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The Egyptian Journal of Internal Medicine
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Nutritional modifications to ameliorate stress hyperglycemia in critically ill patients: a systematic review

The Egyptian Journal of Internal Medicine volume 36, Article number: 95 (2024) Cite this article

Abstract

Background and aims

Appropriate nutritional support in critical care may favorably influence outcomes by attenuating the detrimental effects of hyperglycemia associated with the critical illness. This systematic review aims to present and evaluate different nutritional interventions to balance risks and rewards for critically ill patients.

Methods

In this systematic review, we searched online databases for several variations of terms related to critically ill patients with stress-hyperglycemia (participants), nutrition modalities (intervention), glycemic control (outcomes), and randomized controlled trials (study design) between the inception of the databases and October 2023.

Results

The literature search and manual searching provided 2589 articles. After removing the duplicates and excluding studies based on their abstracts or full-text assessment, 37 studies were identified as eligible for inclusion. The heterogeneous nature of these investigations precluded us from pooling data and performing meta-analysis to draw robust conclusions based on statistical analyses. The literature review in this area reveals two general perspectives for achieving this goal: optimizing various aspects of providing macronutrient support and nutritional supplementation.

Conclusions

The optimal approach to feeding critically ill patients remains unresolved despite numerous randomized controlled trials. Individual patient characteristics significantly influence optimal nutritional management. However, some general recommendations convey benefits for patients in the intensive care unit (ICU). Early and continuous enteral nutrition is the usual method of providing nutritional support in practice. Hypocaloric feeding and reducing carbohydrate intake are effective methods for managing SIH; however, they should be tailored to each patient’s clinical characteristics. Supplementation with certain nutrients shows promise in specific groups, but more research is needed. Overall, personalized approaches based on ongoing research are the best we have now. Future studies will hopefully refine treatments and improve outcomes for these patients.

Introduction

Critically ill patients experience sudden and complex metabolic and hormonal changes due to the activation of the autonomic stress response [1]. Metabolic changes during critical illness are a part of the body’s adaptive mechanism to survive the condition. It involves a complex interplay of neuroendocrine changes, resulting in increased gluconeogenesis, glycogenolysis, and insulin resistance. Stress hyperglycemia, defined as a blood glucose level above 180 mg/dL in patients without pre-existing diabetes, indicates disrupted glucose metabolism and is linked to a higher risk of infectious complications [2], mortality in both intensive and non-intensive care patients, and prolonged hospital stays [3].

Altered glucose metabolism is not the only adverse effect of critical illness on metabolism. The release of stress hormones, inflammatory mediators, and the dysfunction of anabolic hormones during critical illness contribute to a reduced response to sufficient protein intake, leading to a loss of lean body mass and subsequent clinical complications.

Recently, there has been a growing interest in the “food as medicine” concept. One area where this approach may be particularly beneficial is managing blood glucose levels in response to stress. Appropriate nutritional support may promote recovery by alleviating the negative impact of critical illness on nutritional status, such as the accumulation of energy debt and protein breakdown. However, it is not without risks and may exacerbate hyperglycemia commonly seen in critically ill patients.

The prior review article has examined the impact of hypoglycemic agents and anesthetic techniques on mitigating stress-induced hyperglycemia in critically ill patients [4]. Despite numerous research studies investigating strategies to optimize the benefit-to-risk ratio of nutritional support in critically ill patients, a comprehensive systematic review evaluating these studies is lacking. So, this systematic review aims to present nutritional modifications and assess their safety and effectiveness in managing blood sugar levels in critically ill patients. The goal is to advance research in this field and provide insights to guide future clinical practice.

Methods

Literature search

In this systematic review, we searched online databases PubMed, EMBASE, ISI WEB OF SCIENCE, Scopus, Cochrane Central, Google Scholar, and the trial registry clinicaltrial.gov for randomized controlled trials published between the inception of the databases and October 2023.

