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/1.73m2 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.

Association between the metabolic score for insulin resistance (METS-IR) and estimated glomerular filtration rate (eGFR) among health check-up population in Japan: A retrospective cross-sectional study

“…The relationship between IR and CKD had been demonstrated in previous studies (7)(8)(9)12). Irrespective of diabetes prevalence, a rising trend in HOMA-IR was related to an increased risk of unfavorable renal outcomes during the course of a 12-year prospective cohort study of the general population without CKD (hazard ratio = 2.06, 95% CI: 1.62-2.60, P < 0.001) (7).…”

“…Insulin resistance (IR) is a state of diminished response to insulin in target cells and an important pathogenic mechanism for the development of metabolic diseases. It is present in many chronic diseases, including diabetes, cardiovascular disease, hypertension, and CKD (6,7). Furthermore, several investigations revealed that being overweight and having metabolic syndrome (MS) was significantly linked to a moderate decline in eGFR (7)(8)(9)(10)(11)(12).…”

“…It is present in many chronic diseases, including diabetes, cardiovascular disease, hypertension, and CKD (6,7). Furthermore, several investigations revealed that being overweight and having metabolic syndrome (MS) was significantly linked to a moderate decline in eGFR (7)(8)(9)(10)(11)(12). Therefore, we hypothesized that there might be an association between IR or related surrogate markers and eGFR.…”

Investigating the Relationship of Handgrip Strength and the risk of Chronic Kidney Disease and Mortality though NHANES Studies

“…Furthermore, muscle mass is inversely related to insulin resistance and metabolic syndrome severity 46 . A 12-year longitudinal cohort study revealed that increasing insulin resistance over time was consistently associated with a heightened risk of adverse renal outcomes, irrespective of diabetes prevalence 47 . Chronic renal insu ciency often leads to muscle wasting, which may be worsened by low-protein diets aimed at delaying disease progression.…”

The non-linear relationship between triglyceride-glucose index and risk of chronic kidney disease in hypertensive patients with abnormal glucose metabolism: A cohort study

“…First, IR is associated with an increased risk of metabolic diseases, such as hypertension, abnormal glucose metabolism, hyperuricemia, and dyslipidemia ( 19 , 20 ), which are also risk factors for CKD ( 21 ). Second, animal and human studies demonstrated that hyper-insulinemia increases sodium reabsorption, induces glomerular hyperfiltration, which increases renal injury ( 22 – 24 ).…”