The precise role of C-peptide remains a subject of ongoing research, particularly in the context of type 2 diabetes mellitus (T2DM), characterized by both insulin resistance (IR) and beta cell dysfunction. This study evaluates the association between C-peptide levels and IR, insulin secretion, and beta cell function independent of other risk factors in T2DM patients with and without complications. This cross-sectional study included 91 T2DM participants with or without diabetic complications. Clinical variables, routine biochemical tests, and serum C-peptide levels were measured after overnight fasting. The levels of biomarkers (fasting insulin, C-peptide, resistin, and tumor necrosis factor alpha TNFα) were measured using a Randox Evidence biochip analyzer. Homeostatic model assessment (HOMA) of IR and beta-cell function was calculated using the software HOMA 2 calculator. The C-peptide index was also computed using a widely accepted formula. The mean fasting insulin ( P < .001), homeostatic model assessment of IR ( P = .001), homeostatic model assessment of beta cell function ( P = .002), C-peptide index ( P < .001), and TNFα ( P = .022) were significantly increased with tertiles of C-peptide. Patients with diabetic retinopathy and nephropathy had significantly higher levels of C-peptide. C-peptide levels significantly increased with the number of complications ( P = .010). The C-peptide levels were significantly associated with fasting insulin ( P < .000), homeostatic model assessment of beta cell function ( P = .011), C-peptide index ( P < .000), homeostatic model assessment of IR ( P < .000), and resistin ( P = .018) after adjustment for confounding factors such as age, gender, diabetes duration, body mass index, systolic blood pressure, low-density lipoprotein cholesterol, HbA1c, TNFα, and antidiabetic drugs (metformin and sulfonylurea) in diabetic patients with complications. This study illustrated the clinical utility of C-peptide in microvascular complications such as diabetic nephropathy and diabetic retinopathy. Moreover, C-peptide can be used as an appropriate index for identifying IR in T2DM patients with complications.
Siddiqui et al. (2026) studied this question.