Exploring the changes in insulin resistance among patients with different degrees of renal failure, and its role in their cardiovascular mortality

Abstract

Patients with chronic kidney disease (CKD) are at increased risk of mortality and cardiovascular (CV) disease and those on maintenance haemodialysis (MHD) are at particularly high risk. Insulin resistance (IR) is known as a contributing factor to many of the conditions classified as "classic CV risk factors" and understanding changes in IR is thought to be of key importance in targeting potential medication. A prospective observational study of individuals with CKD was designed to better establish the relationship between CV risk factors and events, before and after the onset of MHD. In addition, a subgroup study was set up to examine if changes in IR affect CV outcome and mortality. 519 patients were recruited for this study, 210 were on MHD at entry and 309 had CKD stages 3, 4 and 5. Subjects were followed prospectively for 24 months and the relationship between body mass index (BMI), blood pressure (BP), total cholesterol (TC), triglycerides (TG), diabetes status and glycosylated haemoglobin (HbA1c) and CV events analysed in both MHD and non-MHD groups using logistic regression. A small study was also carried out to determine the reliability of HbA1c in MHD subjects. 106 of these subjects were recruited into the subgroup study, where baseline assessment of their IR (using the HOMA-IR model) was carried out as well as other relevant tests. 103 subjects reached an endpoint, and analysis of the whole cohort identified high SBP and diabetes as significant CV risk factors. TC was recognized as a protective factor as lower TC was associated with higher CV risk. The mean HOMA-IR increased through the CKD stages 3-5 before significantly falling in the MHD group. HbA1c showed poor association with glycaemia as measured by use of 48-hour continuous glucose monitors (CGM). These results suggest that CV risk factors may vary at different stages of CKD. The “reverse” TC result only in the non-dialysis group differs from current theories, where low cholesterol is considered a CV risk factor putatively as a surrogate marker of malnutrition. This study shows that IR increases as renal function deteriorates but is significantly decreased with MHD. In this cohort changes in IR were not predictive of CVE or mortality.