title: Age governs gender-dependent islet cell autoreactivity and predicts the clinical course in childhood IDDM.
abstract: Most IDDM patients temporarily restore some of their beta-cell function following the initiation of insulin therapy. The aim of this study was to analyse the influence of age, gender, metabolic state at diagnosis and presence of autoantibodies (GAD65 antibodies and ICA) on the duration of the clinical partial remission. In total, 149 consecutively diagnosed IDDM children, 0-16 y old (70F, 79M, mean age 9.5 y) were studied. Partial remission was arbitrarily defined as the period when the insulin dose was below 0.5 U/BW 24 h-1 and HbA1c below 7.5%, and occurred in 119/149 patients with a duration between 1 and 38 months. Cox's regression analysis showed that the factors significantly associated with the duration of remission were age, gender, interaction between age and gender, ICA and a high initial HbA1c, whereas GAD65Ab had no influence. Young boys had the shortest remission period, while adolescent boys had the longest, as compared to young and adolescent girls. The ICA-negative patients (n = 42) had a longer remission period (median 9.7 months) than the ICA-positive children (n = 107; 5.0 months; p = 0.0001), regardless of GAD65Ab status. We speculate that the relative insulin resistance, which is more pronounced in pubertal girls than in boys, may be associated with a more rapid increase of exogenous insulin requirement. These findings are important when evaluating the effect of islet cell autoreactivity on the clinical course of IDDM in children.
authors.affiliation: Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Ortqvist
authors.forename: A
authors.initials: A
authors.lastname: Falorni
authors.forename: A
authors.initials: A
authors.lastname: Scheynius
authors.forename: B
authors.initials: B
authors.lastname: Persson
authors.forename: A
authors.initials: A
authors.lastname: Lernmark
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001323:Autoantibodies / Q000302:isolation & purification*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007223:Infant; D007328:Insulin / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D012074:Remission Induction; D012737:Sex Factors
chemical_list: D001323:Autoantibodies; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D007328:Insulin