EAL

NSA: Serum Proteins (2009)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate the cost-effectiveness and safety of two distinct low-calorie diets.

Inclusion Criteria:

18 years or older
Classified as obese class III and IV (defined as BMI of 40kg/m² or more and 50kg/m² or more, respectively) or severe obesity
Confirmed failure of conventional treatment with a balanced hypocaloric diet and pharmacological drugs and correct therapeutic compliance
In preparation for:
- Bariatric surgery
- Other surgery types that required general anesthesia
- Surgery that requires weight loss due to mechanical problems or respiratory failure because of obesity hypoventilation syndrome.

(All are situations in which the use of LCD are approved in this center.)

Exclusion Criteria:

If very-low-calorie diets (VLCD) were contraindicated, including:

Unstable cardiac disease (ischemic cardiopathy, arrhythmias, heart failure)
Recent or unstable cerebrovascular disease
Kidney (creatinine of 1.4mg per dL or more) failure
Hepatic failure (values of liver biochemistry twice the upper limit of normal)
Severe psychiatric disorders
Pregnancy
Age 65 years old or older
Social problems that could interfere with an appropriate therapeutic follow-up.

Description of Study Protocol:

Recruitment

All individuals presenting at clinic during a 16-month time period (unknown). Patients included in the study during the first eight months of the inclusion period were assigned to Group A. The second eight months, patients were assigned to Group B.

Design

Nonrandomized prospective trial: Individuals (N=67) were placed in one of two different LCD groups.

Intervention

Each individual received one of two structured ponderal loss programs in a third-level medical center, supervised by a team of physicians and nurses. Participants did not receive any weight-loss medication or drugs that could affect carbohydrate metabolism; hypotension treatment was not modified.
Group A followed a one-month diet program, with an initial seven-day inpatient period to verify patients' tolerance to VLCD. The VLCD was a commercial prepared (Modifast, Novartis Nutrition) and totaled 458kcal per day (39.3% carbohydrates, 45.4% protein, 13.7% lipids), to be taken in three meals. Patients were monitored once a week after the initial week.
Group B followed an 800kcal per day mixed LCD (53% carbohydrate, 24% protein, 23% lipids), a commercially prepared menu (Optifast, Novartis Nutrition) combined with a natural food for a three-month period. Patients were monitored once a month.
Both groups drank 2.0L of fluid a day and took a one-hour walk each day.

Statistical Analysis

Intent to treat, descriptive statistics, P<0.05 was considered significant
Parametric tests:
- All variables except diastolic and systolic blood pressures and glycemic variations followed normal distributions
- Quantitative variables were analyzed with student's independent T-tests
- Paired data evaluating changes in various variables after the fasting period were analyzed with student's T-test
- Categorical variables were analyzed using chi square
- Lineal association between variables were carried out using Pearson correlation coefficient
- Binomial logistic regression was used to identify variables associated with the worse response to the ponderal loss program
Non-parametric variables were analyzed using Spearman correlation and the Mann-Whitney U test.

Data Collection Summary:

Timing of Measurements

Anthropometric, hematologic, biochemical and hormonal assessments carried out in all patients after a 12-hour fast (weekly)
Basal biochemical variables measured weekly for Group A and for both groups at the end of the study.

Dependent Variables

Weight
Blood pressure: Diastolic and systolic (large cuff)
Tolerance.

Independent Variables

Insulin resistance (IR) measurements were done using the homeostasis model assessment for insulin resistance (HOMA - IR = fasting glucose mmol per L x fasting insulin mU per ml divided by 22.5), validated in the Mediterranean region; IR diagnosed when the HOMA index was 3.8 or more and fasting insulin value was 6.7 mU per ml or more
Total cholesterol, calculated HDL (HDL-c), calculated LDL (LDL-c) and triglycerides (TG) were determined with enzymatic methods using a Hitachi Modular autoanalyzer
Plasma C-reactive protein (CRP) obtained with IMMAGE analyzer
Insulin level determined using the IMMULITE 2000 multianalysis system.

Baseline Variables - for inclusion in the study

Electrocardiogram
Personal health record
Dietary and physical activity habits (survey)
Social and psychological attributes (questionnaire)
Epworth sleepiness scale
Quality of life (analogical scale)
Physical exam

Description of Actual Data Sample:

Initial N: 67 (21 males, 46 females)
Attrition (final N): 64; three dropouts (two from Group A due to major adverse events and one from Group B due to diet intolerance)
Age: 45.9+12.3 years.

Anthropometrics

BMI of 49.1±7.5kg/m²; not significant between Group A and B for age, gender, weight, BMI, weight:height ratio (W/H), SBP, DBP, glucose, uric acid, TG, total cholesterol, LDL-c, HDL-c, insulin, HOMA-IR and or CRP.

