Fasted C-Peptide Distribution and Associated Clinical Factors in Adults With Longstanding Type 1 Diabetes: Analysis of the Canadian Study of Longevity in Type 1 Diabetes

Objective: Although insulin production is reportedly retained in many people with longstanding type 1 diabetes (T1D), the magnitude and relevance of connecting peptide (C-peptide) production are uncertain. In this study, we aimed to define fasted C-peptide distributions and associated clinical factors. Methods: In a cross-sectional analysis of the Canadian Study of Longevity, fasted serum and urinary C-peptide was measured in 74 patients with longstanding T1D (duration >= 50 years) and 75 age- and sexmatched controls. Extensive phenotyping for complications was performed and patient-reported variables were included. C-peptide distributions were analyzed, and multivariable logistic regression was used to assess the variable association in participants with T1D. Results: The 74 participants with T1D had a mean age of 66 +/- 8 years, a disease duration of 54 (interquartile range 52 to 58) years, and a glycated hemoglobin (A1C) of 7.4%+/- 0.8% (56.8 +/- 9.15 mmol/mol). The 75 controls had a mean age of 65 +/- 8 years and an A1C of 5.7%+/- 0.4% (38.4 +/- 4.05 mmol/mol). Participants with T1D had lower fasted serum C-peptide than controls (0.013 +/- 0.022 vs 1.595 +/- 1.099 nmol/L, p<0.001). Of the participants with T1D, C-peptide was detectable in 30 of 73 (41%) serum samples, 32 of 74 (43%) urine samples, and 48 of 74 (65%) for either serum or urine. The variables independently associated with detectable serum or urinary C -peptide were lower total daily insulin requirement (odds ratio 2.351 [for 1 lower unit/kg], p=0.013) and lower hypoglycemia worry score (odds ratio 1.059 [for 1 point lower on the worry subscore of the Hypoglycemia Fear Survey], p=0.030). Conclusions: Although detectable C -peptide in longstanding diabetes was common, the magnitude of concentration was extremely low when compared with age- and sex -matched controls. Despite minimal detectability, its presence is validated by lower insulin requirements and strongly associated with lower hypoglycemia worry. (c) 2023 Canadian Diabetes Association.