DM: Protein (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To compare the metabolic effects of 5 weeks of a high-protein (lower carbohydrate) diet with a control "healthy" diet (usual protein and carbohydrate) in individuals with type 2 diabetes
Inclusion Criteria:
  • "Mild", untreated (no oral hypoglycemic agents or insulin) type 2 diabetes
  • Weight stable for > 3 mo

 

Exclusion Criteria:
  • Complications of diabetes (kidney disease, macroalbuminuria, proliferative retinopathy, neuropathy); peripheral vascular disease; serious psychological disorders; liver disease; untreated thyroid disease; hematologic abnormalities; congestive heart failure; angina; cancer
  • Weight > 136 kg
Description of Study Protocol:

Recruitment

 Not provided

Design

 Comparison of metabolic effects (e.g.: glucose, insulin, glycated hemoglobin, lipids) after 5 weeks of a control diet vs 5 weeks of a higher protein, lower carbohydrate diet, with a 2-5 week washout period between diets. 

Blinding used (if applicable)

 Not applicable

Intervention (if applicable)

  •  control or "healthy" diet (15% protein, 55% carbohydrate mainly as starches, 30% fat with 10% as mono, 10% as poly and 10% as saturated fatty acids)
  • higher protein, lower carbohydrate diet (30% protein, 40% carbohydrate, 30% fat (same proportions of fatty acids as above)
  • All foods provided (6-day rotating cycle) for outpatient consumption

Statistical Analysis

  •  Student's t test for paired variates
  • 24-hr area responses calculated by trapezoid rule
  • no power calculations
Data Collection Summary:

Timing of Measurements

 Baseline and 5 weeks (2 full days in a metabolic unit each time); compliance measures every 2-3 days during the 5 weeks

Dependent Variables

  • Plasma glucose: glucose oxidase method (Beckman glucose analyzer)
  • Total glycated hemoglobin: boronate affinity HPLC
  • Serum immunoreactive insulin: standard double-antibody radioimmunoassay method (Incstar, MN)
  • Glucagon: radioimmunoassay kit (Linco Research, St Louis) 
  • C-peptide: radioimmunoassay kit (Diasorin, MN)
  • total cholesterol, HDL cholesterol, triacylglycerol: automated method (Ortho-Clinical Diagnostics Vitros 950 analyzer)
  • LDL cholesterol: calculated (Friedewald formula)
  • Microalbumin: (Beckman-Coulter Array 360 analyzer)

Independent Variables

  •  control or "healthy" diet (15% protein, 55% carbohydrate mainly as starches, 30% fat with 10% as mono, 10% as poly and 10% as saturated fatty acids)
  • higher protein, lower carbohydrate diet (30% protein, 40% carbohydrate, 30% fat (same proportions of fatty acids as above)
  • All foods provided (6-day rotating cycle) for outpatient consumption

 Control Variables

  • Age 
  • Duration of diabetes  
  • Weight change (digital scale, wearing street clothes and no shoes)
  • BMI (calculated)
  • ß blockers/diuretics
  • blood pressure (Dinamap instrument with digital readout)
  • creatinine and urea nitrogen as dietary compliance measures (same automated method as the lipids)

 

Description of Actual Data Sample:

Initial N: 12 (10 males, 2 females)

Attrition (final N): 12

Age: mean 61 (range 39-79)

Ethnicity: not reported

Other relevant demographics: none provided

Anthropometrics: BMI mean 31 (range 22-37); weight mean 97 kg (range 75-121)

Location: Department of Veteran's Affairs Medical Center, Minneapolis, MN

 

Summary of Results:

 

Variables

Control Diet after 5 wks. Mean ± SEM

High protein, reduced carbohydrate diet after 5 wks.                    Mean ± SEM

Statistical difference between diets

Fasting blood glucose (mg/dl)

114±6

114±6

NS

24-hr integrated glucose response (mg.h/dL)

 614±130

 378±75

 P<0.02

Glycosylated hemoglobin (%)

7.7±0.3 

 7.3±0.2

 P<0.05

Fasting serum insulin (µU/mL)

17.3±3.0

18.4±3.5

NS

24-hr integrated insulin response (µU.h/mL)

1120±285

1327±315

NS

24-hr integrated glucagon response (pg.h/mL)

127±63

525±136

P<0.01

Fasting triacylglycerol (mg/dL)

199±20

161±23

P<0.03

 

Other Findings

  •  C-peptide, free fatty acid concentrations (NEFA, HDL,LDL, total cholesterol) and microalbumin were not significantly different after the two diets.
  • The glucose concentration was consistently lower after the high-protein diet, particularly in the evening.
  • None of the subjects lost or gained > 1 kg with either diet; BMI did not change
  • The ratio of urine urea to creatinine with the high-protein diet was double that with the control diet, indicating excellent compliance
  • Glycosylated hemoglobin decreased by 0.8% in the high protein diet (from 8.1 +/- 0.3 to 7.3 +/- 0.2%) and decreased by 0.3% in controls (from 8.0 +/- 0.2 to 7.7 +/- 0.3%).
Author Conclusion:
  • A high-protein diet lowers blood glucose postprandially in persons with type 2 diabetes and improves overall glucose control, with little change in insulin concentration
  • The metabolic changes can be attributed to the increase in protein or the decrease in carbohydrate content of the diet, or both, rather than other confounding factors.
Funding Source:
Reviewer Comments:
  • While this study has a small number of subjects (the subjects are really not representative of type 2 diabetes as they are untreated with medications)and lasts for a relatively short length of time, its strength lies in the study design: the diet intervention is well constructed, compliance measures are appropriate, and there is exquisite detail for outcome measures.
  • Because the energy increase in protein was compensated for by reduction in carbohydrate (to maintain weight stability), it's not possible to determine if higher protein or lower carbohydrate produced the significant changes
  • A limitation for the lipids is that patients appeared to be on lipid lowering agents and there is no comment as to whether or not they were changed, started, or stopped during the study.  In addition, ß-blockers/diuretics and duration are mentioned as control variables, but no further information is provided.
  • There is no discussion of type (e.g.: plant vs animal) of protein, or whether the total grams of protein were from all foods, or just high biological value foods) 
  • Erratum: mean 24-h integrated insulin area response for control diet was reported as high-protein diet
  • Cross reference Nuttall et al, J Clin Endocrinol Metab, 2003 for other hormone and metabolic results from this same study
  • No power calculations

 

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? No
3. Were study groups comparable? ???
  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? ???
  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? 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? 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? N/A
  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? 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)? ???
  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