Abstract
Since little is known about the disposition index (DI) in autoantibody-positive individuals, we have assessed whether DI has a similar association between insulin secretion and sensitivity to the association observed in other populations. In TrialNet Pathway to Prevention (TNPTP;
n
= 6,620) and Diabetes Prevention Trial–Type 1 (DPT-1;
n
= 704) study participants, two secretion-sensitivity pairs, each representing a DI, were analyzed cross-sectionally at baseline: area under the curve (AUC) C-peptide/AUC glucose (AUC ratio) and Matsuda index (MI) from TNPTP oral glucose tolerance tests (oral DI), first-phase insulin response (FPIR), and 1 / fasting insulin (1/FI) from DPT-1 from intravenous glucose tolerance tests (DI). Participants were followed for progression to type 1 diabetes (T1D). Within the normal and diabetes glucose ranges, associations of AUC ratio with MI in TNPTP and FPIR with 1/FI in DPT-1 had inverse curvilinear patterns with convexities to the origin. After logarithmic transformations to linearize the secretion and sensitivity measures, the inverse slope was steeper for the diabetes range (
P
< 0.0001). In a Cox regression model including the AUC ratio and MI as variables and another model including FPIR and 1/FI, the interaction terms of secretion × sensitivity (i.e., the DI/oral DI) predicted stage 3 T1D in both (
P
< 0.0001). The DI remained significantly predictive (
P
< 0.0001) when the DPT-1 risk score was added as a covariate in regression models. In autoantibody-positive populations, insulin secretion is inversely related to sensitivity in a quasi-hyperbolic relationship in normal and diabetes ranges of glucose. The DI can be represented by a statistical and physiologic interaction between secretion and sensitivity that is predictive of stage 3 T1D.