title: The relationship between BMI and insulin resistance and progression from single to multiple autoantibody positivity and type 1 diabetes among TrialNet Pathway to Prevention participants.
abstract: The incidence of type 1 diabetes is increasing at a rate of 3-5% per year. Genetics cannot fully account for this trend, suggesting an influence of environmental factors. The accelerator hypothesis proposes an effect of metabolic factors on type 1 diabetes risk. To test this in the TrialNet Pathway to Prevention (PTP) cohort, we analysed the influence of BMI, weight status and insulin resistance on progression from single to multiple islet autoantibodies (Aab) and progression from normoglycaemia to diabetes.
  
  
  
  HOMA1-IR was used to estimate insulin resistance in Aab-positive PTP participants. Cox proportional hazards models were used to evaluate the effects of BMI, BMI percentile (BMI%), weight status and HOMA1-IR on the progression of autoimmunity or the development of diabetes.
  
  
  
  Data from 1,310 single and 1,897 multiple Aab-positive PTP participants were included. We found no significant relationships between BMI, BMI%, weight status or HOMA1-IR and the progression from one to multiple Aabs. Similarly, among all Aab-positive participants, no significant relationships were found between BMI, weight status or HOMA1-IR and progression to diabetes. Diabetes risk was modestly increased with increasing BMI% among the entire cohort, in obese participants 13-20 years of age and with increasing HOMA1-IR in adult Aab-positive participants.
  
  
  
  Analysis of the accelerator hypothesis in the TrialNet PTP cohort does not suggest a broad influence of metabolic variables on diabetes risk. Efforts to identify other potentially modifiable environmental factors should continue.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN, USA.|Department of Endocrinology, Edward Hines Junior VA Hospital, Hines, IL, USA.
authors.forename: Farah A
authors.initials: FA
authors.lastname: Meah
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.|Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Linda A
authors.initials: LA
authors.lastname: DiMeglio
authors.affiliation: Benaroya Research Institute, Diabetes Program, Seattle, WA, USA.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Janice S
authors.initials: JS
authors.lastname: Blum
authors.affiliation: Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA.|Department of Medicine, Division of Diabetes, Endocrinology & Metabolism, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Jay M
authors.initials: JM
authors.lastname: Sosenko
authors.affiliation: Department of Medicine, Division of Diabetes, Endocrinology & Metabolism, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA.|Department of Microbiology and Immunology, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Pugliese
authors.affiliation: Health Informatics Institute, University of South Florida, Tampa, FL, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Geyer
authors.affiliation: Health Informatics Institute, University of South Florida, Tampa, FL, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Medicine, Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN, USA. cevansmo@iu.edu.|Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA. cevansmo@iu.edu.
authors.forename: Carmella
authors.initials: C
authors.lastname: Evans-Molina
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000276:immunology* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007328:Insulin
keywords: Accelerator hypothesis; BMI; Diabetes in childhood; HOMA1-IR; Insulin sensitivity and resistance; Pancreatic autoantibodies; Pathway to Prevention; Prediction and prevention of type 1 diabetes; TrialNet; Type 1 diabetes