DF: Obesity (2008)
To investigate the impact of galactose with guar gum on post-prandial Glucagon Like Peptide-1(GLP-1) release and appetite in obese and normal-weight subjects.
- Ages of 20 and 60 years
- In good health.
- Medication use
- History of diabetes or chronic disease
- Participant in other ongoing or former studies that would influence the outcome of the present study.
Recruitment
Ads in local newspapers.
Design
Randomized trial with crossover of obese and normal-weight subjects
- Subjects came to the lab for two visits separated by at least one week
- Fasting from 10:00 pm on the night prior to each visit
- Began venous blood draw at 8:00 am
- Participants consumed:
- A nutrient load (836kJ) consisting of either 50g galactose [d-(+)-galactose; Fagron Farmaceuticals, Nieuwekerk a/d, the Netherlands] and 2.5g guar gum (Meyprofin, Kreuzlingen, Switzerland), dissolved in 250ml water (GG)
- Or 250ml water (W) alone, in randomised order.
- Subjects ate a standard breakfast within 15 minutes
- Blood samples and appetite ratings were completed every 30 minutes, relative to ingestion for a total of two hours.
Intervention
- Participants consumed a nutrient load (836kJ) consisting of either 50g galactose [d-(+)-galactose; Fagron Farmaceuticals, Nieuwekerk a/d, the Netherlands] and 2.5g guar gum (Meyprofin, Kreuzlingen, Switzerland), dissolved in 250ml water (GG) or 250ml water (W) alone, in randomised order.
- After drinking the load, subjects had to eat a standard breakfast. The breakfast (1.9mJ) had an energy density of 3.9kJ per g and consisted of two slices of brown bread (100g), a baked egg (85g) and 300ml skimmed milk. The distribution of energy was carbohydrate, 48,8% energy; protein, 28.5% energy; fat, 22.6% energy. All the subjects reported that the breakfast was much bigger than they would usually eat.
Statistical Analysis
- Shapiro-Wilk test of normality
- One-way repeated-measures ANOVA: Hormonal and appetite differences between GG and W per group
- Hormonal parameters and area under the curve (AUC) were tested with a non-parametric Mann-Whitney U test for differences between groups
- AUC was calculated as incremental AUC over time (two hours)
- Appetite differences for GG and W between obese and lean subjects were tested with factorial ANOVA
- Effect of age tested with a multiple regression analysis
- Means and standard errors of the mean or medians and ranges
- Statistical package: Statview SE+Graphics (1988; Abacus Concepts, Berkeley, CA, USA)
- Level of significance was set at P<0.05.
Timing of Measurements
Blood samples and appetite ratings were measured immediately before and after the meal as well as every 30 minutes following the meal for two hours.
- GLP-1: Measured using an ELISA kit (EGLP −35K; Linco Research) for the non-radioactive quantification of biologically active forms of GLP
- Plasma glucose: Determined using the hexokinase method (Glucose HK 125 kit; ABX Diagnostics, Montpellier, France)
- Free fatty acid (FFA): Measured using the WAKO NEFA C-kit; Wako Chemicals, Neuss, Germany
- Insulin: Measured using a radioimmunoassay method (Insulin RIA-100; Pharmacia, Uppsala, Sweden)
- Appetite ratings: Satiety and desire to eat were rated on anchored 100-mm visual analog scales. For the increase in satiety caused by the meal, the change in satiety from the fasted rating at time 0 was calculated.
Dependent Variables
- GLP-1
- Glucose
- Insulin
- Free fatty acids
- Appetite ratings.
Independent Variables
Galactose/guar supplement.
Control Variables
Age.
Initial N
- 58 total
- 28 (nine male, 19 female) were overweight or obese, according to the WHO classification
- 30 (15 male, 15 female) were normal weight.
Attrition (Final N)
Not applicable.
Age
- Obese group: 44.4±9.8 years
- Normal-weight group: 31.6±12.8 years
- Obese group significantly older (P=0.0002) than normal-weight group.
Ethnicity
Not specified.
Other Relevant Demographics
Not specified.
