EAL

Vitamins and Antioxidants and the Prevention and Treatment of CVD

Citation:

Azadbakht L, Atabak S, Esmaillzadeh A. Soy protein intake, cardiorenal indices, and C-reactive protein in type 2 diabetes with nephropathy: a longitudinal randomized clinical trial. Diabetes Care. 2008; 31(4): 648-654.

PubMed ID: 18184902

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To determine the effects of long-term soy consumption on cardiovascular risk.

Inclusion Criteria:

Proteinuria with total urinary protein excretion between 300mg and 1,000mg per day
Serum creatinine between 1mg and 2.5mg per dL
Blood urea nitrogen between 20mg and 40mg per dL
Systolic and diastolic blood pressure higher than 140mm Hg and 90mm Hg
Provided written informed consent.

Exclusion Criteria:

Not described.

Description of Study Protocol:

Recruitment

A total of 50 diabetic patients with nephropathy were recruited for this study.

Design

Randomized controlled trial.

Blinding Used

Implied with measurements.

Intervention

Subjects were randomized to one of two diets for four years:

Soy protein group: Followed a diet containing 0.8g protein per kg body weight (35% animal proteins, 35% textured soy protein and 30% vegetable proteins)
Control group: Followed a similar diet with 0.8g protein per kg body weight containing 70% animal proteins and 30% vegetable proteins).

Statistical Analysis

Analysis was performed using SPSS for Windows (version 13.0; SPSS) and SAS (version 8.2)
The Kolmogorov-Smirnov test was used to assess whether the variables were normally distributed
Two-way ANOVA was applied to assess the effect of time (baseline, first year, second year, third year and fourth year), group and the interaction term between time and group
Students T-test was used for comparing mean changes of the variables in the soy protein and control groups
To adjust for potential confounders, we used ANCOVA with changes in lipid profiles, plasma glucose, body weight and phytoestrogen intake as covariates
Further adjustments were made for changes in plasma phytoestrogen levels.

Data Collection Summary:

Timing of Measurements

All measurements were done at baseline and every six months for up to four years.

Dependent Variables

Body weight was measured while the subjects were minimally clothed without shoes using digital scales and recorded to the nearest 0.1kg
Height was measured in a standing position, without shoes, using a tape meter while the shoulders were in a normal state
Blood pressure was measured twice after the participants sat for 15 minutes
Serum total cholesterol and triacylglycerol concentrations were measured by using commerically available enzymatic reagents
HDL cholesterol was measured after precipitation of the apolipoprotein B-containing lipoproteins with phosphotungstic acid
LDL cholesterol was calculated according to the Friedenwald method
Plasma phytoestrogen levels were measured by high-performance lipid chromatography to check soy consumption compliance
Cardiovascular risk factors such as C-reactive protein (CRP) and kidney function indexes among patients with type 2 diabetes with nephropathy. A total of twelve hour-fasting blood samples were collected into tubes containing 0.1% EDTA and were centrifuged at 4° degrees Celsius and 500g for 10 minutes to separate the plasma.
Urinary and serum concentrations of creatinine were determined by the Jaffe method, performed in a Hitachi 705 that was set to record the mean absorbance in the interval of 60 seconds to 140 seconds after the start of the reaction
Blood and urinary nitrogen levels were analyzed by enzymatic methods
Proteinuria was assessed by using the tricholoracetic acid and sulfosalicylic acid method.

Independent Variables

Subjects were randomized to one of two diets for four years:

Soy protein group: Followed a diet containing 0.8g protein per kg body weight (35% animal proteins, 35% textured soy protein and 30% vegetable proteins)
Control group: Followed a similar diet with 0.8g protein per kg body weight containing 70% animal proteins and 30% vegetable proteins).

Description of Actual Data Sample:

Initial N: 50 (22 men, 28 women)
Attrition (final N): 41 total (nine excluded for not following the diet; five started dialysis and four did not follow the diet); 18 men, 23 women
Age: Mean 62.1±12.1 years
Other relevant demographics: 70% of subjects in the soy protein group had positive family history for diabetes and 61% in the control group had positive family history for diabetes
Anthropometrics: Subjects were matched for age, BMI and diabetes duration before randomization.
Location: Iran.

Summary of Results:

Key Findings

Soy protein consumption significantly affected cardiovascular risks such as fasting plasma glucose (mean change in the soy protein vs. control groups: -18mg±3mg vs. 11mg±2mg per dL; P=0.03), total cholesterol (-23mg±5mg vs. 10mg±3mg per dL; P=0.01), LDL cholesterol (-20mg±5mg vs. 6mg±2mg per dL; P=0.01) and serum triglyceride (-24mg±6mg vs. -5mg±2mg per dL; P=0.01) concentrations
Serum C-reactive protein levels were significantly decreased by soy protein intake compared with those in the control group (1.31mg±0.6mg vs. 0.33mg±0.1mg per L; P=0.02)
Significant improvements were also seen in proteinuria (-0.15g±0.03g vs. 0.02g±0.01g per day; P=0.001) and urinary creatinine (-1.5mg±0.9mg vs. 0.6mg±0.3mg per dL, P=0.01) by consumption of soy protein
There were no significant changes in body weight or GFR in either group during the four-year trial.

Author Conclusion:

Longitudinal soy protein consumption significantly affected cardiovascular risk factors and kidney-related biomarkers among patients with type 2 diabetes with nephropathy.

Funding Source:

University/Hospital:

Department of Nutrition, School of Public Health, Isfahan University, Iran

Reviewer Comments:

One of the limitations of the current study is that urinary urea nitrogen and urinary creatinine were measured as concentrations rather than as 24-hour excretions
Concentrations of these variables are less relevant to kidney function than 24-hour excretion.

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?	No
	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?	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)?	N/A
	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?	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