Incident Dysglycemia and the Progression to Type 1 Diabetes among Participants in the Diabetes Prevention Trial-Type 1

  1. Jay M. Sosenko, MD (jsosenko{at}med.miami.edu),
  2. Jerry P. Palmer, MD,
  3. Lisa Rafkin-Mervis, MS CDE,
  4. Jeffrey P. Krischer, PhD,
  5. David Cuthbertson, MS,
  6. Jeffery Mahon, MD,
  7. Carla J. Greenbaum, MD,
  8. Catherine C. Cowie, PhD,
  9. Jay S. Skyler, MD and
  10. the Diabetes Prevention Trial-1 Study Group
  1. Division of Endocrinology University of Miami Miami, Florida
  2. Division of Endocrinology/Metabolism University of Washington, Seattle, Washington
  3. Division of Informatics and Biostatistics, University of South Florida, Tampa, Florida
  4. Pediatrics Epidemiology Center, University of South Florida, Tampa, Florida
  5. Department of Epidemiology and Biostatistics, University of Western Ontario, Ontario, Canada
  6. Benaroya Research Institute at Virginia Mason; Seattle, Washington
  7. NIDDK/NIH, Bethesda, Maryland

    Abstract

    Objective: We studied the incidence of dysglycemia and its prediction of the development of type 1 diabetes (T1D) in islet cell autoantibody (ICA)-positive individuals. In addition, we assessed whether dysglycemia was sustained.

    Methods: Participants (n=515) in the Diabetes Prevention Trial-Type 1 (DPT-1) with normal glucose tolerance who underwent periodic oral glucose tolerance tests (OGTTs) were followed for incident dysglycemia (impaired fasting glucose, impaired glucose tolerance, and/or high glucose levels at intermediate time points of OGTTs). Incident dysglycemia at the 6-month visit was assessed for T1D prediction.

    Results: Of 515 participants with a normal baseline OGTT, 310 (60%) had at least one episode of dysglycemia over a maximum follow-up of 7.0 years. Dysglycemia at the 6-month visit was highly predictive of the development of T1D, both in those <13 years (p<0.001) and those ≥13 years (p<0.01). Those <13 years with dysglycemia at the 6-month visit had a high cumulative incidence (94% estimate by 5 years). Among those who developed T1D after a dysglycemic OGTT and who had at least two OGTTs following the dysglycemic OGTT, 33/64 (52%) reverted back to a normal OGTT. However, 26 (79%) of the 33 then had another dysglycemic OGTT prior to diagnosis.

    Conclusion: ICA positive individuals with normal glucose tolerance had a high incidence of dysglycemia. Incident dysglycemia in those ICA-positive is strongly predictive of T1D. Children with incident dysglycemia are at an especially high risk. Fluctuations in and out of the dysglycemic state are not uncommon prior to the onset of T1D.

    Footnotes

      • Received December 2, 2008.
      • Accepted May 21, 2009.

    This Article

    1. Diabetes Care
    1. All Versions of this Article:
      1. dc08-2140v1
      2. dc08-2140v2
      3. 32/9/1603 most recent