#2937 INDIRECT INSULIN RESISTANCE INDICES AND THEIR CUT-OFF VALUES FOR POST-TRANSPLANTATION DIABETES MELLITUS IN KIDNEY TRANSPLANT RECIPIENTS
Authors: Oskooei Sara Sokooti , Szili-Torok Tamas , Heerspink Hiddo Lambers , Dullaart Robin P F , Bakker Stephan J L 
Published: June 2023

Abstract

Background and Aims
Insulin resistance determination in kidney transplant recipients (KTRs) plays an important role to identify KTRs at risk of posttransplantation diabetes mellitus (PTDM) development. Current methods to measure insulin resistance include the hyperinsulinemic-euglycemic (HIEG) clamp technique, and minimal model approximation of the metabolism of glucose (MMAMG). These methods, however, require considerable time and are expense, complex, and invasive. As a result, indirect insulin resistance indices such as homeostasis model assessment-insulin resistance (HOMA-IR), visceral adiposity index (VAI), lipid accumulation product (LAP), or triglycerides-glucose (TyG) index, are used in epidemiological and clinical studies in the general population due to their simplicity and ease of use. However, it is unknown to what extent those indices may contribute to determine insulin resistance and PTDM development in KTRs. Therefore, this study aimed to investigate the role of indirect insulin resistance indices to determine insulin resistance and PTDM development in KTRs.

Method
We included 472 stable outpatient KTRs (with a functioning graft ≥1 year) without diabetes from a prospective cohort study. Crude and multivariable Cox proportional hazards regression analysis were performed to determine whether indirect insulin resistance indices (HOMA-IR, VAI, LAP, and TyG index) were prospectively associated with incident PTDM. We analyzed each measure using receiver operating characteristic (ROC) curve for the development of PTDM. The cut-off value was determined as the value with the highest Youden index score in the specificity dominant area.

Results
During a median 9.6 years [interquartile range (IQR) 6.6–10.2] of follow up, 68 (14%) KTRs developed PTDM. In Cox regression analyses, all indirect insulin resistance indices associated with incident PTDM, independent of potential confounders. ROC curve was 0.764 (95% CI,0.703-0.826) for HOMA-IR, 0.685 (95% CI,0.615-0.757) for VAI, 0.743 (95% CI,0.678-0.808) for LAP, and 0.698 (95% CI,0.629-0.766) for TyG index, with no significant difference between them (p = 0.05). The cut-off values with their corresponding sensitivity and specificity for each indices are presented in Table 1. To test this cut-off value, the association between the indices and incident PTDM was examined by using each index as a categorical variable (HOMA-IR&lt;2.47 vs ≥2.47; VAI&lt;4.01 vs ≥4.01; LAP&lt;87.04 vs ≥87.04; TyG index&lt;4.94 vs ≥4.94). Indirect insulin resistance indices as a categorical variable predicted incident PTDM independent of age, sex, smoking, time to transplantation, systolic blood pressure, eGFR, and medication.

Conclusion
Indirect insulin resistance indices could be used to predict incident PTDM in KTRs. In addition to HOMA-IR, insulin-free surrogates of insulin resistance might serve as useful methods to identify KTRs at risk for PTDM development.