Kinetics of C-peptide during mixed meal test and its value for treatment optimization in monogenic diabetes patients

Aim: The mixed meal tolerance test (MMTT) is a gold standard for evaluating beta-cell function. There is limited data on MMTT in monogenic diabetes (MD). Therefore, we aimed to analyze plasma C-peptide (CP) kinetics during MMTT in young MODY and neonatal diabetes patients as a biomarker for beta-cell function. Methods: We included 41 patients with MD diagnosis (22 GCK, 8 HNF1A, 3 HNF4A, 4 KCNJ11, 2 ABCC8, 1 INS, 1 KLF11). Standardized 3-hour MMTT with glycemia and plasma CP measurements were performed for all individuals. Pancreatic beta-cell response was assessed by the area under the curve CP (AUC(CP)), the baseline CP (CPBase) and the peak CP (CPmax). Threshold points of CPBase, CP90, CPmax and CPAUC were determined from analysis of ROC curves. Results: GCK diabetes patients had significantly higher AUC(CP), CPBase and CPmax compared to HNF4A and KCNJ11 patients. In HNF4A, KCNJ11 and ABCC8 patients with all CP levels < 200 pmol/L, the treatment change attempt to sulfonylurea agent was unsuccessful. The ROC analysis showed that CP baseline threshold equal or higher to 133.5 pmol/L could be used to predict successful switch to oral agents. Conclusion: A pretreatment challenge with MMTT might be used to guide the optimal treatment after molecular diagnosis of MD. (C) 2021 The Authors. Published by Elsevier B.V.