DM: Carbohydrates (2007)

Citation:

Boden G, Sargrad K, Homko C, Mozzoli M, Stein TP.  Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes.  Ann Intern Med 2005; 142:403-411. 

PubMed ID: 15767618
 
Study Design:
Non-Randomized Controlled Trial
Class:
C - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To determine the effects of a low carbohydrate diet on energy intake and expenditure, body weight and body water, glucose metabolism, and insulin sensitivity in obese patients with type 2 diabetes in the controlled environment of a clinical research center.
Inclusion Criteria:
  • obese
  • diagnosis of type 2 diabetes
Exclusion Criteria:
  • endocrine disorders other than diabetes
  • cardiovascular, pulmonary, or renal disease
  • active smoker
Description of Study Protocol:

Recruitment :  advertisements in local newspapers and in the hospital

Design

  • subjects were hospitalized for study and followed usual diet or 7 days
  • during days 8-21 subjects consumed a 21g carbohydrate diet following Dr. Atkins diet plan
  • subjects encouraged to maintain usual level of physical activity

Blinding used (if applicable): NA

Intervention (if applicable)

21g carbohydrate diet

  • subjects allowed unlimited intake of meats, poultry, fish, and eggs; diet gelatin, butter
  • limited amounts of cheese allowed
  • no sauces or snack foods allowed except for Dr. Atkins products
  • amounts of food consumed were weighed and recorded

 Statistical Analysis

  • results from the control period compared with those from the low-carbohydrate period
  • within-patient diet changes calculated using endpoint and analyzed using Wilcoxon signed-rank tests for paired data

 

Data Collection Summary:

Timing of Measurements: 

  • body weights, fasting plasma glucose levels and 24-hour urine outputs measured daily
  • at the end of each day each subject rated level of appetite, satisfaction with diet, energy level, and general level of well-being
  • serial measurements of insulin and glucose on days 1, 8, and 22, using euglycemic hyperinsulinemic clamps

 Dependent Variables

  • body weight
  • body water, using bioelectrical impedance
  • energy intake
  • diet satisfaction, using visual analogue scales
  • plasma total ketone body levels
  • urinary ketone body excretion
  • fasting plasma glucose using glucose analyzer 
  • HbA1c
  • serum insulin, after protein precipitation with polyethylene glycol by radioimmunoassay
  • serum leptin, and ghrelin, using radioimmunoassay
  • mean glucose infusion rates to maintain euglycemia
  • hormone levels
  • serum lipid levels
  • renal function

Independent Variables

  • usual diet or low carbohydrate diet (21 g/day)
  • energy expenditure, using doubly labelled water method (used for 6 patients only)
  • compliance:  all foods provided through research kitchen

 Control Variables

  • loss of body water

 

 

Description of Actual Data Sample:

Initial N: 10; 3 men, 7 women

Attrition (final N):  10

Age: 51±9.5 yrs; range 36-64

Ethnicity: 7 black, 3 white

Other relevant demographics:

  • duration of diabetes:  4.9±4.1 yrs
  • 3 treated by diet alone, 7 on glucose-lowering medications

Anthropometrics

  • height:  169.7±10.4 cm
  • weight: 114.75±12.9 kg
  • BMI: 40.3±5.7

Location:   United States

 

Summary of Results:

Means of measures of metabolic balance in 10 patients

Variables

Low-Carbohydrate Group

Control group

Statistical Significance of Group Difference

Body Weight, kg

112.41 114.43

0.042

Body water, kg

45.94

46.30

 >0.2

Fat-free mass, kg

62.73

62.32

 >0.2

Body weight - water, kg 66.48 68.13 0.049
Calorie intake, kcal/d 2164 3111 0.001
Total Energy expenditure, kcal/d 3190 3284 0.12
Resting energy expenditure, kcal/d 1842 1945 0.048
Calorie deficit, kcal/d 1027    
Predicted weight loss, kg 1.60    

Assessment of Diet Satisfaction:  no difference in diet satisfaction between groups

Profiles of 24-hour plasma glucose, insulin, leptin, and ghrelin

  • Mean fasting plasma glucose levels decreased from 135mg/dL on day 8 to 113 mg/dL on day 22; P=0.025
  • HbA1c decreased from 7.3% on day 8 to 6.8% on day 22; P=0.006
  • Mean 24-hour serum insulin and leptin levels profiles were significantly lower at the end of the low-carbohydrate diet than before the diet, with ghrelin profiles increasing marginally

Serum lipid levels

  • triglyceride levels decreased from 1.84±0.63 mmol/L to 1>1.19±0.03 mmol/L (P<0.001
  • total cholesterol decreased from 4.68 mmol/L to 4.24 mmol/L (P<0.02)
  • LDL cholesterol levels and HDL cholesterol levels did not change

 

Author Conclusion:

The data did not support the concept that weight loss induced by the low-carbohydrate diet was due to different utilization of macronutrients:  after water loss was accounted for, all weight loss was due to fat. 

On the low-carbohydrate diet patients spontaneously reduced their mean energy intake to approximately 2200/kcal/d, which was appropriate for these patients.  The authors do not know what caused this reduction, but it was not diet palatability as patient satisfactions scores were the same for both groups.

Measures of blood glucose, and triglyceride levels improved while patients were on the low-carbohydrate diet.

The low-carbohydrate diet was beneficial for weight and blood glucose control in this short-term study.

Funding Source:
Government: NIH, NCRR
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:

I question whether a 2-week period is long enough to see changes in patient satisfaction with the diet or some of the other measures used in the study, such as HbA1c and serum lipid values.  Small sample size.

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