Background: Mitochondrial DNA (Mt-DNA) copy number (mtDNA-CN) has been proposed as a marker of diabetic kidney disease (DKD) . Most studies are in type 2 diabetes. We determined mtDNA-CN in adults with type 1 diabetes vs. non-diabetic subjects, including associations with complications and risk factors.
Methods: Cross-sectional study: 178 T1D adults (mean (SD) age: 38 (14) yrs, 21 (14) yrs T1D, HbA1c: 8.0 (1.5) %, 36% with complications (CX+)) ; 132 non-diabetic adults (CON) (age: 37 (14) yrs, HbA1c: 5.1 (0.4) %) . mtDNA-CN by RT-PCR (ScienCell, Carlsbad, CA) in DNA from whole blood samples.
Results: T1D vs. CON: Median (LQ, UQ) mtDNA-CN in T1D vs. CON: 270.8 (189.4, 348.1) vs. 320.5 (264.4, 410.5) ; p<0.0001. mtDNA-CN was lower in T1D with vs. without DKD (238.2 (179.6, 309.1) vs. 293.7 (197.6, 364.4) ; p=0.02, but did not differ by retinopathy or macrovascular disease. T1D mtDNA-CN tertiles: The highest tertile had lowest CX rate (25% (tertile 3) vs. 41% (tertiles 1+2) , p=0.03. Detectable C-peptide rates increased with higher mtDNA-CN tertiles (55%, 69%, 79%, p=0.02) . There were no differences by sex, smoking, BMI status, metabolic syndrome, HbA1c, exercise, statins or ACE/ARB. Correlates of mtDNA-CN: In T1D: FBG (r=-0.19, p=0.02) , HDL-C (r=0.17, p=0.03) , WCC (r=-0.16, p=0.04) , sVCAM-1 (r=-0.17, p=0.03) and sICAM-1 (r=-0.20, p=0.02) . In CON: WHR (r=-0.22, p=0.03) ; WCC (r=-0.24, p=0.007) . Independent determinants of mtDNA-CN: In T1D: age (-0.25±0.10; p=0.02) , HDL-C (0.27±0.10; p=0.007) , sICAM-1 (-0.42±0.12; p=0.001) . Area under ROC curve 0.72. In CON: pulse pressure (0.25±013; p=0.047) , WCC (-0.41±0.15; p=0.005) , smoking status (never) (0.22±0.13; p=0.09) ; sex (female) (0.35±0.12; p=0.005) . Area under ROC curve 0.74.
Conclusion: T1D per se is associated with lower mtDNA-CN than CON, particularly with DKD. Higher mtDNA-CN in T1D is associated with detectable C-peptide. Age and inflammation related factors are associated with mtDNA-CN. Longitudinal and intervention studies are merited.
A.S.Januszewski: None. L.Carroll: None. Y.W.Loh: None. D.N.O'neal: None. A.Jenkins: Advisory Panel; Abbott Diabetes, Amgen Inc., Board Member; Insulin for Life , International Diabetes Federation Western Pacific Region, Research Support; JDRF, Medtronic, Mylan N.V., NHMRC Australia.