Glucose and insulin administration while maintaining normoglycemia inhibits whole body protein breakdown and synthesis after cardiac surgery

Hatzakorzian, Roupen; Shum‐Tim, Dominique; Wykes, Linda; Hülshoff, Ansgar; Bui, Helen; Nitschmann, Evan; Lattermann, Ralph; Schricker, Thomas

doi:10.1152/japplphysiol.00175.2014

Cited by 10 publications

(10 citation statements)

References 32 publications

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“…Insulin (1) protects against the depletion of glycogen and triglycerides, (2) prevents liver injury by reducing hepatic inflammation, and (3) prevents the phosphorylation of STAT3, thus restoring physiologic hepatic gluconeogenesis 72 . Intensive insulin therapy has demonstrated benefits in select populations, including patients undergoing cardiac surgery and patients with moderate to severe trauma, but benefits in other populations remain unclear 20,26,27,43,62,115,128,134,136,137 …”

Section: Discussionmentioning

confidence: 99%

“…26,30 The initiation of nutrition support is believed to help with resolution of ebb and flow phases but has not been definitively established. 30,62,63 Notably, some studies have demonstrated that high levels of protein supplementation early in critical illness (presumably during the ebb and flow phases) may be potentially harmful. 64,65…”

Section: Protein Metabolismmentioning

confidence: 99%

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Endogenous Glucose Production in Critical Illness

et al. 2021

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Regulation of endogenous glucose production (EGP) by hormonal, neuronal, and metabolic signaling pathways contributes to the maintenance of euglycemia under normal physiologic conditions. EGP is defined by the generation of glucose from substrates through glycogenolysis and gluconeogenesis, usually in fasted states, for local and systemic use. Abnormal increases in EGP are noted in patients with diabetes mellitus type 2, and elevated EGP may also impact the pathogenesis of nonalcoholic fatty liver disease and congestive heart failure. In this narrative review, we performed a literature search in PubMed to identify recently published English language articles characterizing EGP in critical illness. Evidence from preclinical and clinical studies demonstrates that critical illness can disrupt EGP through multiple mechanisms including increased systemic inflammation, counterregulatory hormone and catecholamine release, alterations in the hypothalamic-pituitary axis, insulin resistance, lactic acidosis, and iatrogenic insults such as vasopressors and glucocorticoids administered as part of clinical care. EGP contributes to hyperglycemia in critical illness when abnormally elevated and to hypoglycemia when abnormally depressed, each of which has been independently associated with increased mortality. Increased EGP may also promote protein catabolism that could worsen critical illness myopathy and impede recovery. Better understanding of the mechanisms and factors contributing to dysregulated EGP in critical illness may help in the development of therapeutic strategies that promote euglycemia, reduce intensive care unit-associated catabolism, and improve patient outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Protein Metabolismmentioning

confidence: 99%

Endogenous Glucose Production in Critical Illness

et al. 2021

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“…Past attempts to create anabolism in cardiac surgery with the administration of high-dose insulin alone have been unsuccessful (15). Although insulin can inhibit ubiquitin-proteasome system-induced proteolysis, insulin also causes hypoaminoacidemia and fails to promote protein synthesis in the absence of circulating AA (10,16,22,44).…”

Section: Discussionmentioning

confidence: 99%

“…Blood and expired air samples were collected, before the infusion, to analyze baseline enrichments. The methods used have been previously described in detail (15). Concentrations of glucose, lactate, AA, insulin, cortisol, total protein, albumin, IL-10, IL-1␤, IL-6, IL-8, and TNF-␣ were determined at 150 min of the preand postoperative study period.…”

Section: Study Populationmentioning

confidence: 99%

“…Given the anabolic and anti-inflammatory properties of insulin, the hyperinsulinemic-normoglycemic clamp (HNC) has lately regained attention as a potential therapy to attenuate changes in the metabolic and inflammatory milieus. While HNC has been demonstrated to preserve normoglycemia and lower plasma FFA levels after cardiac surgery, patients remained catabolic, i.e., showed a negative whole body protein balance (15,46). As insulin leads to hypoaminoacidemia, preventing a decrease in circulating AAs by supplementing exogenous AA may stimulate protein synthesis and induce anabolism.…”

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confidence: 99%

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Hyperinsulinemic-normoglycemic clamp administered together with amino acids induces anabolism after cardiac surgery

Codère-Maruyama

Schricker

Shum‐Tim

et al. 2016

American Journal of Physiology-Regulatory, Integrative and Comp

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Cardiac surgery triggers an inflammatory stress response, leading to protein catabolism, a process that even high-dose insulin therapy alone cannot reverse. To determine whether hyperinsulinemic-normoglycemic clamp and perioperative amino acid (AA) supplementation improves whole body protein balance, 20 patients scheduled for elective coronary artery bypass grafting surgery were randomly assigned to have intra- and postoperative hyperinsulinemic-normoglycemic clamp, with or without intravenous AA supplementation. Primed continuous infusions of [6,6-H]glucose and l-[1-C]leucine were used to quantify whole body protein and glucose metabolism before and after surgery. Adipose tissue and serum cytokines were also analyzed to measure their responsiveness to the anabolic effect of AA administration. During hyperinsulinemic-normoglycemic clamp, AA supplementation successfully stimulated whole body protein synthesis, resulting in a positive whole body protein balance after surgery (insulin: -13.6 ± 4.5 vs. insulin + AA: 2.1 ± 5.4 μmol·kg·h, P < 0.001). Endogenous glucose production was equally suppressed in both groups (insulin: 0.0 ± 3.8 vs. insulin + AA 1.6 ± 1.6 μmol·kg·min, P = 0.230). AA supplementation led to significant changes in serum and tissue IL-6 (insulin: 246.6 ± 111.2 vs. insulin + AA: 124.5 ± 79.3 pg/ml, P = 0.011). In conclusion, hyperinsulinemic-normoglycemic clamp technique, together with AA supplementation, can induce an anabolic state after open-heart surgery, as quantified by a positive whole body protein balance.

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