EAL

NC: Diabetes Management (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To study the short- and long-term effectiveness of a comprehensive weight-reduction program vs. a conventional program in overweight patients with type 2 diabetes
To identify predictors for the degree of weight loss.

Inclusion Criteria:

BMI over 27kg per m2
Type 2 diabetes, based on WHO criteria.

Exclusion Criteria:

History of angina
History of heart failure
History of intermittent claudicaiton
History of proliferative retinopathy
History of treatent with subcutaneous insulin injections, diuretics, beta-blocking agents, drugs for hyperlipidemia or other drugs influencing carbohydrate metabolism.

Description of Study Protocol:

Recruitment

Patients recruited from general practices and from an outpatient diabetes clinic.

Design

Run-in period of three months preceded a two-year treatment period
Post three-month run-in period, subjects were stratified according to sex to either a 24-month comprehensive weight-reduction program or to a 24-month conventional weight-reduction program.

Intervention

Three-month run-in period to ensure weight stabilization:

During "run-in" period, all subjects were seen at least three times
Measurements were obtained during the run-in period following a 12-hour overnight fast
Subjects seen by dietitian twice
- Prior to each visit, subjects completed a three-day food record
- During the visit, the dietitian checked food intake records for accuracy and obtained additional information as necessary
- Subjects were instructed not to change dietary habits during the run-in period.

Following the run-in period, subjects were stratified to one of two 24-month treatment groups:

Conventional Program
- Subjects visit outpatient clinic at 2 month intervals and seen by physician and dietitian every visit
- At each visit the following occurs:
- The various measurement results obtained during run-in period are recorded in booklet form and provided as feedback during each visit
- Dietitian provides dietary education
- Adherence to diet recommendations assessed on each visit via 3-day food record (completed by subject prior to each visit)
Comprehensive Program
Consists of all components of the conventional program plus:
1. Sessions on behavior modification strategies
  - Conducted in group format (eight to 10 subjects)
  - Led by a psychologist experienced in eating disorders
  - Sessions held once per week during the first two months and thereafter at Months Four, Eight, 12, 16 and 20
  - Behavioral strategies taught include self-monitoring, stimulus control techniques, self-reinforcement, cognitive restructuring appraoches and relapse prevention methods.
2. Exercise training
  - Group format (five or six subjects), led by two physiotherapists
  - Three periods of three-month duration
  - Frequency of training sessions
    - Twice per week during Months Three through Six
    - Once per week during Months Nine through 12 and Months 15 through 18.
  - Session content
    - Five minutes warm-up
    - Training on bicycle ergometer for 30 minutes (intensity 60% to 80% of maximal heart rate)
    - 30 minutes of various sports activities
    - Five-minute cool-down.
  - Subjects were encouraged to exercise every day at home and increase regular daily activity.

Statistical Analysis

Run-in clinical and metabolic data on both groups was compared using Wilcoxon's rank-sum test
To compare effects of both programs on various variates, median changes for each were compared at the six-, 12- and 24-month time points, using Wilcoxon's rank sum test
Overall effect of both programs computed by assessing the average difference of the changes for each program over the two-year treatment period using Hodges-Lehmann estimator. Additionally, a 95% confidence interval was computed to compare the effects of each program.
Spearman correlation coefficients used to describe associations between changes in body weight and other variates
Because correlation coefficients were similar for the separate therapy groups, only results of combined analyses were provided
Multiple linear regression techniques were used to investigate whether the magnitude of weight loss at 24 months could be predicted by subject and metabolic characteristics measured at baseline
To avoid confound by treatment, all tested models included a variate-indicating therapy
Variates were built step-by-step into prediction model in forward fashion using the following rules: Significance at 10% level, the maximal increment in variance explained (R²)
Special attention was given to underlying assumptions of Gaussian-distributed residuals.

Data Collection Summary:

Timing of Measurements

During the three-month run-in period: "At least" three times (specific times not indicated)
During the two-year treatment period: Every two months (e.g., Months Two, Four, Six and so on up to Month 24).

Measurements Obtained

Run-in period (post 12-hour overnight fast)

Body weight (without shoes and heavy clothing on calibrated balance scale to nearest 0.1kg)
Body composition (via bioelectrial impedance analysis with tetrapolar device)
Blood pressure measured in supine position (in triplicate with London School of Hygiene mercury sphygmomanometer)
Waist-to-hip ratio (WHR) calculated by dividing waist circumference measure (at level of minimal girth) by hip circumference measure (at level of maximal circumference over buttocks)
Venous blood samples drawn with minimal venous occlusion.

