Dietary Management of Blood Glucose in Medical Critically Ill Overweight and Obese Patients: An Open‐Label Randomized Trial

Abstract

Background: Enteral nutrition (EN) increases hyperglycemia due to high carbohydrate concentrations while providing insufficient protein. The study tested whether an EN formula with very high‐protein‐ and low‐carbohydrate‐facilitated glucose control delivered higher protein concentrations within a hypocaloric protocol. Methods: This was a multicenter, randomized, open‐label clinical trial with parallel design in overweight/obese mechanically ventilated critically ill patients prescribed 1.5 g protein/kg ideal body weight/day. Patients received either an experimental very high‐protein (37%) and low‐carbohydrate (29%) or control high‐protein (25%) and conventional‐carbohydrate (45%) EN formula. Results: A prespecified interim analysis was performed after enrollment of 105 patients (52 experimental, 53 control). Protein and energy delivery for controls and experimental groups on days 1–5 were 1.2 ± 0.4 and 1.1 ± 0.3 g/kg ideal body weight/day (P = .83), and 18.2 ± 6.0 and 12.5 ± 3.7 kcals/kg ideal body weight/day (P < .0001), respectively. The combined rate of glucose events outside the range of >110 and ≤150 mg/dL were not different (P = .54, primary endpoint); thereby the trial was terminated. The mean blood glucose for the control and the experimental groups were 138 (−SD 108, +SD 177) and 126 (−SD 99, +SD 160) mg/dL (P = .004), respectively. Mean rate of glucose events >150 mg/dL decreased (Δ = −13%, P = .015), whereas that of 80–110 mg/dL increased (Δ = 14%, P = .0007). Insulin administration decreased 10.9% (95% CI, −22% to 0.1%; P = .048) in the experimental group relative to the controls. Glycemic events ≤80 mg/dL and rescue dextrose use were not different (P = .23 and P = .53). Conclusions: A very high‐protein and low‐carbohydrate EN formula in a hypocaloric protocol reduces hyperglycemic events and insulin requirements while increasing glycemic events between 80–110 mg/dL.

Narrowing the Protein Deficit Gap in Critically Ill Patients Using a Very High‐Protein Enteral Formula

“…Historically, critical care nutrition literature has focused on energy delivery in critical illness based on the assumption that carbohydrates inhibit protein catabolism, which could decrease the loss of muscle 22,26 . In critical illness however, benefit has not been shown from meeting caloric goals and may be associated with significant side effects, including hyperglycemia 26,27 .…”

Ketogenic Diets in Critical Care?

“…Since C‐reactive protein levels were measured, the authors could assess the level of stress in this group to confirm its mild degree on average. These findings in the present study raise the question of the potential role, if any, for the application of full ketogenic diets in the critically ill because of the seemingly good tolerance of the experimental diet. Recent evidence with ketogenic diets with more extreme carbohydrate limitation and providing energy balance has demonstrated improved glucose control and potential anti‐inflammatory effects in studies in animals .…”

“…The higher protein but lower carbohydrate with similar energy content in the experimental compared with the control diet when fed to provide similar amounts of protein intake led to substantially lower carbohydrate (88 vs 192 g/d) intake with similar amounts of fat (45 vs 57 g/d) in this modest sized study. A “small statistically significant increase in urinary ketones” was noted with the experimental diet, and serum ketones, although not significantly higher at 0.26, could mean at maximum that one‐half of the experimental group had trace ketonemia. This is not totally unexpected, given that 100 g glucose/d is generally thought to be sufficient to eliminate significant ketonemia and ketonuria in man and that 50 g daily or less as carbohydrate is generally the goal for mildly hypocaloric or eucaloric ketogenic diets used clinically to treat epilepsy and more recently type 2 diabetes in the obese .…”

“…The recent results demonstrating the impact of hypocaloric feeding to improve glucose control by principally reducing the level of carbohydrates in overweight or obese medical patients in the intensive care unit (ICU) suggest an interesting and potentially valuable additional maneuver for feeding in the critically ill. The higher protein but lower carbohydrate with similar energy content in the experimental compared with the control diet when fed to provide similar amounts of protein intake led to substantially lower carbohydrate (88 vs 192 g/d) intake with similar amounts of fat (45 vs 57 g/d) in this modest sized study.…”

Medical Foods: Science, Regulation, and Practical Aspects. Summary of a Workshop

“…In surgical populations, a meta-analysis of immunonutrition that evaluated preoperative, perioperative, and postoperative uses of arginine-supplemented diets showed a 41% reduction in infectious complications (the primary outcome) and a reduction in length of stay of 2.38 d ( 76 ). Finally, in critically ill patients with obesity in the ICU, hypocaloric high-protein and low-carbohydrate enteral nutrition has been shown to improve glucose management ( 77 ).…”