EAL

DM: Types of Fat (2014)

Citation:

Heine RJ, Mulder C, Popp-Snijders C, van der Meer J, van der Veen EA. Linoleic-acid-enriched diet: Long-term effects on serum lipoprotein and apolipoprotein concentrations and insulin sensitivity in noninsulin-dependent diabetic patients. Am J Clin Nutr. 1989; 49(3): 448-456.

PubMed ID: 2923077

Study Design:

Randomized Crossover Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To test the long-term effects of a diet enriched with linoleic acid to a P:S of one, without further altering the composition of the diet, on serum lipoprotein and apolipoprotein levels and insulin sensitivity in non-insulin-dependent diabetic patients.

Inclusion Criteria:

Age less than 70 years
Treatment consisting of diet only or a stable dose of sulfonylurea for at least three months before the start of the study
Provided written informed consent
Diagnosed as diabetic according to the criteria established by the World Health Organization (WHO) on diabetes mellitus.

Exclusion Criteria:

Patients with other endocrine diseases
Liver or renal disease as confirmed by biological findings
Those on treatment that would affect lipid or carbohydrate metabolism.

Description of Study Protocol:

Design

Randomized crossover study.

Blinding Used

Implied with measurements.

Intervention

Subjects were randomized to follow one diet for 30 weeks and then crossed over to the second diet:
- Diet low in polyunsaturated to saturated fat ratio (P:S 0.3)
- Diet higher in polyunsaturated to saturated fat ratio (P:S 1.0).
The diets were planned to be isocaloric with the energy intake of the subject calculated from one-week dietary recalls. A computer bank of Dutch food composition was used to assess the diet compositions and to design the appropriate diet for the study. No attempts were made to alter the diet with the exception of the P:S ratio, which was altered by substituting linoleic acid-rich oils and fats for products rich in saturated fatty acids.

Statistical Analysis

Multiple measurements of the variables during the two study periods were taken and the average values of the three final measurements obtained between the weeks of 18 and 30 were calculated
For the analysis, the data from the two sequence groups were pooled
For the statistical evaluation of the treatment responses analysis of variance according to Hills and Armitage was performed
All the results are presented as means ±SEM.

Data Collection Summary:

Timing of Measurements

Measurements made at baseline and every six weeks thereafter.

Dependent Variables

Serum lipoprotein and apolipoprotein levels and insulin sensitivity: Apolipoprotein A1 and A2 were measured using a modification of the immunoturbidimetric assay and apolipoprotein B was measured by radial immunodiffusion
The fatty acid composition of phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) were analyzed separately
Blood glucose was measured by a glucose oxidase method and plasma insulin was measured by the radioimmunoassay with human insulin as a standard
Plasma C peptide was measured by radioimmunoassay with ethanol precipitation with human C peptide as standard
Glycosylated hemoglobin was assayed by a micro-column method
Total cholesterol in serum and in the lipoprotein fractions was measured enzymatically using the Monotest kit.

Independent Variables

Subjects were randomized to follow one diet for 30 weeks and then crossed over to the second diet:
- Diet low in polyunsaturated to saturated fat ratio (P:S 0.3)
- Diet higher in polyunsaturated to saturated fat ratio (P:S 1.0).
The diets were planned to be isocaloric with the energy intake of the subject calculated from one-week dietary recalls
A computer bank of Dutch food composition was used to assess the diet compositions and to design the appropriate diet for the study
No attempts were made to alter the diet with the exception of the P:S ratio which was altered by substituting linoleic acid-rich oils and fats for products rich in saturated fatty acids
Dietary compliance was controlled by one-week dietary recalls at six, 12 and 24 weeks during the two dietary periods.

Description of Actual Data Sample:

Initial N: A total of 17 (eight women, nine men)
Attrition (final N): A total of 14 (six women, eight men)
Age: Range 30 to 69 years
Other relevant demographics:
- Six on diet alone
- Two on tolbutamide
- Four on glibenclamide
- Two on gliclazide.
Anthropometrics: BMI range 19.5kg/m² to 34.0kg/m²
Location: Amsterdam, The Netherlands.

Summary of Results:

Key Findings

Mean body weight was not significantly different during either dietary period
Fasting blood glucose, glycosylated hemoglobin percentages, plasma insulin levels and systolic and diastolic blood pressures were not affected by the change in dietary linoleic acid intake
Total and LDL-cholesterol levels declined by 7.6% (P<0.01) and 9.8% (P<0.01) during the high P:S diet
VLDL, HDL2, and HDL3 cholesterol, triacylglycerol and apolipoprotein A1, A2 and B levels were not affected by the change in P:S
Despite a modest increase of insulin-mediated glucose disposal at physiologic insulinemia during the high P:S diet, no influence was seen on glycemic control, blood glucose, plasma insulin and C peptide responses to mixed meals.

Author Conclusion:

A linoleic-enriched diet in patients with non-insulin-dependent diabetes mellitus (NIDDM) causes a less atherogenic lipoprotein profile but does not influence glycemic control and carbohydrate tolerance.

Funding Source:

University/Hospital:

Department of Internal Medicine, Free University Hospital, Amsterdam, The Netherlands

Reviewer Comments:

Small number of subjects
No washout period between diets.

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?		N/A
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	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?	Yes
	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?		???
	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?	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?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes