• Increase Font Size
  • Decrease Font Size
  • View as PDF

DM: Omega-3 Fatty Acids (2014)

Citation:

Wong CY, Yiu KH, Li SW, Lee S, Tam S, Lau CP, Tse HF. Fish-oil supplement has neutral effects on vascular and metabolic function but improves renal function in patients with type 2 diabetes mellitus. Diabet Med. 2010; 27 (1): 54-60.

PubMed ID: 20121889
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

The purpose of this study was to investigate the effects of 12-week supplementation of fish oil on vascular function as determined by brachial artery flow-mediated dilation (FMD) and circulating levels of endothelial progenitor cells (EPCs), metabolic parameters, high-sensitivity C-reactive protein (hsCRP), oxidative stress markers and renal function in patients with type 2 diabetes.

Inclusion Criteria:
  • Type 2 diabetic, as defined by World Health Organization (WHO) criteria and had received stable treatment with oral glucose-lowering agents (OGLAs) or insulin
  • No history of a prior cardiovascular event including myocardial infarction, unstable angina, stroke and peripheral vascular disease
  • Provided written informed consent.
Exclusion Criteria:
  • Patients with stable angina and positive findings on exercise stress testing or coronary angiography were excluded
  • Glycated hemoglobin (HbA1c) of 11.0% or more, pregnancy and lactation, history of heart failure, myocardial infarction, unstable angina, stroke, serum creatinine over 106mcmol per L, liver failure, gastrointestinal disorders, cancer, chronic alcohol abuse, hypo- or hypertension (resting blood pressure under 90/50mmHg or over 180/110mmHg), therapy with more than three anti-hypertensive agents and severe diabetes complications (proliferative diabetic retinopathy, macroalbuminuria defined as urinary albumin level more than 300mg per day)
  • Painful diabetic peripheral neuropathy requiring morphine derivatives and diabetic foot syndrome defined as ulceration, infection and destruction of deep tissues in the presence of peripheral vascular disease or peripheral neuropathy.
Description of Study Protocol:
  • Recruitment: Patients were recruited from a general outpatient clinic during the March-through-June 2007 time-period 
  • Design: Randomized placebo-controlled trial
  • Blinding used: Double-blind
  • Intervention: Subjects randomized to four grams of fish oil capsules or olive oil (placebo) capsules daily for a period of 12 weeks.

Statistical Analysis

  • Continuous variables were presented as means ±1 standard deviation
  • The normality of variables was tested by the Shapiro-Wilk test with appropriate transformations for those variables not normally distributed and the data were back-transformed for presentation
  • Categorical data are presented as frequencies and percentages
  • Statistical comparisons were performed with Student's T-test or X2 test 
  • Calculations were performed using SPSS software version 14.0; P<0.05 was considered statistically significant.
Data Collection Summary:

Timing of Measurements

Measurements made at baseline and at Week 12.

Dependent Variables

  • Vascular function: Measured by flow-mediated dilation (FMD) of the brachial artery
    • All measurements were performed in a quiet room with the subject supine
    • Ultrasound scans were performed with a high-resolution ultrasonographic scanner equipped with a 7.5MHz linear-array transducer
    • A total of four measurements of the arterial diameter from an end-diastolic frame were averaged to yield the brachial artery diameter during respective experimental stages
    • FMD values were calculated as the percentage change of the brachial artery diameter following reactive hyperaemia compared with the baseline.
  • During each visit, clinical characteristics including body height, weight, waist and hip circumferences and systolic and diastolic blood pressure were measured
  • Fasting venous blood sample was obtained from each study subject to measure blood glucose, HbA1c and serum triglycerides, total cholesterol, high density lipoprotein cholesterol (HDL-C) and LDL-cholesterol levels
  • Circulating levels of endothelial progenitor cells (EPCs) were measured by fluorescence-activated cell analysis.

Independent Variables 

  • Subjects randomized to four grams of fish oil capsules or olive oil (placebo) capsules daily for a period of 12 weeks
  • A three-day diet record (two weekdays and one weekend day) was completed at baseline and post-supplement by a dietitian.
Description of Actual Data Sample:

Initial N

  • ?200 patients with Type 2 diabetes were assessed for eligibility. 151 patients verbally consented to participate in the study.
  • During the initial assessment, 54 patients were deemed ineligible by the exclusion criteria and the remaining 97 patients were randomized.

Attrition (Final N)

  • 97 patients in analysis
  • Fish Oil Group: 49; 23 males; four lost to follow-up
  • Olive Oil Group: 48; 20 males; two lost to follow-up.

Age

  • Subjects receiving fish oil: 61.2±9.0 years
  • Control subjects: Mean, 59.0±9.3 years.

Ethnicity

Not reported.

Other Relevant Demographics

Mean duration of diabetes was 10±7 years in the Fish Oil Group vs. 8±5 years in the Control Group.

Anthropometrics

  • Mean BMI was 25.2±3.7kg/m2 in the Fish Oil Group vs. 26.4±4.4kg/m2 for controls
  • There were no significant differences in age, gender, prevalence of hypertension, dyslipidaemia and smoking, use of anti-hypertensive, lipid-lowering and oral glucose-lowering agents, lipid levels, HbA1c and serum creatinine levels between the two groups at baseline, however patients receiving fish oil had significantly higher fasting blood glucose compared with control subjects (P=0.04).

Location

Hong Kong, China.
Summary of Results:

Key Findings

  • Despite a significant reduction in serum triglycerides (-0.47mmol per L, P<0.01), the 12-week supplement of fish oil did not improve vascular function as determined by FMD (+0.16%, P=0.83) and circulating EPC count (+4 cells per mcL, P=0.78)
  • The fish-oil supplement did not have any significant treatment effects on hsCRP, oxidative stress, low- and high-density lipoprotein and glycated hemoglobin (HbA1c)
  • Serum creatinine was lower (-4.5mcmol per L, P=0.01) in fish-oil treated patients as compared with control subjects.
Author Conclusion:

This study demonstrated that 12 weeks of a fish oil supplement had no significant beneficial effect on vascular endothelial function, but improved renal function without changes in endothelial function, metabolic profiles, blood pressure, inflammation or oxidative stress in patients with type 2 diabetes.

Funding Source:
University/Hospital: University of Hong Kong, Hong Kong, China
Reviewer Comments:

Patients receiving fish oil had significantly higher fasting blood glucose compared with control subjects (P=0.04).

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) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? No
  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? 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