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 (AUCCP), the baseline CP (CPBase), the peak CP (CPmax) 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 AUCCP in the whole cohort was 162.7 nmol/L/180min [IQR 142.9], CPBase 0.4 nmol/L [IQR 0.38], CPmax 1.28 nmol/L [IQR 1.28].
GCK diabetes patients had the best β-cell response, statistically significant differences of AUCCP, CPBase and CPmax were found compared to HNF4A, KCNJ11 and KLF11 patients (p values <0.05).
HNF1A patients had significantly higher levels of AUCCP, CPBase and CPmax 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.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology