HLA-typing, clinical, and immunological characterization of youth with type 2 diabetes mellitus phenotype from the German/Austrian DPV database

TY - JOUR

T1 - HLA-typing, clinical, and immunological characterization of youth with type 2 diabetes mellitus phenotype from the German/Austrian DPV database

AU - Awa, Wendy L

AU - Boehm, Bernard O

AU - Rosinger, Silke

AU - Achenbach, Peter

AU - Ziegler, Anette G

AU - Krause, Stephanie

AU - Meissner, Thomas

AU - Wiegand, Susanne

AU - Reinehr, Thomas

AU - Kapellen, Thomas

AU - Karges, Beate

AU - Eiermann, Thomas

AU - Schober, Edith

AU - Holl, Reinhard W

AU - DPV Initiative and the German BMBF Competence Networks Diabetes Mellitus and Obesity

N1 - © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - AIM: To characterize the clinical and immunological features of HLA-typed youth with pediatric onset of type 2 diabetes mellitus (T2DM).METHOD: One hundred and seven patients with clinically diagnosed T2DM (aged ≤20 yr at diagnosis) were examined. DNA and serum, obtained after a median diabetes duration of 2.2 (Q1-Q3: 0.8-4.6) yr, were used for centralized HLA-typing and autoantibody (GADA, IA-2A, ZnT8A) measurements.RESULTS: 64.6% of patients were female and median age at diagnosis was 13.8 (Q1-Q3: 11.6-15.4) yr. Patients were obese [median body mass index-standard deviation score (BMI-SDS): 2.6 (2.0-3.1)], 88.0% had a family history of diabetes and 40.2% a migration background. Islet autoantibodies were detected in 16 (15.0%), among which 7 (6.5%) had multiple islet autoantibodies. Autoantibody positive patients had poorer metabolic control than autoantibody negative patients [glycosylated hemoglobin A1c (HbA1c): 8.1 (6.9-10.1) % vs. 6.6 (5.9-8.0) %; p = 0.033], while patients with HLA-DR genetic risk had higher BMI-SDS than those with HLA-DRXX [2.6 (2.4-3.7) vs. 2.4 (1.7-2.9); p = 0.007]. Metabolic syndrome (61.7%), microalbuminuria (13.4%), and retinopathy (3.9%) were diagnosed. Therapies used were lifestyle only (35.5%), oral anti-diabetics (OAD) only (43.3 %), insulin +  OAD (15.9%) and insulin only (5.6%). Patients with β-cell autoimmunity or HLA-DR genetic risk more frequently used insulin than confirmed T2DM patients (50.0 vs. 22.0%; p = 0.037) and less often had diabetic relatives (61.1 vs. 86.0%; p = 0.030).CONCLUSION: T2DM was confirmed in about 90% of patients while about 10% with β-cell autoimmunity or HLA-DR genetic risk likely had either T1.5DM or 'double diabetes' or an unknown diabetes type.

AB - AIM: To characterize the clinical and immunological features of HLA-typed youth with pediatric onset of type 2 diabetes mellitus (T2DM).METHOD: One hundred and seven patients with clinically diagnosed T2DM (aged ≤20 yr at diagnosis) were examined. DNA and serum, obtained after a median diabetes duration of 2.2 (Q1-Q3: 0.8-4.6) yr, were used for centralized HLA-typing and autoantibody (GADA, IA-2A, ZnT8A) measurements.RESULTS: 64.6% of patients were female and median age at diagnosis was 13.8 (Q1-Q3: 11.6-15.4) yr. Patients were obese [median body mass index-standard deviation score (BMI-SDS): 2.6 (2.0-3.1)], 88.0% had a family history of diabetes and 40.2% a migration background. Islet autoantibodies were detected in 16 (15.0%), among which 7 (6.5%) had multiple islet autoantibodies. Autoantibody positive patients had poorer metabolic control than autoantibody negative patients [glycosylated hemoglobin A1c (HbA1c): 8.1 (6.9-10.1) % vs. 6.6 (5.9-8.0) %; p = 0.033], while patients with HLA-DR genetic risk had higher BMI-SDS than those with HLA-DRXX [2.6 (2.4-3.7) vs. 2.4 (1.7-2.9); p = 0.007]. Metabolic syndrome (61.7%), microalbuminuria (13.4%), and retinopathy (3.9%) were diagnosed. Therapies used were lifestyle only (35.5%), oral anti-diabetics (OAD) only (43.3 %), insulin +  OAD (15.9%) and insulin only (5.6%). Patients with β-cell autoimmunity or HLA-DR genetic risk more frequently used insulin than confirmed T2DM patients (50.0 vs. 22.0%; p = 0.037) and less often had diabetic relatives (61.1 vs. 86.0%; p = 0.030).CONCLUSION: T2DM was confirmed in about 90% of patients while about 10% with β-cell autoimmunity or HLA-DR genetic risk likely had either T1.5DM or 'double diabetes' or an unknown diabetes type.

KW - Adolescent

KW - Age of Onset

KW - Austria

KW - Autoantibodies

KW - Child

KW - Databases, Factual

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Germany

KW - HLA-DQ Antigens

KW - HLA-DR Antigens

KW - Histocompatibility Testing

KW - Humans

KW - Male

KW - Phenotype

U2 - 10.1111/pedi.12043

DO - 10.1111/pedi.12043

M3 - SCORING: Journal article

C2 - 23627341

VL - 14

SP - 562

EP - 574

JO - PEDIATR DIABETES

JF - PEDIATR DIABETES

SN - 1399-543X

IS - 8

ER -