Postprandial C-peptide is more relevant to hemoglobin A1c levels and diabetic microvascular complications than fasting C-peptide in type 2 diabetes

BACKGROUND Type 2 diabetes mellitus (T2DM), driven by insulin resistance and β cell dysfunction, necessitates reliable assessment of β cell function. C-peptide (CP) measurement, a stable marker of endogenous insulin secretion, is useful for this clinically as it avoids interference from exogenous insulin. While fasting CP (FCP) and postprandial CP (PCP), along with glucose-adjusted indices and ratios, such as FCP/fasting plasma glucose (FPG), 2 hours postprandial CP (2hCP)/postprandial blood glucose (PBG) and CP ratio, are used, their comparative efficacy in reflecting β cell function remains unclear. Hemoglobin A1c (HbA1c), a key glycemic control indicator, theoretically links β cell function to complications, but limited studies have explored the associations between diverse CP indices, HbA1c, and diabetic microvascular complications. AIM To investigate the relationships between different CP indices and HbA1c as well as diabetic microvascular complications in T2DM. METHODS T2DM patients admitted to Department of Endocrinology at Beijing Hospital between July 1, 2021 and December 31, 2021 were included in the study. Clinical and laboratory data were collected, including CP levels, glucose levels, HbA1c levels and diabetic microvascular complications. Statistical analysis was performed using Statistical Package for the Social Sciences 24.0. RESULTS A total of 453 patients were included in the final analysis. Adjusted by confounding factors, CP ratio and CP/blood glucose (BG) ratio were not relevant to HbA1c, but FCP, 2hCP, delta CP, FCP/FPG, 2hCP/PBG and delta CP/BG were still negatively correlated to HbA1c, of which 2hCP/PBG showed the strongest negative correlation (r = -0.485, P < 0.001). Independent of HbA1c and other confounding factors, 2hCP, 2hCP/PBG, delta CP and delta CP/BG were protective factors of diabetic retinopathy while 2hCP, delta CP and FCP/FPG were protective factors of diabetic peripheral neuropathy. CONCLUSION This study indicates that higher levels of CP indices suggest better glucose control and a lower prevalence of diabetic microvascular complications, and PCP indices, particularly 2hCP/PBG, were more relevant to HbA1c and diabetic microvascular complications than FCP indices. These results suggest CP-related indices could be useful biomarkers for diabetes management, warranting further research.