Insulin resistance and hyperinsulinemia in patients with chronic congestive heart failure

Abstract

Congestive heart failure is a condition associated with increased plasma norepinephrine levels. Moreover, norepinephrine has been recently demonstrated to affect glucose homeostasis by decreasing insulin sensitivity. In the present study, eight patients suffering from chronic congestive heart failure and 10 healthy age- and body mass index-matched subjected were submitted to both an oral glucose tolerance test (OGTT; 75 g) and a euglycemic hyperinsulinemic glucose clamp. During the 360 minutes of the glucose clamp, insulin was infused at three different rates (25, 50, and 100 mU/kg/h), while d- 3H glucose infusion allowed determination of glucose turnover. In basal conditions, patients versus controls had similar plasma glucose (5.2 ± 0.1 v 4.9 ± 0.2 mmol/L, P = NS), but higher plasma insulin (125.7 ± 9.2 v 35.7 ± 3.3 pmol/L, P < .01), norepinephrine (5.39 ± 0.13 v 1.47 ± 0.22 nmol/L, P < .001), and free fatty acid (FFA) (927 ± 79 v 792 ± 88 μmol/L, P < .05) levels. In patients, basal plasma norepinephrine correlated with FFA levels ( r = .65, P < .025). After loading glucose, plasma glucose and insulin levels were still significantly higher in patients than controls. Euglycemic hyperinsulinemic glucose clamp produced a lower insulin-mediated inhibition of endogenous (hepatic) glucose production (HGP) and a greater increase in both glucose disappearance rate (Rd) and glucose metabolic clearance rate (gMCR) in patients than in controls during the first two insulin infusion rates (25 and 50 mU/kg/h). By contrast, these differences disappeared during the highest insulin infusion rate (100 mU/kg/h). Insulin-mediated decrease in plasma FFA levels was also lower in patients than controls. In conclusion, our study shows that in patients suffering from chronic congestive heart failure, an insulin-resistant state seems to occur as a consequence of a contemporary increase in plasma norepinephrine levels.