DM: Protein (2007)
To determine if protein restriction beneficially influences glomerular filtration rate (GFR) and albumin excretion rate (AER) and thus plays a role in the prevention or delay of renal disorders in type 2 diabetes mellitus
- type 2 diabetes mellitus.
- microalbuminuria (30-300 Mg/24 h) or detectable albuminuria (> 20 mg/24 h) or diabetes duration > 5 years.
- age <79 years
- Baseline protein intake < 0.8 g/kg/d
- Low compliance in keeping prestudy appointments
- In a period of recovery from severe morbidity
- Protein-losing enteropathy, venous leg/pressureulcer, malignancy, psychiatric/serious psychosocial problems
- Clinically obvious nephropathy
- Reluctant to change diet or to understand diet information
Recruitment
46 general practitioners selected all their patients with type 2 diabetes who met inclusion criteria and not exclusion criteria.
Design
Comparison of a protein-restricted diet (0.8g/kg/d) vs usual dietary guidelines (The Netherlands guidelines) in patients with type 2 diabetes at baseline and every six months (average of 28 months), with primary outcome measures being GFR and AER.
Blinding used (if applicable)
Physician-blinded
Intervention (if applicable)
Both groups received baseline counseling from a dietitian on usual dietary guidelines, focusing on restriction of saturated fat; during the study both groups were provided the same "amount of attention"
Only the protein restricted diet group received information about how to decrease dietary protein intake to 0.8 g/kg/d by partially replacing it, isocalorically, with unsaturated fat and carbohydrates (especially dietary fiber).
Intervention included 30 min meetings with the dietitian at months 1 and 3 after baseline, and then every 3 months till end of study. Consultation included feedback based on repeated dietary interviews and on protein intake estimated from 3-month measurements of 24h urinary urea excretion. Subjects were provided individually designed daily menus, plus variation lists indicating foods that contain equivalent amounts of protein, and a food composition table and recipes (note: not clear if this is just for the protein restricted group, or for both groups)
General practitioners continued to be responsible for treatment of diabetes and medications.
Statistical Analysis
- 2-sided t-test (for differences between the 2 study groups
- x2-test (difference in categorical variables)
- Intention-to-treat analysis
- Best-case analyses
- Note: no power calculations provided
Timing of Measurements
Baseline, 1 month, 3 months, and then every 3 months until end of study
Dependent Variables
- GFR (cimetidine-influenced creatinine clearance as an estimate)
- AER (Beckman Instruments)
Independent Variables
-
Comparison of a protein-restricted diet (0.8g/kg/d) vs usual dietary guidelines (The Netherlands guidelines) in patients with type 2 diabetes at baseline and every six months (average of 28 months), with primary outcome measures being GFR and AER.
- Both groups received baseline counseling from a dietitian on usual dietary guidelines, focusing on restriction of saturated fat; during the study both groups were provided the same "amount of attention"
- Only the protein restricted diet group received information about how to decrease dietary protein intake to 0.8 g/kg/d by partially replacing it, isocalorically, with unsaturated fat and carbohydrates (especially dietary fiber).
- Intervention included 30 min meetings with the dietitian at months 1 and 3 after baseline, and then every 3 months till end of study. Consultation included feedback based on repeated dietary interviews and on protein intake estimated from 3-month measurements of 24h urinary urea excretion. Subjects were provided individually designed daily menus, plus variation lists indicating foods that contain equivalent amounts of protein, and a food composition table and recipes (note: not clear if this is just for the protein restricted group, or for both groups)
- General practitioners continued to be responsible for treatment of diabetes
Control Variables
- Date of diabetes diagnosis
- Ethnic origin
- Gender
- 24-h urinary urea (BM/Hitachi 747/737) + Maroni formula to estimate compliance with protein intake
- Systolic and diastolic blood pressure (mean of second and third reading;Hawksley random-zero meter)
- use of medications
- HbA1c
Initial N: 160: 81 protein-restricted diet (47 men, 34 women); 79 usual diet (41 men, 38 women)
Attrition (final N):
- 131 completed a follow-up of at least 12 months: 63 protein-restrictied diet (40 men, 23 women); 68 usual diet (36 men, 32 women). Gender difference is nonsignificant (p=0.19)
- 94 with complete 24-m follow-up: 50 protein-restricted diet; 44 usual diet
Age: mean 63-65 ± 8yrs
Ethnicity: caucasian except for 2 non-caucasian in each group at baseline
Other relevant demographics: duration of diabetes (6.7 yrs for protein restricted diet-; 7.2 for usual diet)
Anthropometrics : weight (81 kg, both groups); BMI (27.4 for protein restricted diet; 28.2 for usual diet);
Location: Amsterdam, The Netherlands
Variables |
Protein-restricted diet group, baseline n= 131 mean±SD or geometric mean with 25th and 75th percentiles |
Protein-restricted diet group, 24 mo n= 94 mean±SD |
Usual diet group, baseline n= 131 mean±SD or geometric mean with 25th and 75th percentiles
|
Usual diet group 24 mo n= 94 mean±SD |
Dietary protein intake (g/kg/d) |
1.18±0.24 |
1.11+0.20 |
1.15±0.26 |
1.19+0.29 |
GFR (ml/min/1.73m2) |
82±19 |
74 |
85±23 |
75 |
AER (mg/24 h) |
21.2 (10,41) |
16 |
20.5 (8,42) |
14 |
Other Findings
- Average duration of intervention and follow-up was 28 +/- 7 months.
- At 6 months, albuminuria decreased in the experimental group by 12% (0.08 g/kg/day) and increased in the control group by 16% (p = 0.02) but at 12 months there were no differences.
- After first six months, annual decline in GFR in protein-restricted diet group was 4.8±12 ml/min/1.732; in the usual diet group, 6.46±14 (NS). Effect estimate not influenced by adjustment for baseline levels of GFR, albuminuria, blood pressure, age, gender, use of ACE inhibitors, or duration of follow-up
- Best-case analysis (patients in protein-restricted diet group with at least 0.20 g/kg/d decrease in protein intake; patients in usual diet group with no decrease) did not indicate a slower rate of decline in GFR in the experimental group compared to the control group.
- Intention to treat analysis showed no clear effect on GFR (because no substantial protein restriction was achieved)
- In patients with type 2 diabetes and no clinically obvious nephropathy, protein restriction for an average period of 28 months is neither feasible nor efficacious
- It is very unlikely that, had substantial protein restriction been achieved, an effect on renal function would have been observed.
University/Hospital: | Vrije University, University of Maastricht |
- No power calculations provided in statistics section
- Less than 60% of subjects completed the 24 month follow-up
- Subjects did not (were not able to) decrease protein intake, even with good nutrition education techniques. Consequently even use of specialized statistics (intention-to-treat and best-case analysis) did not show a beneficial effect on GFR/AER of protein reduction.
- Cross-reference other articles about this study:
- published baseline and 6 and 12 mo data (Pijls LTJ et al, Nephrology Dialysis Transplantation 1999;14:1445-1453)
- compliance data (Pijls LTJ et al, Eur J Clin Nutr 2000;54:347-352)
- determinants of albuminuria (Pijls LTJ et al, Diabetes Res Clin Pract 2001;52:133-143)
Quality Criteria Checklist: Primary Research
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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.) | N/A | |
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? | Yes | |
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.) | No | |
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? | ??? | |
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)? | Yes | |
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 | |