Reclassification of diabetes type in pediatric patients initially classified as type 2 diabetes mellitus: 15 years follow-up using routine data from the German/Austrian DPV database.

OBJECTIVE: To examine change of diagnosis in patients from the German/Austrian multicenter DPV (Diabetes Patienten Verlaufsdokumentation) database initially classified as type 2 diabetes. METHODS: Patients aged ≤20 years at onset, diagnosed between 1995 and 2010 were followed for at least 6 months. Chi-square/Wilcoxon tests were performed to compare patient groups according to diabetes type after reclassification. RESULTS: From 580 study patients, 60 (10.3%) were reclassified, on average 2.4 years after initial diagnosis as follows: 23 (38.3%) as type 1 diabetes; 9 (15%) as maturity onset diabetes of the young (MODY); 20 (33.3%) as "other specific diabetes forms" and 8 (13.3%) as "remission" of type 2 diabetes. Patients reclassified to type 1 were significantly younger (13.5 ± 2.9 versus 14.0 ± 2.6; p=0.027) and more often ß-cell antibody positive at disease onset (80.0% versus 31.2%; p=0.002), while patients reclassified as MODY had significantly lower BMI-SDS values than 520 patients with confirmed type 2 diabetes (2.5 ± 1.1 versus 0.9 ± 1.1; p<0.001). The latter were also considerably more obese than patients in "remission" and those reclassified to "other specific diabetes forms". CONCLUSION: About 10% of patients in the DPV database, initially diagnosed as type 2 diabetes, were retrospectively reclassified.

Genetic and clinical characteristics of patients with HNF1A gene variations from the German-Austrian DPV database.

OBJECTIVE: To determine prevalence, genetic and phenotype characteristics of patients with hepatocyte nuclear factor-1α (HNF1A) variants in the Diabetes Patienten Verlaufsdokumenation (DPV) multicentre database and to examine the influence of HNF1A mutation type, or location on clinical phenotypes. PATIENTS AND METHODS: Seventy-one DPV patients were labelled as HNF1A-MODY (MODY3). Forty-four patients carried HNF1A mutations, while 27 patients were found to have HNF1A polymorphisms only. Associations between mutation type/position and age at disease onset, HbAlc, body mass index (BMI), diagnosis, family history and treatment modality were analysed using non-parametric statistics (Wilcoxon test). RESULTS: Patients with HNF1A mutations were 36% male, aged 14.1±5.8 years at diagnosis, and slightly overweight (BMI-SDS: +0.8±1.1). Treatment was lifestyle intervention (20.5%), insulin (35.3%), oral anti-diabetic (OAD, 43%) and both insulin+OAD (15.9%). More patients with missense mutations (60%) than patients with nonsense mutations/frameshift (23.8%) did not use insulin (P=0.03). No differences were found with regard to mutation types, isoform or domain. We identified several previously undescribed mutations in the cohort including c.-158insGGGTTGG in the promoter region, G31X, E41X, Q130X, L162P, R245I, A269P, S355X, Q398X, Q473X, Q495X, E508X, P588fs-insGCCA and P588fs-delAC. Patients carrying HNF1A polymorphisms were significantly younger at diagnosis than patients with HNF1A mutations (10.9±4.2 vs 14.19±5.8 years; P=0.027), and all carried I27L, S487N and A98V (n=3). CONCLUSION: HNF1A-MODY is the second most frequent MODY diagnosis registered in the DPV database, and previously undescribed HNF1A mutations account for about one-third of HNF1A-MODY cases. Patients with HNF1A polymorphisms documented as HNF1A-MODY were misclassified. They may have autoantibody-negative type 1B or type 2 diabetes or may have other MODY types.

HLA-DR genotypes influence age at disease onset in children and juveniles with type 1 diabetes mellitus.

OBJECTIVE: To investigate HLA-DR genotype in association with chronological age or calendar year of disease onset and the time trend of genotype frequencies from 1969 to 2009. Additionally, to examine genotype frequency in relation to B-cell-, islet cell antibodies (ICA)-, autoantibodies to insulin-, insulinoma antigen 2 (IA2)-, glutamic acid decarboxylase-antibody positivity, thyroid antibody positivity, thyroid diseases or coeliac antibody positivity. Genotype associations with gender and ethnicity are also analyzed. SUBJECTS AND METHODS: HLA-typed children and juveniles (n=1445) aged 12 years the most prevalent HLA-DR genotype was X/X (18.1%). IA2 positivity was associated with HLA-DR4/X and HLA-DR3/4 positivity (P=0.011), and hypothyroidism was linked to HLA-DR4/4 (P=0.0103). More females carried the HLA-DR4/4 genotype (18.2 vs 12.7% P=0.0048) or were thyroid antibody positive (24.5 vs 14.7% P=0.0001). Larger numbers of <6 year olds were coeliac antibody positive than >12 year olds (14.8 vs 9.1% P=0.0037). No associations between migration background and B-cell-, thyroid- or coeliac-antibody positivity, and no time trend were found. CONCLUSION: HLA-DR genotype associated with age at disease onset, ICA positivity and hypothyroidism; female gender with thyroid antibody positivity and low age of diabetes onset with coeliac antibody positivity.