Anthropometrics
- Obese group had higher BMI (30±2.7 vs. 22.9±1.5, P=0.0001)
- Obese group had higher body fat percentage (38.2±6.1 vs. 20.5±9.0, P=0.0001) than normal-weight group.
Location
Maastricht University, the Netherlands.
Table Two: Concentrations of Glucagon-Like Peptide-1 (GLP-1; pmol per L) and Insulin (mU per L) in Normal-Weight (N=30) and Overweight or Obese Subjects (N=28) After Ingesting Galactose or Guar Gum and a Standard Breakfast (GG) or Water and a Standard Breakfast (W)
[Median and Range (25th and 75th percentiles)]
Minutes |
0 |
30 |
60 |
90 |
120 |
||||||
Median |
Range |
Median |
Range |
Median |
Range |
Median |
Range |
Median |
Range |
||
Normal-Weight Subjects |
GLP-1 (GG) |
3.80 |
2.0-5.9 |
13.7 |
7.7-17.7 |
7.5 |
5.0-10.1 |
5.8 |
4.2-8.5 |
6.4 |
3.2-9.8 |
GLP-1 (W) |
4.1 |
2.0-5.6 |
7.3* |
4.3-11.1 |
5.6 |
3.8-9.1 |
5.7 |
4.1-8.6 |
7.2 |
5.0-9.3 |
|
Overweight/Obese Subjects |
GLP-1 (GG) |
2.0 |
1.0-6.5 |
10.9 |
5.0-15.6 |
6.8 |
4.0-12.0 |
5.7 |
2.9-11.5 |
6.0 |
2.0-9.2 |
GLP-1 (W) |
2.0 |
1.0-4.0 |
5.2 |
1.0-8.8 |
5.0 |
2.8-9.0 |
5.0 |
1.0-7.0 |
4.2 |
2.0-7.9 |
|
Normal-Weight Subjects |
Insulin (GG) |
6.3† |
4.6-7.6 |
18.0 |
14.3-27.4 |
23.9 |
16.2-33.6 |
27.4 |
22.7-43.4 |
34.4 |
25.1-41.6 |
Insulin (W) |
6.0† |
4.8-7.0 |
12.4 |
9.2-22.1 |
35.8 |
28.1-45.9 |
23.1 |
17.9-35.6 |
21.4 |
16.0-27.4 |
|
Overweight/Obese Subjects |
Insulin (GG) |
12.4 |
9.9-13.5 |
30.5 |
22.9-38.5 |
62.1 |
36.2-72.8 |
59.4 |
44.3-82.8 |
60.5 |
45.5-102.4 |
Insulin (W) |
10.5 |
7.9-11.7 |
25.6 |
16.9-34.0 |
62.0 |
42.5-92.2 |
43.0 |
29.0-74.7 |
39.2 |
22.2-60.9 |
*Significant difference between normal-weight and overweight or obese subjects: P=0.02
†Significant difference between normal-weight and overweight or obese subjects: P=0.0001.
