EAL

Weight Management

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The present study was undertaken to evaluate the long-term (1 y) safety and efficacy of a meal replacement strategy in a population of obese patients with NIDDM in comparison to an individualized exchange diet plan (IDP) conforming to the macronutrient recommendations of the American Diabetes Association (ADA).

Inclusion Criteria:

30 y and older at screening
being treated for NIDDM with oral hypoglycemic agents
BMI 27-40 kg/m²
HbA1c of 7-12% inclusive
no change in diabetic medications for 3 months prior to entry into the trial

Exclusion Criteria:

were or had been on insulin therapy
significant diabetes-related complications such as diabetic retinopathy, neuropathy or proteinuria
history of psychiatric or other major medical conditions such as liver disease, kidney disease, and coronary artery disease

Description of Study Protocol:

Recruitment

obese male and females previously diagnosed and being treated for type II DM with oral hypoglycemic agents were recruited

Design

random, permuted, block design

Blinding used (if applicable): implied for measurements

Intervention (if applicable)

IDP: individualized exchange diet plan conforming to macronutrient recommendations of the American Diabetes Association; instructed on use use of food exchanges based on goals that met the criteria as recommended by ADA; > 30% calories from fat, 10-20% from protein and 55-65% from carbohydrates
MR: Meal Replacement - for the first 5 days, replaced 3 meals per day with a soy MR (Slim Fast) and instructed to add fruits and vegetables to their dietary intake; thereafter, 2 meals per day were replaced with the soy MR with continuing use of fruits and vegetables as snacks, plus a sensible third meal for three additional months; after 3 months, 1 to 2 meals per day were replaced with the soy MR and consume correspondingly 1 to 2 sensible meals for the duration of the study
For both groups and individualized caloric target was calculated to achieve a daily caloric deficit of 500 calories per day below estimated resting metabolic rates
each participant received individual consultation with a registered dietitian at baseline, weeks 2, 4, 6, 8 and then monthly for the duration of the 1-y study

Statistical Analysis

data from subjects who returned for their initial follow-up visit after randomization were analyzed on an intention-to-treat basis
data from subject who discontinued study participation before 12 months were included through their last study visit
baseline data and 12-month changes from baseline data were compared between treatment groups using Student's t-test for two independent samples
a chi-square test was used to compare categorical data
outcome variables were repeatedly measured over time; descriptive statistics were used to summarize the outcomes for each study group at each time point; change of each outcome variable from baseline within each diet group was tested using paired t-test; differences between the diet groups at each time point were examines using a general linear model with the baseline value as covariate; a mixed model was used to test the overall diet effect

Data Collection Summary:

Timing of Measurements

12-month study period; measurements taken at baseline

Dependent Variables

weight - balanced-beam doctor's scale; height - wall-mounted stadiometer; BMI
insulin - commercial double antibody I¹²⁵ method
glucose - spectrophotometric technique
HbA1c - not given
serum lipids - total cholesterol, triglyceride, high-density lipoprotien determined using standard enzymatic methods; LDL concentrations calculated using the Friedewald equation
hs-CRP - performed by Quest Diagnositic laboratory
resting metabolic rates were estimated based on lean body mass as measured by bioelectrical impedance analysis according to the Cunningham equation estimate of 13.8 kcal/day/pound of lean body mass

Independent Variables

Control Variables

none given

Description of Actual Data Sample:

Initial N: 104 male and female subjects

Attrition (final N): 11 subjects (3 in MR and 8 in IDP) dropped out during the screening and/or baseline visits; an additional subjects (3 in MR and 8 in IDP) were lost to the study within the first 6 months; these 22 subjects were excluded from the analysis

during the second 6 months, additional 5 dropouts (1 in IDP and 4 in MR)
no subjects withdrew due to serious adverse events
intention-to-treat analysis was also performed including all 104 subjects that showed same statistical results
MR n=46; IDP n=36
drop out rate = 26% over the study period with the majority of loss during screening and initial visits; decreased to 6% after initial dropout
dropout reasons given: not randomized to MR group; time committment

Age: 54.4 to 56.6 were mean ages in the two groups

Ethnicity: not given

Other relevant demographics: not given

Anthropometrics

there were no statistical differences between the two study groups with respect to the baseline demographics
Gender, female: MR 19 (41.3%); IDP 12 (33.3%)
Gender, male: MR 27 (58.7%); IDP 24 (66.7%)
age: MR 54.4 ± 9.3; IDP 56.6 ± 10.4
BMI (kg/m²): MR 32.8 ± 3.7; IDP 33.7 ± 3.6

other baseline data

Variables	MR (n=46)	IDP (n=36)	Compare MR vs IDP (p-value)
HbA1c (%)	7.6 ± 1.4	7.5 ± 1.7	0.774
Fasting glucose (mg/dL)	161.4 ± 44.4	165.4 ± 52.7	0.712
Fasting insulin (uIU/mL)	8.31 ± 5.4	7.51 ± 3.6	0.425
Total cholesterol (mg/dL)	199.8 ± 6.79	180.9 ± 3.75	0.017
Triacylglycerol (mg/dL)	207.7 ± 111.6	217.1 ± 142.3	0.737
LDL cholesterol (mg/dL)	111.3 ± 6.21	97.46 ± 4.22	0.070
HDL cholesterol (mg/dL)	43.2 ± 10.0	41.1 ± 10.0	0.339
hs-CRP (mg/L)	3.69 ± 0.75	3.66 ± 0.69	0.861

Location:

not given

Summary of Results:

