Role of Insulin Resistance in Predicting Progression to Type 1 Diabetes

  1. Ping Xu, MPH1,
  2. David Cuthbertson, MS1,
  3. Carla Greenbaum, MD2,
  4. Jerry P. Palmer, MD3,
  5. Jeffrey P. Krischer, PHD1 and
  6. for the Diabetes Prevention Trial–Type 1 Study Group*
  1. 1Pediatrics Epidemiology Center, University of South Florida, Tampa, Florida
  2. 2Benaroya Research Institute at Virginia Mason, Seattle, Washington
  3. 3Veterans Affairs Puget Sound, University of Washington, Seattle, Washington
  1. Address correspondence and reprint requests to Jeffrey P. Krischer, Division of Informatics and Biostatistics, Pediatrics Epidemiology Center, University of South Florida, 3650 Spectrum Blvd., Suite 100, Tampa, FL 33612. E-mail: jpkrischer{at}epi.usf.edu

Abstract

OBJECTIVE—The purpose of this study was to determine whether insulin resistance is a risk factor for the development of type 1 diabetes in autoantibody-positive first-degree relatives of diabetic family members.

RESEARCH DESIGN AND METHODS—Subjects (n = 186) who had a projected 25–50% risk for diabetes and subjects (n = 170) who had a projected >50% risk for type 1 diabetes in 5 years were followed until clinical diabetes onset or the end of the study as part of the Diabetes Prevention Trial–Type 1. We assessed insulin secretion with the first-phase insulin response (FPIR) and insulin resistance with homeostasis model assessment of insulin resistance (HOMA-IR) from an intravenous glucose tolerance test. The median follow-up was 4.3 years for moderate-risk subjects and 3.7 years for high-risk subjects.

RESULTS—During the follow-up period, 53 subjects in the moderate-risk group and 70 subjects in the high-risk group developed type 1 diabetes. After adjustments for confounders using multivariate analysis, HOMA-IR and the FPIR–to–HOMA-IR ratio were significantly associated with type 1 diabetes in both risk groups. In the moderate-risk population, the hazard ratio (HR) of HOMA-IR was 2.70 (95% CI 1.45–5.06) and the HR of FPIR-to-HOMA-IR was 0.32 (95% CI 0.18–0.57). In the high-risk population, the HR of HOMA-IR was 1.83 (95% CI 1.19–2.82) and the HR of FPIR–to–HOMA-IR was 0.56 (95% CI 0.40–0.78).

CONCLUSIONS—There is clear evidence of the association between insulin resistance and progression to type 1 diabetes. The combination of FPIR and HOMA-IR could be used as a better metabolic indicator for type 1 diabetes risk for prediction and suggests possible intervention strategies for diabetes prevention.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 11 June 2007. DOI: 10.2337dc06-2389.

    Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc06-2389.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

  • *

    ↵* A list of the Diabetes Prevention Trial–Type 1 Study Group members can be found in ref. 17.

    • Accepted May 24, 2007.
    • Received November 21, 2006.
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  1. Published online before print May 29, 2007, doi: 10.2337/dc06-2389 Diabetes Care September 2007 vol. 30 no. 9 2314-2320
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