Acceleration of the loss of the first-phase insulin response during the progression to type 1 diabetes in diabetes prevention trial-type 1 participants

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 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.

FIG. 1.

Diagrammatic representations of the variables of interest included in analysis 2. The time to diagnosis and the times between the first and last FPIR are shown in four hypothetical individuals.

FIG. 2.

Curves of FPIR values during the progression to T1D from the actual serial values of the progressors in analysis 1 and the values derived from the regression model for the other progressors from analysis 2. The curve for analysis 1 is plotted according to the mean times from diagnosis of the FPIR measurements within each yearlong interval. For the purpose of comparison, the curve from analysis 2 was assigned the same starting value of 2.5 years and plotted according to the same time points. The patterns are similar, with a gradual decline from 2.5 to 1.5 years and a marked decline from 1.5 to 0.5 years before diagnosis.