Table 3 Changes in weight and BMI

Variables	Study period	IDP	P-value comparison to baseline	MR	P-value comparison to baseline	P-value comparison between groups
Weight (kg)	1 month	-1.42±0.32	<0.0001	-2.88±0.32	<0.0001	0.0002
	3 months	-2.89±0.56	<0.0001	-5.58±0.46	<0.0001	<0.0001
	6 months	-2.85±0.67	0.0002	-5.24±0.60	<0.0001	0.0031
	12 months	-2.36±0.76	0.0038	-4.35±0.81	<0.0001	0.0670
BMI (kg/m²)	1 month	-0.45±0.10	<0.0001	-0.98±0.11	<0.0001	0.0001
	3 months	-0.92±0.17	<0.0001	-1.87±0.15	<0.0001	<0.0001
	6 months	-0.92±0.22	0.0001	-1.75±0.20	<0.0001	0.0038
	12 months	-0.77±0.25	0.0045	-1.47±0.27	<0.0001	0.0678

Table 4 Changes in metabolic profile from baseline

Variables	Study period	IDP	P-value comparison to baseline	MR	P-value comparison to baseline	P-value comparison between groups
HbA1c (%)	3 months	-0.17	0.292	-1.00	<0.0001	0.0008
	6 months	-0.44	0.080	-9.95	<0.0001	0.110
	12 months	-0.15	0.563	-0.30	0.291	0.594
Glucose (mg/dL)	3 months	-12.98	0.124	-26.17	0.0002	0.046
	6 months	-12.97	0.167	-35.13	<0.0001	0.0002
	12 months	-7.86	0.331	-12.07	0.139	0.595
Insulin (uIU/mL)	3 months	-0.53	0.474	-1.48	0.005	0.651
	6 months	-0.04	0.935	0.19	0.783	0.376
	12 months	0.82	0.372	-0.42	0.439	0.394
Total cholesterol (mg/dL)	3 months	-11.04	0.025	-21.52	<0.0001	0.263
	6 months	-5.97	0.259	-12.8	0.0037	0.916
	12 months	5.26	0.396	-10.76	0.084	0.616
Triacylglycerol (mg/dL)	3 months	-51.01	0.003	-52.12	<0.0001	0.256
	6 months	-40.22	0.024	-36.33	0.002	0.427
	12 months	-28.89	0.119	-28.00	0.038	0.956
LDL (mg/dL)	3 months	-0.48	0.906	-11.04	0.024	0.683
	6 months	3.16	0.500	-5.53	0.149	0.849
	12 months	8.76	0.129	-6.10	0.255	0.615
HDL (mg/dL)	3 months	-0.40	0.656	-0.33	0.762	0.556
	6 months	-1.11	0.589	-0.48	0.535	0.307
	12 months	2.26	0.012	-0.97	0.345	0.410
hs-CRP (mg/L)	3 months	-0.23	0.486	-0.37	0.681
	6 months	-0.26	0.338	-0.97	0.019
	12 months	-0.68	0.179	-0.93	0.028

Other Findings

average weight loss at 6 months: MR -5.24 ± 4.08; IDP -2.85 ± 4.04 kg
average weight loss at 12 months: MR -4.35 ± 5.28; IDP 2.36 ± 4.92 kg
average percentage loss at 12 months: MR -4.57 ± 5.26; IDP 2.25 ± 4.27% (P=0.039)
at each study time point, the percentage of weight loss in the MR group was statistically higher than in the IDP group
during entire study period, the mean % weight loss for the MR group was 2.28 ± 0.64% higher than the IDP group (P=0.0004)
adjusting for baseline HbA1c level, the mean HbA1c was 049 ± 0.22 lower than the IDP group for the entire study period (P=0.0291) by repeated measurement analysis
of the 77 patients who completed 12 months, hs-CRP level was measured in 50 subjects (24 in IDP and 26 in MR); a total of 27 patients were excluded for recent history of systemic infection/inflammation or did not consent to this specific test; patients on statins for treatemtn of dyslipidemia were included in the analysis;
subset analysis based on comparison of subjects with or without statin use revealed no difference in baseline hs-CRP level in IDP as well as in the MR group
all study subjects were taking at least one oral hypoglycemic agent at study entry; the medication profiles were compatible between the two groups
With MR, a significant number of subjects had a reduction of their sulfonylurea (P<0.0001) and metformin (P<0.05) use by 12 months; this change was not observed in IDP group; no significant dosage changes with regard to hypertension medication and cholesterol lowering agents were observed in either group
MR glucose response test demonstrated that the consumption of the soy-based MR resulted in similar effects on glucose levels when compared to Glucerna
overall, the MR was well tolerated; subjects did report 'taste fatique' after first 6 months

Author Conclusion:

The use of soy-based MR in a structured strategy of a reduced calorie diet plan provided clinically significant weight losses in individuals with noninsulin-dependent type II DM.
Due to the overall good compliance of the participants to the dietary regimen, significant changes were made in their medications that control for blood glucose. These changes may, in part, have blunted the significant improvements seen in glycemic control over time.

Funding Source:

University/Hospital:

University of Arizona

Reviewer Comments:

In disagreement with what is written in text, total cholesterol and LDL cholesterol did differ between MR and IDP at baseline. IDP had lower values than MR for TC and LDL.
The variation in baseline triacylglycerol values also seems to be quite high. Given the substantial decreases in TG values in both groups (Table 4), this may be something to consider when interpreting results
In Table 4, no comparison p-values between MR and IDP were given for hs-CRP.
no limitations were given

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?	???
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)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	???
	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?	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?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	???
	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?	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)?	N/A
	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?		???
	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?		???
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	???