The search strategy consisted of several variations of terms related to critically ill patients with stress hyperglycemia (participants), nutrition modalities (intervention), glycemic control (outcomes), and randomized controlled trials (study design) with no language restrictions. The keywords used in the literature search were “hyperglycemia OR glucose intolerance OR hyperinsulinism OR glucose metabolism disorders OR insulin resistance OR Glycemic control OR blood glucose control AND Surgical patients OR surgery OR surgical procedure OR operative procedure AND nutrition OR enteral OR parenteral OR feeding AND Critical illness OR critical care OR critically ill OR intensive care AND Randomized controlled trial, Traumatic, medical”. The keywords from each part were combined using Boolean operators. Reference lists of the included studies were also manually examined to identify any additional relevant studies.

Eligibility criteria and study selection

We aimed to include all studies that had the following characteristics:

RCTs (study design) conducted to evaluate the effects of nutritional modification (intervention) on at least one measurement of glycemic control in adults (age > 18 years) with stress-induced hyperglycemia (SIH) in critical illness without diabetes (population).

After importing the retrieved studies and removing duplicate records using bibliography management software (EndNote®), two reviewers (F.R. and M.N.) independently screened the titles and abstracts for relevance in the first stage of study selection. They then extracted and selected eligible full-text and abstract-form studies. In the second stage, two investigators independently examined the full texts of the selected studies using a standardized eligibility form that was based on our pre-specified PICO criteria.

Data extraction

We extracted the following data from the included studies: the last name of the first author, year of publication, study location, treatment and follow-up duration, sample size, and our pre-specified PICO information. Other extraction data included mean age, body mass index (BMI), gender of the study population, and baseline glucose levels. We used a standardized data sheet based on the Cochrane Consumers and Communication Review Group’s data extraction template.

Risk of bias assessment

We assessed the methodological quality of the included studies using the Cochrane quality assessment tool, which evaluated the following domains: (a) random sequence generation, (b) allocation concealment, (c) blinding of participants and personnel, (d) blinding of outcome assessment, (e) incomplete data outcome, and (f) selective outcome reporting. Judgment about the risk of bias arising from each domain is determined based on the responses to the signaling questions on a checklist (low risk, high risk, or unclear).

Two investigators independently conducted the screening, data extraction, and risk of bias assessment. Any discrepancies were attempted to be resolved through thorough discussion. A third investigator (Sh.F.) was also considered to adjudicate and resolve any differences.

Results and discussion

The literature search and manual searching provided 2589 articles. After removing the duplicates (958 articles) and excluding studies based on their abstracts or full-text assessment (1568 articles), 37 studies were identified as eligible for inclusion (Fig. 1).

Fig. 1
figure 1

PRISMA flow diagram

Full size image

Tables 1 and Supplementary Material 1 represent the characteristics of the studies and participants included in the systematic review and risk of bias assessment, respectively.

Table 1 Characteristics of the included studies
Full size table

The heterogeneous nature of these investigations precluded us from pooling data and performing meta-analysis to draw robust conclusions based on statistical analyses. A comprehensive literature review identified two primary perspectives on nutritional modifications for managing blood sugar levels in critically ill patients. These perspectives, along with corresponding recommendations, are discussed in detail in the following sections.

  • Optimize various aspects of providing macronutrient support, including timing, delivery method, and the composition of nutritional formulas.

  • Optimize various aspects of providing macronutrient support, including timing, delivery method, and the composition of nutritional formulas.

Optimize various aspects of providing macronutrient support

Insights into the timing and route of administration

Although there is no consensus on the tolerable level of starvation in critically ill patients without harmful consequences, these recommendations are available based on guideline evidence [5]:

  • Initiate nutrition as soon as possible, preferably within 24–48 h of the onset of critical illness.

  • Enteral nutrition is the preferred method for providing nutritional support to critically ill patients.

  • Total or supplemental parenteral nutrition should be considered if enteral nutrition is contraindicated or the nutrition target is not met.

  • Evidence suggests that patients receiving parenteral nutrition had significantly higher blood glucose levels than those receiving enteral nutrition [6].

Pilika et al. [7] conducted a randomized controlled trial (RCT) to examine the impact of enteral nutrition timing on insulin resistance in neurosurgical patients. The authors reported that the number of patients who developed insulin resistance and the amount of insulin administered to control glycemia were significantly higher in the late nutrition group. They suggested that initiating nutrition within 72 h in the neurosurgical ICU (intensive care unit) would be preferable.

