April 2018 E-Journal Club

April Traineeship Group PhotoGreetings,

We hosted a 3-day traineeship in April, and enjoyed interacting with such a motivated and enthusiastic group. Spring has been slow to arrive this year, so our trainees missed the usual display of Charlottesville Dogwoods, but did get to see our Redbuds in bloom.

Our journal club for April was a randomized study of an EN formulas with decreased carbohydrates, to investigate the impact on critical illness associated hyperglycemia and glucose control.

April Citation:

Wewalka M, Drolz A, Seeland B, et al. Different enteral nutrition formulas have no effect on glucose homeostasis but on diet-induced thermogenesis in critically ill medical patients: a randomized controlled trial. Eur J Clin Nutr. 2018 Apr;72(4):496-503.


This was single center, randomized, unblinded, study of 60 medical ICU patients to compare a reduced carbohydrate/increased fat EN formula with a standard EN formula on glucose control, glucose variability and insulin requirements. The reduced-CHO formula provided 45% fat/37% CHO, while the standard formula provided 30% fat/55% CHO and both formulas provided 1 kcal/mL. EN was started within 72 hours of ICU admission and study formulas were continued for 7 days, or until patients were able to take food by mouth. Indirect calorimetry was completed at baseline and on study days 3 and 7, and calorie goals were established as 25% above resting energy expenditure.

The primary study outcome was daily average blood glucose and secondary outcomes included 24-hour insulin requirements, glucose variability and “nutrition related side effects.”

Inclusion and Exclusion Criteria:

Inclusion criteria:

Adult, medical ICU patients, mechanically ventilated with fraction of inspired oxygen (FiO2) ≤60% who required nutrition support.

Exclusion criteria:

Patients with a history of diabetes, or those with hemodynamic shock (lactate of ≥4 mmol/l), severe hypertriglyceridemia (≥450 mg/dl) or other contraindications for receiving EN (intestinal obstruction or severe GI bleeding)

Major Results:

Baseline characteristics were similar between the 2 groups. The average duration of EN was 6.0 ± 1.7 days in the low-carbohydrate group and 5.9 ± 2.1 days in the standard group, with 73.3% of all patients completing the entire study duration of seven days. In those patients who did not completed the full 7 study days, in the low-carbohydrate group, 23.3% died and 3.3% no longer needed EN, whereas in in the standard feeding group, 20% died and 6.7% no longer needed EN.

The average amount of EN provided (percent of goal) was not significantly different between the groups (low-carb: 79%, standard 83.3 %). Overall calorie intake (EN, parenteral glucose, and propofol) tended to be similar between the groups throughout the study, but there was a trend towards increased calorie provision in the standard group on study day 2 (low-carb 1487 kcal/day, standard 1697 kcal/day; p = 0.066).

Fasting plasma glucose was elevated but similar in both groups (low-carb: 128 mg/dl, standard: 123 mg/dl; p = 0.570). Average daily blood glucose concentration was higher in the low-carb group on day 1 (low-carb: 143 mg/dl, standard: 137 mg/dl; p = 0.048) but did not differ any day thereafter as well as over the entire study period (p = 0.655). Hyperglycemic event rate, glucose AUC and ∆ glucose were comparable between the groups.

Daily insulin demand per 24 h and total insulin demand over the course of the whole study period were similar between groups. There was a low rate of hypoglycemic events (low-carb: n = 2/927; standard: n = 1/934 episodes, p = 1.0), however, both events in the low-carb group were episodes of severe hypoglycemia.

There was no significant difference in the incidence of hypertriglyceridemia, cholestasis, increased gastric residual volumes, diarrhea, emesis or metoclopramide use between the two groups. There was a trend towards increased erythromycin use in patients that received the low-carb feeding (p = 0.055).

At baseline, indirect calorimetry revealed that VO2, VCO2, REE, RQ, and non-protein RQ did not differ between the two groups. Over the study period, energy expenditure progressively increased in the low-carb EN group (1556 kcals baseline, 1640 kcals day 3, 1844 kcals day 7) but remained unchanged in the standard feeding group (1563 kcals baseline, 1604 kcals day 3, 1530 kcals day 7).

Author’s Conclusions:

“…fat-based and glucose-based EN influence glucose homeostasis and insulin demand similarly, yet diet-induced thermogenesis was substantially higher in critically ill patients receiving fat-based enteral nutrition.”


The results of this study were a bit surprising to our group because there was not even a small difference in insulin requirements between the 2 groups. Past studies with decreased CHO/increased fat formulas have generally reported a modest decrease in insulin requirement, even if they had limited effect on overall glucose control. The lack of difference in insulin requirements is even more surprising considering that the calorie goals (25% greater than actual calorie expenditure) in this study were more than we would normally provide.

One possible reason for the lack of difference in insulin requirements (despite a difference in carbohydrate provision) was the overall modest daily insulin requirements in both groups, which is perhaps not surprising when you remember that patients with a history of diabetes were excluded. This study had a modest number of patients in each group, so it is also possible that chance differences in insulin resistance or response to illness in some patients affected the results.

The difference in energy expenditure between the groups as the study progressed, was even more perplexing. I am not aware of a reason why a reduced CHO/increased fat EN formula would result in greater energy expenditure. This difference in energy expenditure between the groups on day 3 and day 7 suggests that there may have been a chance difference in response to illness over time. Some patients in the reduced CHO/increased fat formula group may have had a more complicated admission with increased hospital acquired complications, which increased both energy expenditure and insulin resistance.

Our Take Home Message(s)

  1. This study suggests that the provision of a reduced-carbohydrate/increased fat EN formula has limited effects on insulin requirements and glucose control in non-diabetic ICU patients.
  2. This study may have been too small to reliably rule out effects related to chance differences between the groups.
  3. A larger study would be required to know if reduced-carbohydrate/increased fat formulas affect energy expenditure in the ICU


Other News on the UVAHS GI Nutrition Website: (www.ginutrition.virginia.edu):

Latest PG Article: When a Registered Dietitian Becomes the Patient: Translating the Science of the Low FODMAP Diet to Daily Living

Upcoming Webinars:

  • June 19th— Jejunal Feeding:   Myths, Physiology, Evidence and Clinical Experience by Carol Rees Parrish, MS, RD


Joe Krenitsky MS, RDN

PS – Please feel free to forward on to friends and colleagues.