Mitochondrial DNA copy number in adults with and without Type 1 diabetes

• Published in: Diabetes research and clinical practice Vol. 203; p. 110877
• Main Authors: Jenkins, Alicia J., Carroll, Luke M., Huang, Michael L.H., Wen-Loh, Yik, Mangani, Abubakar, O'Neal, David N., Januszewski, Andrzej S.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.09.2023
• Subjects: Complications; Humans; Mitochondria; Mitochondrial DNA copy number; Risk factors; Type 1 diabetes; Mitochondrial DNA copy number; Mitochondria; Type 1 diabetes; Complications; Humans; Risk factors; risk factors; complications; humans; mitochondrial DNA copy number; mitochondria
• ISSN: 0168-8227; 1872-8227; 1872-8227
• DOI: 10.1016/j.diabres.2023.110877

•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.