Type 1 diabetes patients born to immigrants to Sweden increase their native diabetes risk and differ from Swedish patients in HLA types and islet autoantibodies

Pediatr Diabetes. 2010 Dec;11(8):513-20. doi: 10.1111/j.1399-5448.2010.00637.x.

Abstract

Aim: To determine whether type 1 diabetes mellitus (T1DM) patients, having parents who immigrated to Sweden, have increased T1DM risk before 18 yr compared with countries of origin. We also determined whether they have different human leukocyte antigen (HLA) genetic markers and islet autoantibodies at diagnosis compared with Swedish patients.

Methods: A total of 1988 (53% males) newly diagnosed and confirmed T1DM patients <18 yr registered within the Better Diabetes Diagnosis (BDD) study (May 2005 to September 2008) were included. Participants were classified into three groups: Swedish, non-Swedish, and Mixed-origin patients according to country of origin of two generations (parents and grandparents). These groups were compared with respect to T1DM HLA markers and islet autoantibodies [glutamic acid decarboxylase autoantibodies (GAD65Ab), insulin autoantibodies (IAA), and islet antigen-2 autoantibodies (IA-2Ab)].

Results: Only 30 (1.5%) patients were born outside Sweden. Swedish patients constituted 66%, non-Swedish patients 8%, Mixed origins 17%, and 9% were of uncertain origin. Confirmed T1DM in patients within the study was 22 (95% CI: 21-23) patients/10(5)/yr rate for Swedish patients compared with 14 (95% CI: 13-15) among non-Swedish patients. The HLA-DQ8 haplotype (p < 0.0001) and DQ2/8 genotype (p < 0.02) predominated among Swedish compared with non-Swedish patients. In contrast, DQ2 was the most frequent haplotype among non-Swedish patients [OR = 1.5 (95% CI: 1.0-2.0), p < 0.04]. Multiple (≥2) autoantibodies (p < 0.04) and specifically IA-2Ab (p < 0.001) were most prevalent among the Swedish patients. Multiple autoantibodies were associated with DQ8 among the Swedish patients only (p < 0.001).

Conclusion: Patients born to parents who had immigrated to the high T1DM incidence environment of Sweden have, compared with Swedish patients, more frequent HLA-DQ2 genetic markers and are diagnosed more often with GAD65Ab.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autoantibodies / analysis
  • Autoantibodies / genetics
  • Child
  • Child, Preschool
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Emigrants and Immigrants
  • Female
  • Glutamate Decarboxylase / genetics
  • Glutamate Decarboxylase / immunology
  • HLA-DQ Antigens / genetics
  • HLA-DQ Antigens / immunology
  • Humans
  • Infant
  • Islets of Langerhans / immunology
  • Male
  • Sweden / epidemiology

Substances

  • Autoantibodies
  • HLA-DQ Antigens
  • HLA-DQ2 antigen
  • HLA-DQ8 antigen
  • Glutamate Decarboxylase