title: 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).
  
  
  CONCLUSIONS
  In our study IR is an important risk factor for cardiovascular morbidity and ESRD in a diabetic CKD population.
authors.affiliation: Nephrology Department, Centro Hospitalar do Algarve, Faro, Portugal. Electronic address: andrefragoso@iol.pt.
authors.forename: André
authors.initials: A
authors.lastname: Fragoso
authors.affiliation: Nephrology Department, Centro Hospitalar do Algarve, Faro, Portugal.
authors.forename: Filipa
authors.initials: F
authors.lastname: Mendes
authors.affiliation: Nephrology Department, Centro Hospitalar do Algarve, Faro, Portugal; Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Silva
authors.affiliation: Nephrology Department, Centro Hospitalar do Algarve, Faro, Portugal; Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal.
authors.forename: Pedro Leão
authors.initials: PL
authors.lastname: Neves
mesh_terms: D000368:Aged; D015415:Biomarkers; D001786:Blood Glucose / Q000032:analysis; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology / Q000401:mortality / Q000503:physiopathology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000401:mortality / Q000503:physiopathology*; D058065:Diabetic Cardiomyopathies / Q000453:epidemiology / Q000401:mortality / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000401:mortality / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007676:Kidney Failure, Chronic / Q000150:complications / Q000453:epidemiology / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010044:Outpatient Clinics, Hospital; D011174:Portugal / Q000453:epidemiology; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin
keywords: CKD; CKD progression; Cardiovascular disease; Diabetic nephropathy; ESRD; Insulin resistance