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

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-De and 5'INS (5'insulin gene) polymorphisms we re assessed in 2532 diabetic patients tall phenotypes) diagnosed under 40 y ears of age. Autoantibodies and body mass index (expressed as a standard de viation score by comparison to age-matched and sex-matched control subjects ; SDS-BMI) were measured in 1986 siblings or offspring of Type I diabetes p atients (0-39 years), Results. In patients aged 15-39 years at diagnosis, the male-to-female rati o was 1.5 or more regardless of their antibody status and significantly hig her (p < 0.001) than that in the age-matched Belgian general population. Th ere 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-DQ B1*0302 (p <less than or equal to> 0.003) but stratification in age groups and multivariate analysis identified age as the major determinant of male-t o-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 anti body-negative relatives (n = 1791). This phenomenon tended to restricted to male relatives who were positive only for glutamate decarboxylase antibodi es (n = 44). Conclusions/interpretation. The male-to-female excess in Belgian diabetic p atients diagnosed in early adulthood is not specific for Type I diabetes an d not HLA-De or 5'INS restricted. Our data suggest that, similar to Spe II (non-insulin-dependent) diabetes mellitus, the metabolic burden of obesity and insulin resistance could preferentially precipitate postpubertal clinic al onset in male subjects with slowly progressive subclinical (immune-media ted) diabetes.