Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications
Design and Methods: C-peptide was measured in an untimed blood sample in the SDRNT1BIO cohort of 6076 people with type 1 diabetes followed for an average of 5.2 years.
Results: In regression models adjusted for age at onset and duration, effect sizes for C-peptide ≥200 versus <5 pmol/l were as follows: insulin dose at baseline 27% lower (p=2×10−39), HbA1c during follow-up 4.9 mmol/mol lower (p=3×10−13), hazard ratio for hospital admission for diabetic ketoacidosis during follow-up 0.44 (p=0.0001), odds ratio for incident retinopathy 0.51 (p=0.0003). Effects on risk of serious hypoglycemic episodes were detectable at lower levels of C-peptide, and the form of the relationship was continuous down to the limit of detection (3 pmol/l). In regression models contrasting C-peptide 30 to <200 with <5 pmol/l, the odds ratio for self-report of at least one serious hypoglycemic episode in the last year was 0.56 (p=6×10−8), and the hazard ratio for hospital admission for hypoglycemia during follow-up was 0.52 (p=0.03).
Conclusion: These results in a large representative cohort suggest that even minimal residual C-peptide secretion could have clinical benefit in type 1 diabetes, in contrast to a follow-up study of the DCCT intensively-treated cohort where an effect on hypoglycemia was seen only at C-peptide levels ≥130 pmol/l. This has obvious implications for design and evaluation of trials of interventions to preserve or restore pancreatic islet function in type 1 diabetes.