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.
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 diabeticpatients (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 diabetespatients (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 diabeticpatients 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.
Authors: E Bakhtadze; H Borg; G Stenström; P Fernlund; H J Arnqvist; A Ekbom-Schnell; J Bolinder; J W Eriksson; S Gudbjörnsdottir; L Nyström; L C Groop; G Sundkvist Journal: Diabetologia Date: 2006-05-31 Impact factor: 10.122
Authors: I Weets; I Truyen; I Verschraegen; B Van der Auwera; J De Schepper; H Dorchy; M-C Lebrethon; L Van Gaal; P Van Rooy; D G Pipeleers; F K Gorus Journal: Diabetologia Date: 2006-03-29 Impact factor: 10.122
Authors: S Sipetic; J Maksimovic; H Vlajinac; I Ratkov; S Sajic; D Zdravkovic; T Sipetic Journal: J Endocrinol Invest Date: 2012-09-24 Impact factor: 4.256
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Authors: I Weets; L Kaufman; B Van der Auwera; L Crenier; R P A Rooman; C De Block; K Casteels; E Weber; M Coeckelberghs; Z Laron; D G Pipeleers; F K Gorus Journal: Diabetologia Date: 2004-04 Impact factor: 10.122
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Authors: A Giulietti; C Gysemans; K Stoffels; E van Etten; B Decallonne; L Overbergh; R Bouillon; C Mathieu Journal: Diabetologia Date: 2004-01-31 Impact factor: 10.122