Table 4

Associations between biomarker measures and time to progression to kidney dysfunction during two window lengths

10-Year window3-Year window
EventsHR (95% CI)*HR (95% CI)EventsHR (95% CI)*HR (95% CI)
CKD
 sTNFR-1641.29 (1.16–1.45)1.36 (1.23–1.49)231.61 (1.43–1.82)1.56 (1.40–1.74)
 sTNFR-2741.55 (1.38–1.74)1.63 (1.47–1.82)251.77 (1.52–2.06)1.97 (1.70–2.29)
 sE-selectin611.31 (1.14–1.50)1.23 (1.08–1.40)231.42 (1.19–1.70)1.38 (1.18–1.61)
 PAI-1 active741.23 (1.06–1.43)1.15 (0.95–1.39)251.30 (1.03–1.65)1.18 (0.87–1.61)
 PAI-1 total741.23 (1.02–1.49)1.14 (0.94–1.39)251.55 (1.23–1.94)1.52 (1.24–1.87)
 sICAM-1741.09 (0.86–1.37)1.02 (0.79–1.31)250.84 (0.53–1.32)0.88 (0.56–1.38)
 sVCAM-1630.82 (0.60–1.12)0.88 (0.65–1.17)230.74 (0.42–1.30)0.76 (0.41–1.40)
 IL-6610.85 (0.66–1.09)0.91 (0.75–1.10)211.11 (0.90–1.37)1.13 (0.96–1.33)
 Fibrinogen461.96 (1.36–2.83)1.74 (1.24–2.45)182.59 (1.50–4.47)2.13 (1.29–3.51)
 CRP640.93 (0.76–1.15)0.88 (0.67–1.15)231.06 (0.77–1.47)0.99 (0.63–1.56)
 Composite scores
  Acute-phase reagents461.34 (1.05–1.72)1.25 (0.99–1.57)181.51 (1.09–2.10)1.56 (1.19–2.04)
  Cytokines/adipokines611.53 (1.27–1.85)1.70 (1.34–2.15)213.58 (2.45–5.23)3.25 (2.20–4.81)
  Thrombosis461.92 (1.37–2.70)1.77 (1.20–2.61)182.91 (1.86–4.54)2.45 (1.50–4.01)
  Endothelial dysfunction601.82 (0.78–4.24)1.59 (1.06–2.38)232.28 (1.21–4.28)2.16 (1.27–3.68)
MA
 sTNFR-11161.09 (0.97–1.23)1.08 (0.97–1.20)391.19 (1.02–1.38)1.10 (0.83–1.44)
 sTNFR-21431.31 (1.18–1.46)1.25 (1.10–1.42)441.32 (1.15–1.52)1.19 (0.97–1.46)
 sE-selectin1171.20 (1.07–1.35)1.17 (1.04–1.33)401.10 (0.92–1.33)0.96 (0.70–1.32)
 PAI-1 active1411.22 (1.07–1.38)1.10 (0.96–1.27)431.13 (0.90–1.42)0.97 (0.70–1.34)
 PAI-1 total1431.22 (1.06–1.41)1.17 (1.00–1.36)441.27 (0.99–1.63)1.22 (0.93–1.61)
 sICAM-11431.16 (0.97–1.40)1.19 (0.99–1.42)441.02 (0.71–1.46)1.07 (0.78–1.47)
 sVCAM-11000.85 (0.67–1.09)0.93 (0.76–1.15)361.03 (0.70–1.53)1.11 (0.85–1.45)
 IL-61130.96 (0.84–1.08)1.02 (0.93–1.13)380.97 (0.72–1.30)1.05 (0.84–1.32)
 Fibrinogen701.01 (0.80–1.27)1.01 (0.79–1.30)260.72 (0.46–1.12)0.62 (0.38–1.03)
 CRP1150.95 (0.79–1.14)0.95 (0.77–1.18)380.88 (0.63–1.23)0.83 (0.48–1.43)
 Composite scores
  Acute-phase reagents700.84 (0.63–1.11)0.86 (0.60–1.24)260.57 (0.31–1.05)0.41 (0.18–0.92)
  Cytokines/adipokines1131.26 (1.06–1.50)1.30 (1.04–1.63)381.47 (0.99–2.16)1.28 (0.75–2.20)
  Thrombosis701.53 (1.12–2.08)1.26 (0.89–1.78)260.96 (0.57–1.62)0.87 (0.41–1.86)
  Endothelial dysfunction991.61 (1.19–2.19)1.47 (1.06–2.04)361.08 (0.60–1.95)0.83 (0.48–1.45)
  • Boldface indicates significance at P < 0.05.

  • *Initial model adjusted for concurrent HbA1c %.

  • †Covariate-adjusted model also adjusted for sex, concurrent duration of type 1 diabetes, cholesterol (CKD), triglycerides (MA), and blood pressure. Time to MA was also adjusted for AER values measured concurrently with biomarkers.

  • ‡Composite scores were created by combining the standardized individual biomarkers as follows: acute-phase reactants (fibrinogen and CRP), cytokines/adipokines (sTNFR-1/2, active PAI-1, total PAI-1, and IL-6), thrombosis (fibrinogen, active PAI-1, and total PAI-1), and endothelial dysfunction (sICAM-1, inverse of sVCAM-1, and sE-selectin). The inverse z score of sVCAM-1 was used because of its consistent inverse relationship with the outcomes of interest.