Diabetologia

, Volume 44, Issue 1, pp 40–47

Male-to-female excess in diabetes diagnosed in early adulthood is not specific for the immune-mediated form nor is it HLA-DQ restricted: possible relation to increased body mass index

Authors

  • I. Weets
    • Diabetes Research Center, Free University, Brussels, Belgium
  • J. Van Autreve
    • Diabetes Research Center, Free University, Brussels, Belgium
  • B. J. Van der Auwera
    • Diabetes Research Center, Free University, Brussels, Belgium
  • F. C. Schuit
    • Diabetes Research Center, Free University, Brussels, Belgium
  • M. V. L. Du Caju
    • Department of Pediatrics, University of Antwerp, Antwerp, Belgium
  • K. Decochez
    • Diabetes Research Center, Free University, Brussels, Belgium
  • I. H. De Leeuw
    • Department of Endocrinology, University of Antwerp, Antwerp, Belgium
  • B. Keymeulen
    • Diabetes Research Center, Free University, Brussels, Belgium
  • C. Mathieu
    • Department of Endocrinology, Catholic University, Leuven, Belgium
  • R. Rottiers
    • Department of Endocrinology, University of Ghent, Ghent, Belgium
  • H. Dorchy
    • Department of Diabetology, Children's University Hospital Queen Fabeola, Brussels, Belgium
  • E. Quartier
    • Diabetes Research Center, Free University, Brussels, Belgium
  • F. K. Gorus
    • Diabetes Research Center, Free University, Brussels, Belgium
  •  the Belgian Diabetes Registry
    • Belgian Diabetes Registry, Brussels, Belgium
Article

DOI: 10.1007/s001250051578

Cite this article as:
Weets, I., Van Autreve, J., Van der Auwera, B. et al. Diabetologia (2001) 44: 40. doi:10.1007/s001250051578

Abstract

Aims/hypothesis. We investigated whether the reported HLA-DQ/DR restricted male-to-female (M:F) excess in Type I (insulin-dependent) diabetes mellitus also exists in Belgian patients, is specific for immune-mediated diabetes, remains genotype-restricted after adjustment for age at diagnosis, and is associated with sex-dependent environmental factors.¶Methods. Autoantibodies, HLA-DQ and 5'INS (5'insulin gene) polymorphisms were assessed in 2532 diabetic patients (all phenotypes) diagnosed under 40 years of age. Autoantibodies and body mass index (expressed as a standard deviation score by comparison to age-matched and sex-matched control subjects; SDS-BMI) were measured in 1986 siblings or offspring of Type I diabetes patients (0–39 years).¶Results. In patients aged 15–39 years at diagnosis, the male-to-female ratio was 1.5 or more regardless of their antibody status and significantly higher (p < 0.001) than that in the age-matched Belgian general population. There was no sex bias in patients under 15 years of age. Overall, the male-to-female ratio was significantly higher in patients without HLA-DQA1 * 0301-DQB1*0302 (p≤ 0.003) but stratification in age groups and multivariate analysis identified age as the major determinant of male-to-female ratio. The SDS-BMI increased (p < 0.01) in male antibody-positive relatives (n = 103) but not in female antibody-positive (n = 92) or in antibody-negative relatives (n = 1791). This phenomenon tended to be restricted to male relatives who were positive only for glutamate decarboxylase antibodies (n = 44).¶Conclusions/interpretation. The male-to-female excess in Belgian diabetic patients diagnosed in early adulthood is not specific for immune-mediated Type I diabetes and not HLA-DQ or 5'INS restricted. Our data suggest that, similar to Type II (non-insulin-dependent) diabetes mellitus, the metabolic burden of obesity and insulin resistance could preferentially precipitate postpubertal clinical onset in male subjects with slowly progressive subclinical (immune-mediated) diabetes. [Diabetologia (2001) 44: 40–47]

Keywords Diabetes, sex, autoantibodies, islet cell cytoplasmic antibodies, glutamate decarboxylase antibodies, IA-2 antibodies, HLA-DQ genotype, insulin gene polymorphisms, X chromosome, body mass index.

Copyright information

© Springer-Verlag Berlin Heidelberg 2001