DM: Prevention and Treatment of CVD (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To meaure the effect of sodium intake on blood pressure and albumin excretion rate (AER) in type 2 diabetic patients with and without microalbuminuria; and to determine any possible relationship with insulin sensitivity.
Inclusion Criteria:
  • type 2 diabetes
  • persistent microalbumiuria
  • blood pressure below 140/90 mmHg in the absence of antihypertensive treatment
Exclusion Criteria:
None specifically mentioned.
Description of Study Protocol:

Recruitment:   20 subjects recruited from a diabetes clinic at a university hospital;  an additional 21 subjects matched for age, sex, BMI, duration of diabetes, and blood pressure, but with normal albumin excretion were also recruited.

Design :  Randomized Crossover Trial - all subjects underwent, in random order, two consecutive 7-day periods with low or high sodium content. 

Blinding used (if applicable): not blinded; subjects on the high-sodium diet received sodium tablets. 

Intervention (if applicable):

  • low sodium diet:  25 mmol NaCl, 60 mmol potassium, 20 mmol calcium
  • high sodium diet:  exactly the same, except that subjects received 250 mmol NaCl, with added sodium in the form of 500 mg sodium chloride tablets

Statistical Analysis

  • mean blood pressure calculated as diastolic values plus one third of the difference between systolic and diastolic blood pressure
  • all data expressed as means ± SEM
  • for AER the values are expressed as median with the 25th and 75th percentiles, unless
  • differences between means of parameters within groups were tested for significance using the paired t test or analysis of variance
  • between group differences were assessed using the unpaired t test
  • linear regression analysis was done to determine the correlation between different parameters

 

Data Collection Summary:

Timing of Measurements: 

  • 24-hour urinary sodium excretion during last 3 days of each diet period
  • in 9 patients with and 9 without microalbuminuria insulin sensitivity and kidney function were measured at the end of the high-sodium diet 

Dependent Variables

  • blood pressure; 24-hour ambulatory blood pressure measurements obtained using a Takeda device
  • whole body insulin sensitivity, using the euglycemic, hyperinsulinemic clamp technique
  • glomerular filtration rate and effective renal plasma flow were measured by plasma clearances of Cr-EDTA and para-aminohippurate
  • plasma free insulin, renin activity, aldosterone, and urinary albumin concentrations; measured by flame photometry

Independent Variables

  • high or low sodium diet
  • compliance was assessed by 24-hour urinary sodium excretion

Control Variables

 

Description of Actual Data Sample:

Initial N:  20 patients with microalbuminuria and 21 patients without microalbuminuria; 31 men, 10 women

Attrition (final N): 41

Age: 56 - 62 years

Ethnicity: not specified

Other relevant demographics: mean duration of diabetes 9-10 years; no significant differences between groups

Anthropometrics mean BMI 28-29 years

Location: Italy

 

Summary of Results:

Other Findings

  • At the end of each diet period there was no difference between the two groups in mean 24-h urinary sodium excretion, potassium excretion, plasma aldosterone concentrations, or renin activity.
  • After switching to the high sodium diets, subjects with microalbuminuria showed a significant increase in 24-h mean arterial blood pressure (7.1% increase, P<0.0001), but no significant change occurred in subjects with normoalbuminuria
  • a significant increase is urinary AER occured in microalbuminuric subjects during the high-salt period, from 80-108 (P<0.001), but no change occured in normoalbuminuric subjects
  • after the high-salt diet GFR values were comparable in the two groups
  • during the euglycemic hyperinsulinemic clamp, whole-body glucose disposal was lower in the microalbuminuric group (p=0.007).
  • When data were pooled, salt-induced changes in 24-h mean blood pressure were directly related to the increase in AER observed after a high-sodium diet (r=0.41; p=0.008).
  • The interglomerular pressure (PGC) calculated at the end of the high-salt diet was directly associated with AER (r=0.40; p=0.009).
  • Salt-induced changes in mean blood pressure (r=-0.59; p=0.01) were inversely related to insulin sensitivity.

 

Author Conclusion:

After a high-sodium diet microalbuminuric type 2 diabetic patients have a blood pressure which is sensitive to salt intake and an increased AER.  These features are strongly associated with greater insulin resistance.

Sensitivity of blood pressure to salt may be an intermediate phenotype which could prove useful in identifying type 2 diabetic patients at increased risk for cardiorenal complications.  The results provide further support for encouraging type 2 diabetic patients with microalbuminuria to decrease salt intake.

Funding Source:
Reviewer Comments:

Only 9 of the 20 microalbuminuric subjects and only 9 of the 21 normoalbuminuric subjects were tested for insulin sensitivity and kidney function at the end of the high-salt diet - cannot use these findings.

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? No
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) No
  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? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  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.) 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? 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? N/A
  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? No
  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? No
  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)? N/A
  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? No
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