DM: Protein Amount (2014)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

The purpose of this study was to determine the effect of moderate dietary protein restriction on the progression of renal disease in a cohort of individuals with type 1 diabetes with diabetic nephropathy over a 6-month period.

 

 

Inclusion Criteria:

1. Type 1 diabetes mellitus for >=10 yr

2. Proteinuria for >=2 yr

3. Presence of diabetic retinopathy

Exclusion Criteria:
Additional renal, urinary tract or cardiac causes for persistent proteinuria.
Description of Study Protocol:

Recruitment:  Subjects attending the renal diabetic clinical Johannesburg Hospital, South Africa were asked to participate.

Design:

Subjects were randomly assigned to an unrestricted protein diet (UPD)(>1.6 g/kg) or moderately restricted protein diet (LPD)(0.8 g/kg). Data collected at baseline and at 6 months.

Blinding Used (if applicable):  not specified

Intervention (if applicable):

  • Individuals were assessed by the same nutritionist at the start of the study at 3 and 6 months later.
  • Usual Protein Group:  ate their usual diets.  Subjects with a low protein intake at the start of the study were asked to increase their protein intake to 1.6 gm/kg/day/.
  • Low Protein Group:  consumed an isoenergetic diet containing 0.8 g/kg/day protein.
  • no distinctions made between animal and plant proteins.
  • subjects were instructed on study diets and individualized based on usual food intake.
  • no attempt was made to improve glycemic control

Statistical Analysis: 

  • Student's  t test used for comprisons between groups
  • changes within each group were compared using analyis of variance or Student's t tests
  • Wilcoxon rank-sum test and signed-rank test used for nonparametric data where appropriate
  • urine protein and albumin excretion reslults were logarithmetically transformed befor statistical analyis because of their positively skewed distribution

 

Data Collection Summary:

Timing of Measurements:

  • GFR: Determined using 51Cr-labeled EDTA injection
  • blood sampling at 5, 10, 20, 30, 60, 120, 180 and 240 minutes.

 Dependent Variables:

  • GFR
  • urinary albumin excretion
  • blood pressure
  • glycemic control

Independent Variables

  • Usual Protein Group:  ate their usual diets.  Subjects with a low protein intake at the start of the study were asked to increase their protein intake to 1.6 gm/kg/day/.
  • Low Protein Group:  consumed an isoenergetic diet containing 0.8 g/kg/day protein.
  • Compliance assessed by
    • comprehensive diet recall
    • Monitoring of protein intake: calculated from total urea nitrogen as measured in a 24-h urine collection.

 Control Variables:  not specified

Description of Actual Data Sample:

Initial N:  26

Final N:  22 subjects (11 in each group) completed the study—3 subjects were unable to comply with the study protocol and 1 subject was killed in an auto accident.

Age and Anthropometrics:

  LPD n=11 UPD n=11
Age, yr 30 29
BMI 23.8 26.0
Duration of Diabetes, yr 4 4

Ethnicity:  white

Location:  South Africa

Summary of Results:

Proteinuria and GFR

Patients consuming the UPD showed a progressive decrease in GFR of 1.3 ml/min/mo with no change in proteinuria.

Patients consuming the LPD showed a marked decrease in the degree of proteinuria (2.15-1.13 g/d, P=0.036) and a stabilization of GFR.

Urine urea protein:

Over the 6 month study period, urinary urea protein increased in the UPD group (425±136 to 720±122 mmol/d) (P=0.0004) and decreased in the LPD group (385±138 to 276±57 mmol/d ) (P<0.032).

Dietary assessment:

Protein intake was an average of data from 3 and 6 months:

  Baseline g/kg 3 + 6 months g/kg Significance
UPD 1.33 2.00 (P<0.0001)
LPD 1.13 0.87  (P=0.12)

Changes in GFR:

 

Baseline

ml/min/1.73m2

3 + 6 months

ml/min/1.73m2

Significance
UPD 66±28 58±26 (P<0.01)
LPD 50±19 53±23 NS

Changes in urinary albumin excretion:

 

Baseline

mg/24 hour

3 + 6 months

mg/24 hour

Significance
UPD 1167 1475 (P<0.01)
LPD 884 815 (P=0.036)

HbA1c

Glycemic control in these subjects showed a slight improvement over the study period (UPD from 13.9±2.4 to 12.4±5.5 and LPD from 12.0±3.4 to 11.7±4.6, normal range 4% to 8%).

Blood pressure:

Subjects in this study were hypertensive and there were no differences by time or group.

6 months study period

 

systolic

mm Hg

diastolic

mm Hg

MAP

mm Hg

UPD 139±11 86±9 104±9
LPD 140±12 91±6 107±7

Author Conclusion:

Patients consuming the moderately restricted protein diet (0.8 g/kg) showed a marked decrease in the degree of proteinuria, and a stabilization of GFR independently of blood pressure or glycemic control.

Moderate dietary protein restriction can ameliorate progression of overt diabetic nephropathy.

Funding Source:
Government: South African Medical Research Council
Industry:
Eli Lilly
Pharmaceutical/Dietary Supplement Company:
Reviewer Comments:
Well-controlled study that showed stabilization of GFR in subjects on LPD compared to UPD. Subjects in this study were younger and with a shorter duration of diabetes than the majority of similar studies.
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? Yes
  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? Yes
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? 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? Yes
  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? 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)? No
  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? 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