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Table 3 Association of four DNAm ages with development of T1D complication

From: DNA methylation age calculators reveal association with diabetic neuropathy in type 1 diabetes

 Total
N
Events
N
Model 1Model 2
CVD      
 CVD events from DNAm measurement to EDIC year 2049658HR (95% CI)pHR (95% CI)p
  Pan-tissue  1.03 (0.96–1.10)0.4331.03 (0.96–1.11)0.371
  Skin & Blood  1.06 (0.97–1.16)0.2071.07 (0.97–1.18)0.166
  PhenoAge  1.05 (0.99–1.10)0.0861.05 (1.00–1.11)0.061
  GrimAge  1.04 (0.99–1.10)0.1631.04 (0.99–1.10)0.085
Nephropathy and renal function      
 Repeated eGFR from EDIC year 0 to 18 (ml/min/1.73 m2)498NABeta (SE)pBeta (SE)p
  Pan-tissue  − 0.17 (0.10)0.075− 0.18 (0.10)0.063
  Skin & Blood  − 0.20 (0.13)0.119− 0.23 (0.13)0.084
  PhenoAge  − 0.13 (0.08)0.099− 0.14 (0.08)0.068
  GrimAge  0.05 (0.09)0.5310.03 (0.09)0.736
 Sustained eGFR <60 ml/min/1.73 m2 during EDIC year 0-1849823HR (95% CI)pHR (95% CI)p
  Pan-tissue  1.11 (0.99–1.26)0.0771.12 (0.99–1.27)0.075
  Skin & Blood  1.08 (0.94–1.23)0.2871.07 (0.94–1.23)0.318
  PhenoAge  1.06 (0.98–1.15)0.1601.06 (0.97–1.14)0.199
  GrimAge  1.04 (0.96–1.13)0.3151.04 (0.95–1.13)0.432
 Repeated AER from EDIC year 0 to 18 (mg/24 h loge transformed)499NABeta (SE)pBeta (SE)p
  Pan-tissue  0.011 (0.010)0.2730.011 (0.011)0.282
  Skin & Blood  0.021 (0.014)0.1460.021 (0.014)0.138
  PhenoAge  0.023 (0.008)6.78E−30.024 (0.009)4.83E−3
  GrimAge  0.029 (0.009)2.13E−30.032 (0.009)7.23E−4
 AER ≥ 300 mg/24 h during EDIC year 0–1848429HR (95% CI)pHR (95% CI)p
  Pan-tissue  1.04 (0.94–1.15)0.4651.01 (0.91–1.12)0.846
  Skin & Blood  1.05 (0.92–1.19)0.5151.08 (0.94–1.24)0.292
  PhenoAge  1.05 (0.97–1.12)0.2111.04 (0.97–1.12)0.277
  GrimAge  1.06 (0.98–1.14)0.1521.04 (0.96–1.13)0.309
Retinopathy      
 SNPDR during EDIC year 0–1847392HR (95% CI)pHR (95% CI)p
  Pan-tissue  1.02 (0.97–1.08)0.3961.01 (0.95–1.07)0.765
  Skin & Blood  1.06 (0.98–1.14)0.1361.04 (0.96–1.13)0.343
  PhenoAge  1.04 (0.99–1.08)0.1111.03 (0.98–1.07)0.287
  GrimAge  1.04 (0.99–1.08)0.1351.00 (0.95–1.05)0.892
 PDR during EDIC year 0–1848296HR (95% CI)pHR (95% CI)p
  Pan-tissue  1.01 (0.96–1.07)0.5840.99 (0.94–1.05)0.790
  Skin & Blood  1.05 (0.98–1.14)0.1801.03 (0.95–1.12)0.497
  PhenoAge  1.03 (0.99–1.08)0.1311.02 (0.98–1.07)0.400
  GrimAge  1.03 (0.98–1.07)0.2560.99 (0.94–1.04)0.698
 CSME during EDIC year 0–18464108HR (95% CI)pHR (95% CI)p
  Pan-tissue  1.04 (0.99–1.09)0.1761.04 (0.98–1.09)0.179
  Skin & Blood  1.00 (0.94–1.08)0.9350.99 (0.92–1.07)0.827
  PhenoAge  1.04 (1.00–1.08)0.0911.01 (0.97–1.06)0.517
  GrimAge  1.02 (0.97–1.06)0.4281.00 (0.95–1.04)0.843
Neuropathy      
 DPN at EDIC year 13–15431109OR (95% CI)pOR (95% CI)p
  Pan-tissue  1.02 (0.96–1.08)0.5621.02 (0.96–1.09)0.466
  Skin & Blood  0.96 (0.88–1.05)0.3450.96 (0.88–1.05)0.352
  PhenoAge  1.02 (0.98–1.07)0.3561.02 (0.97–1.07)0.448
  GrimAge  1.07 (1.02–1.12)9.24E−31.07 (1.01–1.12)2.17E−2
 CAN at EDIC year 13–18446176OR (95% CI)pOR (95% CI)p
  Pan-tissue  1.01 (0.96–1.07)0.6351.02 (0.97–1.07)0.526
  Skin & Blood  0.99 (0.92–1.06)0.7580.99 (0.92–1.07)0.844
  PhenoAge  1.01 (0.97–1.05)0.6891.00 (0.96–1.05)0.971
  GrimAge  1.06 (1.01–1.11)1.07E−21.06 (1.01–1.11)2.39E−2
  1. Model 1, adjusted for batch, cell proportions, sex, age, and T1D duration at DNAm measurement; model 2, adjusted for all covariates in model 1 plus repeated measures of HbA1c
  2. HR hazard ratio, OR odds ratio, CI confidence interval, SE standard error, CVD cardiovascular diseases, eGFR estimated glomerular filtration rate, AER albumin excretion rate, SNPDR sever non-proliferative diabetic retinopathy, PDR proliferative diabetic retinopathy, CSME clinically significant macular edema, DPN diabetic peripheral neuropathy, CAN cardiovascular autonomic neuropathy