Association of Longitudinal Trajectories of Insulin Resistance With Adverse Renal Outcomes

Abstract

OBJECTIVE: To analyze the relationship between time-serial changes in insulin resistance and renal outcomes. RESEARCH DESIGN AND METHODS: A prospective cohort of subjects from the general population without chronic kidney disease (CKD) underwent a biennial checkup for 12 years (n = 5,347). The 12-year duration was divided into a 6-year exposure period, where distinct HOMA for insulin resistance (HOMA-IR) trajectories were identified using latent variable mixture modeling, followed by a 6-year event accrual period, from which the renal outcome data were analyzed. The primary end point was adverse renal outcomes, defined as a composite of estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 in two or more consecutive checkups or albumin ≥1+ on urine strip. RESULTS: Two distinct groups of HOMA-IR trajectories were identified during the exposure period: stable (n = 4,770) and increasing (n = 577). During the event accrual period, 449 patients (8.4%) developed adverse renal outcomes, and the risk was higher in the increasing HOMA-IR trajectory group than in the stable group (hazard ratio 2.06, 95% CI 1.62-2.60, P < 0.001). The results were similar after adjustment for baseline clinical characteristics, comorbidities, anthropometric and laboratory findings, eGFR, and HOMA-IR. The clinical significance of increasing HOMA-IR trajectory was similar in three or four HOMA-IR trajectories. The increasing tendency of HOMA-IR was persistently associated with a higher incidence of adverse renal outcomes, irrespective of the prevalence of diabetes. CONCLUSIONS: An increasing tendency of insulin resistance was associated with a higher risk of adverse renal outcomes. Time-serial tracking of insulin resistance may help identify patients at high risk for CKD.