); p = 0.008). Significant univariate correlates of mtDNA-cn: T1D: (positive) HDL-C; (negative) fasting glucose, white cell count (WCC), sVCAM-1, sICAM-1; CON: (negative) WHR (waist-hip-ratio). Detectable C-peptide in T1D increased with lowest-highest mtDNA-cn tertiles (54%, 69%, 79%, p = 0.02). Independent determinants of mtDNA-cn: T1D: (positive) HDL-C; (negative) age, sICAM-1; AUROC 0.71; CON: WCC (negative), never smoking, (positive) female, pulse pressure; AUROC 0.74.mtDNA-cn is lower in T1D vs. CON, and in T1D kidney disease. In T1D, mtDNA-cn correlates inversely with age and inflammation, and positively with HDL-C, detectable C-peptide and pump use. Further clinical and basic science studies are merited.CONCLUSIONSmtDNA-cn is lower in T1D vs. CON, and in T1D kidney disease. In T1D, mtDNA-cn correlates inversely with age and inflammation, and positively with HDL-C, detectable C-peptide and pump use. Further clinical and basic science studies are merited. |
| ArticleNumber | 110877 |
| Author | Huang, Michael L.H. O'Neal, David N. Mangani, Abubakar Januszewski, Andrzej S. Jenkins, Alicia J. Carroll, Luke M. Wen-Loh, Yik |
| Author_xml | – sequence: 1 givenname: Alicia J. surname: Jenkins fullname: Jenkins, Alicia J. organization: NHMRC Clinical Trials Centre, The University of Sydney, NSW, Australia – sequence: 2 givenname: Luke M. surname: Carroll fullname: Carroll, Luke M. organization: NHMRC Clinical Trials Centre, The University of Sydney, NSW, Australia – sequence: 3 givenname: Michael L.H. surname: Huang fullname: Huang, Michael L.H. organization: NHMRC Clinical Trials Centre, The University of Sydney, NSW, Australia – sequence: 4 givenname: Yik surname: Wen-Loh fullname: Wen-Loh, Yik organization: NHMRC Clinical Trials Centre, The University of Sydney, NSW, Australia – sequence: 5 givenname: Abubakar surname: Mangani fullname: Mangani, Abubakar organization: NHMRC Clinical Trials Centre, The University of Sydney, NSW, Australia – sequence: 6 givenname: David N. surname: O'Neal fullname: O'Neal, David N. organization: NHMRC Clinical Trials Centre, The University of Sydney, NSW, Australia – sequence: 7 givenname: Andrzej S. surname: Januszewski fullname: Januszewski, Andrzej S. email: andrzej.januszewski@sydney.edu.au organization: NHMRC Clinical Trials Centre, The University of Sydney, NSW, Australia |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/37579994$$D View this record in MEDLINE/PubMed |
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| Keywords | Mitochondrial DNA copy number Mitochondria Type 1 diabetes Complications Humans Risk factors risk factors complications humans mitochondrial DNA copy number mitochondria |
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10.1016/j.diabres.2023.110877_b0155 article-title: Accumulation of 8-hydroxy-2'-deoxyguanosine and mitochondrial DNA deletion in kidney of diabetic rats publication-title: Diabetes doi: 10.2337/diabetes.51.5.1588 – volume: 23 start-page: 1371 issue: 6 year: 2021 ident: 10.1016/j.diabres.2023.110877_b0245 article-title: Metformin and carotid intima-media thickness in never-smokers with type 1 diabetes: The REMOVAL trial publication-title: Diabetes Obes Metab doi: 10.1111/dom.14350 – volume: 41 start-page: 253 issue: 4 year: 2009 ident: 10.1016/j.diabres.2023.110877_b0090 article-title: Higher mitochondrial DNA copy number is associated with lower prevalence of microalbuminuria publication-title: Exp Mol Med doi: 10.3858/emm.2009.41.4.028 |
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| Snippet | •First report of circulating mtDNA-cn in people with Type 1 diabetes and non-diabetic subjects.•Lower mtDNA-cn in adults with vs. without Type 1... Mitochondrial damage is implicated in diabetes pathogenesis and complications. Mitochondrial DNA copy number (mtDNA-cn) in human Type 1 diabetes (T1D) studies... |
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| SubjectTerms | Complications Humans Mitochondria Mitochondrial DNA copy number Risk factors Type 1 diabetes |
| Title | Mitochondrial DNA copy number in adults with and without Type 1 diabetes |
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