Table Three: Concentrations of Glucose (mmol per L) and Free Fatty Acid (FFA; μmol per L) in Normal-Weight (N=30) and Overweight or Obese Subjects (N=28) After Ingesting Galactose or Guar Gum and a Standard Breakfast (GG) or Water and a Standard Breakfast (W), Expressed as Change from Fasted Values (Δ)
[Median and Range (25th and 75th percentiles)]
Minutes |
30 |
60 |
90 |
120 |
|||||
Median |
Range |
Median |
Range |
Median |
Range |
Median |
Range |
||
Normal-Weight Subjects |
Δ glucose (GG) |
0.04 |
-0.3 to 0.2 |
-0.2* |
-0.4 to 0.2 |
0.3 |
-0.3 to 0.8 |
-0.4* |
-0.6 to 0.3 |
Δ glucose (W) |
-0.0* |
-0.3 to 0.2 |
0.7 |
0.2 to 1.5 |
-0.3 |
-0.5 to -0.03 |
-0.3* |
-0.9 to -0.1 |
|
Overweight/Obese Subjects |
Δ glucose (GG) |
0.3 |
-0.2 to 0.6 |
0.3 |
-0.1 to 1.0 |
0.4 |
-0.1 to 1.3 |
0.3 |
-0.4 to 0.7 |
Δ glucose (W) |
0.2 |
-0.1 to 0.6 |
0.8 |
-0.1 to 0.6 |
-0.2 |
-1.0 to 1.1 |
0.0 |
-0.4 to 0.4 |
|
Normal-Weight Subjects |
Δ FFA (GG) |
-104 |
-154 to -38 |
-185 |
-226 to -137 |
-228 |
-276 to -208 |
-252 |
-289 to -214 |
Δ FFA (W) |
-33† |
-100 to -2.5 |
-163 |
-201 to -101 |
-233 |
-290 to -179 |
-239 |
-294 to -175 |
|
Overweight/Obese Subjects |
Δ FFA (GG) |
-148 |
-210 to -75 |
-218 |
-327 to -168 |
-262 |
-393 to -220 |
-283 |
-395 to -238 |
Δ FFA (W) |
-103 |
-155 to -52 |
-213 |
-286 to -156 |
-279 |
-337 to -213 |
-283 |
-345 to -237 |
*Significant difference between normal-weight and overweight or obese subjects: P<0.05
Significant difference between normal-weight and overweight or obese subjects: P=0.04.
The overweight or obese subjects were, on average, older than the lean subjects, but none of the blood parameters assessed were related to age.
Other Findings
- GLP-1
- AUC for GLP-1 (pmol per L*h) concentrations after GG was not different between groups
- Insulin
- Glucose
- Median differences between the overweight or obese and normal-weight group for glucose concentrations were significant at 30 minutes (P=0.04) and 120 minutes (P=0.05) in the W condition
- Overweight or obese subjects had significantly higher glucose concentrations than normal-weight subjects after the ingestion of W
- Higher glucose concentrations in the overweight or obese group than the normal-weight group at 60 minutes (P=0.02) and 120 minutes (P=0.04) between groups in the GG condition.
- Satiety
- Ratings of satiety (AUC) were related to GLP-1 concentrations (AUC) in the normal-weight group after ingesting GG (R=0.20; P=0.01), but not in the overweight or obese group (R=0.07; P=0.74)
- Ratings of satiety and desire to eat did not differ between groups in the W condition
- After ingesting GG, the increase in feelings of satiety was significantly higher in normal-weight subjects at 30 minutes (F1,53=5.28; P=0.02) and 60 minutes (F1,52=4.21; P=0.04), compared with the overweight or obese group.
- In conclusion, obese subjects seem to have a slightly lower sensitivity to GLP-1 release in response to a standard nutrient challenge, such as a standard breakfast, when compared with normal-weight subjects. The sensitivity can be improved to a level comparable to that of normal-weight subjects by the addition of a stronger challenge, for example a galactose or guar gum nutrient load.
- However, since the improvement is not reflected in subjective sensations of satiety, it seems likely that in obese subjects a disturbance in appropriate perception of the feedback, rather than primarily a disturbance in physiological feedback may contribute to obesity.
University/Hospital: | Maastricht University |
- Though it was a crossover trial, it was analyzed as a between- and within-subjects design, with a lot of the emphasis on sub-group analyses comparing obese and normal weight groups, despite differences in the gender and age distribution of these non-randomized comparisons
- Analyses were performed to adjust for age, but there was no mention of adjusting for gender in between-group comparisons. Therefore, though the within-subjects comparisons are valid, differences observed between overweight and normal-weight groups could be explained by residual confounding.
- There was no description of drop-outs or final Ns in the tables.
Quality Criteria Checklist: Primary Research
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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? | No | |
3.1. | Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) | No | |
3.2. | Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? | No | |
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%.) | No | |
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? | No | |
6.6. | Were extra or unplanned treatments described? | No | |
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)? | No | |
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? | Yes | |
10.1. | Were sources of funding and investigators' affiliations described? | No | |
10.2. | Was the study free from apparent conflict of interest? | Yes | |