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Cardiovascular Disease and Micronutrients

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

To evaluate the effects of alpha tocopherol on glucose and lipid metabolism and lipid peroxidation in women with type 2 diabetes.

Inclusion Criteria:
  • Female
  • Aged 40 to 70 years
  • Type 2 diabetes
  • Moderate to severe hypoglycemia
  • Managed with diet or oral hypoglycemic agents
  • Informed consent provided.
Exclusion Criteria:
  • Insulin treatment
  • Hypertension
  • Hormone therapy
  • Smoker
  • Antioxidant use within three months of trial
  • Lipid lowering and non-steroidal anti-inflammatory drugs
  • Use of garlic or fish oil supplements
  • Renal or liver disease
  • Alcohol consumption
  • Poor venous access.
Description of Study Protocol:
  • Recruitment: Admissions to General Hospital No. 46 of the Mexican Institute of Social Security in Villahermosa Tabasco, Mexico
  • Design: Randomized controlled trial
  • Blinding used: Participants blinded; unclear whether investigators were blinded. 

Intervention

  •  Randomized to one of two groups (method not described)
    • Control: One capsule (400mg cornstarch) with breakfast and dinner
    • Vitamin E: One capsule (400 IU d-alpha-tocopherol acetate) with breakfast and dinner.
  • Blood obtained for glucose, glycated hemoglobin, lipids, lipoproteins and antioxidant status
  • Duration of trial was six weeks.

Statistical Analysis

  • Un-paired student's T-test was performed to determine differences in baseline values between groups
  • To assess changes from baseline to end of study between groups, a two-way ANOVA was performed. If a significant difference from baseline was found, a paired T-test was calculated to determine whether the change from baseline in each group was significant.
  • Two-tailed test
  • Significance was equal to P<0.05.
Data Collection Summary:

Timing of Measurements

  • Baseline
  • Six weeks.

 Dependent Variables

  • Glucose control:
    • Glucose
    • Glycated hemoglobin.
  • Lipids and lipoproteins
  • Total serum antioxidant status (based on the capacity of antioxidants in the serum to inhibit oxidation)
  • Peroxidation
    • Malonaldehyde (erythrocytes)
    • Selenium dependent-glutathione peroxidase (erythrocytes)
    • Copper zinc superoxide dismutase activity (erythrocytes).

Independent Variables

  • Placebo
  • 800 IU alpha tocopherol.
Description of Actual Data Sample:

Initial N

N=34

  • Control: N=21
  • Alpha-tocopherol: N=13.

Attrition (Final N)

N=34.

Age

Mean ±SD

  • Control: 55.3±11.6
  • Alpha-tocopherol: 51.3±14.0.

Other Relevant Demographics

No significant differences at baseline.

  Control (Mean ±SEM) Alpha Tocopherol (Mean ±SEM)
Glucose (mg per dL)
264.8±28.4
194.2±19.4
Glycated Hemoglobin (Percentage)
10.5±0.5
10.9±0.8
LDL (mg per dL)
146.9±14.8
103.5±12.0
HDL (mg per dL)
42.8±1.6
38.4±2.9
Triglycerides (mg per dL)                   
231.7±18.4
300.6±60.7
  • Pharmacologic therapy: N=31
  • No pharmacologic therapy: N=3
  • Duration of diabetes (mean ±SD)
    • Control: 9.7±4.5 years
    • Alpha tocopherol: 10.9±2.2 years.

Anthropometrics

Mean BMI

  • Control: 27.3±3.7
  • Alpha tocopherol: 27.8±5.2.

Location

Mexico.

 

Summary of Results:

Glycemic Control

No significant differences between the placebo and alpha tocopherol groups from baseline to post-treatment for glucose and glycated hemoglobin.

Serum Lipids

  • Compared to baseline, there were no significant differences between groups for triglyceride, LDL and HDL at end of treatment
  • An increase in cholesterol levels was observed post-treatment in the alpha-tocopherol group (202.1±49.5 to 239.6±44.4; P=0.012).

Lipid Peroxidation

  • No significant differences in serum malonaldehye or selenium-dependent glutathione perioxidase from baseline to post-treatment between the control and alpha-tocopherol groups
  • Alpha-tocopherol group:
    • Compared to baseline, erythrocyte malonadehyde production decreased after treatment (P<0.0001). This represents a 46% reduction from baseline levels.
    • Erythrocyte Cu,Zn-superoxide dismutase decreased after six weeks of treatment compared to baseline (1,083±295.3 to 876.4±46.6; P<0.0001)
    • Post-treatment total serum antioxidant activity increased compared to baseline values (P<0.001)
  • Control group: Compared to baseline, erythrocyte Cu,Zn-superoxide dismutase increased after six weeks of treatment (P<0.0001).

 

Author Conclusion:

In women with uncontrolled diabetes, supplementation with 800 IU alpha tocopherol for six weeks showed mixed effects on lipid peroxidation, no effect on glycemic control and increased cholesterol levels.

Funding Source:
Government: Fondo de Fomento a la Investigacion of the Instituto Mexicano del Seguro Social
Reviewer Comments:
  • Method of randomization was not indicated and the number of participants was un-equal between groups (21 vs. 13). It was unclear how many subjects were initially enrolled and whether attrition occurred during the study, as no statement was included in the paper to this effect.
  • Small sample size; no power calculation
  • It was unclear what the variable "total antioxidant status" represents
  • No supplement compliance data was provided
  • Serum alpha-tocopherol was not measured.
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? ???
  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? ???
  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? ???
  4.1. Were follow-up methods described and the same for all groups? No
  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%.) ???
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? ???
  4.4. Were reasons for withdrawals similar across groups? ???
  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? 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? 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? ???
  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? No
  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)? 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? No
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