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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
220
laparoscopic Roux-en-Y gastric bypass with a 50 cm biliary limb and a 150 cm alimentary limb
laparoscopic Mini gastric bypass with a gastrojejunostomy at 200 centimeters measured from the ligament of Treitz
medical Center Slotervaart
Amsterdam, North Holland, Netherlands
RECRUITINGglycaemic control
as measured by the difference in HBa1C
Time frame: 12 months FU
glycaemic control
as measured by the difference in HBa1C
Time frame: 6 and 24 months FU
glycaemic control
as measured by the difference in HBa1C and anti-diabetic medication
Time frame: 6, 12 and 24 months FU
Insulin sensitivity
Mixed meal tolerance test for level of insulin sensitivity
Time frame: 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.
Time frame: day of surgery, reoperation
Presence of bacterial DNA/bacterial metabolites - portal vein
in portal vein blood
Time frame: day of surgery, reoperation
Presence of bacterial DNA/bacterial metabolites - liver
in liver
Time frame: day of surgery, reoperation
Presence of bacterial DNA/bacterial metabolites - abdominal adipose tissue
in abdominal adipose tissue depots
Time frame: day of surgery, reoperation
Expression and differentiation of intestinal immunological cells - GALT
in GALT
Time frame: day of surgery, reoperation
Expression and differentiation of intestinal immunological cells - abdominal adipose tissue
in abdominal adipose tissue depots
Time frame: day of surgery, reoperation
Expression and differentiation of intestinal immunological cells - liver
in liver
Time frame: day of surgery, reoperation
Expression and differentiation of intestinal immunological cells - peripheral blood
in peripheral blood
Time frame: day of surgery, reoperation
Expression and differentiation of immunological cells
ILC's, macrophages
Time frame: 12 and 24 months FU
Expression and differentiation of inflammatory markers
IL6, IRX3 and 5
Time frame: 12 and 24 months FU
Small intestinal and fecal microbiota composition
feces
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: baseline, 12, 24 months FU
Excreted metabolites
urine
Time frame: 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.
Time frame: baseline, 12, 24 months FU
Quality of life
Quality of life (IWQOL lite) 5 domain questionaire, 31 items: 1 never true - 5 always true
Time frame: baseline, 12, 24 months FU
Cardiac / ventricular hypertrophy
Electrocardiogram (ECG)
Time frame: baseline, 12, 24 months FU
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