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

• Published in: Diabetes (New York, N.Y.) Vol. 62; no. 12; pp. 4179 - 4183
• Main Authors: SOSENKO, Jay M, SKYLER, Jay S, BEAM, Craig A, KRISCHER, Jeffrey P, GREENBAUM, Carla J, MAHON, Jeffrey, RAFKIN, Lisa E, MATHESON, Della, HEROLD, Kevan C, PALMER, Jerry P
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-12-2013
• Subjects: Adolescent; Adult; Analysis; Autoantibodies - blood; Biological and medical sciences; Child; Child, Preschool; Development and progression; Diabetes; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - prevention & control; Diabetes. Impaired glucose tolerance; Disease Progression; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Genetic aspects; Glucose - administration & dosage; Glucose Tolerance Test; Humans; Insulin; Insulin - blood; Insulin - immunology; Insulin Resistance - physiology; Male; Measurement; Medical diagnosis; Medical sciences; Original Research; Pancreatic beta cells; Physiological aspects; Prediabetic State - blood; Regression analysis; Type 1 diabetes; United States; Endocrinopathy; Prevention; Immunopathology; Pancreatic hormone; Type 1 diabetes; Autoimmune disease; Acceleration; Insulin
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db13-0656

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.