HTN: Protein (2007)

Citation:
 
Study Design:
Class:
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Quality Rating:
Research Purpose:
To determine whether dietary supplementation with soy protein containing phytoestrogens affected insulin resistance, glycemic control and cardiovascular risk in post-menopausal women with diet-controlled type 2 diabetes.
Inclusion Criteria:
  • Postmenopausal as defined by periods absent for over one year and elevated follicle-stimulating hormone
  • Type 2 diabetes mellitus as defined by fasting BG over 7.0mmol per L or a 2h post-prandial BG over 11.1mmol per L after a 75-gram OGTT.
Exclusion Criteria:
  • Secondary cause of hyperglycemia
  • Current or previous (in the preceding six months) use of estrogen therapy
  • Treatment with insulin or oral hypoglycemic agents
  • Untreated hypothyroidism
  • History of drug or alcohol abuse
  • History of breast or uterine cancer.
Description of Study Protocol:

Recruitment

Not discussed. 

Design

  • Randomized double-blind, placebo-controlled crossover study with a two-week washout period between the 12-week study periods
  • The supplement intervention was alternated during the second intervention period. 

Blinding Used

Randomization was done by the supplying company, with the randomization code kept secret from subjects and investigators involved in the study.

Intervention

  • Soy intervention: 30g of isolated soy protein with 132mg isoflavones (53% genistein, 37% daidzein, and 10% glycitein). No soluble fiber was included and the sachet provided 243kcal. A sachet was consumed daily for 12 weeks along with an isocaloric diet.
  • Placebo intervention: A control sachet of 30g of pure microcrystalline cellulose without kcaloric value was administered daily for 12 weeks, along with an isocaloric diet.

Statistical Analysis

  • A power test of two-sided significance at 5% and 80% power, indicated that 33 subjects were needed per group to detect a 12% difference in LDL between treatments.
  • Changes at the end of the soy treatment were compared with results at the end of the placebo phase with a paired Student's T-test for biochemical data and the Wilcoxon's aigned-rank test for clinical observations
  • The period and carryover effect that may have occurred from the crossover design were tested with a Student's T-test.
Data Collection Summary:

Timing of Measurements

BP and blood samples were obtained at screening, baseline and every six weeks for each of the two phases of the study. 

Dependent Variables

  • SBP and DBP measured after 10 minutes of rest in a sitting position with an automated device
  • Fasting BG
  • HbA1C
  • Insulin resistance
  • Total cholesterol, LDL-C, HDL-C, Cholesterol-HDL ratio, TGs
  • Plasma hormones and creatinine.

Independent Variables

  • 30g of isolated soy protein with 132mg isoflavones daily for 12 weeks
  • 30g of pure microcrystalline cellulose daily for 12 weeks.

Control Variables

  • Isocaloric diet instruction
  • Typical level of physical activity by instruction.
Description of Actual Data Sample:
  • Initial N: 40 post-menopausal women were screened; 33 were eligible for inclusion
  • Attrition (final N): 32 completed the study; data for 31 subjects were used for analysis of lipid results; data for 29 subjects were used for analysis of effect on BP
  • Age: 62.5±6.77 years (mean±SD)
  • Ethnicity: Not discussed
  • Other relevant demographics: Time from diagnosis of type 2 diabetes, 2.6±2.7 years
  • Anthropometrics: BMI, 32.2±5.0 at screening.

Mean Weight(kg) Throughout the Study

Soy baseline Soy at 12 weeks Percentage change Placebo baseline Placebo at 12 weeks Percentage change Tx difference

81.2±13.1

81.7±12.7

+0.77±1.81

81.6±13.1

81.7±13.1

+0.19±1.91

0.369

Location

United Kingdom.

 

Summary of Results:
  • Initial N: 40 post-menopausal women were screened; 33 were eligible for inclusion
  • Attrition (final N): 32 completed the study; data for 31 subjects were used for analysis of lipid results; data for 29 subjects were used for analysis of effect on BP
  • Age: 62.5±6.77 years (mean±SD)
  • Ethnicity: Not discussed
  • Other relevant demographics: Time from diagnosis of type 2 diabetes, 2.6±2.7 years
  • Anthropometrics: BMI, 32.2±5.0 at screening.

Mean Weight(kg) Throughout the Study

Soy baseline Soy at 12 weeks Percentage change Placebo baseline Placebo at 12 weeks Percentage change Tx difference

81.2±13.1

81.7±12.7

+0.77±1.81

81.6±13.1

81.7±13.1

+0.19±1.91

0.369

Location

United Kingdom.

 

Author Conclusion:
Short-term dietary soy phytoestrogen supplementation reduces insulin resistance and improves glycemic control in post-menopausal women with type 2 diabetes, while reducing their cardiovascular risk by lowering LDL cholesterol.
Funding Source:
Reviewer Comments:
  • Subjects were instructed to maintain their diabetes diet and level of physical activity and to minimize ingestion of soy and soy-based products for the duration of the study. This was reinforced at all visits.
  • Compliance was checked by counting all returned medication at each visit during the study
  • The two-week washout period between the soy and placebo trials was deemed to be adequate, based on insulin levels and insulin resistance returning to baseline
  • Data for three subjects were not included in the analysis for effect on BP because their medications were changed during the trial period.
  • The mean BP was relatively high at baseline and throughout the study.
  • Ethnicity, smoking or current alcohol use was not reported
  • The isoflavone dose in this study was higher than that commonly consumed in Asian counries (20mg to 80mg per day), where soy is a staple.
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? ???
  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? 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? 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)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? ???
  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? ???
  10.1. Were sources of funding and investigators' affiliations described? ???
  10.2. Was the study free from apparent conflict of interest? ???