Table 2.
Univariate analysis of risk factors versus further worsening retinopathy, new onset of nephropathy, or new onset of neuropathy during EDIC study#
| Characteristics | Three-step or more ETDRS scale progression from DCCT closeout through EDIC study years 13–16 |
Development of microalbuminuria or worse (AER ≥ 40 mg/24 h) from DCCT closeout through EDIC study years 15–16 |
Development 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 value | Event (N = 50) | Nonevent (N = 145) | P value | Event (N = 74) | Nonevent (N = 91) | P value | |
| Demographic | |||||||||
| Age at EDIC study baseline (years) | 33.6 ± 7.0 | 34.3 ± 6.6 | 0.52 | 32.6 ± 6.9 | 34.5 ± 6.6 | 0.09 | 34.7 ± 6.3 | 32.5 ± 6.5 | 0.04 |
| Women (%) | 52.8 | 43.3 | 0.18 | 58.0 | 44.8 | 0.11 | 44.6 | 48.4 | 0.63 |
| Diabetes duration at EDIC study baseline (years) | 10.5 ± 4.4 | 11.0 ± 5.0 | 0.64 | 10.1 ± 3.9 | 10.7 ± 4.8 | 0.70 | 10.8 ± 4.6 | 10.4 ± 4.7 | 0.52 |
| DCCT treatment group intensives (%) | 44.0 | 65.5 | 0.002 | 48.0 | 60.7 | 0.12 | 56.8 | 56.0 | 0.93 |
| Glycemia control | |||||||||
| DCCT mean A1C | |||||||||
| % | 8.7 ± 1.7 | 7.5 ± 1.3 | <0.0001 | 8.8 ± 1.6 | 7.7 ± 1.4 | <0.0001 | 8.3 ± 1.7 | 7.7 ± 1.3 | 0.04 |
| mmol/mol | 72 ± 18.6 | 58 ± 14.2 | 73 ± 17.5 | 61 ± 15.3 | 67 ± 18.6 | 61 ± 14.2 | |||
| EDIC study mean A1C up to EDIC study year 16 | |||||||||
| % | 8.6 ± 1.2 | 7.6 ± 0.9 | <0.0001 | 8.9 ± 1.2 | 7.7 ± 1.0 | <0.0001 | 8.3 ± 1.3 | 7.7 ± 0.9 | 0.004 |
| mmol/mol | 70 ± 13.1 | 60 ± 9.8 | 74 ± 13.1 | 61 ± 10.9 | 67 ± 14.2 | 61 ± 9.8 | |||
| Medical at EDIC study baseline | |||||||||
| Mean blood pressure (mmHg) | 90.2 ± 10 | 88.5 ± 7.9 | 0.23 | 90.9 ± 8.7 | 88.4 ± 8.2 | 0.10 | 89.9 ± 7.4 | 87.9 ± 8.7 | 0.19 |
| Hypertension (%)† | 8.8 | 1.6 | 0.017 | 8.0 | 3.5 | 0.19 | 2.7 | 5.5 | 0.38 |
| Triglycerides (mg/dL) | 81.3 ± 40 | 77.6 ± 44 | 0.39 | 82.9 ± 42 | 74.5 ± 40 | 0.21 | 86.3 ± 57 | 75.8 ± 34 | 0.63 |
| HDL cholesterol (mg/dL) | 52.9 ± 13 | 50.3 ± 13 | 0.15 | 52.1 ± 12 | 51.5 ± 13 | 0.74 | 50.8 ± 15 | 50.6 ± 11 | 0.67 |
| LDL cholesterol (mg/dL) | 113 ± 28 | 108 ± 28 | 0.16 | 114 ± 27 | 108 ± 28 | 0.08 | 119 ± 31 | 106 ± 27 | 0.004 |
| Overweight (%)‡ | 55.0 | 54.1 | 0.90 | 62.0 | 53.1 | 0.28 | 60.8 | 49.5 | 0.15 |