Insights into the feeding methodology

Intermittent (administering a bolus volume of nutrients at specific intervals) and continuous enteral feeding are two standard modes used to provide nutrition to critically ill patients. The current recommendation in this field for improved control of SIH is:

  • Enteral nutrition should be administered continuously in the ICU [8, 9].

Most studies have demonstrated that continuous feeding is comparable or superior to sequential feeding (SF) in managing glycemic control in ICU patients’ stress-induced hyperglycemia (SIH) [10,11,12,13]. However, Ren et al.’s study [14] showed that the average blood glucose level in the SF method (three times daily) was not inferior to continuous feeding and led to a lower occurrence of hyperglycemia.

More high-quality randomized controlled clinical trials and meta-analyses are needed to evaluate each method’s other long-term consequences, such as long-term hyperglycemia, insulin resistance, and skeletal muscle autophagy [9, 15,16,17].

Insights into the nutrition composition

Multiple research studies have concentrated on various enteral formulas to assess their impact on glycemic control and revealed:

  • Hypocaloric nutrition (30–65% of the calculated calory requirement) has been shown to benefit glycemic control in ICU patients compared to the full-calorie feeding group (which had a goal of 90–100% of the calculated requirement) when patients receive the same protein content [18,19,20,21,22,23].

  • Reducing carbohydrate intake (8.5% to 30%) is significantly associated with improved glycemic control and reduced insulin requirements in critically ill patients. This association had a greater effect size in trials involving patients with diabetes mellitus (DM) [19, 24,25,26,27,28,29,30].

  • The ideal lipid emulsion (LE) combination has not been conclusively determined. However, plasma glucose and insulin levels were lower in the n-3 fatty acid-enriched than soybean lipid emulsion in the conducted study [31].

  • A few studies evaluated the metabolic effects of different carbohydrate types in enteral or parenteral nutrition in the ICU. No significant differences in glycemic variability were observed between diabetes-specific enteral formulas with or without fructose [32]. However, the enteral isomaltose group exhibited superior metabolic effects compared to the control group [33]. Additionally, parenteral nutrition utilizing a glucose solution demonstrated better metabolic outcomes than a fructose solution [34].

Hypocaloric nutrition

Hypocaloric nutrition is a strategy that intentionally restricts energy intake and reduces insulin demand while ensuring that protein or fat macronutrients still meet metabolic needs. Although hypocaloric nutrition has been associated with some metabolic benefits, such as lower and less severe episodes of hyperglycemia or decreased insulin consumption in critically ill patients. However, most studies addressing this concept have shown no significant impact on clinical outcomes [18,19,20,21,22,23] (Table 1).

These beneficial metabolic events were also reported in high-protein, hypocaloric nutrition. Rice et al. [19] conducted a multicenter trial to assess the impact of this approach on critically ill overweight and obese patients. They examined an experimental enteral nutrition formula with a very high protein content (37%) and low carbohydrate content (29%), compared to a control formula with a high protein content (25%) and standard carbohydrate content (45%). Protein delivery was consistent across all groups during the study period, but energy delivery was significantly lower in the experimental group. They showed a decrease in average blood glucose levels and the frequency of insulin administration in the high-protein, hypocaloric nutrition group.

Petros et al. demonstrated that hypocaloric feeding (11.3 ± 3.1 kcal/kg/day) in the first 7 days in critically ill patients resulted in lower insulin demand and reduced gastrointestinal intolerance. Still, it was associated with more nosocomial infections than normocaloric feeding (19.7 ± 5.7 kcal/kg/day) [21]. The higher rate of nosocomial infections may be attributed to the lower protein intake in these patients.

Reducing carbohydrate intake

The provision of exogenous carbohydrates is associated with increased insulin utilization and glucose variability [29]. Therefore, manipulating carbohydrate intake, particularly by reducing carbohydrate provision in enteral or parenteral nutrition, is one of the most extensively studied strategies for achieving improved glycemic control.

