DF: Obesity (2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

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.

Inclusion Criteria:
  • Ages of 20 and 60 years
  • In good health.
Exclusion Criteria:
  • Medication use
  • History of diabetes or chronic disease
  • Participant in other ongoing or former studies that would influence the outcome of the present study.
Description of Study Protocol:

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.
Data Collection Summary:

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.

Description of Actual Data Sample:

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.

Summary of Results:

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.
Author Conclusion:
  • 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.
Funding Source:
University/Hospital: Maastricht University
Reviewer Comments:
  • 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
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