It has been reported that insulin resistance appears at an earlier stage of chronic kidney disease (CKD). However, few data are available concerning what factors of metabolic abnormalities, such as apolipoprotein (Apo) profile or acidosis, might be associated with insulin resistance in patients with CKD. We used the hyperinsulinemic euglycemic glucose clamp technique to examine insulin sensitivity in patients without diabetes (n = 29) with different stages of renal function. Results were compared with those in healthy subjects (n = 10) and related to various affecting variables. In healthy subjects, the glucose disposal rate (GDR) was 9.93 +/- 1.33 mg/kg/min. The GDR of patients with CKD (6.91 +/- 2.46 mg/kg/min) was significantly less than that of healthy subjects ( P < 0.01), which shows diminished insulin sensitivity in patients with CKD. There was a negative correlation between GDR and serum creatinine level ( r = -0.449; P < 0.05) and positive correlations between GDR and creatinine clearance ( r = 0.549; P < 0.01) and Apo A-1/B levels ( r = 0.396; P < 0.05). Of particular relevance is the observed close correlation between GDR and bicarbonate level, with an extremely high predictive value for degree of acidosis ( r = 0.611; P < 0.0005). Stepwise multivariate regression analysis selected bicarbonate (F = 13.28) and Apo A-1/B levels (F = 6.58) as independent contributing variables. We found that insulin resistance correlated linearly with decline in renal function. Independent variables related to insulin resistance were bicarbonate and Apo A-1/B levels in patients with CKD.