EAL

DM: Prevention and Treatment of CVD (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine the effect of a high-protein (HP) diet compared to a lower-protein (LP) diet on insulin sensitivity and changes in body composition in subjects with type 2 diabetes during energy restriction, and during energy balance after weight loss.

Inclusion Criteria:

type 2 diabetes

Exclusion Criteria:

proteinuria

Description of Study Protocol:

Recruitment

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Design

Comparison, by diet (high protein vs lower protein), of insulin sensitivity and body composition at 0 and 8 weeks (weight loss period) and after a further 4 weeks (weight stable period) in individuals with type 2 diabetes

Blinding used (if applicable)

None described

Intervention (if applicable)

High protein diet: 30% energy from protein, 40% from carbohydrate, and matched for fatty acid profile (8% saturated, 12% mono, 5% poly)
Lower protein diet: 15% energy from protein, 60% from carbohydrate, and matched for fatty acid profile (8% saturated, 12% mono, 5% poly)
First eight weeks (weight loss period) kcal were restricted to 1600; during the last 4 weeks, caloric intake was increased by 30%, and protein was increased by 7 g in the LP diet and 21 g in the HP diet.
Foods were eaten on an outpatient basis, with fixed menu plans, and with subjects receiving preweighed key foods (about 60% of energy intake)
Meeting every two weeks with research dietitian for dietary instructions/assessment

Statistical Analysis

repeated measures ANOVA
one-way ANOVA (baseline differences between diets and men and women)
no power calculations

Data Collection Summary:

Timing of Measurements

Baseline (0), 8, and 12 weeks

Dependent Variables

Fat amount and distribution: dual-energy X-ray absorptiometry (DEXA), wks 0 and 12
Insulin sensitivity: continuous low-dose glucose (SSPG) and insulin (SSPI) infusion test (3 hr) for steady-state plasma glucose and insulin (refinement of a modified Harano test), weeks 0 and 12
Fasting plasma glucose: enzymatic kit/Cobas-Bio analyzer
Fasting serum total cholesterol: enzymatic kit/Cobas-Bio analyzer
Fasting serum triacylglycerol: enzymatic kit/Cobas-Bio analyzer
Fasting plasma HDL cholesterol: precipitation of LDL and VLDL/Cobas-Bio analyzer
LDL cholesterol: calculated with a modified Friedewald equation
Fasting insulin: radioimmunoassay kit (Pharmacia & Upjohn Diagnostics)
HbA1c: high-performance liquid chromatography

Independent Variables

High protein diet: 30% energy from protein, 40% from carbohydrate, and matched for fatty acid profile (8% saturated, 12% mono, 5% poly)
Lower protein diet: 15% energy from protein, 60% from carbohydrate, and matched for fatty acid profile (8% saturated, 12% mono, 5% poly)
First eight weeks (weight loss period) kcal were restricted to 1600; during the last 4 weeks, caloric intake was increased by 30%, and protein was increased by 7 g in the LP diet and 21 g in the HP diet.
Foods were eaten on an outpatient basis, with fixed menu plans, and with subjects receiving preweighed key foods (about 60% of energy intake)
Meeting every two weeks with research dietitian for dietary instructions/assessment
Food records, 3 consecutive days (2 weekdays, 1 weekend day) every 2 weeks: Diet/1 Nutrition Calculation software, (Xyris Software, 1998)
physical activity: 24-hr activity recall
alcohol (subjects asked not do drink during the study

Control Variables

type 2 diabetes
age
gender
Urine urea and creatinine from 24-h urine collections: Hitachi autoanalyzer (Roche)
medications
blood pressure

Description of Actual Data Sample:

Initial N: 66

Attrition (final N): 54 (19 men, 35 women). 18% dropout rate. 2 subjects withdrew before commencement. 10 subjects (5 from each diet group) withdrew throughout the study.

Age: men, 64 yrs; women, 60 y. 26 on HP diet, 28 on LP diet.

