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DM: Omega-3 Fatty Acids (2014)

Citation:

Rossing P, Hansen BV, Nielsen FS, Myrup B, Holmer G, Parving HH. Fish oil in diabetic nephropathy. Diabetes Care, 1996; 19 (11): 1,214-1,219.

PubMed ID: 8908382
 
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 aim of this study was to evaluate the potential beneficial effect of fish oil on albuminuria, glomerular filtration rate, systemic blood pressure and dyslipidemia.

Inclusion Criteria:
  • Insulin-dependent from the time of diagnosis and received at least three daily injections of human insulin
  • Provided written informed consent.
Exclusion Criteria:
Diuretic treatment for edema.
Description of Study Protocol:
  • Recruitment: Recruited from the Steno Diabetes Center 
  • Design: Randomized controlled trial
  • Blinding used: Double-blind.

Intervention

  • After a run-in period of four weeks, during which 21ml of olive oil was given, patients were randomized to either 21ml of cod liver oil (4.6g n-3 fatty acids per day) or 21ml of olive oil (control) for one year
  • The cod liver oil was given as an Eskisol Fish Oil emulsion, which has a low content of A and D vitamins.

Statistical Analysis

  • Urinary excretion of albumin, IgG, and IgG4 and the fractional clearances of these proteins were logarithmically transformed before statistical analysis because of their positively skewed distribution and are given as geometric means
  • Plasma triglyceride, VLDL-cholesterol and apolipoprotein(a) concentrations are given as median range. All other data are given as means ±SE.
  • All comparisons of normally or log-normally distributed parameters were done with a Student's T-test. Intergroup comparisons were done using unpaired and intragroup comparisons using paired design.
  • Non-normally distributed parameters were compared using the Wilcoxon rank-sum test for intragroup comparisons and the Mann-Whitney U-test for comparisons between groups
  • P≤0.05 was considered significant (two-tailed).
Data Collection Summary:

Timing of Measurements

Measurements made at baseline and at three, six, nine and 12 months.

Dependent Variables

  • Blood glucose concentration was measured by means of OneTouch II
  • Electrolytes, urate, hemoglobin, bilirubin, aspartate aminotransferase, total cholesterol, HDL-cholesterol, triglyceride concentrations and leukocyte and platelet counts were measured using conventional laboratory techniques
  • Serum creatinine was measured using a reaction rate kinetic technique eliminating pseudo creatines
  • HbA1c was measured by high-pressure liquid chromatography
  • The LDL-cholesterol and VLDL-cholesterol were calculated with the use of Friedewald's formula
  • Glomerular filtration rate was measured by a venous injection of edetic acid labeled with 3.7MBq sodium chromate-51 at 9:00 a.m. and determined the radioactivity in plasma from samples of venous blood taken from the other arm at 180, 200, 220 and 240 minutes after injection
  • Blood pressure was measured every 15 minutes during the day (7:00 a.m. to 11:00 p.m.) and every 30 minutes during the night (11:00 p.m. to 7:00 a.m.). Values were averaged for each hour before calculating the 24-hour average blood pressure.
  • Urine samples analyzed for albumin, IgG, IgG4, retinol binding protein, sodium, phosphorus, creatinine and urea.

Independent Variables 

  • Randomization to either 21ml of cod liver oil (4.6g n-3 fatty acids per day) or 21ml of olive oil (control) for one year
  • The cod liver oil was given as an Eskisol Fish Oil emulsion, which has a low content of A and D vitamins.
Description of Actual Data Sample:

Initial N

  • 48 fulfilled inclusion criteria
  • 36 subjects were randomized.

Attrition (Final N)

  • 29 (19 men, 10 women)
  • Fish Oil Group: Nine men, five women
  • Olive Oil Group: 10 men, five women.

Age

  • Fish Oil Group: Mean, 32±7 years
  • Olive Oil Group: Mean, 34±10 years.

Ethnicity

Not reported.

Other Relevant Demographics

?Mean duration of diabetes in the Fish Oil Group was 20±4 years vs. 20±6 years in the Olive Oil Group.

Anthropometrics
Mean BMI

  • Fish Oil Group 24.5±3.8kg/m2
  • Olive Oil Group: 23.2±2.2kg/m2.

The two groups were comparable regarding age, sex, duration of diabetes, retinopathy status, smoking habits, insulin dosage, albuminuria, arterial blood pressure and glomerular filtration rate.

Location

Denmark.
Summary of Results:

Key Findings

  • Albuminuria increased by 22% (1% to 46%) in the Fish Oil Group vs. 15% (-11-49%) in the Placebo Group (NS)
  • Glomerular filtration rate decreased from 116±7ml to 105±7ml per minute per 1.73m2 vs. from 108±6ml to 103±7ml per minute per 1.73m2, for fish oil and placebo, respectively (NS)
  • No significant changes occurred in 24-hour ambulatory blood pressure: From 141±4/82±2mmHg to 142±5/83±2mmHg vs. from 140±4/78±2mmHg to 144±4/80±3mmHg for fish oil and placebo, respectively (NS)
  • In the Fish Oil Group, serum triglycerides (median range) decreased from 0.97mmol (0.5 to 4.0mmol) per L to 0.8mmol (0.4 to 3.0mmol) vs. from 1.01mmol (0.4 to 2.0mmol) per L to 1.09mmol (0.4 to 2.0mmol) per L in the Placebo Group (P<0.05) and VLDL-cholesterol decreased from 0.45mmol (0.23 to 1.88mmol) per L to 0.37mmol (0.21 to 1.43mmol) per L vs. from 0.44mmol (0.21 to 0.94mmol) per L to 0.41mmol (0.17 to 1.94mmol) per L (P<0.05)
  • However, total and LDL-cholesterol rose in the Fish Oil Group, as compared with the Placebo Group.
Author Conclusion:

This study does not suggest that fish oil has beneficial effects on albuminuria, kidney function, blood pressure and dyslipidemia in normotensive IDDM patients suffering from diabetic nephropathy.

Funding Source:
University/Hospital: Department of Biochemistry and Nutrition, Technical University of Denmark
Not-for-profit
Steno Diabetes Center
Other non-profit:
Reviewer Comments:
  • Small numbers of subjects in groups
  • The authors identified that a limitation to the present study is the number of patients completing the 12-month follow-up was less than determined in the pre-study calculation of 34 patients.
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? No
  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? No
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? 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