Persistent C-Peptide Levels and Proliferative Retinopathy in Childhood-Onset Type 1 Diabetes (T1D)

Persistent C-peptide levels may protect against complications in T1D. To test this hypothesis, 185 subjects from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, a 30-year prospective study of childhood onset (<17 years) T1D, had serum C-peptide levels measured by Mercodia ultra-sensitive ELISA at their 25 year exam. Eighteen (9.7%) subjects had detectable C-peptide levels. Those with and without detectable C-peptide did not differ in age (51.8 vs. 51.1 years, p=0.70), age of onset (9.7 vs. 8.1 years, p=0.12), diabetes duration (42.1 vs. 43.0 years, p=0.61), or HbA_1c at either baseline (8.1 vs. 8.5%, p=0.22) or 25 years (7.8 vs. 7.8%, p=0.91). In those with detectable C-peptide, non-HDL cholesterol levels were lower at baseline (104.4 vs. 124.1 mg/dl, p=0.01), but not 25 years (112.6 vs. 119.5 mg/dl, p=0.44) and pump use was marginally lower at 25 years (31.2% vs. 55.3%, p=0.07). Proliferative retinopathy was lower in those with detectable C-peptide levels (33.5% vs. 55.1%, p=0.08) and this difference remained marginally significant (p=0.08) after controlling for duration of T1D, HbA_1c and non-HDL cholesterol. No significant differences in overt nephropathy (5.6% vs. 22.7%, p=0.13), peripheral neuropathy (61.1% vs. 77.2%, p=0.15), or renal failure (0 vs. 4.2%, p=1.00) were found between the two groups when analyzed separately. When those with either retinopathy or nephropathy were combined, those with detectable C-peptide levels had lower rates of these complications (33.3% vs. 58.1%, p=0.045). This association remained significant in logistic regression after controlling for duration of diabetes and HbA1c with a statistically significant odds ratio 0.39 (95% CI: 0.08-0.94). When those with neuropathy were added to the overall microvascular complication group, no significant differences were found (p=0.13). These findings are consistent with the hypothesis that proliferative retinopathy and possibly nephropathy in T1D may be influenced by persistent C-peptide secretion.