Sleeve-gastrectomy Efficacy in Morbid Obese Patient With a Focus on the Role of Inflammation

Study Overview
=================
Brief Summary
-----------------
Despite the wide range of studies concerning the positive effects of bariatric surgery on metabolic state of morbid obese patient, it is necessary to further investigate the specific role of the sleeve-gastrectomy intervention, going not only to research results in terms of safety or efficacy on the treatment of comorbidities, but also aimed to understand whether the improvement of metabolic and cardiovascular parameters is due to total weight loss or rather to visceral fat loss, and how much of this improvement is attributable to changes in inflammatory status. The primary endpoint of the study is to evaluate the effect of sleeve-gastrectomy on metabolic parameters (glyco-lipidic assessment, vitamins), bone-remodelling parameters (vitamin D, parathormone) and cardiovascular parameters (blood pressure, flow-mediated dilation, indexed left ventricular mass, inter-ventricular septum, carotid intima-media thickness) in a large obese population on the basis of total weight loss (TWL), variation of visceral fat area (VFA), variation of peri-renal fat thickness and insulin resistance index (Homeostasis Model Assessment-insulin resistance - HOMA). In addition the investigators set themselves the objective of assessing whether the presence of comorbidities (diabetes and hypertension) can influence the effects of the intervention on the above parameters, and whether the levels of the NETs and of adipokines such as chemerin in the pre- and post-intervention can correlate with the metabolic-vascular dysfunction, and play a role in its eventual improvement.

Official Title
-----------------
Sleeve-gastrectomy Efficacy in the Treatment of Metabolic and Vascular Dysfunction of Morbid Obese Patient With a Focus on the Role of Inflammation

Conditions
-----------------
Morbid Obesity

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - BMI ≥ 40 kg / m2 (or ≥ 35 kg / m2 with at least one comorbidity), aged between 18 and 65 years. Exclusion Criteria: renal or hepatic impairment heart failure (New York Heart Association - NYHA II-IV) secondary causes of obesity major psychiatric disorders

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Surgery patients<br>Obese patients undergoing laparoscopic sleeve gastrectomy | |
| Non-surgery patients<br>Obese patients not undergoing laparoscopic sleeve gastrectomy (delayed or refused proposed treatment) | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| flow-mediated dilation | ultrasound evaluation | One year | 
| obesity-related cardiomyopathy | cardiac ultrasonography | One year | 
| insulin resistance | HOMA index | One year | 
| ectopic adiposity | ultrasound evaluation of visceral fat | One year | 
| inflammation | high sensitivity C reactive protein, sclerostin, osteopontin, cathepsin K, IL-10 | One year | 
| blood pressure | systolic and diastolic blood pressure | One year | 
| carotid intima-media thickness | ultrasound evaluation | One year | 
| microcirculatory function | Laser-Doppler flowmetry | One year | 
| aortic stiffness | tonometry | One year | 
| cardiovascular assessment | anti-hypertensive therapy variation (number of drugs) | One year | 
| dyslipidemia | total cholesterol, triglycerides, HDL, LDL | One year | 
| liver function | Evaluation of Non-alcoholic fatty liver disease (NAFLD) fibrosis score according to the following formula: -1.675 + 0.037 × age (years) + 0.094 × BMI (kg/m2) + 1.13 × IFG/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio - 0.013 × platelet (×109/l) - 0.66 × albumin (g/dl). Cutoffs: NAFLD Score < -1.455 = low grade fibrosis; NAFLD Score -1.455 - 0.675 = indeterminate score; NAFLD Score > 0.675 = high grade fibrosis. | One year | 
| biliary acid and sterols assessment | laboratory analysis | One year | 
| bone metabolism assessment | vitamin D, PTH | One year | 
| nutritional assessment | sideremia, vitamin B12, folates | One year | 
| adipose tissue quantification | bioimpedentiometry | One year | 
| adipokines | chemerin, leptin and adiponectin plasmatic dosage | One year | 
| NETs | Neutrophil extracellular traps dosage | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| inflammatory bone remodeling markers | sclerostin, osteopontin, cathepsin K | One year | 
| macrophages commitment markers | interleukin-10 | One year |