title: Evaluation of leptin levels in subjects at risk for type 1 diabetes.
abstract: Type 1 diabetes (T1DM) is increasing in incidence worldwide, particularly in young children. Studies have suggested that weight gain in early childhood may play a role in determining disease risk, with increased risk in children who have gained more weight. We hypothesized that leptin may be involved by promoting a Th1-type immune response in individuals at risk for the development of T1DM. Insulin, GAD65, and IA-2 autoantibodies and leptin levels were measured in relatives of T1DM patients and in control subjects. After adjusting for HLA risk and age, autoantibody-positive relatives were compared with sex- and BMI-matched autoantibody-negative control subjects. BMI-matched individuals had similar leptin levels, and the leptin levels increased with increasing BMI Z-score, as expected. However, we did not demonstrate higher leptin levels in autoantibody-positive relatives, compared with autoantibody-negative control subjects. Thus, elevations in leptin levels do not appear to be a major determinant of whether an individual develops autoimmunity. If elevated BMI and associated elevations in leptin levels are risk factors for the initiation and/or progression of autoimmunity, they may act more as permissive factors in this process, in the setting of a certain degree of genetic predisposition.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195-7710, USA. lgilliam@u.washington.edu
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Gilliam
authors.forename: Richard A
authors.initials: RA
authors.lastname: Jensen
authors.forename: Pam
authors.initials: P
authors.lastname: Yang
authors.forename: David S
authors.initials: DS
authors.lastname: Weigle
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
authors.forename: Catherine
authors.initials: C
authors.lastname: Pihoker
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D015992:Body Mass Index; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000097:blood; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood*; D008297:Male; D012306:Risk
chemical_list: D001323:Autoantibodies; D000949:Histocompatibility Antigens Class II; C096322:ICA512 autoantibody; D007328:Insulin; D020738:Leptin; C505804:GAD55, human; D005968:Glutamate Decarboxylase