91% obese class III and IV
97% has associated complications
68.2% hypertensive
56.7% arthrosis
50.7% dyslipidemia
50.7% obstructive sleep apnea syndrome (OSAS)
50.9% basal fasting hyperglycemia (BFH) or diabetes (DM)
25.4% hyperuricemia
55.4% mood disorders (DSM-IV criteria) (predominantly in women, P<0.02)
96.5% metabolic syndrome (MS) (defined by adult treatment panel III-NCEP criteria)
72.3% previous history of overweight in first degree relatives
85.1% reported sedentary lifestyle
46% nibbling erroneous eating habit
26% great eater erroneous eating habit
90.8% physical limitations
69.4% social limitations.

Location: Alicante, Spain.

Summary of Results:

Changes in Both Study Groups (Basal Level to Final Level) -- Variables	Group A (458 kcal per day)	Group B (800 kcal per day)	Statistical Significance of Group Difference
Weight (kg)	9.2 (0.9)	8.7 (1.1)	P=0.73
% ponderal loss	7.2 (0.8)	6.8 (0.7)	P=0.70
SBP (mm Hg)	11.8 (4)	6.5 (4.4)	P=0.39
DBP (mm Hg)	5.9 (3.2)	6.8 (3.1)	P=0.85
Glucose (mg per dL)	18.6 (6.3)	12.1 (5.7)	P=0.45
TG (mg per dL)	54.4 (13.7)	2.5 (7.5)	P=0.002*
Cholesterol (mg per dL)	37.7 (6.1)	8.1 (6.3)	P=0.33
LDL-c (mg per dL)	3.45 (4.7)	-3.38 (5.6)	P=0.37
HDL-c (mg per dL)	-6.9 (2.8)	-3 (1.7)	P=0.22

Other Findings

86.2% followed the corresponding diet program correctly
Both groups lost significant weight (P<0.001 both groups) and lowered BMI (P<0.001 both groups), SBP (P=0.01 A, P<0.001 B); glucose (P=0.008 A, P=0.04 B), HOMA-IR (P=0.003 A, P<0.001 B)
Group B lowered DBP (P=0.04) and insulin (P<0.001) but not Group A
Group A lowered TG (P=0.001) and total cholesterol (P=0.006) and LDL-c (P<0.001), and HDL-c (P=0.034) but not Group B
Neither group lowered CRP
Logistic regression showed female gender was the only indicator of bad response to the ponderal loss program, defined as a ponderal loss inferior to 5% (OR=5.7, 1.17 to 28.3; P=0.03)
At the end of therapy, prevalence of type 2 diabetes showed 47.2% (CI, 0.23 to 0.71), (19.3% initial, 9.1% final) relative reduction, BFH a 36.5% (CI, 0.19 to 0.57), (31.6% initial, 20% final), and IR a 27.6% (CI, 0.17 to 0.41) (75% initial, 54.2% final) among all participants (P<0.001)
Quality of life showed a subjective improvement of 84.4% (CI, 0.73 to 0.91) of the population, and a six-month follow-up indicated a 52.6% (CI, 0.4 to 0.64, P<0.05) change in dietary habits
36 patients had mild complications associated to the VLCD (16.4% gastrointestinal, 19.4% anxiety) with no differences between groups
During the month of treatment, patients in Group A had medical leave of absence because of asthenia; two patients had severe complications (a cerebral TIA and a self-limited atrial fibrillation)
Total therapy costs [health care personal assistance, hospitalization, medication costs, complementary explorations, and indirect (sick leave) expenses] for Group A and Group B structured rapid ponderal loss programs were 3,018.9 and 582.6 euros, respectively.

Author Conclusion:

The three-month 800kcal per day VLCD was more cost-effective and safer than the one-month 458kcal per day diet.

Funding Source:

University/Hospital:	Alicante General University Hospital
Other:	Novartis -- but only for translation of manuscript
In-Kind support reported by Industry:	Yes

Reviewer Comments:

Strengths:
- Statistical analysis was appropriate
- Controlled trial
Weaknesses
- Nonrandomized
- Group A diet provided insufficient calories (evidenced by the asthenia); a more moderate VLCD may be in order
- Generalizability limited due to subjects only from this clinic in Spain
- Cost variable not explained in detail; how did they arrive at the costs?

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?		No
	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?	No
	1.3.	Were the target population and setting specified?	No
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?	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?	Yes
	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?	No
	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.)	No
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	Yes
	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?	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?		No
	7.1.	Were primary and secondary endpoints described and relevant to the question?	No
	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?	No
	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?	No
9.	Are conclusions supported by results with biases and limitations taken into consideration?		No
	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