Low risk HLA-DQ and increased body mass index in newly diagnosed type 1 diabetes children in the Better Diabetes Diagnosis study in Sweden

• Published in: INTERNATIONAL JOURNAL OF OBESITY Vol. 36; no. 5; pp. 718 - 724
• Main Authors: Carlsson, A, Kockum, I, Lindblad, B, Engleson, L, Nilsson, A, Forsander, G, Karlsson, A-K, Kernell, A, Ludvigsson, J, Marcus, C, Zachrisson, I, Ivarsson, S-A, Lernmark, Å
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2012; Nature Publishing Group
• Subjects: Adolescent; Age; Age Factors; Antigens; Autoantibodies; Biological and medical sciences; Body mass; Body Mass Index; Body weight; Child; Child, Preschool; Children; Cohort Studies; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - genetics; Diabetes. Impaired glucose tolerance; Diagnosis; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epidemiology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Evaluation; Female; GAD65 autoantibodies; General aspects; Genetic Predisposition to Disease; Genotype & phenotype; Genotypes; Haplotypes; Health aspects; Health Promotion and Disease Prevention; Health Sciences; Histocompatibility antigen HLA; Histocompatibility antigens; HLA genotype; HLA histocompatibility antigens; HLA-DQ Antigens - genetics; Humans; Hybridization; Hypotheses; Hälsovetenskap; IA-2 autoantibodies; insulin autoantibodies; Insulin resistance; Internal Medicine; islet autoantibodies; Islets of Langerhans; Leukocytes; Male; Medical and Health Sciences; Medical sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Medicine & Public Health; Metabolic Diseases; Nutrition and Dietetics; Näringslära; Näringslära och dietkunskap; Obesity; Obesity - epidemiology; Obesity - genetics; Objectives; Odds Ratio; original-article; Overweight; Pathogenesis; Patients; Pediatrics; Physiological aspects; Polymerase chain reaction; Probes; Prospective Studies; Public Health; Risk factors; Risk groups; Sweden - epidemiology; Type 1 diabetes; Sweden; Europe; Finland; HLA genotype; insulin autoantibodies; islet autoantibodies; body mass index; GAD65 autoantibodies; IA-2 autoantibodies; Endocrinopathy; Autoimmunity; HLA-System; Pancreatic hormone; Major histocompatibility system; Class II histocompatibility antigen; Autoimmune disease; Early stage; Low risk; Body mass index; Diagnosis; Child; Class I histocompatibility antigen; Nutritional status; Endocrine pancreas; Human; Immunopathology; Typing; Antibody; Nutrition disorder; Langerhans islet; Autoantibody; Genotype; Metabolic diseases; Insulin; Type 1 diabetes
• ISSN: 0307-0565; 1476-5497; 1476-5497
• DOI: 10.1038/ijo.2011.122

Objective: Type 1 diabetes and obesity has increased in childhood. We therefore tested the hypothesis that type 1 diabetes human leukocyte antigen DQ (HLA-DQ) risk genotypes may be associated with increased body mass index (BMI). Design: The type 1 diabetes high-risk HLA-DQ A1 * 05:01-B1 * 02:01/A1 * 03:01-B1 * 03:02 genotype along with lower risk DQ genotypes were determined at the time of clinical onset by PCR and hybridization with allele-specific probes. BMI was determined after diabetes was stabilized. Subjects: A total of 2403 incident type 1 diabetes children below 18 years of age were ascertained in the Swedish national Better Diabetes Diagnosis (BDD) study between May 2005 to September 2009. All children classified with type 1 diabetes, including positivity for at least one islet autoantibody, were investigated. Results: Overall, type 1 diabetes HLA-DQ risk was negatively associated with BMI ( P <0.0008). The proportion of the highest risk A1 * 05:01-B1 * 02:01/A1 * 03:01-B1 * 03:02 genotype decreased with increasing BMI ( P <0.0004). However, lower risk type 1 diabetes DQ genotypes were associated with an increased proportion of patients who were overweight or obese ( P <0.0001). Indeed, the proportion of patients with the low-risk A1 * 05:01-B1 * 02:01/A1 * 05:01-B1 * 02:01 genotype increased with increasing BMI ( P <0.003). The magnitude of association on the multiplicative scale between the A1 * 05:01-B1 * 02:01/A1 * 05:01-B1 * 02:01 genotype and increased BMI was significant ( P <0.006). The odds ratio in patients with this genotype of being obese was 1.80 (95% confidence interval 1.21–2.61; P <0.006). The increased proportion of overweight type 1 diabetes children with the A1 * 05:01-B1 * 02:01 haplotype was most pronounced in children diagnosed between 5 and 9 years of age. Conclusions: Susceptibility for childhood type 1 diabetes was unexpectedly found to be associated with the A1 * 05:01-B1 * 02:01/A1 * 05:01-B1 * 02:01 genotype and an increased BMI. These results support the hypothesis that overweight may contribute to the risk of type 1 diabetes in children positive for HLA-DQ A1 * 05:01-B1 * 02:01.