Clinical trial NCT00770276: Mannheim Obesity Study
Official title: Mannheim Obesity Pilot Study: Evaluation of Metabolic Und Cardiovascular Risk in Obesity
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Obesity
Keywords: obesity WHO I-III
metabolic syndrome
Framingham risk score
subclinical atherosclerosis
endothelial dysfunction
Lead sponsor: Universitätsmedizin Mannheim
Sponsor class: OTHER
First posted: 2008-10-09
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 88
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: outpatient department of an university hospital

Brief summary: MOPS: Mannheim Obesity Pilot Study

Introduction:

Obesity is a central feature of the metabolic syndrome. With increasing prevalence of overweight and obesity, the incidence of WHO III° obesity will further augment. In this subset of obese patients, metabolic complications and cardiovascular risk are major clinical issues. Epidemiological data show that with increased BMI mortality rises (1). The SOS-Study demonstrated, for the first time, that bariatric surgery and consecutive weight reduction are associated with a decrease in cardiovascular and overall mortality. Significant mortality in this study was caused by cardiovascular events and cancer.

Metabolic Syndrome - MS - Despite varying definitions of the metabolic syndrome, obesity is one of its central features. Depending on the definition used, it can represent an obligate criterion (IDF) or a facultative parameter (WHO and ATP III). Even though not obligate, extreme obesity is a central risk factor for most other parameters of the metabolic syndrome.

Endothelial dysfunction -ED- represents the initial step of atherosclerosis (3). An appropriate measurement is the evaluation by retinal analysis. Epidemiological data demonstrate increased cardiovascular risk with retinal vessel pathology (4).

Detailed description: Methods and procedures

Study design:

We conducted a prospective study in obesity WHO III° with consecutive enrollment. The study protocol was approved by the local ethics committee. Patients were recruited within an integrated concept designed for individuals seeking weight reduction. This network encompassed a complex approach by nutrition specialists, bariatric surgeons, endocrinologists, ENT specialists and psychologists. Patients could present themselves at any of the aforementioned specialists for study inclusion. Those who consented were followed, after conventional weight loss (diet, activity) or bariatric surgery 1 year later.

Evaluation:

Using a standardized form, we evaluated the medical and obesity history as well as associated metabolic complications (impaired glucose metabolism, elevated Cholesterol and NASH). We further inquired about regular medication, related diseases and classic cardiovascular risk factors (Framingham risk score: cardiovascular disease, family history of cardiovascular disease, nicotine abuse and arterial hypertension).

Anthropometry - Subsequently, a complete physical examination was conducted, taking into consideration the use of an adequate cuff to measure blood pressure. We further recorded circumferences of the neck, arm and waist (midway between the lower rib margin and iliac crest, with a measuring tape at the end of gentle expiration). Body weight and height were determined by calibrated scales to the nearest 0.1kg and cm, respectively.

Metabolism - Metabolic analysis was performed after an overnight fast. Baseline measurements included blood glucose, insulin, cholesterol, HDL, LDL, triglycerides and liver enzymes. Every individual without known diabetes was screened for the presence of impaired glucose metabolism by means of an OGTT. To exclude endocrine obesity we measured TSH levels and performed a one mg dexamethasone suppression test.

Intima media thickness (IMT) - Measurement of the intima media thickness of the right carotid artery was performed in order to detect subclinical vascular disease. Imaging protocol was executed according to the consensus statement of the American Society of Echocardiography (5).

Structural and functional endothelial dysfunction: Arterial and venous ratio (AVR) and flicker reaction - DVA was used for digital fundus imaging as well as conventional fundus examinations and retinal vessel analysis (RVA, imedos, Jena, Germany). Structural endothelial dysfunction was determined by arterial-venous ratio (AVR). After mydriasis with phenylephrine 10% and tropicamide 1%, images centred on the macula, the inferior arcade and the optic disc were recorded in both eyes. AVR was calculated by software after marking arteries and veins within two diameters of the optic disc (RVA, imedos, Jena, Germany).

Functional endothelial dysfunction was measured by flicker reaction of retinal vessels. This technique records dilatation of retinal vessels during and after exposure to flickering light. We used 1.5 mm segments of vessels within two disc diameters, which showed no crossing or bifurcation, and had a tortuosity \< 30°. After baseline calibration, flickering light was shown for 20 seconds via interruption of continuous light at 12.5 Hz. During this period and for further 80 seconds, vessel diameter was continuously measured. To achieve higher reliability, this procedure was performed three times. Flicker of the artery and vein was expressed as the maximum in percent of the baseline diameter. Adjustment for eye movement was performed automatically by software. Details of this technique were published elsewhere (6-7).

BIA - Body composition was determined preoperatively by BIA. All patients were required to rest for 30 minutes, after which BIA was performed by applying 4 silver electrodes, with 2 detecting electrodes placed at the ulnar aspect of the right wrist and the right medial malleolus. After connecting the electrodes to the multiple-frequency BIA instrument (BIA 2000, Data Input, Darmstadt, Germany), measurements were recorded in real time via computer. The calculations for BCM, ECM, ECM/BCM, fat and TBW were performed using Nutri 2000 software (Data Input, Darmstadt, Germany).

Endpoints - The endpoint of our study was the identification of cardiovascular risk and metabolic complications or factors representing these risks in a population with obesity WHO. Therefore, we measured parameters of the metabolic syndrome, endothelial dysfunction and subclinical atherosclerosis. Patients, who gave informed consent, are followed after conventional weight loss (diet, activity) or bariatric surgery yearly. The decision for the type of intervention is connected to a complex process. According to the German obesity society subjects with more than 40 kg/m2 and patients with a BMI \> 35 kg/m2 with obesity associated disease have the indication for bariatric surgery. After drafting of an expert's opinion for coverage of the costs by the health insurance patients may attend bariatric surgery. Because of the noncommittal character of the guideline of the German obesity society to health insurances not all patients will be able to get coverage for their surgery costs. Patients who are not able to get cost coverage or refuse surgery represent the conservative treatment (activity, diet). The interventional group will be treated by bariatric surgery (sleeve gastrectomy, Roux-en-Y gastric bypass). Therefore, the study has observational character.

Eligibility criteria: Inclusion Criteria:

* obesity WHO I-III

Exclusion Criteria:

* pregnancy
* acute vascular event within the last 3 months

Primary outcomes:
measure: Metabolic syndrome
timeFrame: baseline, after 1 and 2 years
measure: Framingham risk score
timeFrame: baseline, 1 and 2 years
measure: Subclinical atherosclerosis (IMT)
timeFrame: baseline, 1 and 2 years
measure: Endothelial dysfunction
timeFrame: baseline, 1 and 2 years
Secondary outcomes:
measure: Change in body weight
timeFrame: baseline, 1 and 2 years
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: University hospital of Mannheim
state: BW
Study officials:
References:
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