Run-in period, visits with dietitian (measures obtained before each visit)

Three-day food record (two weekdays and one weekend day)
Food record information converted to energy and macronutrient intake (using Dutch Food Composition Table 1986 and nutrient software package "voeding" (current version: Stichting NEFO, TNO-voeding, Zeist, the Netherlands).

Two-year treatment period

Every two months (e.g., Months Two, Four, Six and so on up to Month 24): Three-day food record (two weekdays and one weekend day) converted to energy and macronutrient intake (as described in run-in period).

Dependent Variables

Primary aim clinical variables

Body weight (without shoes and heavy clothing on calibrated balance scale to nearest 0.1kg)
Body fat percentage (via bioelectrial impedance analysis with tetrapolar device)
WHR (calculated by dividing waist circumference measure, at level of minimal girth, by hip circumference measure, at level of maximal circumference over buttocks
Systolic blood pressure (mmHg)
Diastolic blood pressure (mmHg)
Blood pressure was measured in the supine position (in triplicate with London School of Hygiene mercury sphygmomanometer).

Primary aim metabolic variables (obtained in fasting state)

HbA1c (percentage): Inter-assay coefficient of variation (CV) of 3.3%, determined by ion-exchange high-performance liquid chromotography (modular diabetes monitoring system, Bio-Rad Lab BV, Veenendaal, Netherlands)
Plasma insulin (intra-assay CV 7%): Measured by RIA (insik4, Sorin Biomedia, Saluggia, Italy)
C-peptide (intra-assay CV 4%): By RIA (Diagnostic Systems Lab, Texas, USA)
Triglycerides (intra- and inter-assay CV 0.5 and 3.5%): Measured enzymatically by GPO-PAP method (Boehringer Mannheim GmbH, Mannheim, Germany)
Serum cholesterol (intra- and inter-assay CV 0.8 and 1.1%): Measured enzymatically by CHOD-PAP method (Boehringer Mannheim GmbH, Mannheim, Germany)
HDL2: Performed by density gradient ultracentrifugation, using modification of procedure described by Terpstra et al (inter-assay CV 8.6%).

Independent Variables

Behavior modification
Exercise training.

Control Variable

Diet

Moderate energy-restricted diet designed to reduce usual energy intake by 500kcal, with minimum intake of 1,000kcal every 24 hours
Diet prescription composed of:
- 50% to 55% carbohydrate
- 15% protein
- 30% fat calories (emphasizing use of unsaturated fat).
Cholesterol: Under 300mg per day
Fiber: Approximately 25g.

Description of Actual Data Sample:

Variables	Comprehensive Program	Conventional Program
Gender (M/F)	9/18	10/16
Age (Years)	59	58.5
BMI (kg/m²)	31.3	32.8
HgA1C	8	7.5

Summary of Results:

Differences (95% CI) between change in body weight in CPP, compared to CVP after six and 24 months of treatment were -2.2kg (-4.0kg, -0.3kg), P=0.03 and -1.3kg (-3.3kg, 0.7kg), P=0.21, respectively
CPP resulted in greater decrease (95% CI) of HbA1c after six months: -0.8% (-1.2%, -0.2%), P=0.01, but not after two years: -0.4% (-1.0%, 0.1%), P=0.12
The only serum lipid that decreased significantly was serum total cholesterol in the CPP, compared to CVP at six and 12 months: -0.4mmol (-0.7mmol, -0.1mmol) per L (P=0.04) and -0.4mmol (-0.8mmol, -0.1mmol) per L (P=0.03), respectively.

Author Conclusion:

In the short-term (six months), the comprehensive program produced significantly lower HgA1C levels, but this difference did not persist to 12 months
The long-term outcome of the conventional program was not significantly different from that of the comprehensive program.

Funding Source:

Reviewer Comments:

Limitations

Included patients who were already treated for "quite a while" at the outpatient diabetic clinic
Authors do not state whether subjects were randomly assigned to groups
Actual timing of measurements during the run-in period were not specified
Due to outliers, median values were used to compare characteristics of subjects during the run-in period, however no P-values were provided to indicate significance
The run-in period was used to ensure "weight stabilization before outset of study," however no statistics were run to indicate that this occurred.

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?	???
2.	Was the selection of study subjects/patients free from bias?		???
	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?	???
3.	Were study groups comparable?		???
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	???
	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?	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%.)	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?		???
	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?		Yes
	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?	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?		???
	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?	???
	7.5.	Was the measurement of effect at an appropriate level of precision?	???
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	???
	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?	N/A
	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)?	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?	???
	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?	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