| Smoker (%) | 28.6 | 18.9 | 0.10 | 26.0 | 18.6 | 0.27 | 29.7 | 18.7 | 0.10 |
| Retinopathy at EDIC study baseline (%) | |||||||||
| No retinopathy (10/10) | 30.8 | 27.9 | 20.0 | 34.5 | 21.6 | 35.2 | |||
| Microaneurysm only (20/<20) | 30.8 | 41.0 | 0.22 | 34.0 | 39.3 | 0.008 | 40.5 | 42.9 | 0.01 |
| Mild NPDR (35/<35) | 20.0 | 24.6 | 30.0 | 17.9 | 24.3 | 15.4 | |||
| Moderate NPDR or worse (43/≤43+) | 18.9 | 6.6 | 16.0 | 8.3 | 13.5 | 6.6 | |||
| Renal at EDIC study baseline | |||||||||
| AER (mg/24 h) | 10.1 | 7.2 | 0.0002 | 10.1 | 7.2 | 0.0009 | 101.1 | 7.2 | 0.007 |
| Median (interquartiles) | (6, 20) | (4, 12) | (7, 17) | (4, 10) | (6, 20) | (6, 12) | |||
| AER ≥40 (%) | 14.3 | 4.1 | 0.008 | 0 ∼ | 0 ∼ | n/a | 16.2 | 2.2 | 0.001 |
| Neuropathy at EDIC study baseline (%) | |||||||||
| Confirmed clinical neuropathy | 12.2 | 6.6 | 0.15 | 12.0 | 7.6 | 0.35 | 0 | 0 | n/a |
| Abnormal autonomic function | 15.1 | 2.8 | 0.003 | 9.1 | 5.7 | 0.44 | 0 | 0 | n/a |
| Skin collagens at EDIC study baseline | |||||||||
| FUR (pmol/mg) | 878 ± 251 | 686 ± 179 | <0.0001 | 875 ± 236 | 706 ± 194 | <0.0001 | 821 ± 233 | 691 ± 212 | 0.0001 |
| CML (pmol/mg) | 580 ± 138 | 503 ± 117 | <0.0001 | 569 ± 125 | 513 ± 130 | 0.009 | 571 ± 119 | 502 ± 130 | <0.0001 |
| Pentosidine (pmol/mg) | 27.7 ± 7.6 | 24.6 ± 6.9 | 0.002 | 27.5 ± 8.0 | 24.8 ± 6.8 | 0.02 | 27.1 ± 6.9 | 24.0 ± 6.7 | 0.005 |
| Fluorescence (pmol/mg) | 193 ± 43 | 183 ± 52 | 0.01 | 194 ± 42 | 181 ± 51 | 0.02 | 192 ± 46 | 175 ± 40 | 0.007 |
| Acid-soluble collagen (%) | 0.54 ± 0.4 | 0.56 ± 0.3 | 0.03 | 0.54 ± 0.4 | 0.57 ± 0.3 | 0.11 | 0.50 ± 0.2 | 0.57 ± 0.3 | 0.10 |
| Pepsin-soluble collagen (%) | 6.0 ± 3.5 | 7.2 ± 3.0 | 0.0001 | 6.1 ± 2.7 | 7.2 ± 3.4 | 0.02 | 6.0 ± 2.4 | 7.3 ± 3.5 | 0.02 |
| GSPNE (nmoles/mg) | 2.8 ± 0.7 | 2.3 ± 0.5 | <0.0001 | 2.7 ± 0.5 | 2.4 ± 0.6 | 0.0001 | 2.7 ± 0.7 | 2.3 ± 0.6 | <0.0001 |
| CEL (pmol/mg) | 164 ± 120 | 134 ± 96 | 0.06 | 147 ± 83 | 144 ± 116 | 0.14 | 161 ± 115 | 135 ± 94 | 0.09 |
| G-H1 (pmol/mg) | 66 ± 42 | 65 ± 27 | 0.40 | 74 ± 47 | 64 ± 29 | 0.42 | 62 ± 36 | 62 ± 26 | 0.55 |
| MG-H1 (nmol/mg) | 0.91 ± 0.5 | 0.73 ± 0.4 | 0.004 | 0.90 ± 0.6 | 0.76 ± 0.4 | 0.10 | 0.92 ± 0.6 | 0.68 ± 0.3 | 0.006 |
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.