EAL

DM: Prevention and Treatment of CVD (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To compare the effects on lipid levels, glycemic control, and diurnal blood pressure of two diets rich in stearic or palmitic acid, with a carbohydrate-rich diet in NIDDM patients.

Inclusion Criteria:

1. Type 2 diabetes mellitus

2. Postprandial C-peptide responses within the normal range

3. Caucasian

4. Non-smoker

Exclusion Criteria:

Excluded if not included above.

Description of Study Protocol:

Recruitment: 15 patients recruited from Aarhus University Hospital in Aarhus, Denmark.

Design: Randomized crossover design. After a 2-week run-in study participants were randomized to three 3-week treatments (isoenergetic - adjusted, if needed).

Blinding Used (if applicable):

Blinding was used.

Intervention:

1. Each participant experienced each of these 3 treatments in a randomized succession. Participants went back to their habitual diet for a 2-week washout period in between each diet.

a diet rich in stearic acid (40 E% [percent total energy] CHO, 44 E% fat [20 E% SFA, 13 E% stearic acid] , and 15 E% protein)
a diet rich in palmitic acid (40 E% CHO, 45 E% fat [20 E% SFA and 16 E% palmitic acid], and 15 E% protein), or
a diet rich in carbohydrates (51 E% CHO, 29 E% fat [10 E% SFA], and 18 E% protein).

2. During the 3 diet periods, participants received frozen special meat dishes, sauces, rolls, and cakes from the hospital kitchen.

3. The nutrient content of three whole meal composites, representing the three planned intervention diets, were analyzed as well as the fatty acid content of the foods.

4. Participants also weighed and recorded their food for 7 days before the study began and during the last week of each dietary intervention period to estimate energy intake and composition. The diet records were then coded by a dietitian.

Statistical Analysis

no indication of period effect was found for any variable
Blood glucose and insulin AUCs were calculated according to the method of Jenkins et al.
When data were consistent with the hypothesis of normality, a paired t test was used, otherwise Wilcoxon's test for paired differences was used.
multiple comparisons between mean values were made by analysis of variance (repeated measures) follwed by Fisher's least significant differences test.
P <0.05 was considered statistically significant

Data Collection Summary:

Timing of Measurements

Fructosamine, HbA1C, fasting blood glucose, lipids, and lipoproteins, endothelins, Lp(a), and 24-hour ambulatory blood pressure was measured before the study began and on one of the last days for each of the three diets. Blood samples were also taken at the beginning and end of each diet period to measure participant compliance.
Day profiles of glucose, insulin, free fatty acids (FFAs) and TG were measured and compared to a high-CHO test menu three days before the end of each diet. The profiles from the last day of the stearic acid and the palmitic acid diets were also compared to the responses of a fat-rich test menu.

Dependent Variables

HbA_1Cmeasured by commercial kit
Fructosamine measured by microdetermination
Fasting blood glucose by glucose oxidase method
Diurnal blood pressure
Triglycerides and lipoproteins measured on Enichom chem 1 analyzer
Lipoprotein (a) measured by a Pharmacia Apo(a) immunoradiometric assay.
Serum insulin measured by an enzyme-linked immunosorbent assay

Independent Variables

stearic acid intake
palmitic acid intake
carbohydrate intake
before and at the end of each diet period blood samples were collected for analysis of the fatty acid composition of serum triglycerides as a measurement of compliance.

Control Variables

Description of Actual Data Sample:

Initial N: 15 subjects, 7 women, 8 men

Attrition (Final N): 15

Age: 53 ±9 years

Ethnicity: white

Other relevant demographics: Of the 15 patients who participated in the study, 4 were treated with diet alone and 11 with diet and oral antidiabetic drugs (metformin, sulfonylureas, and a combination of metformin and sulfonylureas).

The mean duration of diabetes was 6 ±5 years

Anthropometrics: BMI 29.7 ±5.0 kg/m², weight 84.8 ±14.4 kg, and HbA_1C7.7 ±1.5%.

