The Effects of the Laparoscopic Roux-en-Y Gastric Bypass and Laparoscopic Mini Gastric Bypass on the Remission of Type II Diabetes Mellitus (DIABAR)

The Effects of the Laparoscopic Roux-en-Y Gastric Bypass and the Laparoscopic Mini Gastric Bypass on the Remission of Type II Diabetes Mellitus and the Pathophysiological Mechanisms That Drive the Conversion of Malign to Benign Obesity

It is estimated that there will be 439-552 million people with type 2 diabetes mellitus (T2DM) globally in 2030. Type 2 Diabetes Mellitus is present in one quarter of patients at the bariatric outpatient clinic. It is undecided which metabolic surgery grants best results in the remission of T2DM and which procedure does that at the lowest rate of surgical complications, long term difficulties and side effects. Non alcoholic fatty liver disease (NAFLD) is present in 80% of all morbidly obese subjects and is a major risk factor for development of insulin resistance and non alcoholic steatohepatis (NASH). It is increasingly recognized that the immune system, possibly driven by innate lymphoid cells (ILC's), and the intestinal microbiome are major players in this obesity related disease and the switch from benign to malign (insulin resistance and T2DM) obesity. However, the exact mechanisms of action behind the surgery-driven switch back from malign to benign obesity are unknown.Primary objective is to evaluate and compare the glycaemic control in T2DM within the first year of LRYGB and LMBG. Secondary aim is to gain insight in the pathophysiological mechanisms that drive the conversion of malign to benign obesity.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes Mellitus; Obesity, Morbid
• Intervention / Treatment: Procedure: laparoscopic Roux-en-Y gastric bypass; Procedure: laparoscopic Mini gastric bypass

Detailed Description

Metabolic surgery has proven to be a viable long-term solution in the treatment of morbid obesity and its comorbidities. It induces rapid remission of type 2 diabetes mellitus (T2DM). Type 2 Diabetes Mellitus is present in one quarter of patients at the bariatric outpatient clinic. Non alcoholic fatty liver disease (NAFLD) is present in 80% of all morbidly obese subjects and is a major risk factor for development of insulin resistance and non alcoholic steatohepatis (NASH), with the latter becoming the major indication for liver transplantation in the USA. It is increasingly recognized that the immune system, possibly driven by innate lymphoid cells (ILC's), and the intestinal microbiome are major players in this obesity related disease and the switch from benign to malign (insulin resistance and T2DM) obesity. However, the exact mechanisms of action behind the surgery-driven switch back from malign to benign obesity are unknown. Also, it is undecided which metabolic surgery grants best results in the remission of T2DM and which procedure does that at the lowest rate of surgical complications, long term difficulties and side effects. The Laparoscopic Roux-en-Y Gastric Bypass (LRYGB), an efficient but complex procedure, is the golden standard in the Netherlands. The Laparoscopic Mini Gastric Bypass (LMGB) is technically less challenging and has been introduced to overcome some of the limitations of LRYGB. It has been hypothesized that the LMGB has a more rapid and durable glycaemic control, possibly due to the altered constitution and the augmented length of the biliary limb. There is reason to believe that the improved glycaemic control might become apparent within the first year of surgery and that it might remain thereafter. However, it is unknown what order of magnitude is to be expected and whether subgroups of T2DM patients will benefit the LMGB more. Also, it is unknown whether and to what extent intestinal microbiota and immunological tone can predict the metabolic response (improvement in insulin sensitivity) and NAFLD/NASH reduction and whether differences are expected between these two surgeries. Increased understanding of the pathophysiological mechanisms as well as their relationship to metabolic disturbances are thought to be of crucial importance to discover new diagnostic and therapeutical targets in obesity associated insulin resistance/T2DM and NAFLD/NASH. Primary objective is to evaluate and compare the glycaemic control in T2DM within the first year of LRYGB and LMBG. Secondary aim is to gain insight in the pathophysiological mechanisms that drive the conversion of malign to benign obesity.

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Anne-Sophie van Rijswijk, MD; Phone Number: +31205124460; Email: anne-sophie.vanrijswijk@slz.nl
• Study Contact Backup: Name: Maurits de Brauw, MD PhD; Email: maurits.debrauw@slz.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1066EC
      • Recruiting
      • Medical Center Slotervaart
      • Contact: Anne-Sophie van Rijswijk, MD; Phone Number: +31205014460; Email: anne-sophie.vanrijswijk@slz.nl
      • Contact: Maurtis de Brauw, MD PhD; Email: maurits.debrauw@slz.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI ≥35 and ≤50 kg/m2
• Diagnosis and treatment of T2DM at intake at bariatric ward with use of anti-diabetic medication.
• American Society of Anaesthesiologist Classification (ASA) ≤3
• All patients are required to lose 6 kilograms of weight prior to surgery

Exclusion Criteria:

• Known genetic basis for insulin resistance or glucose intolerance
• Type 1 DM
• Prior Bariatric surgery
• Patients requiring a concomitant intervention (such as cholecystectomy, ventral hernia repair)
• Auto-immune gastritis
• Known presence of gastro-esophageal reflux disease
• Known presence of large hiatal hernia requiring concomitant surgical repair
• Coagulation disorders (PT time > 14 seconds, aPTT ((dependent on laboratory methods) or known presence of bleeding disorders (anamnestic))
• Known presence of hemoglobinopathy
• Uncontrolled hypertension (RR > 150/95 mmHg)
• Renal insufficiency (creatinine > 150 umol/L)
• Pregnancy
• Breastfeeding
• Alcohol or drug dependency
• Primary lipid disorder
• Participation in any other (therapeutic) study that may influence primary or secondary outcomes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Laparoscopic Roux-en-Y gastric bypass	Procedure: laparoscopic Roux-en-Y gastric bypass; laparoscopic Roux-en-Y gastric bypass with a 50 cm biliary limb and a 150 cm alimentary limb; Other Names: gastric bypass
Experimental: Laparoscopic Mini Gastric Bypass; laparoscopic Mini gastric bypass	Procedure: laparoscopic Mini gastric bypass; laparoscopic Mini gastric bypass with a gastrojejunostomy at 200 centimeters measured from the ligament of Treitz; Other Names: One anastomosis gastric bypass, omega loop gastric bypass

