EAL

DM: Prevention and Treatment of CVD (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

to examine the potential of a phytosterol-enriched spread to lower total and LDL cholesterol in subjects with type 2 diabetes with moderate hypercholesterolemia
to study the efficacy of the spread under real-life conditions
to assess whether the phytosterol-enriched spread has an effect on parameters of glycemic control

Inclusion Criteria:

type 2 diabetes for at least one year with a stable medication
serum LDL greater-than-or-equal-to 3.6 mmol/l
no treatment with hypolipidemic agents
not on a hypocaloric diet

Exclusion Criteria:

Excluded if not included above.

Description of Study Protocol:

Recruitment

advertisements in local newspapers
out-patient unit of the German Research Institute in Dusseldorf
practices of diabetologists

Design: randomized, double-blind, placebo-controlled study in two parallel groups over a period of 12 weeks

Blinding used (if applicable): all spread packages were identical except for registration number

Intervention (if applicable)

subjects received coded tubs containing 10g of either a low-fat spread or a phytosterol-enriched low-fat spread
subjects asked to consume two tubs daily, equivalent to 1.6 g phytosterols
no other dietary counseling given
subjects returned unused tubs to clinic

Statistical Analysis

differences in changes between both groups at fixed times compared using unpaired 2-sided t tests
changes within groups compared to baseline by paired 2-sided t tests
to assess the overall effect of treatment, repeated measurement of analysis of variance was performed using the original values of the variables at all time points.

Data Collection Summary:

Timing of Measurements

fasting blood samples taken at 0, 4, 8 and 12 weeks
changes in body weight, lifestyle, medication, and intercurrent illnesses assessed at 0, 4, and 8 weeks

Dependent Variables

total cholesterol
HDL
LDL calculated using the Friedewald formula
triglycerides
fructosamine
whole blood glucose
HbA1c

Independent Variables

low-fat spread or a phytosterol-enriched low-fat spread
changes in dietary intake assessed using a dietary intake questionnaire given at beginning at end of study

Control Variables

Description of Actual Data Sample:

Initial N: 85; 45 women

Attrition (final N): 81; two dropped out due to poor compliance and another two due to dislike of the spread

Age: 60±8 y for experimental group

Ethnicity: not specified

Other relevant demographics: 50 participants habitually used margarine, 26 used butter, and 9 did not use spread before entering the study

Anthropometrics

weight 81.9 ±12.0 kg
BMI 28.3±4.7
The two groups were comparable with regard to age, gender distribution, weight, and BMI. Changes in body weight and food choices were insignificant.

Location: Germany

Summary of Results:

Variables	Placebo Group		Phytosterol-enriched spread group
	Baseline	12 weeks	Baseline	12 weeks
Total Cholesterol, mmol/l	6.42±0.81	6.36±0.67	6.4±0.83	6.28±1.00
LDL, mmol/l	4.11±0.73	4.01±0.63	4.33±0.65	4.13±0.82
HDL, mmol/l	1.37±0.37	1.40±0.42	1.25±0.37	1.31±0.38
LDL/HDL ratio	3.18±0.92	3.08±0.94	3.74±1.19	3.35±1.02*
triglycerides, mmol/l	2.26±1.36	2.24±1.39	1.99±1.01	1.84±1.04*

*significantly different from baseline (p<0.05)

Other Findings

In the repeated mesure analysis of variance the change of total and LDL was significantly different between the groups overall (p=0.003 and p=0.027, respectively) even after adjustment for baseline values (p=0.002 and p=0.047, respectively).

The HDL cholesterol change from baseline was significantly different between groups after 8 weeks, but the repeated measurement analysis did not show a significant difference between the two groups (p=0.057, after adjustment for initial values p=0.093).

In contrast, the change in the LDL/HDL ratio versus baseline was significantly different between the two groups overall (repeated measurement analysis: p=0.007, after adjustment for initial values p=0.036).

There were no significant changes in blood glucose, fructosamine, or HbA1c at 12 weeks.

Author Conclusion:

A phytosterol-enriched spread is effective in lowering total and LDL cholesterol in a large group of patients with type 2 diabetes. However, the effect is modest and transient.

The glycemic control improved slightly in the subjects using the phytosterol-enriched spread, but the repeated measurement analysis did not reveal significant differences over time.

Funding Source:

Reviewer Comments:

I believe that the authors tend to overstate the effects of the phytosterol-enriched spread as they phrase their conclusions.

This study was funded by the Unilever Corporation.

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%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	No
	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?	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)?	No
	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?	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?		No
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	No