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NNNS: Stevia (stevioside) (2010)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
  • Does stevioside taken with a test meal exert a lowering of the postprandial blood glucose response?
  • Can stevioside be used in treatment of type 2 diabetes?
Inclusion Criteria:

Inclusion Criteria

  • Twelve type 2 diabetic paients (four females and eight males) with a mean age of 65.8±1.6 years
  • A diabetes duration of 6.0±1.3 years
  • A mean body mass index of 28.5±1.0m2 per kg
  • A mean HbA1c of 7.4±0.4% were included in the study
  • Recruited from outpatient clinic at Aarhus University Hospital
    1. Type 2 diabetes (treated by diet or oral anti-diabetic medication)
    2. Diabetes onset at an age greater than 40 years
    3. Diabetes duration longer than one year and hemoglobin A1c (HbA1c) less than 10%
    4. Body mass index between 25 kg/m2 and 32kg/m2.

 

Exclusion Criteria:

The exclusion criteria were:

  1. Treatment with insulin within the last six months
  2. Enrollment in a clinical trial of drugs within the last three months
  3. Significant cardiovascular, psychological, neurological, renal or endocrine disease (apart from diabetes), alcohol or drug abuse or acute illness
  4. Fasting levels of glucose less than four mmol or greater than 12 mmol per L on the day of the experiment
  5. Treatment with glucocorticoids.
Description of Study Protocol:
  • Recruitment: Recruited from outpatient clinic at Aarhus University Hospital, Denmark
  • Design: Short-term, paired, cross-over, where each subject received each treatment.
  • Blinding used (if applicable): None identified.

Intervention

  • A standard test meal was served either with one gram of stevioside or with one gram of maize starch (placebo) encapsulated in gelatin and administered orally. The extracts of leaves of the stevia rebaudiana plant were purchased from Steviaform Industrial S/A. Maringa, Parana, Brazil (lot. no. 9.80.130).
  • The total energy content of the test meal was 412kcal (16%  protein, 30% fat, 54% carbohydrate).

Statistical Analysis

  • Student's paired T-test to compare effects of stevioside with placebo
  • Data given as a mean ±SEM
  • Calculated insulinogenic index as ratio between AUC1.insulin and AUC1.glucose
  • Conversion factors are as follows: For glucose, mg per dL =0.05551mmol per L and for insulin, mcU per ml =6.0pmol per L.
Data Collection Summary:

Timing of Measurements

  • Two separate days at least one week apart
  • Measured at -30, zero, 10, 20, 30, 45, 60, 90, 120, 180 and 240 minutes.

 Dependent Variables

  • Glucose
  • Insulin
  • Triglyceride
  • Free fatty acids
  • Total cholesterol
  • Low-density lipoprotein (LDL) cholesterol
  • High-denisty lipoprotein  (HDL) cholesterol
  • Glucagon-like peptide-1 (GLP-1)
  • Gastric inhibitory polypeptide (GIP)
  • Glucagon
  • Glycated hemoglobin A1c
  • N
  • K
  • Creatinine
  • Hemoglobin
  • Urine Volume
  • Urine albumin, glucose, Na and K
  • Blood pressure.

Independent Variables

  • One gram stevioside
  • One gram maize starch.

Control Variables

Mixed meal.

Description of Actual Data Sample:
  • Initial N: 12 type 2 diabetic patients (four females, eight males)
  • Attrition (final N): None
  • Age: 65.8±1.6 years
  • Ethnicity: Danish

Other Relevant Demographics

  • Mean BMI: 28.5±1.0m2/kg
  • Mean HbA1c: 7.4±0.4%
  • Location: Denmark.

 

Summary of Results:

Table One: Effects of Orally-Administered Stevioside (Compared to Control) on Postprandial Levels of Glucagon, GLP-1 GIP (Presented as Area Under the Response Curves) and Blood Pressure in Type 2 Diabetic Subjects

Variables Control Stevioside P-Value
Glucagon (AUC 1, pmol/L-240 min.)
348±46
281±33
<0.021
GLP-1 (AUC1, pmol/L-240 min.)
2,208±253
1,529±296
NS
GIP (AUC1, pmol/L-240 min.)
7,412±635
6,747±1,023
NS
Mean Systolic BP (mmHg) -30 to 0 minutes
146±4
143±5
NS
15 to 240 minutes
143±4
138±4
NS
Mean Diastolic BP (mmHg) -30 to 0 minutes
86±3
88±3
NS
15 to 240 minutes
87±2
84±3
NS

Note: One gram of stevioside or maize starch was administered at Time Point Zero together with a mixed meal. Results are mean ±SEM, N=12.

Other Findings Stevioside

  1. Stevioside reduced the postprandial blood glucose response by 18±5% (P<0.004), compared to placebo
  2. Stevioside tended to enhance the area under the insulin response curve from Time Point Zero to 240 minutes, but not statistically significant
  3. Stevioside caused a 40% increase in the insuliongenic index, compared to control
  4. Stevioside seemed to reduce the postprandial glucagon levels, while the postprandial GLP-1 and GIP did not significantly differ on the two occasions
  5. Also, systolic and diastolic blood pressures were not altered by stevioside administration, compared to control
  6. Postprandial plasma leveI of triglycerides increased from Time Point Zero to 240 minutes with no differences between the two treatment groups.
Author Conclusion:
  • In conclusion, stevioside reduces postprandial blood glucose and tends to potentiate the insulin secretion in type 2 diabetic patients
  • The study seems to confirm the knowledge of the native people in Paraguay and Brazil
  • Stevioside is a potential drug or food additive for improving diabetes regulation.
Funding Source:
Not-for-profit
Danish Institute of Agricultural Sciences, Aurhus, Denmark
Reviewer Comments:
  • Comprehensive on details of methods and conclusions
  • Effect of difference between maize starch and stevioside appears very small to require this very detailed documentation. However, it may have taken this very detail to show a difference.
  • Author used words and phrases such as "thus it can be hypothesized," "apparently," "may not be of functional importance," "indicates," "may have beneficial." These words make the documentation less than conclusive, however still points in the positive direction.
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? No
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) N/A
  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? Yes
  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.) Yes
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? Yes
4. Was method of handling withdrawals described? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  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? 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? ???
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? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  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? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? Yes
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)? ???
  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