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Vitamins and Antioxidants and the Prevention and Treatment of CVD

Citation:

Jenkins DJ, Kendall CW, Banach MS, Srichaikul K, Vidgen E, Mitchell S, Parker T, Nishi S, Bashyam B, de Souza R, Ireland C, Josse RG. Nuts as a replacement for carbohydrates in the diabetic diet. Diabetes Care. 2011; 34: 1,706-1,711.

 

PubMed ID: 21715526
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To test the effect on glycemic control and serum lipids of substituting nuts as a source of fat and vegetable protein to replace carbohydrate foods in the diets of patients with type 2 diabetes.

Inclusion Criteria:
  • Men or post-menopausal women with type 2 diabetes who were taking anti-diabetic agents other than acarbose with medications stable for the previous the months
  • HbA1c values at screening between 6.5% and 8%
  • Provided written informed consent
  • No significant cardiovascular, renal or liver disease or a history of cancer
  • Accepted after surgery or myocardial infarction if they had an event-free six-month period before the study.
Exclusion Criteria:
Not described.
Description of Study Protocol:

Recruitment

Subjects were recruited by a newspaper advertisement and from previous studies from April 2007 to September 2008.

Design

Randomized controlled trial.

Blinding Used

Implied with measurements.

Intervention

  • Subjects were randomized to one of three treatments for three months. Supplements were provided at 475kcal per 2,000kcal diet as mixed nuts (75g per day), muffins or half portions of both.
  • The nuts supplied consisted of a mixture of unsalted and mostly raw almonds, pistachios, walnuts, pecans, hazelnuts, peanuts, cashews and macadamias
  • General dietary advice conformed to the National Cholesterol Education Program Adult Treatment Panel III and the American Diabetes Association guidelines to reduce saturated fat and cholesterol intakes.

Statistical Analysis

  • Results are expressed as mean ±SD or 95% CI.
  • The significance of treatment differences was assessed by the CONTRAST statement in SAS version 9.2, which allows comparisons of repeated measures over time based on a T-test statistic with equal weighting for each value
  • The primary analysis was intention-to-treat including all randomized subjects (N=117)
  • Pearson correlations were used to examine the relation of nut intake to changes in HbA1c, lipids and apolipoproteins
  • The dose response analyses on nut and MUFA intakes (percent energy) and change in study outcomes were performed by regression analyses, pooling the responses across the three treatment groups.
Data Collection Summary:

Timing of Measurements

Measurements were made at baseline and after three months.

Dependent Variables

  • Blood glucose was measured in the hospital routine analytical laboratory by a glucose oxidase method
  • Serum lipids and HbA1c: HbA1c was analyzed within two days of collection on whole blood collected in EDTA Vacutainer tubes and measured by a designated high-performance liquid chromatography (HPLC) method
  • Serum samples stored at -70C were analyzed for lipids and apolipoproteins and oxidative products were analyzed at the end of the study
  • LDL cholesterol was calculated by the method of Friedewald et al
  • CRP was measured by end point nephelometry and oxidized LDL was measured chemically as conjugated dienes and thiobarbituric acid-reactive substances in the LDL fraction and oxidized serum proteins were measured as protein thiols.

Independent Variables

  • Subjects were randomized to one of three treatments for three months. Supplements were provided at 475kcal per 2,000kcal diet as mixed nuts (75g per day), muffins or half portions of both
  • Participants were counseled to substitute the supplement calories where possible for the carbohydrate foods in their original diets
  • General dietary advice conformed to the National Cholesterol Education Program Adult Treatment Panel III and the American Diabetes Association guidelines to reduce saturated fat and cholesterol intakes
  • Diets were analyzed in 115 participants with baseline data using a computer program based on the data from the USDA and international glycemic tables
  • Energy requirements were calculated for each participant using the Harris-Benedict equation, allowing for physical activity.
Description of Actual Data Sample:

Initial N

A total of 117 subjects.

Attrition (Final N)

A total of 117 in the intent-to-treat analysis. The study reported a 12% dropout rate.

  • A total of 40 in the nuts group (26 males, 14 females)
  • A total of 38 in the half dose group (26 males, 12 females)
  • A total of 39 in the muffins group (26 males, 13 females).

Age

  • Mean age in the nuts group was 63 years
  • Mean age in the half dose group was 62 years
  • Mean age in the muffins group was 61 years.

Ethnicity

  • Nut group:
    • 58% European
    • 25% Indian
    • 10% Far Eastern
    • 8% African
    • 0% Hispanic
    • 0% Native American.
  • Half-dose group:
    • 66% European
    • 21% Indian
    • 8% Far Eastern
    • 5% African
    • 0% Hispanic
    • 0% Native American.
  • Muffins group:
    • 46% European
    • 33% Indian
    • 8% Far Eastern
    • 8% African
    • 3% Hispanic
    • 3% Native American.

Other Relevant Demographics

  • Mean duration of diabetes seven years for nut group
  • Mean duration of diabetes eight years for half dose group
  • Mean duration of diabetes eight years for muffin group.

Anthropometrics

  • Mean BMI:
    • 29kg/m2 for nut group
    • 30kg/m2 for half dose group
    • 29kg/m2 for muffin group.
  • No differences were seen at baseline in diet, blood pressure or anthropometric measurements between groups.

Location

Toronto, Canada.

 

Summary of Results:

Key Findings

  • The relative increase in MUFAs was 8.7% energy on the full nut dose compared with muffins
  • There were no significant changes in blood glucose or body weight between or within groups
  • Using an intention-to-treat analysis (N=117), full-nut dose (mean intake 73g per day) reduced HbA1c (-0.21% absolute HbA1c units; 95% CI: -0.30 to -0.11; P<0.001) with no change after half-nut dose or muffin
  • Full-nut dose was significantly different from half-nut dose (P=0.004) and muffin (P=0.001) but no difference was seen between half-nut dose and muffins
  • LDL cholesterol also decreased significantly after full-nut dose compared with muffin
  • The LDL cholesterol reduction after half-nut dose was intermediate and not significantly different from other treatments
  • Apolipoprotein (apo B) and the apo B: apoA1 ratio behaved similarly
  • Nut intake related negatively to changes to  HbA1c (R=-0.20, P=0.033) and LDL cholesterol (R=-0.24, P=0.011)
  • Total and LDL cholesterol decreased significantly after full-nut dose compared with muffin (both P<0.001) but there were no significant differences between groups in terms of HDL cholesterol, triglycerides or blood pressure.

 

Author Conclusion:

Two ounces of nuts daily as a replacement for carbohydrate foods improved both glycemic control and serum lipids in type 2 diabetes.

Funding Source:
Government: Canada Research Chair Endowment of the Federal Government of Canada
Reviewer Comments:

The authors noted that the strengths of this study include its novelty as one of the first to assess nuts in type 2 diabetes coupled with measurement of HbA1c and blood lipids at three time points in the last month to increase the validity of the assessment of blood lipids and glycemic control.

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? Yes
  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? 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? 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? 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? Yes
  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