Frequency and characteristics of MODY 1 (HNF4A mutation) and MODY 5 (HNF1B mutation): Analysis from the DPV database

Abstract

Objective. To characterize initial presentation and clinical course of patients with rare HNF4A- and HNF1B-MODY in a large multinational registry. Design, setting and participants. Within the DPV (Diabetes Patienten Verlaufsdokumentation) registry, 44 patients with HNF4A- and 35 patients with HNF1B-MODY were characterized and compared to type 1 diabetes (T1D) / type 2 diabetes (T2D) in patients < 20 years. Main outcome measure. Clinical and laboratory parameters, therapy, and quality of metabolic control, extrapancreatic symptoms in HNF1B-MODY patients. Results. Patients with both MODY types were significantly older than T1D patients at time of diagnosis (HNF4A 13.8 years and HNF1B 13.5 years, vs. T1D 8.8 years, p<0.0001). Mean C-peptide at diagnosis was higher for HNF4A-MODY than T1D (1.8 ng/ml vs. 0.9 ng/ml, p <0.01). 36.4% of patients with HNF4A-MODY and 65.7% of patients with HNF1B-MODY are treated with insulin, while 20.5% and 8.6% receive oral antidiabetics (OADs) only (p<0.05 and p<0.01 vs. T2D). At the most recent visit, HbA1c levels were lower in HNF4A and HNF1B-MODY compared to T1D (mean 6.5% and 6.1% vs 7.9% in T1D, p<0.0001). In 40% of patients with HNF1B-MODY extrapancreatic symptoms were reported. Several clinical predictors previously described to differentiate between MODY and T1D or T2D could be revalidated by logistic regression analyses in this cohort. Conclusion The population-based DPV registry enabled us to precisely characterize phenotype and treatment in these two rare MODY-types. Although phenotype of HNF4A-and HNF1B-MODY shows distinct differences to T1D and T2D, 38% of patients are initially misclassified as T1D or T2D.