Bariatric Surgery on obesity-and Diabetes-associated Abnormalities of Hemostasis, Inflammation and Vascular Function. (FIBRINO)

Effects of Bariatric Surgery on obesity-and Diabetes-associated Abnormalities of Hemostasis, Inflammation and Vascular Function.

The goal of this prospective cohort study is to examine circulating biomarkers before and after weight loss in patients with obesity, with or without concomitant diabetes, undergoing bariatric surgery. The main questions that are being addressed are:

• Do biomarkers of hemostasis, including coagulation, fibrinolysis, and platelet function improve following surgery and if so, is that improvement more pronounced in patients with diabetes?
• Do biomarkers of endothelial function and other aspects of vascular function improve following surgery and if so, is that improvement more pronounced in patients with diabetes?
• Do biomarkers of inflammation, including markers of adipocyte function, improve following surgery and if so, is that improvement more pronounced in patients with diabetes?
• The possible role of circulating extracellular vesicles reflecting biological functions above will also be investigated (optional) Participants will be asked to attend in total five study visits before and after surgery including a final visit at two years post-surgery. Comparisons will be performed within- as well as between groups.

Study Overview

• Status: Completed
• Conditions: Diabetes Complications; Surgery; Coagulation Disorder; Obesity Associated Disorder
• Intervention / Treatment: Procedure: Laparoscopic Roux-en-y gastric bypass

Detailed Description

In this single centre, prospective, parallel group, cohort study, patients meeting the eligibility criteria are recruited at the department of surgery at Ersta hospital, Stockholm, Sweden. Patients with obesity and type 2 diabetes (T2D) are matched for age and sex with the group of patients with obesity without T2D. During the study the participants attend five study visits: at baseline, at the morning of surgery (after two weeks of low calory diet), 6 weeks, 1 year and 2 years after surgery. At each study visit a nurse records blood pressure, weight, height, and waist/hip circumferences. In addition, the nurse recalls the medical history and any medication use including contraceptive hormones and analgesics. Fat mass is determined using bioelectric impedance. Venous blood samples are collected with the patients in the supine position after overnight fasting and at least 20 minutes of rest. For later analyses, 25 mL of blood is collected in citrate tubes and centrifuged for 20 min at 2000 x g in room temperature. Plasma aliquots are subsequently stored at minus 80 degrees Celsius. Blood test regarding values at baseline (not the primary outcome variables) will be analysed at the local hospital laboratory. Examples of those basic variables are concentrations of glucose, insulin, blood cell counts and lipids.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Age 18-70 years old
• Planned for Roux-en-y gastric bypass surgery
• Obesity fulfilling criteria for bariatric surgery (according to the European Association for the Study of Obesity guidelines, ref. Yumuk et al. European Guidelines for Obesity Management in Adults. Obes Facts 2015;8:402-42.)

Exclusion criteria:

• Ongoing treatment with anticoagulant medication
• Ongoing treatment with antiplatelet medication other than acetylsalicylic acid
• Type 1 diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Obesitysurgery with diabetes; One group with obesity and concomitant type 2 diabetes	Procedure: Laparoscopic Roux-en-y gastric bypass; Obesity surgery
Other: Obesitysurgery and non-diabetes; One group with obesity alone	Procedure: Laparoscopic Roux-en-y gastric bypass; Obesity surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood tests for endothelial function comparing two years after surgery with baseline (below referred to as "changes in").	Outcome measure: Change in Hyaluronan (ng/ml); Change in Syndacan-1 (ng/ml); Change in E-selectin (ng/ml); Change in Thrombomodulin (pg/ml); Change in von Willebrand factor (%)	before surgery - 2 years after surgery
Blood tests for fibrinolysis comparing two years after surgery with baseline (below referred to as "changes in").	Outcome measure: Change in PAI-1 activity (IU/ml); Change in Fibrinogen (pg/ml); Change in tPA activity (IU/ml); Change in PAP complex (ng/ml); Change in turbidimetric values - LagC (s); Change in turbidimetric values - LagL (s); Change in turbidimetric values - MaxAbsC (au); Change in turbidimetric values - MaxAbsL (au; Change in turbidimetric values - Lys50MA (s); Change in turbidimetric values - CRC (au/s); Change in turbidimetric values - CRL (au/s)	before surgery - 2 years after surgery
Blood tests for inflammation comparing two years after surgery with baseline (below referred to as "changes in").	Outcome measure: Change in high sensitivity CRP (microg/ml); Change in soluble IL6 receptor (ng/mL); Change in IL6 (pg/mL); Change in soluble gp130 (ng/mL); Change in TNFalfa (pg/ml)	before surgery - 2 years after surgery
Blood tests for extracellular vesicles comparing two years after surgery with baseline (below referred to as "changes in").	Exploratory analyses of extracellular vesicles (EV) in plasma using flow cytometry. EV exposing antigens of cell specific origin and/or biologically active molecules will be assessed. Outcome measure: Change in number of EVs (number of EV/micoL)	before surgery - 2 years after surgery

Collaborators and Investigators

• Sponsor: Ersta Diakoni
• Collaborators: Karolinska Institutet
• Investigators: Principal Investigator: Anders Thorell, Professor, Karolinska Institutet Danderyds sjukhus/Ersta sjukhus

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: April 13, 2023
• First Submitted That Met QC Criteria: October 2, 2023
• First Posted (Actual): October 6, 2023

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Bariatric surgery; Fibrinolysis
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hematologic Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hemorrhagic Disorders; Diabetes Mellitus; Obesity; Hemostatic Disorders; Blood Coagulation Disorders; Inflammation; Diabetes Complications
• Other Study ID Numbers: 2014/1793-31/1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No