Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease

Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease. In uremic patients resistance to the action of insulin has been documented, but it is not known at what stage of renal disease it appears. We therefore examined 29 patients with IgA glomerulonephritis (IgAGN) and 21 patients with adult polycystic kidney disease (ADPKD) in different stages of renal failure, and in addition, healthy age-matched subjects. Insulin sensitivity and other variables of glucose metabolism were assessed using a frequent sampling intravenous glucose tolerance test (minimal-model technique). Glomerular filtration rate (GFR) was assessed in renal patients using the inulin-clearance technique. Mean insulin sensitivity index (SI), that is, insulin sensitivity, was significantly lower ( P N = 16; 14 males, mean age 42 ± 3 years; mean SI 8.6 ± 0.8min -1 μU/ml). The mean SI was not significantly different in patients with renal disease of immune (IgAGN) or non-immune (ADPKD) origin, and it was not correlated with GFR ( r = 0.01, P r = -0.23, P r = -0.03, P N = 19; 17 males, mean age 41 ± 2 years; mean GFR 119 ± 5 ml/min/1.73m 2 ; mean SI 5.1 ± 0.7min -1 μU/ml), in patients with mild to moderate renal failure ( N = 16; 15 males, 46 ± 3 years; 67 ± 4 ml/min/1.73m 2 ; 5.1 ± 0.7min -1 μU/ml) and in patients with advanced renal failure ( N = 15; 13 males, 46 ± 3 years; 25 ± 2 ml/min/1.73m 2 ; 4.7 ± 0.6min -1 μU/ml). Mean fasted plasma insulin concentration, the area under the curve for plasma insulin concentration (AUC) and total insulin delivery (TID) during the glucose tolerance test were significantly higher in patients than in healthy subjects, reflecting hyperinsulinemia in renal patients. Further, fasted plasma insulin concentration ( r = -0.32, P r = -0.62, P r = -0.34, P