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 (CP_Base) and the peak CP (CP_max). Threshold points of CP_Base, CP₉₀, CP_maxand CP_AUCwere determined from analysis of ROC curves.

Results: GCK diabetes patients had significantly higher AUC_CP, CP_Baseand CP_maxcompared 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.