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
glycaemic control	as measured by the difference in HBa1C	12 months FU

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
glycaemic control	as measured by the difference in HBa1C	6 and 24 months FU
glycaemic control	as measured by the difference in HBa1C and anti-diabetic medication	6, 12 and 24 months FU
Insulin sensitivity	Mixed meal tolerance test for level of insulin sensitivity	baseline, 12, 24 months FU
NAFLD/NASH	NAFLD/NASH parameters in liver biopsy measured with the Steatosis, Activity and Fibrosis (SAF) score according to Bedossa et al (2012).For each patient a SAF score summarizing the main histological lesions will be defined. The steatosis score (S) will assess the quantities of larger or median-sized lipid droplets but not foamy microvesicules from 0 to 3 (S0 <5%; S1 5-33%; S2 34-66% and S3>67%). Activity grade (A) from 0-4 is the unweighted addition of hepatocyte ballooning (0-2) and lobular inflammation (0-2). Stage of fibrosis will be assessed using the score described by NASH-CRN as follows; stage 0 (F0) no fibrosis; stage 1 (F1) 1a or 1b perisinusoidal zone 3 or 1c portal fibrosis; stage 2 (F2) persinusoidal and periportal fibrosis without bridging; stage 3 (F3) bridging fibrosis and stage 4 (F4) cirrhosis. A diagnostic algorithm which will be used during this study can be found in the original paper published by Bedossa et al.	day of surgery, reoperation
Presence of bacterial DNA/bacterial metabolites - portal vein	in portal vein blood	day of surgery, reoperation
Presence of bacterial DNA/bacterial metabolites - liver	in liver	day of surgery, reoperation
Presence of bacterial DNA/bacterial metabolites - abdominal adipose tissue	in abdominal adipose tissue depots	day of surgery, reoperation
Expression and differentiation of intestinal immunological cells - GALT	in GALT	day of surgery, reoperation
Expression and differentiation of intestinal immunological cells - abdominal adipose tissue	in abdominal adipose tissue depots	day of surgery, reoperation
Expression and differentiation of intestinal immunological cells - liver	in liver	day of surgery, reoperation
Expression and differentiation of intestinal immunological cells - peripheral blood	in peripheral blood	day of surgery, reoperation
Expression and differentiation of immunological cells	ILC's, macrophages	12 and 24 months FU
Expression and differentiation of inflammatory markers	IL6, IRX3 and 5	12 and 24 months FU
Small intestinal and fecal microbiota composition	feces	2, and 6 weeks, 6 months, as well as 12 and 24 months after surgery
Peripheral blood inflammatory markers	ILC's, macrophages, T/B-cells and dendritic cells	2, and 6 weeks, 6 months, as well as 12 and 24 months after surgery
Eating habits	G-food craving questionnaire (FCQ-T) 21 item questionaire scale 0 (never) - 6 (always)	baseline, 12, 24 months FU
Eating habits	10 questions, scale 0-10 for instance 0 not hungry -10 very hungry / satiety / craving salty food / craving sweet food / craving fat food	baseline, 12, 24 months FU
Excreted metabolites	urine	baseline, 12, 24 months FU
Bio electric impedance	body composition as assesed by bioelectical impedance analysis (BIA): the measurement of body fat in relation to lean body mass.	baseline, 12, 24 months FU
Quality of life	Quality of life (IWQOL lite) 5 domain questionaire, 31 items: 1 never true - 5 always true	baseline, 12, 24 months FU
Cardiac / ventricular hypertrophy	Electrocardiogram (ECG)	baseline, 12, 24 months FU

Collaborators and Investigators

• Sponsor: Slotervaart Hospital
• Collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Maurits de Brauw, MD PhD, Head of department of Surgery

Publications and helpful links

General Publications

• van Rijswijk A, van Olst N, Meijnikman AS, Acherman YIZ, Bruin SC, van de Laar AW, van Olden CC, Aydin O, Borger H, Beuers UHW, Herrema H, Verheij J, Apers JA, Backhed F, Gerdes VEA, Nieuwdorp M, de Brauw LM. The effects of laparoscopic Roux-en-Y gastric bypass and one-anastomosis gastric bypass on glycemic control and remission of type 2 diabetes mellitus: study protocol for a multi-center randomized controlled trial (the DIABAR-trial). Trials. 2022 Oct 22;23(1):900. doi: 10.1186/s13063-022-06762-3.

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2017
• Primary Completion (Anticipated): November 1, 2021
• Study Completion (Anticipated): November 1, 2021

Study Registration Dates

• First Submitted: October 13, 2017
• First Submitted That Met QC Criteria: October 30, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): November 9, 2017
• Last Update Submitted That Met QC Criteria: November 8, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Morbid Obesity; Type 2 diabetes mellitus; Roux-en-Y gastric bypass; Mini gastric bypass
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Obesity; Obesity, Morbid
• Other Study ID Numbers: P1729

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