Table 2

Univariate analysis of risk factors versus further worsening retinopathy, new onset of nephropathy, or new onset of neuropathy during EDIC study#

CharacteristicsThree-step or more ETDRS scale progression from DCCT closeout through EDIC study years 13–16Development of microalbuminuria or worse (AER ≥ 40 mg/24 h) from DCCT closeout through EDIC study years 15–16Development of confirmed clinical neuropathy or abnormal autonomic function from DCCT closeout to EDIC study years 13–14 or 16–17*
Event
(N = 91)Nonevent
(N = 122)P valueEvent
(N = 50)Nonevent
(N = 145)P valueEvent
(N = 74)Nonevent
(N = 91)P value
Demographic
 Age at EDIC study baseline (years)33.6 ± 7.034.3 ± 6.60.5232.6 ± 6.934.5 ± 6.60.0934.7 ± 6.332.5 ± 6.50.04
 Women (%)52.843.30.1858.044.80.1144.648.40.63
 Diabetes duration at EDIC study baseline (years)10.5 ± 4.411.0 ± 5.00.6410.1 ± 3.910.7 ± 4.80.7010.8 ± 4.610.4 ± 4.70.52
 DCCT treatment group intensives (%)44.065.50.00248.060.70.1256.856.00.93
Glycemia control
 DCCT mean A1C
  %8.7 ± 1.77.5 ± 1.3<0.00018.8 ± 1.67.7 ± 1.4<0.00018.3 ± 1.77.7 ± 1.30.04
  mmol/mol72 ± 18.658 ± 14.273 ± 17.561 ± 15.367 ± 18.661 ± 14.2
 EDIC study mean A1C up to EDIC study year 16
  % 8.6 ± 1.27.6 ± 0.9<0.00018.9 ± 1.27.7 ± 1.0<0.00018.3 ± 1.37.7 ± 0.90.004
  mmol/mol70 ± 13.160 ± 9.874 ± 13.161 ± 10.967 ± 14.261 ± 9.8
Medical at EDIC study baseline
 Mean blood pressure (mmHg)90.2 ± 1088.5 ± 7.90.2390.9 ± 8.788.4 ± 8.20.1089.9 ± 7.487.9 ± 8.70.19
 Hypertension (%)8.81.60.0178.03.50.192.75.50.38
  Triglycerides (mg/dL)81.3 ± 4077.6 ± 440.3982.9 ± 4274.5 ± 400.2186.3 ± 5775.8 ± 340.63
  HDL cholesterol (mg/dL)52.9 ± 1350.3 ± 130.1552.1 ± 1251.5 ± 130.7450.8 ± 1550.6 ± 110.67
  LDL cholesterol (mg/dL)113 ± 28108 ± 280.16114 ± 27108 ± 280.08119 ± 31106 ± 270.004
  Overweight (%)55.054.10.9062.053.10.2860.849.50.15
  Smoker (%)28.618.90.1026.018.60.2729.718.70.10
Retinopathy at EDIC study baseline (%)
 No retinopathy (10/10)30.827.920.034.521.635.2
 Microaneurysm only (20/<20)30.841.00.2234.039.30.00840.542.90.01
 Mild NPDR (35/<35)20.024.630.017.924.315.4
 Moderate NPDR or worse (43/≤43+)18.96.616.08.313.56.6
Renal at EDIC study baseline
 AER (mg/24 h)10.17.20.000210.17.20.0009101.17.20.007
 Median (interquartiles)(6, 20)(4, 12)(7, 17)(4, 10)(6, 20)(6, 12)
 AER ≥40 (%)14.34.10.0080 ∼0 ∼n/a16.22.20.001
Neuropathy at EDIC study baseline (%)
 Confirmed clinical neuropathy12.26.60.1512.07.60.3500n/a
 Abnormal autonomic function15.12.80.0039.15.70.4400n/a
Skin collagens at EDIC study baseline
 FUR (pmol/mg)878 ± 251686 ± 179<0.0001875 ± 236706 ± 194<0.0001821 ± 233691 ± 2120.0001
 CML (pmol/mg)580 ± 138503 ± 117<0.0001569 ± 125513 ± 1300.009571 ± 119502 ± 130<0.0001
 Pentosidine (pmol/mg)27.7 ± 7.624.6 ± 6.90.00227.5 ± 8.024.8 ± 6.80.0227.1 ± 6.924.0 ± 6.70.005
 Fluorescence (pmol/mg)193 ± 43183 ± 520.01194 ± 42181 ± 510.02192 ± 46175 ± 400.007
 Acid-soluble collagen (%)0.54 ± 0.40.56 ± 0.30.030.54 ± 0.40.57 ± 0.30.110.50 ± 0.20.57 ± 0.30.10
 Pepsin-soluble collagen (%)6.0 ± 3.57.2 ± 3.00.00016.1 ± 2.77.2 ± 3.40.026.0 ± 2.47.3 ± 3.50.02
 GSPNE (nmoles/mg)2.8 ± 0.72.3 ± 0.5<0.00012.7 ± 0.52.4 ± 0.60.00012.7 ± 0.72.3 ± 0.6<0.0001
 CEL (pmol/mg)164 ± 120134 ± 960.06147 ± 83144 ± 1160.14161 ± 115135 ± 940.09
 G-H1 (pmol/mg)66 ± 4265 ± 270.4074 ± 4764 ± 290.4262 ± 3662 ± 260.55
 MG-H1 (nmol/mg)0.91 ± 0.50.73 ± 0.40.0040.90 ± 0.60.76 ± 0.40.100.92 ± 0.60.68 ± 0.30.006
  • Data are mean ± SD, unless otherwise indicated.

  • #Analyses only included subjects who were at risk for an outcome during the EDIC study, with those subjects with a pre-existing outcome during the DCCT being excluded. The retinopathy analysis excluded those who underwent scatter photocoagulation during the DCCT (n = 2). The nephropathy analyses excluded those who had AER >40 mg/24 h at DCCT closeout (n = 20). The neuropathy analysis excluded those who had confirmed clinical neuropathy or abnormal autonomic neuropathy (n = 30) at DCCT closeout. NPDR, nonproliferative diabetic retinopathy.

  • *Confirmed clinical neuropathy at EDIC study years 13–14 or abnormal autonomic function at EDIC study years 13–14 or 16–17.

  • †Hypertension was defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg.

  • ‡Overweight was defined as BMI ≥25 kg/m2.