Chronic Kidney Disease-Induced Insulin Resistance: Current State of the Field.

PURPOSE OF REVIEW: Insulin resistance is an early complication of chronic kidney disease (CKD) associated with worsening cardiovascular outcomes. This review will evaluate mechanisms responsible for CKD-induced insulin resistance and therapies currently available.

RECENT FINDINGS: Recent mechanisms have been identified including SIRPα and specific E3 ubiquitin ligases causing insulin resistance in CKD. The hallmark finding in these mechanisms is degradation of the insulin receptor substrate 1 (IRS1) which impairs intracellular insulin signaling and ultimately metabolism. The mechanisms responsible for insulin resistance in CKD include inflammation, oxidative stress, elevations in aldosterone, angiotensin II, uremic toxins, and metabolic acidosis. Potential treatments currently available for CKD-induced insulin resistance include lifestyle modification and metformin. Potential future treatments may include glucagon-like peptide agonists, SGLT2 inhibitors, and thiazolidinediones. Investigations into molecular mechanisms responsible for insulin resistance in CKD may provide new therapeutic targets while current therapies may prevent the catabolic sequelae of CKD and ameliorate its cardiovascular consequences.