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TRANSLATIONAL PHYSIOLOGY

Insulin resistance in critically ill patients with acute renal failure

¹Department of Medicine, Division of Nephrology, and ²Division of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee; ³Maine Medical Center Research Institute, Scarborough, Maine; ⁴University of California, San Francisco; ⁵University of California, San Diego, California; and ⁶Cleveland Clinic Foundation, Cleveland, Ohio

Submitted 4 January 2005 ; accepted in final form 18 April 2005

Mortality in critically ill patients with acute renal failure (ARF) remains high. Hyperglycemia associated with insulin resistance has been associated with adverse outcomes in critically ill intensive care unit (ICU) patients but has not been examined specifically in patients with ARF. We used data from a subcohort (n = 90) of the Program to Improve Care in Acute Renal Disease (PICARD), an observational study of 618 adult ICU patients with ARF in whom nephrology service consultation was obtained. We obtained simultaneous measurements of serum glucose, insulin, insulin-like growth factor (IGF)-I, and IGF-1 binding proteins (IGFBP) in 90 patients. Daily glucose determinations were obtained from a larger fraction of the PICARD cohort (n = 509). Among the 90 patients with intensive metabolic monitoring, glucose concentrations in survivors were significantly lower than in nonsurvivors throughout the 5-wk period (P = 0.008, adjusted P = 0.013). In the larger PICARD cohort (n = 509), hyperglycemia was also significantly associated with in-hospital mortality. Mean insulin concentrations were significantly higher (431 ± 508 vs. 234 ± 189 pmol/l, P = 0.03), mean homeostasis model of insulin resistance levels were significantly higher (24.1 ± 30.0 vs. 11.7 ± 12.5, P = 0.04), and IGFBP-3 concentrations were significantly lower (1,190 ± 498 vs. 1,470 ± 581 µg/l, P = 0.02) among nonsurvivors compared with survivors. Insulin resistance as defined by hyperglycemia in the setting of higher insulin concentrations may be associated with mortality in critically ill patients with ARF. The IGF-IGFBP axis may play an important role in this process.

glucose; homeostasis model of insulin resistance; insulin-like growth factor-1; insulin-like growth factor binding protein-3; catabolism

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