The Disposition Index in Autoantibody-Positive Individuals at Risk for Type 1 Diabetes

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 resistance to the association observed in other populations. In TrialNet Pathway to Prevention (TNPTP; n=6620) 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: AUC C-peptide/AUC glucose (AUC Ratio) and Matsuda Index (MI) from TNPTP OGTTs (oral DI), first-phase insulin response (FPIR) and 1/fasting insulin (1/FI) from DPT-1 from IVGTTs (DI). Participants were followed for progression to type 1 diabetes. 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 x sensitivity (i.e., the DI/ODI), predicted stage 3 type 1 diabetes 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 type 1 diabetes.