The purpose of this study was to see if patients with type 2 diabetes with microalbuminuria would have changes in constituents of proteinuria and renal hemodynamics after additive combination therapy of glycemic control, low protein diet (LPD) and ACE inhibitors.
Type 2 diabetic adults with the absence of renal disease other than diabetic nephropathy.
- Non-type 2 diabetics
- Renal disease other than diabetic nephropathy
- Use of medication other than insulin, oral hyperglycemic agents and anti-hypertensive agents.
Recruitment
Subjects were recruited from the hospital during the study.
Design
10 type 2 diabetics with microalbuminuria (seven males, three females; Group Mic).
After hospitalization, patients in Group Mic were placed on a diabetic diet and individualized medication (insulin or oral anti-hyperglycemic agents) for one to three weeks to achieve glycemic control (GC). Once the subjects achieved blood glucose control, they were placed on a low protein diet (0.7gm of protein per kilogram per day) for one week (GC+LPD). Thereafter, the patients were also given a one-week administration of enalapril (GC+LPD+ACEI).
Statistical Analysis
- Values were expressed as mean values ±SD or median with range
- To test for differences among three groups or repeated values in each individual, the Kruskal-Wallis test or the repeated Friedman test were used, respectively
- After multiple comparisons revealed a significant difference, statistically significant differences between two groups or two repeated values in each individual were calculated using the Mann-Whitney test or the Wicoxon signed-ranks test, respectively.
Timing of Measurements
24-hour urine samples and blood samples taken in a fasting state were collected from all subjects on the first day of the GC period and the last day of each therapy.
Dependent Variables
Albumin (Alb), IgG, ceruloplasmin (CRL), alpha2-macroglobulin (a2), creatinine and urea nitrogen, 24-hour creatinine clearance (Ccr), the 24-hour renal clearance of each plasma protein (Alb, IgG, CRL, a2) and the protein intake.
Independent Variables
- (GC): Diabetic diet and individualized medication (insulin/oral antihyperglycemic agents) for one to three weeks to achieve glycemic control
- (GC+LPD): Once the subjects achieved blood glucose control, they were placed on a low protein diet (0.7 grams of protein per kilogram per day) for one week
- (GC+LPD+ACEI): Thereafter, the patients were also given a one-week administration of enalapril.
- Initial N: 10 (seven males, three females)
- Attrition (final N): Three of the 10 patients left the hospital before the third period had been completed because of their individual circumstances (final N=7)
- Age: 63.1±5.31 years
- Ethnicity: Likely Japanese secondary to location of study
- Other relevant demographics:
- Four had hypertension, average BP was: 127±21.1 / 70.2±8.7
- Total cholesterol: 204.5±55.3
- HDL cholesterol: 52.1±12.3
- Triglycerides: 109.4±43.8
- HgtA1c: 9.3±1.3.
- Anthropometrics: BMI=24.6±5.9
- Location: Akita University Hospital, Akita, Japan.
Type 2 DM Patients with Microalbuminuria |
Baseline (N=10) | After GC (N=10) | After GC+LPD (N=10) | After GC+LPD+ACEI (N=7) | Significance |
Creatinine Clearance |
108±12.8 |
90±13.3a
|
86.1±9.8
|
73.20.1c
|
Statistically significant differences after first and third treatment period |
C-Albumin |
2.2
(0.81-4.4) |
0.89a |
0.76b |
0.57c |
Statistically significant differences after first, second and third treatment periods |
C-IgG |
0.74 |
0.56a |
0.36b |
0.24c |
Statistically significant differences after first, second and third treatment periods |
C-Ceruloplasmin |
2.9 |
1.8a |
1.5b |
0.92c |
Statistically significant differences after first, second and third treatment periods |
C-a2-Macroglobulin |
43 |
23 |
19 |
11c |
Statistically significant differences after third treatment period |
aP<0.05 when compared to baseline values
bP<0.05 when compared with values after glycemic control therapy
cP<0.05 when compared with values after the combination therapy of glycemic control and low protein diet.
The findings suggest that each of three short-term therapies consisting of GC, GC+LPD and GC+LPD+ACEI reduced proteinuria in microalbuminuric type 2 DM patients not through the improvement of renal size and charge selectivities, but through improvement of renal hemodynamics.
University/Hospital: | Akita University Hospital |
- The sample size was small. No control group.
- For the purpose of CKD project, the period three (GC+LPD+ACEI) is not of interest.
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? | No | |
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? | No | |
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? | No | |
3.1. | Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) | N/A | |
3.2. | Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? | No | |
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? | 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? | No | |
6.1. | In RCT or other intervention trial, were protocols described for all regimens studied? | N/A | |
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? | No | |
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? | No | |
6.6. | Were extra or unplanned treatments described? | No | |
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? | No | |
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)? | 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? | No | |
10. | Is bias due to study's funding or sponsorship unlikely? | Yes | |
10.1. | Were sources of funding and investigators' affiliations described? | No | |
10.2. | Was the study free from apparent conflict of interest? | Yes | |