Young persons who develop DR may represent a high-risk group for early development of other complications. In young persons with youth-onset T1D, we evaluated associations between DR status and markers of other T1D complication risk. Youth (N=127), mean age 21.7 y (range 10.7-31.9), mean T1D onset 6.3 y (range 0.5-17.6) underwent DR assessment (ETDRS-protocol 7 field fundus photos); renal, neuropathic, and CVD risk screenings; and risk screening by blood/urine studies. DR was classified as none (No DR, 37%), mild nonproliferative (Mild DR, 46%), and more than mild NPDR (Advanced DR, 17%). More severe DR was associated with greater age, T1D duration, A1c, and weight status (Table). DR severity was associated with neuropathy, vascular stiffness by pulse wave (aortic AIx), and inflammatory, oxidative stress, and endothelial activation markers (CRP, isoprostane, e-selectin). Paradoxically, greater DR was associated with less PAI-1. After adjustment for age, T1D duration, weight, and A1c by ANCOVA, DR status was associated with differences in cooling threshold (7.6, 8.6, 12.3, p=.0003) and e-selectin (39.8, 34.0, 46.0, p=.02). Young persons with DR have high risk for neuropathic, renal, and CVD complications. While PAI-1 is lower, markers of inflammation and oxidative stress are higher in this group. Optimal glycemic control must be prioritized to prevent or delay DR progression and other complications in young persons with DR.
Unadjusted Associations Between Clinical Factors and DR Status, *indicates ln transformed p value
| Clinical Factor | No DR (n=47) Mean or Median or % | Mild DR (n=59) Mean or Median or % | Advanced DR (n=21) Mean or Median or % | P value ANOVA or Chi-square |
| Age (yrs)/T1D Duration (yrs)/A1c (%) | 18.9/13.2/8.0 | 22.6/15.8/8.6 | 25.8/19.6/9.1 | <.0001/<.0001/.03 |
| Sex (% male)/Overweight/obese (%) | 60/32 | 36/61 | 48/57 | .05/.009 |
| Urinary Albumin Excretion* /eGFR per 1.73m2 | 7.3/128.2 | 6.4/141.2 | 9.3/140.6 | .04/.02 |
| Neuropathy (MNSI)/Warm Threshold/Cold Threshold | 1.3/14.6/7.1 | 1.9/15.3/8.6 | 3.0/18.2/13.4 | .004/.005/<.001 |
| Mean SBP/Mean DBP/Aortic AIx | 110/68/2.0 | 112/71/9.0 | 115/74/11.1 | .2/.008/.003 |
| PAI1* (ng/ml)/CRP* (mg/l)/IGF1 (ng/ml) | 36.8/0.8/207.5 | 26.2/2.5/160.6 | 14.4/2.7/138.8 | <.001/.002/.002 |
| E-selectin(ng/ml)/Urine isoprostane* (ng/ml) | 40.8/0.20 | 34.5/0.34 | 41.8/0.40 | .1/.002 |
| Clinical Factor | No DR (n=47) Mean or Median or % | Mild DR (n=59) Mean or Median or % | Advanced DR (n=21) Mean or Median or % | P value ANOVA or Chi-square |
| Age (yrs)/T1D Duration (yrs)/A1c (%) | 18.9/13.2/8.0 | 22.6/15.8/8.6 | 25.8/19.6/9.1 | <.0001/<.0001/.03 |
| Sex (% male)/Overweight/obese (%) | 60/32 | 36/61 | 48/57 | .05/.009 |
| Urinary Albumin Excretion* /eGFR per 1.73m2 | 7.3/128.2 | 6.4/141.2 | 9.3/140.6 | .04/.02 |
| Neuropathy (MNSI)/Warm Threshold/Cold Threshold | 1.3/14.6/7.1 | 1.9/15.3/8.6 | 3.0/18.2/13.4 | .004/.005/<.001 |
| Mean SBP/Mean DBP/Aortic AIx | 110/68/2.0 | 112/71/9.0 | 115/74/11.1 | .2/.008/.003 |
| PAI1* (ng/ml)/CRP* (mg/l)/IGF1 (ng/ml) | 36.8/0.8/207.5 | 26.2/2.5/160.6 | 14.4/2.7/138.8 | <.001/.002/.002 |
| E-selectin(ng/ml)/Urine isoprostane* (ng/ml) | 40.8/0.20 | 34.5/0.34 | 41.8/0.40 | .1/.002 |
M. Katz: None. G.L. King: Research Support; Self; Sanofi-Aventis. J. Sun: Other Relationship; Self; Novartis Pharmaceuticals Corporation. Research Support; Self; Genentech, Inc., Optovue, Incorporated, Boston Micromachines Corporation, Adaptive Sensory Technology, Kalvista Pharmaceuticals, Inc.. Other Relationship; Self; Novo Nordisk Inc. L.M. Laffel: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US, MannKind Corporation, Roche Diagnostics Corporation, Dexcom, Inc., Insulet Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Johnson & Johnson Diabetes Institute, LLC..
