Acceleration of the Loss of the First-Phase Insulin Response During the Progression to Type 1 Diabetes in Diabetes Prevention Trial–Type 1 Participants
- Jay M. Sosenko1⇑,
- Jay S. Skyler1,
- Craig A. Beam2,
- Jeffrey P. Krischer2,
- Carla J. Greenbaum3,
- Jeffrey Mahon4,
- Lisa E. Rafkin1,
- Della Matheson1,
- Kevan C. Herold5,
- Jerry P. Palmer6,
- and the Type 1 Diabetes TrialNet and Diabetes Prevention Trial–Type 1 Study Groups*
- 1Division of Endocrinology, University of Miami, Miami, Florida
- 2Division of Informatics and Biostatistics, University of South Florida, Tampa, Florida
- 3Benaroya Research Institute at Virginia Mason, Seattle, Washington
- 4Department of Epidemiology and Biostatistics, University of Western Ontario, London, Ontario, Canada
- 5Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut
- 6VA Puget Sound Health Care System, Division of Endocrinology, Metabolism, and Nutrition, University of Washington, Seattle, Washington
- Corresponding author: Jay M. Sosenko, .
We studied the change in the first-phase insulin response (FPIR) during the progression to type 1 diabetes (T1D). Seventy-four oral insulin trial progressors to T1D from the Diabetes Prevention Trial–Type 1 with at least one FPIR measurement after baseline and before diagnosis were studied. The FPIR was examined longitudinally in 26 progressors who had FPIR measurements during each of the 3 years before diagnosis. The association between the change from the baseline FPIR to the last FPIR and time to diagnosis was studied in the remainder (n = 48). The 74 progressors had lower baseline FPIR values than nonprogressors (n = 270), with adjustments made for age and BMI. In the longitudinal analysis of the 26 progressors, there was a greater decline in the FPIR from 1.5 to 0.5 years before diagnosis than from 2.5 to 1.5 years before diagnosis. This accelerated decline was also evident in a regression analysis of the 48 remaining progressors in whom the rate of decline became more marked with the approaching diagnosis. The patterns of decline were similar between the longitudinal and regression analyses. There is an acceleration of decline in the FPIR during the progression to T1D, which becomes especially marked between 1.5 and 0.5 years before diagnosis.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db13-0656/-/DC1.
* For a complete list of the Type 1 Diabetes TrialNet and Diabetes Prevention Trial–Type 1 Study Groups, see Supplementary Data online.
See accompanying commentary, p. 3990.
- Received April 24, 2013.
- Accepted July 9, 2013.
- © 2013 by the American Diabetes Association.
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