Objective: This systematic review and meta-analysis aimed to investigate the predictive ability of plasma connecting peptide (C-peptide) levels in discriminating type 1 diabetes (T1D) from type 2 diabetes (T2D) and to inform evidence-based guidelines in diabetes classification.
Methods: We conducted a holistic review and meta-analysis using PubMed, MEDLINE, EMBASE, and Scopus. The citations were screened from 1942 to 2021. The quality criteria and the preferred reporting items for systematic reviews and meta-analysis checklist were applied. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022355088).
Results: A total of 23,658 abstracts were screened and 46 full texts reviewed. Of the 46 articles screened, 12 articles were included for the meta-analysis. Included studies varied by race, age, time, and proportion of individuals. The main outcome measure in all studies was C-peptide levels. A significant association was reported between C-peptide levels and the classification and diagnosis of diabetes. Furthermore, lower concentrations and the cutoff of <0.20 nmol/L for fasting or random plasma C-peptide was indicative of T1D. In addition, this meta-analysis revealed the predictive ability of C-peptide levels in discriminating T1D from T2D. Results were consistent using both fixed- and random-effect models. The I2 value (98.8%) affirmed the variability in effect estimates was due to heterogeneity rather than sampling error among all selected studies.
Conclusion: Plasma C-peptide levels are highly associated and predictive of the accurate classification and diagnosis of diabetes types. A plasma C-peptide cutoff of ≤0.20 mmol/L is indicative of T1D and of ≥0.30 mmol/L in the fasting or random state is indicative of T2D.
Keywords: Beta; C-peptide; Predictive; Type mellitus; beta-cell function; diabetes; predictive ability of C-peptide; type 1 diabetes; type 2 diabetes.
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