The Predictive Potential of C-Peptide in Differentiating Type 1 Diabetes From Type 2 Diabetes in an Outpatient Population in Abu Dhabi

Abstract

We aimed to investigate the predictive potential of plasma connecting peptide (C-peptide) in differentiating type 1 diabetes (T1D) from type 2 diabetes (T2D) and to inform evidence-based diabetes classification criteria. A retrospective review was performed of all the patients with diabetes visiting an outpatient diabetology, endocrinology, general practice and family medicine tertiary health care center between January 2016 and December 2021. Two hundred twelve individuals with diabetes were included, 85 (44.8%) with T1D and 127 (55.2%) with T2D. Mean (SD) age at diagnosis was 35.9 (15.1) years, and 112 (52.8%) men. Median (interquartile range [IQR]) duration of diabetes was 3.8 (3.0-4.5) years (T1D, 3.9 [3.5-4.6]; T2D, 3.4 [2.4-4.4]; P = 0.001). Body mass index was <18.5 kg/m2 in 5 (2.5%) individuals (T1D, 5; T2D, none), 18.5 to <25 kg/m2 in 57 (28.5%) (T1D, 32; T2D, 25), 25 to <30 kg/m2 in 58 (29%) (T1D, 28; T2D, 30), and >30 kg/m2 in 80 (40.0%) (T1D, 20; T2D, 60). Median (IQR) glycosylated hemoglobin was 7.4% (6.7%-8.5%) (T1D, 8.3% [7.2%-9.9%]; T2D, 7% [6.3%-7.6%]; P = 0.0001). Median (IQR) C-peptide concentration was 0.59 nmol/L (0.01-1.14 nmol/L) (T1D, 0.01 nmol/L [0.003-0.05 nmol/L]; T2D, 1.03 nmol/L [0.70-1.44 nmol/L]; P = 0.0001). C-peptide concentration of ≤0.16 nmol/L showed 92.9% sensitivity, 1-specificity of 2.4%, and AUC of 97.2% (CI, 94.7%-99.6%; P = 0.0001) in differentiating T1D from T2D. To our knowledge, this is the first study in the Middle East and North Africa region highlighting the role of C-peptide in diabetes classification. The estimated cutoff point for C-peptide concentration (≤0.16 nmol/L) will certainly help in accurately classifying the T1D and will rule out the routine clinical judgmental approaches in the region, especially in those scenarios and periods where it is always difficult to diagnose the diabetes type. Quantifying the cutoff for C-peptide is among the vital strengths of this study that will provide a better treatment plan in diabetes care management. Also, we evaluated concomitant glucose levels to rule out the phenomenon of falsely low C-peptide values in the setting of hypoglycemia or severe glucose toxicity. Based on our findings, C-peptide testing could be included in postulating an evidence-based guideline that differentiates T1D from T2D. Despite this, our study has some limitations, including the selection bias due to the retrospective design and low C-peptide levels could be indicative of low pancreatic reserves due to other causes or long-standing T2D, and quantifying these reasons requires additional resources and time.