The Acceleration of the Loss of the First-Phase Insulin Response during the Progression to Type 1 Diabetes in Diabetes Prevention Trial-Type 1 Participants

  1. The Diabetes Type 1 TrialNet and Diabetes Prevention Trial-Type 1 Study Groups (see Online Appendix)
  1. Division of Endocrinology; University of Miami; Miami, Florida
  2. Division of Informatics and Biostatistics; University of South Florida; Tampa, Florida
  3. Division of Informatics and Biostatistics; University of South Florida; Tampa, Florida
  4. Benaroya Research Institute at Virginia Mason; Seattle, WA
  5. Department of Epidemiology and Biostatistics; University of Western Ontario, London ,ON
  6. Division of Endocrinology; University of Miami; Miami, Florida
  7. Division of Endocrinology; University of Miami; Miami, Florida
  8. Department of Immunobiology, Yale University School of Medicine; New Haven, Connecticut
  9. VA Puget Sound Health Care System; Division of Endocrinology, Metabolism, and Nutrition; University of Washington; Seattle, Washington
  1. Corresponding Author: Jay M. Sosenko Email: jsosenko{at}med.miami.edu

Abstract

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 of 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 non-progressors (n=270) with adjustments 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.

  • Received April 24, 2013.
  • Accepted July 9, 2013.

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