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DM: Protein Amount (2014)

Citation:

Velázquez LL, Sil AMJ, Goycochea RMV, Torres TM, Castañeda LR. Effect of protein restriction diet on renal function and metabolic control in patients with type 2 diabetes: A randomized clinical trial. Nutr Hosp. 2008; 23: 141-147.

PubMed ID: 18449450
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To assess the effect of a low protein diet (LPD) on renal function and metabolic control in three sub-groups of patients with type 2 diabetes those with or without nephropathy.

Inclusion Criteria:
  • Provided written informed consent
  • Previously diagnosed type 2 diabetes with fasting blood glucose level greater than 126mg per dL or use of anti-diabetic medications and between the ages of 40 and 80 years
  • Urinary albumin excretion rate was measured and patients were classified as normoalbuminuria (UAER less than 30mg per 24 hours), microalbuminuria (UAER 30mg to 299mg per 24 hours) or macroalbuminuria (UAER greater than 300mg per 24 hours).
Exclusion Criteria:
  • Malignant hypertension
  • Previous history of congestive heart failure or myocardial infarction
  • Hepatic cirrhosis, cancer, severe obesity (body mass index 35kg/m2 or more)
  • Recurrent urinary infection
  • End-stage renal disease (glomerular filtration rate less than 15ml per minute)
  • No use of hypolipidemic agents.
Description of Study Protocol:

Recruitment

The patients were selected from a previous cross-sectional study conducted to find diabetic nephropathy presence in primary care units attended by the hospital.

Design

Randomized clinical trial.

Blinding Used

Implied with measurements.

Intervention

Subjects were randomized to one of two diets for four months:

  • Low-protein diet group (LPD) was instructed to decrease protein intake to 0.6g to 0.8g per kg weight per day
  • Normal-protein diet group (NPD)
  • The prescribed diets were designed according to BMI and gender of patients
  • The macronutrients were designated according to percentages of daily caloric intake (carbohydrates 50%, fat 30% and 20% protein).
  • Dietary estimations were performed according to recommendations of the American Diabetes Association (ADA) as closely as possible.

Statistical Analysis

  • Data are expressed as means ± standard deviation (SD)
  • Nominal variables were analyzed with chi square (X2) test to assess differences in prevalence among groups
  • Intergroup comparisons of UAER, GFR, variables of metabolic control, and lipid profile in the LPD and NPD groups were analyzed by unpaired T-tests while intragroup comparisons were performed by paired T-test
  • Differences were considered statistically significant when P<0.05
  • Statistical analysis was performed using SPSS version 11.0.
Data Collection Summary:

Timing of Measurements

  • The study was performed after a three-month intervention period
  • Measurements made at baseline and at four months.

 Dependent Variables

  • Body weight was measured in light-weight clothing on standard calibrated scales and stadiometers were used to measure height
  • Body mass index (BMI) was calculated by dividing weight in kg by squared height in meters (kg/m2)
  • Waist circumference was measured midway between the lower rib margin and the iliac crest
  • Systolic and diastolic blood pressure was measured three times with a mercury sphygmomanometer after the patient remained seated after five minutes; averages of the second and third determinations were used for analysis
  • Renal function and metabolic control: Fasting venous blood samples were obtained after a 12-hour fast, at baseline and at four months
  • Serum total glucose and lipid profile were analyzed with an automated instrument
  • LDL cholesterol was calculated by the Friedewald equation
  • Hemoglobin HbA1c was determined by an ion-exchange high-performance liquid chromatography procedure
  • Urinary albumin excretion (UAER) was measured by 24-hour timed sterile urine samples and analyzed by nephelometry. Urinary nitrogen was calculated by a formula [nitrogen intake =urinary urea nitrogen (urea/2)].
  • Glomerular filtration rate (GFR) was assessed using creatinine clearance
  • Protein intake was estimated from 24-hour urinary urea excretion by means of the Jaffe method.

Independent Variables 

Subjects were randomized to one of two diets for four months:

  • Low-protein diet group (LPD) was instructed to decrease protein intake to 0.6g to 0.8g per kg weight per day
  • Normal-protein diet group (NPD)
  • The prescribed diets were designed according to BMI and gender of patients
  • The macronutrients were designated according to percentages of daily caloric intake (carbohydrates 50%, fat 30%, and 20% protein)
  • Dietary estimations were performed according to recommendations of the American Diabetes Association (ADA) as closely as possible
  • Customary diet and economical food resources were identified by a dietitian and a food frequency questionnaire was applied as well as 24-hour recalls to adjust nutritional therapy.
Description of Actual Data Sample:
  • Initial N: 69 patients eligible, 60 were randomized (22 women and seven men in the low protein diet group and 14 women and 17 men in the normal protein diet group)
  • Attrition (final N): 60 subjects included in the analysis
  • Age:
    • Mean age in the LPD group: 68±9.3 years
    • Mean age in the normal protein diet group: 60.3±10.1 years
  • Other relevant demographics: Known duration of diabetes:
    • LPD group: 18.7±8.8 years
    • Normal protein diet group: 15.0±9.0 years.
  • Anthropometrics: Those in the LPD group were significantly older and the proportion of patients with hypertension was significantly higher as well. The LPD group had a higher proportion of women and longer diabetes-evolution time, but these differences were not statistically significant.  
  • Location: Mexico City.

 

 

 

 

Summary of Results:

Key Findings

  • Daily protein intake was significantly lower in the LPD group (0.82g±0.36g per kg weight vs. 1.2g±0.48g per kg weight; P<0.05)
  • In LPD-group normoalbuminuric patients, fasting blood glucose was significantly reduced after four months (156.3mg±51.7mg to 95.3mg±35.8mg per dL; P<0.05)
  • Subjects with microalbuminuria had significant decreases in HbA1c after the intervention period in both groups (LPD: 8.2%±1.6% to 7.2%±1.8%; P<0.05 and NPD, 8.8%±1.9% to 7.1%±0.8%, P<0.05), as well as macroalbuminuric patients who received the NPD (8.1%±1.8% to 6.9%±1.6%, P<0.05)
  • In normoalbuminuric and microalbuminuric patients, there were no significant changes in UAER or GFR after either diet
  • However, renal function improved among patients with macroalbuminuria who received the LPD, as UAER decreased (1,280.7mg±1,139.7mg to 444.4mg±329.8mg per 24 hours; P<0.05) and GFR increased (56.3ml±29.0ml to 74.2ml±40.4ml per minute; P<0.05).
Author Conclusion:

Moderate protein restriction in patients with type 2 diabetes and macroalbuminuria can delay the progression of diabetic renal disease. We consider that in patients with normoalbuminuria and microalbuminuria, the effect of the protein-restriction in the diet should be confirmed in a long-term study.

Funding Source:
Other: Promotion Fund of the Mexican Institute of Social Security grant IMSS-2004/205
Reviewer Comments:
  • It is unclear whether there were any dropouts from the study with 60 randomized and also in the analysis.
  • Small numbers of subjects in the groups of patients classified as having normoalbuminuria (UAER less than 30mg per 24 hours), microalbuminuria (UAER 30mg to 299mg per 24 hours) or macroalbuminuria (UAER more than 300mg per 24 hours)
  • Those in the LPD group were significantly older and the proportion of patients with hypertension was significantly higher as well.
  • The LPD group had a higher proportion of women and longer diabetes-evolution time, but these differences were not statistically significant.
  • Nonetheless, statistical analyses adjusted to the previous mentioned variables were not statistically significant when comparing both groups.
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? ???
  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? ???
  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%.) ???
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? ???
  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? Yes
  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? 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? ???
  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)? ???
  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