EAL

DM: Types of Fat (2014)

Citation:

Dullaart RP, Beusekamp BJ, Meijer S, Hoogenberg K, van Doormaal JJ, Sluiter WJ. Long-term effects of linoleic-acid-enriched diet on albuminuria and lipid levels in type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion. Diabetologia. 1992; 35(2): 165-172.

PubMed ID: 1547922

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 investigate the effects of a linoleic-acid enriched diet on albuminuria and lipid levels in type 1 (insulin-dependent) diabetic patients with elevated urinary albumin excretion (overnight urinary albumin excretion rate between 10mcg and 200mcg per minute).

Inclusion Criteria:

Between the ages of 21 and 65 years
Duration of diabetes for at least five years
Serum creatinine 120mcgmol per L
Type 1 diabetic with elevated urinary albumin excretion levels (between 10mcg and 200mcg per minute)
Suffering from ketosis-prone diabetes and insulin dependent
Provided written informed consent.

Exclusion Criteria:

History of renal disease or other renal abnormality
Hypertension (systolic blood pressure 160mm Hg or higher and diastolic blood pressure 95mm Hg or higher)
Change in anti-hypertensive medication within three months before randomization
Pregnancy or liver disease.

Description of Study Protocol:

Recruitment

Patients with type 1 diabetes and elevated urinary albumin excretion were recruited from outpatient clinics.

Design

Randomized controlled trial.

Blinding Used

Implied with measurements.

Intervention

For two years, subjects were randomized to usual diet (control) or a diet to increase dietary polyunsaturated:saturated fatty acid ratio to 1.0 by replacing saturated fat with linoleic acid-rich products
The patients in the high linoleic acid diet group were advised to replace butter or saturated margarines with polyunsaturated margarines and restrict their intake of saturated fat from meat and milk products
After two years, the composition of the usual diet was 16±3% of energy from saturated fat, 7±3% of energy from linoleic acid, with a P:S ratio of 0.56±0.25, while the composition of the high linoleic acid diet was 13±2% of energy from saturated fat, 11±2% of energy from linoleic acid, with a P:S ratio of 0.96±0.16.

Statistical Analysis

Comparison of baseline variables and of differences in change between groups was performed by the Wilcoxon test for unpaired observations
Changes in variables within a group were analyzed by two-way analysis of variance according to Friedman
Adjustment for multiple comparisons was carried out using Duncan's method
Differences in prevalence of variables among groups were analyzed by chi-square statistics
Relative risks (95% CI) were calculated for progression of albuminuria
Multiple regression analysis was carried out to evaluate the independent contribution of parameters
Baseline U_albV are given in percent change (median 95% CI)
Other data are expressed as mean ±SD or mean ±SEM
P values less than 0.05 were considered to be significant.

Data Collection Summary:

Timing of Measurements

Measurements made at baseline, and after one and two years.

Dependent Variables

At every visit three consecutive timed overnight urine samples and one 24-hour urine specimen were collected.Urinary albumin was measured by a double-antibody radioimmunoassay.
Glomerular filtration rate (GFR) and ERPF were measured simultaneously using I-iothalamate and I-hippuran
Blood pressure was measured using a standard sphygmomanomter
Retinopathy was assessed by fundoscopy through dilated pupils and classified for the worst eye as absent, background or proliferative
Hemoglobin A_1c was measured by colorimetry
Cholesterol and triglycerides were measured enzymatically using automated methods
VLDL cholesterol was calculated by the Friedewald formula.

Independent Variables

For two years, subjects were randomized to usual diet (control) or a diet to increase dietary polyunsaturated:saturated fatty acid ratio to 1.0 by replacing saturated fat with linoleic acid-rich products
A complete diet history was documented; dietary records were obtained using the recall technique covering one week (including a weekend) and cross-checked with each patient by a dietitian
The composition of the diet was analyzed with a computer-assisted nutrient database.

Description of Actual Data Sample:

Initial N: A total of 38 subjects were randomized
Attrition (final N): A total of 36 (28 females, eight males), with 16 in the high linoleic acid diet group (HLAD) and 20 in the usual diet group (UD)
Age: Mean age in HLAD group was 44±12 years vs. 41±14 years in the UD group
Other relevant demographics: Mean duration of diabetes was 24±11 years in the HLAD group vs. 20±10 years in the UD group
Anthropometrics: Mean BMI in the HLAD group was 24.1±2.4kg/m² vs. 20±10kg/m² in the UD group. Clinical characteristics, GFR, metabolic control and dietary composition were similar in the two groups at baseline.
Location: The Netherlands.

Summary of Results:

Key Findings

In the HLAD group, linoleic acid intake rose from 7±4% to 11±2% as a percentage of energy and the polyunsaturated:saturated fatty acids ratio rose from 0.60±0.28 to 0.96±0.16 (P<0.001 compared to usual diet group)
In both groups, body weight increased during the two-year period
There were no significant differences in HbA1c between the groups, and no significant changes in 24-hour glucose profiles or insulin dose during the course of the study
The median increase in albuminuria was 58% (95% CI: 13 to 109; P<0.02) during the first year and 55% (95% CI: 11 to 127; P<0.01) during the second year
Glomerular filtration rate (GFR) remained unaltered and filtration fraction tended to rise (P<0.05 compared to usual diet group)
In the usual diet group, albuminuria did not significantly increase by 16% (95% CI: -17 to 38) and GFR declined during the second year
Blood pressure tended to rise similarly in both groups
Multiple regression analysis showed an independent effect of the high linoleic acid diet on the progression of albuminuria as well as the lack of decrease in glomerular filtration rate
Compared to baseline, low density lipoprotein cholesterol and apolipoprotein B levels decreased in the high linoleic acid diet group (P<0.05)
Compared to baseline, total and HDL cholesterol declined in both groups (P<0.05)
There were no significant differences between groups in terms of total cholesterol, HDL cholesterol, LDL cholesterol or triglycerides.

Author Conclusion:

A linoleic acid-enriched diet reduces atherogenic lipoproteins but does not have a beneficial effect on and might even promote renal functional abnormalities in type 1 diabetic patients with elevated urinary albumin excretion.

Funding Source:

Not-for-profit

Dutch Diabetes Research Fund

Other non-profit:

Reviewer Comments:

Long term study. Small numbers of subjects in groups.

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%.)	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)?	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?	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