Ethnicity: not provided

Other relevant demographics: none provided

Anthropometrics: Authors indicate no significant differences between variables (age, BMI, weight, glucose, insulin, SBP, DBP) by diet for men or women at baseline

Location: CSIRO Health Sciences and Nutrition, Adelaide, Australia

Summary of Results:

HP Diet LP Diet

Variables^*	0 wk mean±SEM	8 wk mean±SEM	12wk mean±SEM	0 wk mean±SEM	8 wk mean±SEM	12 wk mean±SEM	Difference between diets
Weight (kg)	97.7±17.4	93.2±16.7	92.2±16.8	91.4±18.2	86.9±16.9	86.6±16.8	NS
Fat mass (men)	38.7±5.0		35.5±2.6	34.8±5.2		30.4±2.4	NS
Fat mass (women)	42.8±2.6		37.5±2.5	39.9±3.2		37.0±3.1	p<0.05
Fasting glucose	8.44±0.41	7.30±0.28	7.70±0.31	7.76±0.24	7.02±0.21	7.33±0.30	NS
Fasting insulin	16.3±7.2	12.1±6.5	13.3±6.8	16.5±7.7	14.0±10.8	14.8±9.2	NS
HbA1c	6.42±0.83		5.88±0.78	6.30±0.77		5.79±0.59	NS
Total cholesterol	5.16±0.17	4.64±0.18	4.81±0.16	5.16±0.25	4.82±0.22	5.15±0.25	p<0.01
Triglyceride	2.02±0.15	1.56±0.13	1.68±0.14	2.17±0.21	1.76±0.11	1.94±0.16	NS
LDL chol	3.32±0.16	3.02±0.15	3.13±0.15	3.23±0.20	3.12±0.20	3.32±0.22	p<0.05
HDL chol	0.93±0.03	0.92±0.03	0.92±0.04	0.95±0.05	0.91±0.04	0.96±0.03	NS

*while units were not provided, fat mass is probably kg; fasting insulin is mU/L, HbA1c is %, and fasting glucose and lipids are all mmol/L

Other Findings

Dietary fiber was significantly lower and dietary cholesterol, significantly higher on the high protein diet compared to the lower protein diet
Urinary urea/creatinine ratio was significantly different between diets, indicating good dietary compliance. Dietary records also indicated good compliance (HP = 28% protein, 42% carbohydrate, 28% fat; LP = 16% protein, 55% carbohydrate, 26% fat)
There was a significant sex by diet interaction for
- total fat mass (women lost more on the HP diet whereas men lost more on the LP diet, p=0.01
- abdominal fat mass (women lost more on the HP diet whereas men lost more on the LP diet, p<0.02
Total lean mass was reduced significantly (2.1%) with both diets, NS between diets
SSPG concentrations decreased significantly from baseline to week 12 (12.1 to 10.7 mmol/l, p= 0.01), NS between diets; the same was true for SSPI (523 to 428 pmol/l, p=0.003) with no effect of diet or sex
SBP fell significantly by 8 mmHg and DBP by 4 mmHg at week 8 (p<0.01), NS between diets. During weight stabilization period, SBP rose by 3 mmHg and DBP by 1 mmHg (p<0.001)
Decreases in glucose lowering medications occurred in 5 subjects from the HP diet group and 3 from the LP group; antihypertensive and lipid-lowering medication doses as well as exercise levels remained the same throughout the study.

Author Conclusion:

Both dietary patterns resulted in improvements in the CVD risk profile as a consequence of weight loss

A HP diet resulted in greater reductions in total and abdominal fat mass in women and greater LDL-c reduction in both sexes, and suggest it is a valid diet choice for reducing CVD risk in type 2 diabetes.

Funding Source:

Industry:

Meadow Lea Foods

Food Company:

Reviewer Comments:

18% dropout rate
Demographics of subjects not well described
The strengths of this study include dietary compliance measures, consideration of a number of covariates/confounders, and multivariate analyses (e.g.: comparison of outcomes by sex/diet).
Because the energy increase in protein was compensated for by a reduction in carbohydrate, it's not possible to determine if higher protein or lower carbohydrate produced the significant changes.
Power calculations were not provided, so it may be that there were not enough subjects

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?		???
	4.1.	Were follow-up methods described and the same for all groups?	???
	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?	???
	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)?	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