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Title: 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: Weets, Ilse ×
Van Autreve, Jan
Van der Auwera, Bart
Schuit, Frans
Du Caju, Marc
Decochez, Katelijn
De Leeuw, Ivo
Keymeulen, Bart
Mathieu, Chantal
Rottiers, Raoul
Dorchy, Harry
Quartier, Erik
Gorus, Frans #
Issue Date: Feb-2001
Publisher: Springer-Verlag Heidelberg
Series Title: Diabetologia vol:44 issue:1 pages:40-7
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 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.
URI: 
ISSN: 0012-186X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gene Expression Unit
Clinical Residents Medicine
Clinical and Experimental Endocrinology
× corresponding author
# (joint) last author

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