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1 Division of Nephrology, Vanderbilt University Medical Center, Nashville, TN, USA
2 Division of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
3 Maine Medical Center Research Institute, Scarborough, ME, USA
4 University of California San Francisco, San Francisco, CA, USA
5 University of California San Diego, San Diego, CA, USA
6 Cleveland Clinic Foundation, Cleveland, OH, USA
* To whom correspondence should be addressed. E-mail: alp.ikizler{at}vanderbilt.edu.
Background: 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. Methods: 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 in 90 patients. Daily glucose determinations were obtained from a larger fraction of the PICARD cohort (n = 509). Results: Among the 90 patients with intensive metabolic monitoring, glucose concentrations in survivors were significantly lower than in non-survivors throughout the five week 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 (HOMA-R) levels were significantly higher (24.1 ± 30.0 vs. 11.7 ± 12.5, P=0.04) and insulin-like growth factor binding protein 3 concentrations were significantly lower (1190 ± 498 vs. 1470 ± 581 µg/L, P=0.02) among non-survivors compared with survivors. Conclusions: 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.
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