CI: Enteral Nutrition and Diabetes (2006)

Citation:

Mesejo A, Acosta, JA, Ortega, J, Vila, J, Fernandez, M, Ferreres, J.,Sanchix, JC, Lopex, F, Comparison of a high-protein disease-specific enteral formula with a high-protein enteral formula in hyperglycemic critically ill patients. Clinical Nutrition, 2003:22(3); 295-305.

PubMed ID: 12765670
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
The purpose was to evaluate if the administration of a disease specific high-protein formula with similar caloric percentage of fat and carbohydrates to hyperglycemic critically ill patients achieves greater control of glycemia and reduces insulin requirements when compared to a conventional high-protein formula. The main differences in the formulas were related to the content and type of carbohydrates, the content and type of fat, and the addition or lack of dietary fiber. The goal for control of BG values was between 100 and 200 mg/dL for both the control and the treatment groups.
Inclusion Criteria:
  • 18 years old with a history of diabetes type 1 or 2 and/or stress-induced hyperglycemia with basal glycemia equal to or greater than 160 mg/dL in the first 24 h after admission
  • enteral nutrition for 5 or more days
Exclusion Criteria:
  • acute kidney failure (creatinine>2.5 mg/dL)
  • liver failure (bilirubin >2 mg/dL)
  • APACHE II score <10 or > 25
  • obesity with a Body Mass Index < 30 (kg/m²)
Description of Study Protocol:

Recruitment The study was carried out between November 1999 and January 2001 in the ICU wards of two university hospitals in Spain with critically ill medical and trauma patients.

 

Design Prospective, randomized, controlled, single-blind trial in two University Hosptial Intensive Care Units in Spain

 

Blinding used (if applicable) This was a single-blind trial.

 

Intervention (if applicable)

1) Control Enteral formula (Isosource Protein) containing 1.2 kcal/cc with P/C/F distribution of 22/49/29%, 0 g fructose, 0 g fiber 

2) Treatment Enteral Formula (Novasource Diabet Plus containing 1.2 kcal/cc with a P/C/F distribution of 20/40/40 %, 16 g fructose, 7.5 g Hydrolized Gual Gum (Benefiber). 

 

Statistical Analysis

Qualitative variables were described by its frequencies and percentage, continuous variables by the mean +standard deviation or alternatively by the median (quartile 1; quartile 3).  In the univariate analysis the X² or alternatively Fisher's exact test were used to analyze the qualitative variables.  Continuous data were assessed for normality by Shapiro-Wilk test.  Comparison was done with the Student's t-test for normal data and the Mann-Whitney U-test for non-normal distribution.  When multiple comparisons were performed the level of significance was corrected by Bonferroni method.  This test was used regardless of the departures from normality of insulin values assuming the robustness of the test.  To analyze global mortality in the ICU, regardless of the administered formula, a logistical regression model was used, including those variables that showed an association that was at least marginally significant (P<0.15) in the univariate analysis.  Then, variables were excluded if likelihood did not decrease significantly and the parameters of the remainder variables did not change more than 15%.  Pearson's correlation index was used for ICU length of stay analysis and Spearman's correlation index was used for the days of mechanical ventilation.  Stat significance set at P<0.05.

Data Collection Summary:

Timing of Measurements  Baseline and days 1 through 14 for plasma glucose levels, capillary glucose levels, insulin requirements, insulin units per g received CHO, insulin units/g received CHO/kg. Days 1, 7, 14 for levels of lipids by peripheric blood samples at 8 AM (cholesterol, triglycerides, HDL, LDL), visceral protein, reactant proteins, hormones (glucagon & insulin), immunological parameters.  APACHE II scores on days 1, 7, 14.  Acquired infections during hospitalization were registered for each patient in accordance  with criteria fo the Center for Disease Control.  ICU-acquired infection was considered to be that registered after 48 h stay.

 

Dependent Variables

  • Plasma glucose level (measured at 8 AM daily by peripheral venipuncture)
  • Capillary blood glucose (CBG) level measured every 6 hours per finger stick (averaged for daily value)
  • Insulin/day requirements (regulated insulin infusion to CBG levels every 6 hours depending on administration protocol. Insulin levels were calculated by chemiluminescence. 
  • Insulin/g CHO received
  • Insulin/g CHO received/kg
  • Secondary endpoints: lipid and protein metabolic control by peripheral blood sampling, infection rate, days of mechanical ventilation, ICU length of stay, mortality, tolerance and complications related to diets or tube feeding, APACHE II score.

Independent Variables

Enteral Formula:

  1. Treatment group:  Disease specific high-protein formula (Novasource Diabet Plus) with similar caloric percentage of fat and carbohydrates and difference related to content and type of carbohydrates, the content and type of fat, and the addition of dietary fiber; (P/C/F % distribution of 20/40/40 & 4.8 g Nitrogen, 7.5 g Hydrolized guar gum - Benefiber)
  2. Control group:  High protein enteral formula (Isosource Protein) with P/C/F % distribution of 22/49/29 & 5.28 g Nitrogen, 0  hydrolized guar gum.

Control Variables

 No significant differences between groups for APACHE II score on admission or at days 7 or 14.

Description of Actual Data Sample:

 

Initial N: 50  (24 control with 71% male; 26 treatment with 92)

Attrition: Final N = 46 (21 control and 25 treatment)

Age: Treatment group 65.2±14.95 and Control group 64.6±9.63 (p=0.86)

Ethnicity: none given

Other relevant demographics: none given

Anthropometrics BMI - Study Group = 24.7±2.57 and Control Group = 25.7±2.41 (p=0.15)

Location: 2 University Hospital Intensive Care Units in Spain

 

Summary of Results:

 

Variables

Treatment Group

N = 26

Control group

N = 24

Statistical Significance of Group Difference

Plasma glucose level (mg/dl)

176.8±44.01*

222.8±47.12*

p=0.001

Capillary glucose level (mg/dl)

163.1±45.62*

216.4±56.75*

p=0.001

Insulin/day (IU) 8.73 (2.3-27.5)+ 30.2 (21.5-57.1)+ p=0.001
Insulin/g CHO received 0.07 (0.02-0.22)+ 0.18 (0.11-0.35)+ p=0.02

Insulin/g CHO received/kg

0.98 (0.26-3.59)+

2.13 (1.44-4.58)+

p=0.04

*mean ± standard deviation and +median quartile 1; quartile 3;

Other Findings 

There were no significant differences between the control and treatment groups for:

  • acquired infections (p=0.7)
  • ICU length of stay
  • days of mechanical ventilation
  • mortality
  • digestive complications related to diets or tube feeding.
  • laboratory values for lipids, visceral protein, reactant proteins, hormones or immunological parameters at days 1, 7, and 14  
Author Conclusion:

Feeding critically ill medical or trauma patients a disease-specific high protein formula significantly reduces plasma and capillary BG levels and insulin requirements when compared with a conventional high-protein enteral formula. However, there are no significant differences in the rate of acquired infections, ICU length of stay, days of mechanical ventilation or mortality between the groups.  Gastrointestinal tolerance of both formulas was satisfactory and related complications were lower than those reported in other studies.

Funding Source:
University/Hospital: Hospital Clinico Universitario, Valencia Spain, Hospital General Universitario, Alicante Spain, Institut Municipal per la Investigacio Medica
Reviewer Comments:

Statistical analysis of the research was supported by Novartis Consumer Health, Spain.

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? Yes
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? Yes
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? ???
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? ???