Diabetes-specific formulas (DSFs), in general, have a low total carbohydrate content (35–40% of total calories) and a high-fat content (40–50% of total calories), especially in the form of monounsaturated fatty acids (MUFAs), when compared to standard polymeric formulas. They also feature a variety of carbohydrate sources and are recommended for use in patients with persistent hyperglycemia.

In 2003, Mesejo et al. [30] conducted a multicenter randomized trial to investigate whether a DSF formula would improve glucose control in critically ill hyperglycemic patients. The results revealed a significant improvement in glycemic control and a reduction in insulin requirements among the patients who consumed the low-carbohydrate formula. After the publication of this study, several other studies also revealed the beneficial metabolic effects of various low-carbohydrate enteral formulas with different nutrient compositions [19, 24,25,26,27,28,29]. Furthermore, the carbohydrate-restrictive strategy (CRS) has been reported to be as effective as intensive insulin therapy (IIT) but with a reduced risk of hypoglycemia [35].

Among the studies examining the effectiveness of CRS, two studies by van Steen and Wewalka [27, 36] did not demonstrate a significant positive impact on glucose regulation in the low-carbohydrate group. Various protocols for providing nutrition and monitoring glucose had an effect on these results.

To reach a definitive conclusion about the effectiveness of the CRS strategy, Eckert et al. [37] conducted a meta-analysis and proposed that reducing carbohydrate intake is significantly associated with improved glycemic control and reduced insulin requirements in critically ill patients. This association had a greater effect size in trials involving patients with diabetes. Patients with diabetes may benefit more from this strategy than non-diabetic patients. One potential explanation is that diabetic patients may experience lower levels of stress hyperglycemia, and low-intensity strategies such as reducing carbohydrate intake may be more beneficial for them compared to non-diabetic individuals.

In addition, another meta-analysis was conducted incorporating findings from 18 randomized controlled trials, comparing the metabolic effects of DSF high in MUFA with standard formulas (STDF) [38]. This analysis focused on adult patients diagnosed with type 1 diabetes, type 2 diabetes, or SIH. The results of this meta-analysis provided evidence that a DSF, comprising oral supplements and tube feeds enriched with MUFAs, yielded improvements in glucose control and metabolic risk factors compared to the STDF in patients diagnosed with diabetes or SIH. The heterogeneity observed in the study population, consisting of patients with DM and those experiencing SIH without diabetes, renders the conclusion inconclusive, specifically for individuals just with SIH.

Despite the potential of DSF to improve glycemic control and insulin requirements, the recently published studies have not demonstrated any superior clinical outcomes, such as ICU length of stay, mechanical ventilation, and mortality, compared to control groups. The extent of carbohydrate reduction is another factor that may affect the metabolic and clinical outcomes of DSF. This is because low-carbohydrate formulas often contain higher fat content than standard formulas, and a high fat content may lead to insulin resistance. The percentage of carbohydrate reduction varied significantly among the studies, ranging from 8.5 to 30%. Hence, determining the optimal amount of carbohydrates is another issue that requires further investigation.

Ideal lipid emulsion

The ideal LE combination should be tailored to the patient’s condition, the critical illness’ severity, and overall nutritional needs. For example, it has been suggested that n-3 fatty acids modulate inflammatory responses [39, 40], which may decrease insulin resistance. Tappy et al. [31] conducted a trial in surgical intensive care patients who received total parenteral nutrition (TPN) using either an n-3 fatty acid-enriched or soybean lipid emulsion. Plasma glucose and insulin levels were lower in the TPN-n-3 group, but the difference did not reach statistical significance. Additionally, the energy expenditure was significantly lower in the TPN-n-3 group.

Various carbohydrate types in critical illness

Modifications in the nutritional composition aimed at reducing or preventing stress hyperglycemia were not limited to adjusting macronutrient proportions. Some studies evaluated the metabolic effects of different carbohydrate types in critical illness.

