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

Farah A. Meah, Linda A. DiMeglio, Carla J. Greenbaum, Janice S. Blum, Jay M Sosenko, Alberto Pugliese, Susan Geyer, Ping Xu, Carmella Evans-Molina, The Type 1 Diabetes Trialnet Study Group For The Type 1 Diabetes Trialnet Study Group

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Aims/hypothesis: 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. Methods: 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. Results: 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. Conclusions/interpretation: 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.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalDiabetologia
DOIs
StateAccepted/In press - Mar 19 2016

Fingerprint

Type 1 Diabetes Mellitus
Autoantibodies
Insulin Resistance
Weights and Measures
Autoimmunity
Proportional Hazards Models
Incidence

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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. / Meah, Farah A.; DiMeglio, Linda A.; Greenbaum, Carla J.; Blum, Janice S.; Sosenko, Jay M; Pugliese, Alberto; Geyer, Susan; Xu, Ping; Evans-Molina, Carmella; For The Type 1 Diabetes Trialnet Study Group, The Type 1 Diabetes Trialnet Study Group.

In: Diabetologia, 19.03.2016, p. 1-10.

Research output: Contribution to journalArticle

Meah, Farah A. ; DiMeglio, Linda A. ; Greenbaum, Carla J. ; Blum, Janice S. ; Sosenko, Jay M ; Pugliese, Alberto ; Geyer, Susan ; Xu, Ping ; Evans-Molina, Carmella ; For The Type 1 Diabetes Trialnet Study Group, The Type 1 Diabetes Trialnet Study Group. / 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. In: Diabetologia. 2016 ; pp. 1-10.
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abstract = "Aims/hypothesis: 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. Methods: 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. Results: 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. Conclusions/interpretation: 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.",
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AU - Greenbaum, Carla J.

AU - Blum, Janice S.

AU - Sosenko, Jay M

AU - Pugliese, Alberto

AU - Geyer, Susan

AU - Xu, Ping

AU - Evans-Molina, Carmella

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