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

Diabetologia. 2001 Jan;44(1):40-7. doi: 10.1007/s001250051578.


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 2,532 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 HLADQA1*0301-DQB1*0302 (p < or = 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 antibodypositive relatives (n = 103) but not in female antibody-positive (n = 92) or in antibody-negative relatives (n = 1,791). 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies / blood
  • Belgium / epidemiology
  • Body Mass Index*
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Genotype
  • Glutamate Decarboxylase / immunology
  • HLA-DQ Antigens / analysis*
  • HLA-DQ Antigens / genetics
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Multivariate Analysis
  • Sex Factors*


  • Autoantibodies
  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DQA1 antigen
  • HLA-DQB1 antigen
  • Glutamate Decarboxylase