Kumbier et al. [32] conducted a randomized, controlled, double-blinded crossover clinical trial to assess whether the presence of fructose interferes with glycemic variability. They randomly assigned patients to receive one of two diabetes-specific diets (fructose-based versus maltodextrin-based) to evaluate the impact of these formulas on glucose variability. The study results indicated no difference in glycemic variability among critically ill patients who used diabetes-specific enteral formula, with or without fructose. Egi et al. [33] also conducted a pilot randomized crossover trial to assess the impact of an enteral formula based on isomaltose on glucose control. The primary point of the study was to determine the average and highest blood glucose levels during the feeding period. The levels were found to be significantly lower in the isomaltose group. They also reported a lower variability in glucose levels in the isomaltose group compared to the control group.

Adolph’s study [34] demonstrated that parenteral nutrition using a glucose solution and lipid emulsion regimen led to lower blood glucose concentration and insulin activity compared to parenteral nutrition using a fructose solution and lipid emulsion.

Insights into nutritional supplements

Micronutrients and conditionally essential amino acids like glutamine offer potential immunomodulatory effects, prompting research into their use for managing stress hyperglycemia in critically ill patients.

  • Promising metabolic effects of loading dose 7.5 g of magnesium sulfate IV infusions in patients with stress hyperglycemia [41].

  • The controversial effect of vitamin D supplementation regarding the route and duration of administration was observed in managing SIH [42, 43].

  • Administration of a single high-dose vitamin D3 (500,000 IU) within a week of admission for patients with 25-hydroxy-vitamin D plasma concentrations below 12.5 ng. ml−1c [44].

  • Alanyl-glutamine (Ala-Gln) supplementation (0.5 g/kg/day) attenuated hyperglycemia and improved insulin sensitivity in ICU patients without multiple organ failures or septic shock [45,46,47,48,49].

  • Supplementation with L-carnitine and α-lipoic acid (ALA) has also been shown to improve insulin resistance in separate studies, as measured by HOMA-IR [50, 51].

  • Two different herbal formulations modified HuangLian JieDu decoction and fenugreek seed powder had promising effects on managing SIH [52, 53].

Magnesium sulfate

Heidary et al. [41] conducted a randomized clinical trial to evaluate the effect of a magnesium loading dose (7.5 g of magnesium sulfate in 500 mL normal saline as an intravenous infusion over an 8-h period) on insulin resistance in patients with stress hyperglycemia. Their results suggested significant differences between the group that received magnesium and the placebo group in the mean changes of their blood glucose concentration from baseline. Furthermore, the researchers noted significant improvements in insulin resistance indices in the group that received magnesium compared to the group that received a placebo.

Vitamin D

Data from studies investigating the effects of vitamin D supplementation on glycemic indices and insulin resistance in non-ICU patients are controversial. Some of these studies showed positive effects of vitamin D supplementation on decreasing fasting glucose, HbA1C, or insulin resistance [54], while others could not confirm these findings [55,56,57].

Alizadeh et al. [42] studied the effects of vitamin D supplementation on stress hyperglycemia in critically ill patients. Patients in the vitamin D group received a single dose of 600,000 IU of vitamin D3 as an intramuscular injection at the time of recruitment. On day 7, patients in the vitamin D group had significantly higher levels of vitamin D and adiponectin in their plasma, which serves as a biomarker of insulin sensitivity, compared to the placebo group. However, no significant differences were observed in the serum glucose, insulin, HOMA-IR, and HOMA-AD levels between the groups. The researchers attributed the inadequate and non-significant response to vitamin D supplementation to the slow absorption of vitamin D when administered intramuscularly and the short duration of the study, which may not be sufficient to demonstrate any potential therapeutic benefits of vitamin D3 in managing stress hyperglycemia.

Besides, Paez et al. [43] showed that daily administration of 1000 international units of vitamin D plus 1000 mg of calcium reduced blood glucose concentration and undesirable events, such as hypoglycemia, defined as blood glucose levels below 100 mg/dL after 72 h. These two studies provide evidence of the potential therapeutic benefits of vitamin D3 in managing stress hyperglycemia. They also emphasize the need for additional research in this area, particularly regarding the most effective route of administration, duration of follow-up, and timing of vitamin D3 administration.

