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DM: Nutritive Sweeteners (2014)

Citation:

Brunner S, Holub I, Theis S, Gostner A, Melcher R, Wolf P, Amann-Gassner U, Scheppach W, Hauner H. Metabolic effects of replacing sucrose by isomaltulose in subjects with type 2 diabetes: A randomized double-blind trial. Diabetes Care. 2012; 35(6): 1,249-1,251.

PubMed ID: 22492584
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To test the hypothesis that replacement of sucrose with isomaltulose in sweet foods and beverages improves metabolic control in patients with type 2 diabetes.

Inclusion Criteria:
  • Patients with type 2 diabetes
  • More than 18 years of age
  • Provided written informed consent
  • BMI 25 to 40kg/m2
  • HbA1c 6.5% to 9.0%
  • Treated by diet alone or with oral anti-diabetic agents.
Exclusion Criteria:
Not described.
Description of Study Protocol:

Recruitment

Recruited through advertisements between March 2007 and December 2008 in two study centers (Munich and Wuerzburg, Germany).

Design

Randomized controlled trial.

Blinding Used

Double blind.

Intervention

The participants received sweet foods and beverages (biscuits, toffees, milk drinks, etc.) containing either 50g of isomaltulose or sucrose per day in a double-blinded fashion for a period of 12 weeks and were asked to maintain their habitual diet but to refrain from other sweetened foods besides the test products.

Statistical Analysis

A sample size of 55 was calculated per each group and the study had a power of 80% to show a statistically significant difference of at least 0.3% in HbA1c at week 12 between the groups with a type 1 level error of 0.05, assuming a common standard deviation of 0.5.

 

Data Collection Summary:

Timing of Measurements

  • Measurements made at study entry and at weeks six and 12
  • Venous blood was taken in the morning after a 12-hour overnight fast

Dependent Variables

  • HbA1c at week 12: Measured by a certified laboratory 
  • Commercial ELISA kits were used to measure oxidized LDL, leptin and adiponectin
  • Fasting glucose, serum fructosamine, insulin, C-peptide, proinsulin, nonesterified fatty acids (NEFA), total cholesterol, triglycerides, LDL, HDL cholesterol and standard clinical parameters were analyzed by a certified laboratory.

Independent Variables 

The participants received sweet foods and beverages (biscuits, toffees, milk drinks, etc.) containing either 50g of isomaltulose or sucrose per day in a double-blinded fashion for a period of 12 weeks and were asked to maintain their habitual diet but to refrain from other sweetened foods besides the test products.
Description of Actual Data Sample:
  • Initial N: 110 recruited and randomized, 57 in the isomaltulose group and 53 in the sucrose group
  • Attrition (final N): 100 subjects completed the study, gender not specified, 52 in the isomaltulose group and 48 in the sucrose group
  • Age: Over 18 years of age
  • Other relevant demographics:
    • Baseline HbA1c in the sucrose group 7.39±0.66, week 12 HbA1c in the sucrose group 7.39±0.78
    • Baseline HbA1c in the isomaltulose group 7.20±0.60, week 12 HbA1c 7.24±0.76.
  • Anthropometrics: Baseline patient characteristics were comparable, with the exception of higher BMI at baseline in the patients receiving sucrose (32.3±4.5kg/m2 vs. 29.9±4.2kg/m2, P=0.007).
  • Location: Germany.
Summary of Results:

Key Findings

  • Isomaltulose did not significantly affect HbA1c at 12 weeks [sucrose 7.39%±0.78%; isomaltulose 7.24%±0.76%; regression coefficient 0.02 (95% CI: -0.21 to 0.25), P=0.844]
  • Triglyceride levels increased in the sucrose group (from 151mg to 179mg per dL) and decreased in the isomaltulose group (from 159mg to 144mg per dL), resulting in a significant difference between groups [b: 34.01(6.59 to 61.44), P=0.016]
  • Weight change was not reported
  • After 12 weeks, there were no significant differences between groups in terms of:
    • Fasting glucose
    • Insulin levels
    • Total cholesterol
    • HDL-cholesterol
    • LDL-cholesterol
    • Other secondary parameters.
Author Conclusion:

Isomaltulose did not influence glycemic control assessed in HbA1c in type 2 diabetes under free-living conditions, but was associated with lower triglyceride levels.

Funding Source:
Other: Suedzucker AG, Mannheim/Ochsenfurt, Germany
Reviewer Comments:
  • Sample was not well described
  • Baseline patient characteristics were comparable, with the exception of higher BMI at baseline, in the patients receiving sucrose (32.3±4.5kg/m2 vs. 29.9±4.2kg/m2, P=0.007)
  • The authors mentioned this was the first study to investigate the effects of a 12-week dietary intervention with 50g per day isomaltulose compared with sucrose in sweet foods and beverages in type 2 diabetes patients under free-living conditions.
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? No
  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? No
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
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) Yes
  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%.) 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? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes