Intermittent vs Continuous Enteral Nutrition in Glycaemic Control of Diabetic ICU Patients

This randomized controlled clinical trial was conducted in the 25-bed tertiary intensive care unit of the Anesthesiology and Reanimation Department at Ankara Training and Research Hospital. Ethical approval was obtained from the institutional review board, and written informed consent was provided by the legal representatives of all participants. The study was carried out between December 2023 and June 2024, including 25 adult diabetic patients (14 males, 11 females; mean age: 73.44 ± 8.97 years) who were receiving clinical nutrition therapy in the ICU.

The purpose of this study was to compare the effects of continuous enteral nutrition (CE) and intermittent enteral nutrition (IE) on glycemic control and selected metabolic parameters. Sample size was calculated using G*Power software, indicating that a minimum of 24 participants (12 per group) would be needed to detect a large effect size (1.39) with 80% power and a 5% type I error rate.

All patients initially began enteral feeding at 40 mL/hour according to standard ICU protocol, with gradual increases based on individual tolerance. Once patients reached 80% of their estimated energy requirement without feeding intolerance, they were randomized into one of two groups:

CE group (Control, n=12): Received enteral nutrition in a near-continuous fashion with scheduled breaks.

IE group (n=13): Received nutrition in defined intermittent periods, alternating with fasting intervals.

Energy needs were estimated using the ESPEN guideline formula (25 kcal/kg/day), and a diabetic-specific enteral formula was administered accordingly.

Blood glucose levels were measured five times per day (06:00, 11:00, 16:00, 21:00, and 01:00) using a bedside glucometer. In addition, all participants had the following data collected:

Clinical scores: SOFA, mNUTRIC, and APACHE II

Baseline and Day 7 measurements of serum total cholesterol and triglycerides

Daily laboratory parameters: serum glucose, ALT, AST, GGT, albumin, CRP, BUN, creatinine, sodium, and potassium

The intervention lasted for 7 days and aimed to evaluate whether the method of enteral nutrition delivery (CE vs. IE) affects metabolic responses and glycemic outcomes in diabetic ICU patients. Findings from this study may help inform nutritional strategies in critical care for individuals with diabetes.

• Intermittent Enteral Nutrition (Other): Intermittent Enteral Nutrition (IE): The intervention involves intermittent enteral nutrition using a diabetic-specific enteral formula, administered in 5 separate sessions daily with scheduled breaks between feedings. Each feeding session is followed by a break (1-2 hours). Energy needs are calculated based on the ESPEN guideline (25 kcal/kg/day). This protocol is designed to assess the effects of intermittent feeding in critically ill diabetic patients.
• Continuous Enteral Nutrition (CE) (Other): Continuous Enteral Nutrition (CE): The intervention involves continuous enteral nutrition provided via a diabetic-specific enteral formula, administered 24 hours a day with 1-hour breaks between feeding sessions. The feeding rate starts at 40cc per hour and is gradually increased based on tolerance. Energy needs are calculated using the ESPEN guideline (25 kcal/kg/day).

Primary outcomes

• Blood Glucose Levels (mg/dL) [Five measurements per day at 06:00, 11:00, 16:00, 21:00, and 01:00, for 7 consecutive days]: The primary outcome measure will be the effect of continuous versus intermittent enteral nutrition on glycemic control in critically ill diabetic patients. Blood glucose levels will be monitored 5 times per day using a glucose meter (GlucoNavii, Korea). Measurements will be taken at the following times: 06:00, 11:00, 16:00, 21:00, and 01:00.

Secondary outcomes

• Serum Triglyceride Levels (mg/dL) [Baseline (Day 1) and Day 7]: Serum triglyceride levels will be measured to assess the impact of enteral nutrition on lipid metabolism. Blood samples will be collected at baseline (Day 1) and on Day 7 of intervention.
• Serum Cholesterol Levels (mg/dL) [Baseline (Day 1) and Day 7]: Serum cholesterol levels will be measured to assess the impact of enteral nutrition on lipid metabolism. Blood samples will be collected at baseline (Day 1) and on Day 7 of intervention.
• Serum Albumin Levels (g/dL) [Daily measurements for 7 consecutive days]: Serum albumin levels will be assessed as an indicator of nutritional status and response to enteral feeding protocols. Blood samples will be drawn daily for 7 days.
• Serum CRP (C-Reactive Protein) Levels (mg/L) [Daily measurements for 7 consecutive days]: Serum CRP levels will be monitored to evaluate the inflammatory response in critically ill patients receiving enteral nutrition. Blood samples will be drawn daily for 7 days.
• Serum Alanine aminotransferase (ALT) Levels (U/L) [Daily measurements for 7 consecutive days]: Serum levels of ALT will be monitored to assess liver function and potential liver injury in response to enteral nutrition protocols. Blood samples will be drawn daily for 7 days.
• Serum Aspartate aminotransferase (AST) Levels (U/L) [Daily measurements for 7 consecutive days]: Serum levels of AST will be monitored to assess liver function and potential liver injury in response to enteral nutrition protocols. Blood samples will be drawn daily for 7 days.
• Serum Gamma glutamyl transferase (GGT) Levels (U/L) [Daily measurements for 7 consecutive days]: Serum levels of GGT will be monitored to assess liver function and potential liver injury in response to enteral nutrition protocols. Blood samples will be drawn daily for 7 days.
• Serum Blood Urea Nitrogen (BUN) Levels (mg/dL) [Daily measurements for 7 consecutive days]: Serum levels of BUN will be assessed to evaluate kidney function in critically ill patients receiving enteral nutrition. Blood samples will be drawn daily for 7 days.
• Serum Creatinine Levels (mg/dL) [Daily measurements for 7 consecutive days]: Serum levels of creatinine will be assessed to evaluate kidney function in critically ill patients receiving enteral nutrition. Blood samples will be drawn daily for 7 days.
• Sequential Organ Failure Assessment (SOFA) Score [First day of admission to the ICU]: The SOFA score evaluates the function of six organ systems-respiratory, cardiovascular, hepatic, coagulation, renal, and neurological-in critically ill patients. It is used to monitor the extent of organ dysfunction and predict clinical outcomes in the intensive care unit (ICU). Unit of Measure: Score (0-24 scale) Interpretation: Higher scores indicate greater organ dysfunction and worse prognosis.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age 18 or older

Diagnosis of diabetes

Receiving enteral nutrition

Indication for at least 7 days of ICU admission to perform the study

Exclusion Criteria:

* Under 18 years old

Having specific needs that would require a completely different type of treatment, such as cancer or cystic fibrosis

Pregnancy

Expected to stay in the ICU for less than 7 days

Receiving oral feeding or TPN (Total Parenteral Nutrition)

• Results publication: Ren CJ, Yao B, Tuo M, Lin H, Wan XY, Pang XF. Comparison of sequential feeding and continuous feeding on the blood glucose of critically ill patients: a non-inferiority randomized controlled trial. Chin Med J (Engl). 2021 Jul 20;134(14):1695-1700. doi: 10.1097/CM9.0000000000001684. PMID 34397596

• Aslı Akyol Mutlu, Prof., Study director, Hacettepe University