Location: Denmark

Summary of Results:

The average energy content of the 3 diets was 2,358 ±310 kcal/day and the average energy content of the habitual diet was 2,188 + 250 kcal/day (47 + 3 E% CHO, 17 + 2 E% protein, 34 ±5 E% total fat, 14 ±2 E% SFA, 2 ±2 E% alcohol, 254 ±37 E% cholesterol, 28 ±2 g/day fiber.

Overall, adherence to each of the diets was good.

Lipid and lipoprotein levels at the start and after 3 weeks' intervention

	Stearic acid-rich diet	Palmitic acid-rich diet	Carbohydrate-rich diet	P Value
total cholesterol at start ,mmol/l	6.0±1.2	5.6±1.2	5.5 ±1.1	0.02
total cholesterol at end, mmol/l	5.0 ±1.2	5.3 ±1.3	4.9 ±1.2	0.03
LDL cholesterol at start, mmol/l	3.7 ±1.1	3.4± 1.0	3.4 ±1.1	0.04
LDL cholesterol at end, mmol/l	3.1 ±1.0	3.2 ±1.1	3.0 ±1.1	0.5
HDL cholesterol at start, mmol/l	1.3± 0.4	1.2± 0.3	1.2± 0.2	0.3
HDL cholesterol at end, mmol/l	1.1 ±0.2	1.2 ±0.2	1.1 ±0.2	0.2
Total cholesterol/HDL ratio at start	5.0 ±1.9	4.9 ±1.6	4.7± 1.4	0.3
total cholesterol/HDL ratio at end	4.7 ±1.7	4.9± 1.8	4.6 ±1.4	0.3
LDL/HDL ratio at start	3.1 ±1.3	3.0 ±1.2	2.8± 1.1	0.4
LDL/HDL ratio at end	2.9 ±1.1	2.9 ±1.2	2.7± 1.0	0.6
Triglyderides at start, mmol/l	2.2± 1.3	2.1± 1.3	2.0 ±1.2	0.5
Triglycerides at end, mmol/l	1.8± 1.0	2.1 ±1.4	1.8 ±1.3	0.3

Fructosamine:

Concentrations decreased significantly during the 3 diet periods

Stearic acid diet: 419 ±102 to 377 ±76 µmol/l (P = 0.02)

Palmitic acid diet: 412 ±69 to 383 ±64 µmol/l (P = 0.02)

CHO diet: 429 ±78 to 377 ±71 µmol/l (P = 0.003)

Serum lipids:

Total cholesterol: Increased significantly after the palmitic acid-rich diet vs. the stearic acid-rich diet and CHO-rich diet; however, during the stearic acid-rich and CHO-rich diets, total cholesterol decreased 11-16% whereas no change was observed with the palmitic acid-rich diet.

LDL and HDL cholesterol: Decreased during the stearic acid-rich and CHO-rich diets, but did not attain statistical significance.

TG composition: During the stearic acid-rich diet, stearic acid and oleic acid increased; during the palmitic acid-rich diet, palmitic acid increased.

After the 3 intervention diets, no significant differences were observed in TG, LDL or HDL cholesterol levels.

No difference in effects between the diet periods were seen for fructosamine, HbA1C, fasting blood glucose, or diurnal BP.

Author Conclusion:

This study has demonstrated for the first time that a diet rich in palmitic acid was not as effective in lowering cholesterol levels as diets rich in stearic acid and CHO for patients with type 2 diabetes mellitus. Development of foods containing stearic acid rather than the more atherogenic saturated fatty acids may allow a wider choice of acceptable foods for patients with type 2 diabetes mellitus. It should be stressed, however, that high-fat foods have high energy density and can contribute to the development of obesity, which plays an important role in type 2 diabetes.

Funding Source:

Government:

Danish Medical Research Council

Not-for-profit

Reviewer Comments:

Well designed study that included a lot of detail.

Small sample size with no withdrawals. Randomized crossover design used so there were no "groups" per se.

The article references that the US Food and Drug Administration proposes that an intervention period of 3 weeks in sufficient to see changes in blood lipids.

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)	N/A

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?	N/A
	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?	N/A
	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?	???
	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?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	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)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	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