ESPE Abstracts

Background: Mixed meal tolerance test (MMTT) is a gold standard for evaluating β-cell function. There is limited data on MMTT and β-cell function in MODY patients.

Objective: The aim was to analyze plasma C-peptide (CP) levels during MMTT in MODY patients as a biomarker of β-cell function.

Methods: The cohort consisted of 39 patients with MODY genes mutations: 20 with GCK, 8 - HNF1A, 3 - HNF4A, 4 - KCNJ11, 2 - ABCC8, 1 - INS, 1 - KLF11. 59% were children (<18 years, n=23), and 41% - adults (18-27 years, n=16). The youngest patient with performed MMTT was 2.5 years old (KCNJ11).

MMTT was performed following standardized technique: after an overnight fast all patients ingested 6 mL/kg (maximum 360 mL) of standard liquid meal (1 kcal/mL). Blood samples for CP and glycemia levels were taken 10 min prior to the meal (t_-10), at the meal time (t₀), and time points: t₁₅, t₃₀, t₆₀, t₉₀, t₁₂₀, t₁₅₀, t₁₈₀. The results of CP were available at each time point for all subjects.

Area under the curve CP (AUC_CP), the baseline CP (CP_Base), the peak CP (CP_max) concentrations were evaluated for all subjects and compared between MODY groups.

The cutoff of stimulated CP<0.2 nmol/L was used in our study and described by other authors as a predictor of poor β-cell response and absolute insulin deficiency.

Results: The median of participants' age was 190 months [IQR 129]. The median of diabetes duration was 44 months [IQR 112]. The median of AUC_CP in the whole cohort was 162.7 nmol/L/180min [IQR 142.9], CP_Base – 0.4 nmol/L [IQR 0.38], CP_max 1.28 nmol/L [IQR 1.28].

GCK diabetes patients had the best β-cell response, statistically significant differences of AUC_CP, CP_Base and CP_max were found compared to HNF4A, KCNJ11 and KLF11 patients (p values <0.05).

HNF1A patients had significantly higher levels of AUC_CP, CP_Base and CP_max compared to HNF4A and KCNJ11 patients (p values <0.05).

Six patients (3 HNF4A, 1 KCNJ11, 1 ABCC8, 1 KLF11) had all CP levels <0.2 nmol/L. These HNF4A, KCNJ11, ABCC8 patients had unsuccessful treatment change trial and they are all treated with insulin. Six HNF1A and 3 KCNJ11 patients had successful treatment change to oral sulfonylurea agents.

Conclusion: As expected GCK diabetes patients preserved the best β-cell function. A pretreatment challenge with MMTT might be a useful indicator to predict therapeutic success with oral sulfonylurea treatment after genetic diagnosis.