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

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.

Inclusion Criteria:

Type 2 diabetic adults with the absence of renal disease other than diabetic nephropathy.

Exclusion Criteria:
  • Non-type 2 diabetics
  • Renal disease other than diabetic nephropathy
  • Use of medication other than insulin, oral hyperglycemic agents and anti-hypertensive agents.
Description of Study Protocol:

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. 
Data Collection Summary:

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.

 

 

Description of Actual Data Sample:
  • 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.
Summary of Results:

 

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
(0.49-2.5)

0.76b 
(0.29-1.6)

0.57c
(0.26-1.1)

 Statistically significant differences after first, second and third treatment periods
C-IgG

0.74
(0.67-3.1)

0.56a
(0.35-0.2)

0.36b
(0.19-1.2)

0.24c
(0.11-1.1)

 Statistically significant differences after first, second and third treatment periods
C-Ceruloplasmin

 2.9
(1.6-7.2)

1.8a
(0.8-4.0)

1.5b
(0.47-2.6)

0.92c
(0.15-1.9)

 Statistically significant differences after first, second and third treatment periods
C-a2-Macroglobulin

 43
(19-110)

23
(11-120)

19
(6.0-52)

 11c
(7.4-44)

 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.

Author Conclusion:

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.  

Funding Source:
University/Hospital: Akita University Hospital
Reviewer Comments:
  • 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
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