INSULIN-RESISTANCE AND HYPERINSULINEMIA ARE ALREADY PRESENT IN PATIENTS WITH INCIPIENT RENAL-DISEASE

In uremic patients resistance to the action of insulin has been docume nted, but it is not known at what stage of renal disease it appears. W e therefore examined 29 patients with IgA glomerulonephritis (IgAGN) a nd 21 patients with adult polycystic kidney disease (ADPKD) in differe nt stages of renal failure, and ill addition, healthy age-matched subj ects. Insulin sensitivity and other variables of glucose metabolism we re assessed using a frequent sampling intravenous glucose tolerance te st (minimal-model technique). Glomerular filtration rate (GFR) was ass essed in renal patients using the inulin-clearance technique. Mean ins ulin sensitivity index (SI), that is, insulin sensitivity, was signifi cantly lower (P < 0.001) in all patients combined than in matched heal thy subjects (N = 16; 14 males, mean age 42 +/- 3 years; mean SI 8.6 /- 0.8 min(-1) mu U/ml). The mean SI was not significantly different i n patients with renal disease of immune (IgAGN) or non-immune (ADPKD) origin, and it was not correlated with GFR (r = 0.01, P < 0.52), intac t PTH (r = 0.23, P < 0.11) or calcitriol concentration (r = -0.03, P < 0.82). Consequently, the mean SI was similar in renal patients with G FR within the normal range (N = 19; 17 males, mean age 41 +/- 2 years: mean GFR 119 +/- 5 ml/min/1.73 m(2); mean SI 5.1 +/- 0.7 min(-1) mu U /ml), in patients with mild to moderate renal failure (N = 16, 15 male s, 46 +/- 3 years: 67 +/- 4 ml/min/1.73 m(2); 5.1 +/- 0.7 min(-1) mu U /ml) and in patients with advanced renal failure (N = 15; 13 males. 46 +/- 3 years. 25 +/- 2 ml/min/1.73 m(2); 4.7 +/- 0.6 min(-1) mu U/ml). Mean fasted plasma insulin concentration, the area under the curve fo r plasma insulin concentration (AUC) and total insulin delivery (TID) during the glucose tolerance test were significantly higher in patient s than in healthy subjects, reflecting hyperinsulinemia in renal patie nts. Further, fasted plasma insulin concentration (r= -0.32, P < 0.009 ): AUC (r = -0.62. P < 0.0001) and TID (r = -0.34. P < 0.001) in patie nts were significantly correlated with insulin sensitivity (SI). Thr p resent data document that insulin resistance and concomitant hyperinsu linemia are present early in the course of renal disease: that is, eve n in patients with GFR within the normal range, irrespective of the ty pe of renal disease. This observation may have potential implications with respect to the high cardiovascular morbidity and mortality in pat ients with renal disease.