Although vitamin D deficiency is linked to poorer patient outcomes, the VITdAL-ICU study in 2014 found that regular administration of high-dose vitamin D did not improve hospital length of stay or 6-month mortality for critically ill patients with vitamin D deficiency. However, patients with severe deficiency may benefit. The European Society for Clinical Nutrition and Metabolism (ESPEN) suggests the administration of a single high-dose of vitamin D3 (500,000 IU) within a week of admission for patients with 25-hydroxy-vitamin D plasma concentrations below 12.5 ng. ml−1 [44].

Glutamine

In critical illness, the demand for glutamine may surpass the body’s capacity to produce it. Glutamine improves nitrogen balance and may reduce protein catabolism.

Glutamine restores intracellular levels of glutathione and modifies heat shock proteins [58]. Furthermore, glutamine modulates fatty acid oxidation [59]. Several studies have evaluated the effects of 0.5 g/kg/day of Ala-Gln parenteral supplementation on glucose homeostasis for at least 5 days. Their results have shown that Aln-Gln supplementation attenuated hyperglycemia and improved insulin sensitivity in critically ill patients [45,46,47,48,49].

Apart from the metabolic effects of glutamine in critical illnesses, studies evaluating the clinical outcomes of glutamine supplementation in critically ill patients appear to be contradictory. Although some studies have demonstrated the beneficial or neutral effects of glutamine supplementation in critical illness [60,61,62,63], the results of the largest randomized controlled trial on glutamine supplementation in critically ill patients (REDOX) showed an increase in the patients’ mortality rate [64]. To explain this controversy, we should consider that glutamine metabolism varies in different situations. REDOX utilized high doses of glutamine in ICU patients with multiple organ failures and septic shock, who exhibited a high level of inflammation in their bodies, the situation that immune cells may utilize a significant portion of the available glutamine [65]. This could potentially exacerbate the inflammatory response and reduce the patient’s chances of survival. In addition, the complex glutamine metabolism in critically ill patients may result in unpredictable effects of glutamine supplementation [66]. Further studies are needed to unravel the glutamine metabolism in critically ill patients to identify patients who may benefit from glutamine supplementation.

Supplementation with L-carnitine and α-lipoic acid (ALA) has also been shown to improve insulin resistance, as measured by HOMA-IR, in separate studies [50, 51].

L-Carnitine

In another study, Nejati et al. [50] evaluated the effect of 1.5 g per day of L-carnitine supplementation for 6 days on patients with acute ischemic stroke during the early phase of critical illness. Their results revealed improved insulin resistance, as assessed by HOMA-IR, as well as decreased insulin concentrations and levels of C-reactive protein, which is an inflammatory marker, in these patients.

α-Lipoic acid (ALA)

Hejazi et al. [51] demonstrated the significant beneficial effects of a 10-day supplementation of 900 mg ALA on the severity of inflammation, measured by C-reactive protein levels, and the total antioxidant capacity in critically ill patients. These patients were expected to stay in the ICU for at least seven days and required enteral feeding. Their results also revealed that patients who received ALA supplementation had lower blood glucose levels and improved insulin sensitivity (measured by HOMA-IR) compared to the patients who received a placebo. However, the groups had no significant difference in clinical outcomes, such as the length of ICU/hospital stay, ICU/hospital mortality, 28-day mortality, and ventilator-free days.

Herbal formulas

Two studies evaluate the effects of supplementing two different herbal formulas, which have been found to be effective in traditional medicine for glycemic management in critically ill patients.

Kooshki et al. [52] conducted a randomized controlled clinical trial on 60 adult patients who were randomly divided into two groups. The intervention group received 3 g of fenugreek seed powder orally twice a day, in addition to their regular insulin therapy, for a duration of 10 days. Their data showed that the average glucose levels were significantly lower in the intervention group compared to the control group. Wang et al. [53] demonstrated that the use of modified HuangLian JieDu decoction (a well-known Chinese herbal remedy) as a supplementary medication for early enteral nutrition led to a reduced occurrence of hyperglycemia and gastric retention in septic patients. They also reported that the duration of mechanical ventilation and ICU stay were significantly shorter in the intervention group compared to the control group. However, the 60-day mortality rate was not significantly different between the groups.

