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

doi:10.1007/s00125-016-3924-5

. 2016 Jun;59(6):1186-95.

doi: 10.1007/s00125-016-3924-5. Epub 2016 Mar 19.

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^{1

2}, Linda A DiMeglio^{3

4}, Carla J Greenbaum⁵, Janice S Blum⁶, Jay M Sosenko^{7

8}, Alberto Pugliese^{8

9}, Susan Geyer¹⁰, Ping Xu¹⁰, Carmella Evans-Molina^{11

12}; Type 1 Diabetes TrialNet Study Group

Affiliations

¹ Department of Medicine, Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN, USA.
² Department of Endocrinology, Edward Hines Junior VA Hospital, Hines, IL, USA.
³ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁴ Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
⁵ Benaroya Research Institute, Diabetes Program, Seattle, WA, USA.
⁶ Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
⁷ Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA.
⁸ Department of Medicine, Division of Diabetes, Endocrinology & Metabolism, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA.
⁹ Department of Microbiology and Immunology, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA.
¹⁰ Health Informatics Institute, University of South Florida, Tampa, FL, USA.
¹¹ Department of Medicine, Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN, USA. cevansmo@iu.edu.
¹² Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA. cevansmo@iu.edu.

PMID: 26995649
PMCID: PMC5081287
DOI: 10.1007/s00125-016-3924-5

Free PMC article

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 et al. Diabetologia. 2016 Jun.

Free PMC article

. 2016 Jun;59(6):1186-95.

doi: 10.1007/s00125-016-3924-5. Epub 2016 Mar 19.

Authors

Affiliations

¹ Department of Medicine, Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN, USA.
² Department of Endocrinology, Edward Hines Junior VA Hospital, Hines, IL, USA.
³ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁴ Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
⁵ Benaroya Research Institute, Diabetes Program, Seattle, WA, USA.
⁶ Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
⁷ Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA.
⁸ Department of Medicine, Division of Diabetes, Endocrinology & Metabolism, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA.
⁹ Department of Microbiology and Immunology, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA.
¹⁰ Health Informatics Institute, University of South Florida, Tampa, FL, USA.
¹¹ Department of Medicine, Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN, USA. cevansmo@iu.edu.
¹² Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA. cevansmo@iu.edu.

PMID: 26995649
PMCID: PMC5081287
DOI: 10.1007/s00125-016-3924-5

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.

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.

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Conflict of interest statement

Duality of interest The authors declare that there is no duality of interest associated with this manuscript.

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References

1. Onkamo P, Vaananen S, Karvonen M, Tuomilehto J. Worldwide increase in incidence of Type I diabetes--the analysis of the data on published incidence trends. Diabetologia. 1999;42:1395–1403. - PubMed
1. DIAMOND Project Group. Incidence and trends of childhood type 1 diabetes worldwide 1990–1999. Diabetic medicine. 2006;23:857–866. - PubMed
1. Patterson CC, Dahlquist GG, Gyurus E, Green A, Soltesz G. Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study. Lancet. 2009;373:2027–2033. - PubMed
1. Lawrence JM, Imperatore G, Dabelea D, et al. Trends in incidence of type 1 diabetes among non-hispanic white youth in the United States, 2002–2009. Diabetes. 2014;63:3938–3945. - PMC - PubMed
1. Donath MY, Hess C, Palmer E. What is the role of autoimmunity in type 1 diabetes? A clinical perspective. Diabetologia. 2014;57:653–655. - PubMed

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[1] Onkamo P, Vaananen S, Karvonen M, Tuomilehto J. Worldwide increase in incidence of Type I diabetes--the analysis of the data on published incidence trends. Diabetologia. 1999;42:1395–1403. - PubMed

[2] Onkamo P, Vaananen S, Karvonen M, Tuomilehto J. Worldwide increase in incidence of Type I diabetes--the analysis of the data on published incidence trends. Diabetologia. 1999;42:1395–1403. - PubMed

[3] DIAMOND Project Group. Incidence and trends of childhood type 1 diabetes worldwide 1990–1999. Diabetic medicine. 2006;23:857–866. - PubMed

[4] DIAMOND Project Group. Incidence and trends of childhood type 1 diabetes worldwide 1990–1999. Diabetic medicine. 2006;23:857–866. - PubMed

[5] Patterson CC, Dahlquist GG, Gyurus E, Green A, Soltesz G. Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study. Lancet. 2009;373:2027–2033. - PubMed

[6] Patterson CC, Dahlquist GG, Gyurus E, Green A, Soltesz G. Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study. Lancet. 2009;373:2027–2033. - PubMed

[7] Lawrence JM, Imperatore G, Dabelea D, et al. Trends in incidence of type 1 diabetes among non-hispanic white youth in the United States, 2002–2009. Diabetes. 2014;63:3938–3945. - PMC - PubMed

[8] Lawrence JM, Imperatore G, Dabelea D, et al. Trends in incidence of type 1 diabetes among non-hispanic white youth in the United States, 2002–2009. Diabetes. 2014;63:3938–3945. - PMC - PubMed

[9] Donath MY, Hess C, Palmer E. What is the role of autoimmunity in type 1 diabetes? A clinical perspective. Diabetologia. 2014;57:653–655. - PubMed

[10] Donath MY, Hess C, Palmer E. What is the role of autoimmunity in type 1 diabetes? A clinical perspective. Diabetologia. 2014;57:653–655. - PubMed

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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

Affiliations

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

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