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

  • I. Weets
  • J. Van Autreve
  • B. J. Van der Auwera
  • F. C. Schuit
  • M. V. L. Du Caju
  • K. Decochez
  • I. H. De Leeuw
  • B. Keymeulen
  • C. Mathieu
  • R. Rottiers
  • H. Dorchy
  • E. Quartier
  • F. K. Gorus
  •  the Belgian Diabetes Registry
Article

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

Authors and Affiliations

  • I. Weets
    • 1
  • J. Van Autreve
    • 1
  • B. J. Van der Auwera
    • 1
  • F. C. Schuit
    • 1
  • M. V. L. Du Caju
    • 2
  • K. Decochez
    • 1
  • I. H. De Leeuw
    • 3
  • B. Keymeulen
    • 1
  • C. Mathieu
    • 4
  • R. Rottiers
    • 5
  • H. Dorchy
    • 6
  • E. Quartier
    • 1
  • F. K. Gorus
    • 1
  •  the Belgian Diabetes Registry
    • 7
  1. 1. Diabetes Research Center, Free University, Brussels, BelgiumBE
  2. 2. Department of Pediatrics, University of Antwerp, Antwerp, BelgiumBE
  3. 3. Department of Endocrinology, University of Antwerp, Antwerp, BelgiumBE
  4. 4. Department of Endocrinology, Catholic University, Leuven, BelgiumBE
  5. 5. Department of Endocrinology, University of Ghent, Ghent, BelgiumBE
  6. 6. Department of Diabetology, Children's University Hospital Queen Fabeola, Brussels, BelgiumBE
  7. 7. Belgian Diabetes Registry, Brussels, BelgiumBE

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