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Treating hyperglycemia improves skeletal muscle protein metabolism in cancer patients after major surgery

Biolo, Gianni MD, PhD; De Cicco, Marcello MD; Lorenzon, Stefania MD; Dal Mas, Viviana MD; Fantin, Dario MD; Paroni, Rita MD; Barazzoni, Rocco MD; Zanetti, Michela MD; Iapichino, Gaetano MD; Guarnieri, Gianfranco MD

doi: 10.1097/CCM.0b013e318174de32
Clinical Investigations

Objective: Cancer and surgical stress interact to aggravate insulin resistance, protein catabolism, and glutamine depletion in skeletal muscle. We compared the effects of insulin-mediated euglycemia and moderate hyperglycemia on kinetics of protein and selected amino acids in skeletal muscle of female cancer patients after major surgery.

Design: In each patient, a 24-hr period of insulin-mediated tight euglycemia (mean blood glucose, 5.8 ± 0.4 mmol/L) preceded or followed a 24-hr control period of moderate hyperglycemia (mean blood glucose, 9.6 ± 0.6 mmol/L) on the first and second day after surgery, in randomized order, according to a crossover experimental design.

Setting: Intensive care unit, cancer hospital.

Patients: Cancer patients after abdominal radical surgery combined with intraoperative radiation therapy.

Interventions: Intensive (57 ± 11 units/24 hrs) and conventional (25 ± 5 units/24 hrs) insulin treatment during total parenteral nutrition.

Measurements and Main Results: Muscle metabolism was assessed at the end of each 24-hr period of euglycemia and of hyperglycemia by leg arteriovenous catheterization with stable isotopic tracers. We found that euglycemia as compared with hyperglycemia was associated with higher (p < .05) fractional glucose uptake (16% ± 4% vs. 9% ± 3%); higher (p < .05) muscle protein synthesis and neutral net protein balance (−3 ± 3 vs. −11 ± 3 nmol phenylalanine·100 mL−1·min−1, respectively); lower (−52% ± 12%, p < .01) muscle nonprotein leucine disposal (an index of leucine oxidation) and higher (p < .05) plasma leucine concentrations; and higher (3.6 ± 1.7 times, p < .01) net de novo muscle glutamine synthesis and plasma glutamine concentrations (p < .05). Euglycemia was associated with higher (23% ± 7%, p < .05) plasma concentrations of arginine but did not affect either arginine release from muscle or plasma concentration and muscle flux of asymmetrical dimethylarginine. Rate of muscle proteolysis correlated (p < .05) with muscle release of asymmetrical dimethylarginine.

Conclusions: Treating hyperglycemia improves skeletal muscle protein and amino acid metabolism in cancer patients after major surgery.

From the Division of Internal Medicine, Department of Clinical, Morphological and Technological Sciences, University of Trieste, Trieste, Italy (GB, SL, VDM, RB, MZ, GG); Intensive Care Unit, National Cancer Institute, Aviano, Italy (MDC, DF); Department of Medicine, Surgery, and Dental Science (RP), and the Intensive Care Unit (GI), University of Milan, Milan, Italy.

The authors have not disclosed any potential conflicts of interest.

Supported, in part, by grants from “Ministero Università Ricerca Scientifica e Tecnologica” PRIN 2003 and from Novartis Medical Nutrition.

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© 2008 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins