The Metabolic Progression to Type 1 Diabetes as Indicated by Serial Oral Glucose Tolerance Testing in the Diabetes Prevention Trial–Type 1
- Jay M. Sosenko1⇓,
- Jay S. Skyler1,
- Kevan C. Herold2,
- Jerry P. Palmer3 and
- the Type 1 Diabetes TrialNet and Diabetes Prevention Trial–Type 1 Study Groups
- 1Division of Endocrinology, University of Miami Miller School of Medicine, Miami, Florida
- 2Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut
- 3VA Puget Sound Health Care System, Division of Endocrinology, Metabolism, and Nutrition, University of Washington, Seattle, Washington
- Corresponding author: Jay M. Sosenko, .
Type 1 diabetes (T1D) is often first recognized when signs and symptoms occur, yet the pathogenetic development of T1D usually begins years before that. Pancreatic autoantibodies commonly become elevated long before diagnosis (1). Although data indicate that the first-phase insulin response (FPIR) is also abnormal well before diagnosis (2–5), the development and progression of metabolic abnormalities had not been well characterized until the recent performance of T1D prevention trials (6–8). The unique designs of these trials provided the opportunity to perform longitudinal studies that have yielded new insights into metabolic changes that occur during the progression to T1D. This review will describe what we have learned about the metabolic natural history of T1D from the Diabetes Prevention Trial–Type 1 (DPT-1).
A description of DPT-1.
DPT-1 included two separate trials, the parenteral and oral insulin trials (6,7). The objective of both trials was to delay or prevent the occurrence of T1D by interfering with the immunologic processes that result in the disorder. The parenteral insulin trial consisted of an intervention group that received subcutaneous ultralente insulin at a dose of 0.125 units/kg twice daily and a control group that received no insulin. The intervention group was admitted annually to a unit for 4 days during which a continuous infusion of recombinant human regular insulin was administered. The oral insulin trial included an intervention group, which received a once-daily dose of 7.5 mg recombinant human insulin crystals, and a placebo control group.
In both trials, individuals were required to be nondiabetic, aged 1–45 years, and first- or second-degree relatives of T1D patients. Two phases determined further eligibility for the trials. In the screening phase, the relatives were tested for islet cell autoantibody (ICA) positivity. Those positive then participated in a risk assessment phase. This included an intravenous glucose tolerance test …