Weight Management

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To compare the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria.
Inclusion Criteria:
Inclusion criteria not described.
Exclusion Criteria:
  • Normoalbuminuria
  • Macroalbuminuria
  • Stimulated serum C-peptide levels < 600 pmol/L
Description of Study Protocol:

Recruitment

Methods not described. 

Design:  Randomized Controlled Trial.  Randomization was performed with the use of sealed envelopes.

Blinding used (if applicable):  all endpoints were completed by an independent committee whose members were unaware of the treatment assignments 

Intervention (if applicable)

  • Conventional treatment in accordance with 1988 recommendations of the Danish Medical Association or intensive treatment with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin, overseen by a project team (doctor, nurse, and dietitian)
  • Intensive therapy group:  aim of dietary intervention was <30% fat, <10% saturated fat, light to moderate exercise 3 - 5 times/week for at least 30 minutes, smoking cessation courses, ACE inhibitors, angiotensin II receptor antagonists, vitamin-mineral supplement, and aspirin, and oral hypoglycemics if patients were unable to maintain glycosylated hemoglobin values < 6.5%
  • Patients in intensive therapy group were offered individual consultations every third month during the 8 year follow up while the conventional therapy group occurred at the request of the patients' personal physicians

Statistical Analysis

160 patients were needed to detect a 35% reduction in relative risk of end points with a power of 0.7.  Primary end point was analyzed according to intention-to-treat principle, with event curves for time to first event based on Kaplan-Meier analysis, and treatments were compared with the log rank test.  A Cox regression model was used to calculate the hazard ratio for the primary end point.  Rate ratios were estimated with use of grouped survival model.  Measured variables compared by means of ANCOVA, with baseline values as covariates to adjust for differences between groups.  In the case of a non-gaussian distribution, the Mann-Whitney test was used.  A chi-square test was used to compare categorical variables.

Data Collection Summary:

Timing of Measurements

Biochemical and clinical data were collected every third month in the intensive therapy group.  End point examinations were performed and biochemical and clinical status determined after 4 and 8 years of intervention in both groups.

Dependent Variables

  • Composite of death from cardiovascular causes, nonfatal myocardial infarction, CABG, percutaneous coronary intervention, nonfatal stroke, revascularization, amputation or vascular surgery for peripheral atherosclerotic artery disease after 8 years of intervention
  • Incidence, development or progression of diabetic nephropathy after 4 years of intervention 
  • Blood samples
  • Blood pressure

Independent Variables

  • Conventional treatment in accordance with 1988 recommendations of Danish Medical Association or intensive treatment with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin

Control Variables

  • Age
  • Duration of diabetes
  • Sex
  • End point status at baseline
Description of Actual Data Sample:

Initial N: 160 subjects; 80 were randomized to receive conventional treatment and 80 to receive intensive treatment

Attrition (final N):  63 completed conventional therapy, 67 completed intensive therapy

Age: mean age 55.1 years

Ethnicity: not mentioned

Other relevant demographics:  mean follow up was 7.8 years

Anthropometrics:  Baseline demographic and clinical characteristics and biochemical status of the patients in the conventional therapy group and the intensive therapy group were similar.

Location: Denmark

 

Summary of Results:

 

 

Conventional Therapy (n=63)

Intensive Therapy (n=67)

P value

BMI - Men

0.4 +/- 0.4

0.7 +/- 0.4 0.61
BMI - Women 1.3 +/- 1.3 2.3 +/- 1.2 0.29

Waist circumference - Men (cm)

4 +/- 2

3 +/- 1

0.23

Waist circumference - Women (cm) 5 +/- 5 6 +/- 3 0.81
Hip circumference - Men (cm) 2 +/- 1 0 +/- 1 0.14
Hip circumference - Women (cm) -1 +/- 3 5 +/- 4 0.048
SBP (mmHg) -3 +/- 3 -14 +/- 2 <0.001
DBP (mmHg) -8 +/- 2 -12 +/- 2 0.006
Current smokers (number of patients) -6 -5 0.73
Median Energy intake (kcal) -43 -57 0.33
Range Energy intake (kcal) -3706 to 999 -1610 to 1042 --
Protein (% of intake) 1.1 +/- 0.4 1.6 +/- 0.4 0.56
Carbohydrates (% of intake) 4.8 +/- 0.9 9.3 +/- 0.9 0.002
Alcohol (% of intake) 0.9 +/- 0.9 -0.5 +/- 1.1 0.82
Fat (% of intake) -6.8 +/- 0.9 -10.4 +/- 0.9 <0.001
Saturated fat (% of intake) -4.4 +/- 0.4 -6.9 +/- 0.5 <0.001
Median Exercise (min/week) 0 30 0.38
Range Exercise (min/week) -720 to 630 -480 to 750 --
Fasting plasma glucose (mg/dl) -11 +/- 11 -52 +/- 8 <0.001
Glycosylated hemoglobin (%) 0.2 +/- 0.3 -0.5 +/- 0.2 <0.001
Median Fasting serum C peptide (pmol/L) -53 -112 0.18
Range Fasting serum C peptide (pmol/L) -709 to 2555 -958 to 1429 --

Median Stimulated serum C peptide (pmol/L)

-270 -332 0.43
Range Stimulated serum C peptide (pmol/L) -1309 to 3488 -1974 to 1515 --
Fasting serum triglycerides (mg/dl) 9 +/- 43 -41 +/- 14 0.015 
Fasting serum total cholesterol (mg/dl) -3 +/- 7 -50 +/- 4 <0.001
Fasting serum LDL cholesterol (mg/dl) -13 +/- 6 -47 +/- 5 <0.001
Fasting serum HDL cholesterol (mg/dl) 7 +/- 1 6 +/- 2 0.90
Median Serum creatinine (mmol/L) 21 24 0.57
Range Serum creatinine (mmol/L) -16 to 661 -6 to 181 --
Median Urinary albumin excretion (mg/24 hours) 30 -20 0.007
Range Urinary albumin excretion (mg/24 hours) -251 to 4729 -230 to 5474 --
Median Urinary sodium excretion (mmol/24 hours) -21 -21 0.86
Range Urinary sodium excretion (mmol/24 hours) -440 to 286 -225 to 302 --

GFR

-32 +/- 3

-30 +/- 3

0.68

Other Findings

The decline in glycosylated hemoglobin values, systolic and diastolic blood pressure, serum cholesterol and triglyceride levels measured after an overnight fast, and urinary albumin excretion rate were all significantly greater in the intensive therapy group than the conventional therapy group.

Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease (hazard ratio 0.47, 95% confidence interval, 0.24 to 0.73), nephropathy (hazard ratio, 0.39, 95% confidence interval, 0.17 to 0.87), retinopathy (hazard ratio 0.42, 95% confidence interval, 0.21 to 0.86) and autonomic neuropathy (hazard ratio 0.37, 95% confidence interval, 0.18 to 0.79). 

Author Conclusion:
We found that a targeted, long-term (mean 7.8 years) intensified intervention involving mutliple risk factors reduced the risk of cardiovascular events by about 50% among patients with type 2 diabetes and microalbuminuria.
Funding Source:
Reviewer Comments:
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? 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? ???
  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)? 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? Yes
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