Adiposity, Physical Function, and Their Associations With Insulin Resistance, Inflammation, and Adipokines in CKD

Abstract Rationale and Objectives Adiposity and physical fitness levels are major drivers of cardiometabolic risk, but these relationships have not been well-characterized in chronic kidney disease (CKD). We examined the associations of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intrahepatic fat and physical function with inflammation, insulin resistance, and adipokines in patients with CKD Study Design Prospective cohort study Setting and Participants: Participants with Stage 3-5 CKD not receiving chronic dialysis, followed at one of 8 clinical sites in the Chronic Renal Insufficiency Cohort study, and who underwent MRI of the abdomen at an annual CRIC Study visit (n=419) Predictors VAT volume, SAT volume, intrahepatic fat, body mass index (BMI), waist circumference (WC), and time taken to complete the 400 m walk test (physical function) Outcomes Markers of inflammation (IL1-beta, IL-6, TNF-R1, and TNF-R2), insulin resistance (HOMA-IR), and adipokines (adiponectin- total and high molecular weight [HMW], resistin, and leptin). Analytical Approach Multivariable linear regression of VAT and SAT volume, intrahepatic fat and physical function, with individual markers (log-transformed values) adjusting for relevant covariates Results Mean age of the study population was 64.3 years; 41% were females, and the mean eGFR was 53.2 (+/- 14.6) ml/min/1.73 m2. Over 85% were overweight or obese, and 40% had diabetes. Higher VAT volume, SAT volume, and liver proton density fat fraction, were associated with lower levels of total and HMW adiponectin, higher levels of leptin and insulin resistance, lower HDL cholesterol and higher serum triglycerides. A slower 400m walk time was associated only with higher levels of leptin, total adiponectin, plasma IL-6 and TNFR-1 and did not modify the associations between fat measures and cardiometabolic risk factors Limitations Lack of longitudinal data and dietary details Conclusions Various measures of adiposity are associated with cardiometabolic risk factors. Physical function was also associated with the cardiometabolic risk factors studied and does not modify the associations between fat measures and cardiometabolic risk factors. Longitudinal studies of the relationship between body fat and aerobic fitness with cardiovascular and kidney disease progression are warranted.