EAL

DM: Protein (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To compare hormone and metabolic effects after 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 certain hormones and metabolites 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 on a 6-day rotating cycle for outpatient consumption

Statistical Analysis

Student's t test for paired variates, or Wilcoxon's rank sum
net 24-h area responses calculated based on the 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

total alpha-amino nitrogen: total concentration (method of Goodwin)
plasma TSH: Abbott Architect (IL)
GH: Quest (MN)
B12 and folate: chemiluminescence
Total T3 and free T4: chemiflex
IGF-1: RIA (Quest)
Homocysteine:HPLC
Urinary free cortisol: HPLC purification step followed by a cortisol binding assay (method specific for cortisol
Urinary aldosterone: RIA
Urinary calcium and magnesium: atomic absorption spectrophotometry
Urinary phosphorus: colorimetry (J&J Vitros instrument)
oxidized protein: calculated from 24-h urine urea nitrogen excretion and total body water

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 on a 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
creatinine and urea nitrogen as dietary compliance measures: automated method from Ortho-Clinical Diagnostics

Description of Actual Data Sample:

Initial N: 12 (10 males, 2 females)

Attrition (final N): 12

Age: mean of 61 (range 39-79)

Ethnicity: not reported

Other relevant demographics: none provided

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

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

Summary of Results:

Other Findings

Urinary free cortisol increased significantly on the high protein compared to the control diet by Wilcoxon (P<0.02) but not by Student's t-test
aldosterone and 24-h calcium excretion remained unchanged
serum TSH, free T4 and total T3 were unchanged, indicating that lower carbohydrate doesn't affect thyroid function.
serum IGF-1 increased significantly on the high protein compared to the control diet (p < 0.05)
serum GH increased nonsignificantly on the high protein diet vs the control diet
serum B12, folate, homocysteine, uric acid and creatinine concentrations were unchanged
While calcium intake increased by 400 mg on the high protein diet, there was no significant difference in urine calcium values between the diets. This indicates that high protein might not affect bone mass
Urinary phosphorus and magnesium showed the same trends as calcium
Increasing the protein content of the diet from 15 to 30% of food energy raised the plasma urea nitrogen, increased urea nitrogen excretion as expected, and urea concentration correlated with an increased total amino acid concentration during the day, indicating excellent compliance
None of the subjects lost or gained > 1 kg with either diet.
The plasma postprandial alpha amino nitrogen concentrations were increased and the 24-h integrated concentration was 2-fold greater on the 30% protein diet; however, the absolute areas over 24-h were similar between the diets (because of the more rapid decrease overnight on the 30% protein diet) indicating an accelerated amino acid removal rate
The calculated urea production rate accounted for 97% of the protein ingested on the 15% protein diet, but only 80% on the 30% diet, suggesting net nitrogen retention on the high protein diet

Author Conclusion:

An increase in dietary protein of the diet from 15 to 30% of food energy in people with untreated, type 2 diabetes, resulted in a number of metabolic adaptations.

Funding Source:

Government:

Dept. of Veterans Affairs

Industry:

Minnesota Beef Council, Colorado and Nebraska Councils

Commodity Group:

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Cross reference Gannon et al, Am J Clin Nutr 2003, for glycemic, insulinemic and lipid results from this same study
While this study has a small number of subjects (and subjects are 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 measuressmall number of subjects; short length of time
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.
There was no discussion of subject medications/OTC supplements or changes in same (e.g.: calcium)
The diet wasn't controlled for calcium, phosphorus or magnesium, so results in this area should be interpreted with caution.
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