C-peptide Involvement in the Progression of Type 2 Diabetes Mellitus Through Triglyceride -centered Lipid Metabolism Disorders

Purpose: Fasting C-peptide (FCP), co-secreted with insulin, plays a critical role in the development of diabetic complications, with both deficiency and excessive secretion linked to adverse outcomes. Type 2 diabetes mellitus (T2DM) is mainly characterized by lipid metabolism disorders, with elevated triglyceride (TG) levels. This study aimed to determine the relationship between FCP levels and lipid metabolism disorders centered around TG and related clinical indicators. Method: Medical records from 1034 patients with T2DM were reviewed, eventually including 607 patients with a median age of 63 years. Pearson’s correlation analysis assessed the correlation between C-peptide levels and metabolic variables. The area under the receiver operating characteristic curve evaluated the predictive performance of TG, uric acid (UA), and fasting blood glucose levels for high C-peptide levels. Univariate and multivariate logistic regression analyses identified independent risk factors affecting C-peptide levels. Results: The median patient age was 63 years, with a diabetic kidney disease prevalence of 47.78%. Patients were divided into quartiles based on FCP levels, revealing significant differences in TG, TyG, and AIP values (P < 0.01). Positive correlations existed between FCP and TG ( r = 0.202**), TyG ( r = 0.247), AIP ( r = 0.285) (P < 0.001), UA ( r = 0.248**), and creatinine ( r = 0.234**). Stratified analysis revealed TG and UA significantly increased C-peptide levels (TG: odds ratio [ OR ] = 5.782, 95% confidence interval [ CI ] = 3.526–9.480, P < 0.001; UA: OR = 4.382, 95% CI = 2.707–7.094, P < 0.001), with TG identified as an independent risk factor ( OR = 1.223, 95% CI = 1.044–1.433, P = 0.013). Conclusion: FCP levels in patients with T2DM are closely associated with lipid metabolism disorders, particularly TG, contributing to target organ damage. Supplementation with C-peptide may not be beneficial for delaying the progression of T2DM or its complications.