Two different herbal formulations modified HuangLian JieDu decoction and fenugreek seed powder had promising effects on managing SIH [52, 53].

Conclusions

While numerous RCTs have investigated nutritional strategies in critically ill patients, a definitive, one-size-fits-all approach remains elusive. Individual patient characteristics significantly influence optimal nutritional management, demanding personalized treatment plans.

Despite this ongoing quest for the “perfect” approach, several key recommendations offer demonstrable benefits for ICU patients. For hemodynamically stable individuals, early initiation of nutritional support within 24–48 h of critical illness onset is crucial. Continuous enteral nutrition typically serves as the preferred method. However, the specific route and modality should be carefully selected based on patient-specific factors such as care needs, nutritional status, and potential complications.

Intriguingly, the administration of diabetes-specific enteral formulas has shown promise in improving glycemic control and reducing insulin requirements. However, recent meta-analyses have not identified any definitive clinical advantages for this specific method.

Furthermore, research into targeted supplementation with individual nutrients like magnesium, vitamin D, and others suggests potential metabolic benefits in specific patient subgroups. However, limitations in study quality and insufficient data currently constrain our ability to confirm or refute their broader clinical significance.

In conclusion, the field of critical illness nutrition continues to evolve with ongoing research efforts. Although a universally optimal approach remains elusive, personalized strategies guided by individual patient characteristics and supported by emerging evidence represent the current best practice. Future high-quality research holds the key to further refining nutritional interventions and optimizing outcomes for critically ill patients.

Availability of data and materials

The data set used in the current study is available on request from (contact name/email id).

Abbreviations

ALA:

α-Lipoic acid

BMI:

Body mass index

CRS:

Carbohydrate-restrictive strategy

DM:

Diabetes mellitus

DSFs:

Diabetes-specific formulas

ESPEN:

The European Society for Clinical Nutrition and Metabolism

HOMA:

Homeostatic Model Assessment

ICU:

Intensive care unit

IIT:

Intensive insulin therapy

LE:

Lipid emulsion

MUFA:

Monounsaturated fatty acids

RCT:

Randomized controlled trial

SF:

Sequential feeding

SIH:

Stress-induced hyperglycemia

STDF:

Standard formulas

TPN:

Total parenteral nutrition

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Acknowledgements

Not applicable.

Funding

This study was financially supported by the Isfahan University of Medical Sciences, Isfahan, I.R. Iran through Grant No. 3400487.

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Authors and Affiliations

  1. Department of Clinical Pharmacy and Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Isfahan, Iran

    Fatemeh Rahimpour, Shadi Farsaei & Azadeh Moghaddas

  2. Department of Clinical Pharmacy and Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Birjand University of Medical Sciences, Birjand, South Khorasan, Iran

    Malihe Nejati

  3. Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Isfahan, Iran

    Awat Feizi

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  1. Fatemeh Rahimpour
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  2. Malihe Nejati
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Contributions

Fatemeh Rahimpour: investigation, methodology, visualization, writing—original draft preparation, and writing—review and editing. Malihe Nejati: investigation, methodology, visualization, writing—original draft preparation, and writing—review and editing. Shadi Farsaei: conceptualization, data curation, formal analysis, funding, acquisition, methodology, project administration, software, supervision, validation, visualization, writing—original draft preparation, and writing—review and editing. Azadeh Moghaddas: methodology, project administration, supervision, and writing—review and editing. Awat Feizi: formal analysis, methodology, software, supervision, and writing—review and Editing.

Corresponding author

Correspondence to Shadi Farsaei.

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The institutional review board approved the employed methodologies, assigning the ethical code IR.MUI.MED.REC.1400.545. Consent to participate is not applicable.

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I, on the behalf of all authors, give my consent for the publication of our manuscript entitled “Nutritional modifications to ameliorate stress hyperglycemia in critically ill patients: A systematic review” to be published in the Egyptian journal of internal medicine.

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Rahimpour, F., Nejati, M., Farsaei, S. et al. Nutritional modifications to ameliorate stress hyperglycemia in critically ill patients: a systematic review. Egypt J Intern Med 36, 95 (2024). https://doi.org/10.1186/s43162-024-00361-1

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