Insulin resistance as a predictor of cardiovascular morbidity and end-stage renal disease

Abstract

Background: Cardiovascular disease (CVD) is the main risk factor of morbidity and mortality in chronic kidney disease (CKD) patients. Insulin resistance (IR) has been reported to be a strong risk factor for CVD. The purpose of this study was to examine the usefulness of IR as a predictor of cardiovascular morbidity and end-stage renal disease (ESRD).

Methods: We followed during a period of 56months 119 type 2 diabetic CKD patients (stages 2 to 4) without history of CVD at the beginning of the study. Several laboratory parameters and left ventricular mass index (LVMI) were analyzed. The degree of IR was estimated by the Homeostasis Model Assessment (HOMA-IR). Cardiovascular morbidity was assessed according to the presence of cardiovascular hospital admission during the study period, defined by admissions caused by coronary heart disease, congestive heart failure, peripheral vascular disease and cerebrovascular disease. The population was divided in two groups: G-1 with cardiovascular admission (n=48) and G-2: without admission (n=71). The multiple logistic regression was used to assess predictors of cardiovascular morbidity and ESRD. The renal survival was evaluated by the Kaplan-Meier and long-rank test.

Results: We found that G-1 patients showed significantly higher HOMA-IR (3.8 vs 0.77, p=0.0001) and that HOMA-IR upper tercile showed significantly higher age, eGFR, LVMI, phosphorus, iPTH and IL-6. In a multivariate logistic regression model HOMA-IR and IL-6 were independent risk factors of cardiovascular morbidity (OR=2.847 [95% CI 1.048-7.735, p=0.012] and OR=2.483 [95% CI 1.221-5.049, p=0.04], respectively). In a univariate logistic regression model patients in the upper tercile presented significantly more cardiovascular admissions that in the lower tercile. CKD progression to ESRD was observed in 24 patients and those in the upper HOMA-IR tercile showed a higher CKD progression to ESRD than the rest of study patients. A multivariate logistic regression model showed that HOMA-IR (OR=1.034, 95% CI (1.005-1.650) p=0.040) was an independent predictor of ESRD. Kaplan-Meier analysis showed a difference in renal survival in the HOMA-IR terciles (log rank=8.093; p=0.017).

Conclusion: In our study IR is an important risk factor for cardiovascular morbidity and ESRD in a diabetic CKD population.

Keywords: CKD; CKD progression; Cardiovascular disease; Diabetic nephropathy; ESRD; Insulin resistance.