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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.

Abstract：

UNLABELLED: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.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Weets I,Van Autreve J,Van der Auwera BJ,Schuit FC,Du Caju MV,Decochez K,De Leeuw IH,Keymeulen B,Mathieu C,Rottiers R,Dorchy H,Quartier E,Gorus FK,Belgian Diabetes Registry.

doi

10.1007/s001250051578

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

40-7

issue

eissn

0012-186X

issn

1432-0428

journal_volume

pub_type

杂志文章

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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.