EAL

NAP: Competition (2007)

Citation:

Jeukendrup AE, Wagenmakers AJM, Stegen JHCH, Gijsen AP, Brouns F, Saris WHM. Carbohydrate ingestion can completely suppress endogenous glucose production during exercise. Am J Physiol. 1999; 276 (4 Pt 1): E672-683.

PubMed ID: 10198303

Study Design:

Non-randomized crossover trial

Class:

C - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

The purposes of this study were to:

Investigate the effect of carbohydrate ingestion on endogenous glucose production during prolonged exercise
To study whether glucose appearance in the circulation could be a limiting factor for exogenous carbohydrate oxidation
To investigate whether large carbohydrate feedings can reduce muscle glycogen oxidation during exercise.

Inclusion Criteria:

Well-trained cyclists.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment: Methods not specified
Design: Non-randomized crossover trial; order of trials was counter-balanced, but not randomized
Blinding used: Not possible; lab tests.

Intervention

Subjects exercised three times for 120 minutes at 50% maximum workload while ingesting water, a 4% glucose solution or a 22% glucose solution
A primed continuous IV glucose infusion was given and the ingested glucose was enriched with the U-13C glucose
During the first minutes, subjects drank an initial bolus (eight ml per kg) and then two ml per kg every 15 minutes
Trials were separated by at least seven days.

Statistical Analysis

Two-way (treatment x time) ANOVA for repeated measures was performed to study differences among the three conditions
A Bonferroni-Dunn post-hoc test was applied in case of significant F-ratios to locate the differences.

Data Collection Summary:

Timing of Measurements

Expired air and blood samples were taken at rest
Glucose kinetics was measured between baseline and then between 45 and 60 minutes.

Dependent Variables

Expired air samples were measured through indirect calorimetry
Blood samples were analyzed for glucose, FFA, glycerol, triacylglycerols, insulin
Plasma glucose enrichment was measured through gas chromatography and mass spectrometry.

Independent Variables

Water, a 4% glucose solution or a 22% glucose solution.

Control Variables

Subjects were instructed to keep diet constant between trials.

Description of Actual Data Sample:

Initial N: Six subjects, gender not mentioned
Attrition: Six
Age: Mean age, 21.8±0.2 years
Ethnicity: Not mentioned
Location: United Kingdom.

Summary of Results:

Time Interval (Minutes)	RER	Total CHO Oxidation	Plasma Glucose Oxidation	Exogenous Glucose Oxidation
Fast: 75 to 90	0.819±0.004	110±4	30±3	0±0
Fast: 90 to 105	0.818±0.007	113±8	30±3	0±0
Fast: 105 to 120	0.807±0.005	100±5	31±3	0±0
4%: 75 to 90	0.832±0.004	119±4	36±2	24±2, P<0.05
4%: 90 to 105	0.837±0.003, P<0.05	120±5	41±1, P<0.05	26±2, P<0.05
4%: 105 to 120	0.831±0.004, P<0.05	118±5	40±3	25±3, P<0.05
22%: 75 to 90	0.863±0.005, P<0.001	146±6, P<0.001	68±4, P<0.001	65±3, P<0.001
22%: 90 to 105	0.865±0.005, P<0.001	152±7, P<0.001	72±5, P<0.001	70±3, P<0.001
22%: 105 to 120	0.864±0.007, P<0.001	153±9, P<0.001	72±6, P<0.001	72±3, P<0.001

Other Findings

Glucose ingestion significantly elevated the carbohydrate oxidation as well as the rates of appearance and disappearance
The rate of glucose appearance equaled the rate of glucose appearance in gut during the 22% glucose solution, whereas endogenous glucose production was completely suppressed
During the 4% glucose solution, endogenous glucose production was partially suppressed, whereas the rate of glucose appearance in gut provided most of the total glucose rate of appearance.

Author Conclusion:

In summary, we conclude that small carbohydrate feedings suppress endogenous glucose production and that large carbohydrate feedings completely block endogenous glucose production, most likely because of increases in plasma insulin and plasma glucose concentration
The entrance of glucose into the systemic circulation seems to be the limiting factor for exogenous carbohydrate oxidation because a large percentage of the rate of glucose appearance in gut was oxidized, whereas only a small percentage of ingested glucose appeared in the bloodstream
Muscle glycogen oxidation at the whole body level was not reduced by glucose ingestion during cycling exercise at 50% VO_2max.

Funding Source:

University/Hospital:

Maastricht University (The Netherlands)

Reviewer Comments:

Inclusion criteria, exclusion criteria and recruitment methods and subjects were not well-defined.

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?		???
	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?	No
	2.2.	Were criteria applied equally to all study groups?	???
	2.3.	Were health, demographics, and other characteristics of subjects described?	No
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
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?	N/A
	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?	No
	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?	N/A
	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)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	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?	N/A
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?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes