EAL

AWM: Low Carbohydrate Diet (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To test the hypothesis that severely obese subjects with a high prevalence of diabetes or the metabolic syndrome would have a greater weight loss, without detrimental effects on risk factors for atherosclerosis, while on a carbohydrate-restricted diet than on a calorie and fat-restricted diet.

Inclusion Criteria:

Aged at least 18 years, BMI of at least 35.

Exclusion Criteria:

Serum creatinine level > 1.5 mg/dl, hepatic disease, severe life-limiting medical illness, inability of diabetic subjects to monitor their own glucose levels, active participation in a dietary program, or use of weight loss medications.

Description of Study Protocol:

Recruitment

Subjects from the Philadelphia Veterans Affairs Medical Center.

Design

Randomized Controlled Trial. Randomized using preestablished algorithm generated from random set of numbers.

Blinding used (if applicable)

Not blinded.

Intervention (if applicable)

Assigned to either low-carbohydrate or low-fat, low-calorie diet for 6 months.

Statistical Analysis

Primary endpoint was weight loss at 6 months. Assuming 2-sided type I error of 5%, 100 subjects (50 per group) would be needed for the study to have 80% power to demonstrate a mean weight loss of 5 kg. Analysis contains info on all subjects with last observation carried forward. Comparison of continuous variables compared using unpaired t tests. Triglycerides, insulin and glucose levels were skewed and log-transformed. Dichotomous variables compared by chi-square analysis. Linear regression and 2-way ANCOVA models used to correct for potential confounding variables and to identify interactions between variables and diet-group assignment.

Data Collection Summary:

Timing of Measurements

Weight measured monthly. At enrollment and at 6 months, other data collected included waist size, self-reported medical history, blood pressure, glucose and serum lipid levels.

Dependent Variables

Weight measured with single calibrated scale
Blood specimens obtained after overnight fast
LDL cholesterol calculated according to Friedewald equation
Serum insulin measured by radioimmunoassay
Insulin sensitivity estimated with use of quantitative insulin-sensitivity check index

Independent Variables

Low carbohydrate (30 g or less/day) or low-calorie, low-fat diet (-500 kcal/day, 30% fat). Diet groups attended separate 2-hour group teaching sessions each week for 4 weeks, followed by monthly 1-hour sessions for 5 additional months. Dietary compliance estimated through 24 hour recall and intake analyzed with software.

Control Variables

Description of Actual Data Sample:

Initial N: 132 subjects, 68 to low-fat, 64 to low-carbohydrate.

Attrition (final N): 79 completed (60% completion), 36 in low-fat, 43 in low-carbohydrate, 19% female. Differences in attrition were statistically significant by month 3. There were no significant differences between the groups in the characteristics of dropouts.

Age: Mean age low-carbohydrate: 54 +/- 9 years, mean age low-fat: 54 +/- 10 years

Ethnicity: Low-carbohydrate: 54% Black, low-fat: 62% Black

Other relevant demographics: Mean BMI 43, prevalence of diabetes 39%, prevalence of metabolic syndrome 43%

Anthropometrics: Subjects were well-matched at baseline.

Location: Philadelphia

Summary of Results:

	Baseline	6 Months	Change	P-value
Kcal/day - low-fat	1848 +/- 1338	1576 +/- 760	-271 +/- 1260	0.33
Kcal/day - low-carb	2090 +/- 1055	1630 +/- 894	-460 +/- 902
Protein/day - low-fat	16 +/- 6%	16 +/- 6%	1 +/- 5%	< 0.001
Protein/day - low-carb	17 +/- 7%	22 +/- 9%	6 +/- 10%
Carbs/day - low-fat	51 +/- 14%	51 +/- 15%	-1 +/- 15%	< 0.001
Carbs/day - low-carb	49 +/- 17%	37 +/- 18%	-13 +/- 21%
Fat/day - low-fat	33 +/- 12%	33 +/- 14%	0 +/- 14%	0.004
Fat-day - low-carb	33 +/- 14%	41 +/- 16%	8 +/- 18%

Other Findings

Subjects on low-carbohydrate diet reported a nonsignificantly greater reduction in caloric intake (P = 0.33).

An analysis including all subjects, with the last observation carried forward for those who dropped out, showed that subjects on the low-carbohydrate diet lost more weight than those on the low-fat diet (-5.8 +/- 8.6 kg vs -1.9 +/- 4.2 kg, 95% CI for the weight loss difference between groups -1.6 to -6.3, P = 0.002) and had greater decreases in triglyceride levels (-20 +/- 43% vs -4 +/- 31%, P = 0.001), irrespective of the use or nonuse of hypoglycemic or lipid-lowering medications.

Blood pressure and total, HDL and LDL cholesterol did not change significantly during the 6-month study or between groups.

Insulin sensitivity, measured only in subjects without diabetes, also improved more among subjects on the low-carbohydrate diet (6 +/- 9% vs -3 +/- 8%, P = 0.01).

The amount of weight lost (P < 0.001) and assignment to the low-carbohydrate diet (P = 0.01) were independent predictors of improvement in triglyceride levels and insulin sensitivity.

Author Conclusion:

Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during 6 months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet, with a relative improvement in insulin sensitivity and triglyceride levels, even after adjustment for the amount of weight lost. The greater weight loss suggests a greater reduction in overall caloric intake, rather than a direct effect of macronutrient composition. This finding should be interpreted with caution, given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study. Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed.

Funding Source:

Government:

Veteran Affairs Healthcare Network

Reviewer Comments:

Diets not isocaloric. 40% dropout rate after 6 months. Only 19% women.

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?		???
	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?	???
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?		No
	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.)	No
	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)?	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?	N/A
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