Insulin resistance and chronic kidney disease progression, cardiovascular events, and death: Findings from the chronic renal insufficiency cohort study

Background: Insulin resistance contributes to the metabolic syndrome, which is associated with the development of kidney disease. However, it is unclear if insulin resistance independently contributes to an increased risk of chronic kidney disease (CKD) progression or CKD complications. Additionally, predisposing factors responsible for insulin resistance in the absence of diabetes in CKD are not well described. This study aimed to describe factors associated with insulin resistance and characterize the relationship of insulin resistance to CKD progression, cardiovascular events and death among a cohort of non-diabetics with CKD. Methods: Data was utilized from Chronic Renal Insufficiency Cohort Study participants without diabetes (N = 1883). Linear regression was used to assess associations with insulin resistance, defined using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The relationship of HOMA-IR, fasting glucose, hemoglobin A1c (HbA1c), and C-peptide with CKD progression, cardiovascular events, and all-cause mortality was examined with Cox proportional hazards models. Results: Novel positive associations with HOMA-IR included serum albumin, uric acid, and hemoglobin A1c. After adjustment, HOMA-IR was not associated with CKD progression, cardiovascular events, or all-cause mortality. There was a notable positive association of one standard deviation increase in HbA1c with the cardiovascular endpoint (HR 1.16, 95% CI: 1.00-1.34). Conclusion: We describe potential determinants of HOMA-IR among a cohort of non-diabetics with mild-moderate CKD. HOMA-IR was not associated with renal or cardiovascular events, or all-cause mortality, which adds to the growing literature describing an inconsistent relationship of insulin resistance with CKD-related outcomes.