Type 2 Diabetes After Sleeve Gastrectomy and Roux-en-Y Gastric Bypass: A Randomised Single Centre Study

Study Overview
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Brief Summary
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Glycaemia, insulin secretion and action in morbidly obes subjects with type 2 diabetes after sleeve gastrectomy ond Roux-en-Y gastric bypass: A randomised single centre study.

Detailed Description
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The Roux-en-Y gastric bypass operation combines restrictive and malabsorptive principles. It is the most commonly performed bariatric procedure worldwide (  50 %). Vertical (sleeve) gastrectomy on the other hand, is a purely restrictive procedure and has gained popularity and is now accepted as a valid procedure accounting for approximately five percent of the bariatric procedures performed worldwide. The remission rate of type 2 diabetes one to two years after bariatric surgery is approximately 70%. Some studies have indicate that the remission rate of type 2 diabetes is higher after gastric bypass than after sleeve gastrectomy. Other studies indicate a similar effect on the reduction in HbA1c. Weight reduction is comparable between gastric bypass and sleeve gastrectomy although some evidence suggets a larger weight loss following gastric bypass surgery. Larger weight loss can clearly contribute to somewhat greater improvement in glucose homeostasis after gastric bypass than after sleeve gastrectomy. Still, one might speculate that changes in gut hormones may contribute to higher remission rates of type 2 diabetes after gastric bypass than after sleeve gastrectomy. Improved β-cell function observed after gastric bypass surgery may be linked to higher postprandial levels of Glucagonlike peptide 1 as seen after gastric bypass surgery. Beta cell function has, to our knowledge, only been addressed in one previous study after sleeve gastrectomy, with the authors reporting an increased first-phase insulin secretion three days after the procedure. Although several studies have addressed changes in gastrointestinal hormones the incretin effect on insulin secretion after gastric bypass has been estimated in only a few studies. To the best of our knowledge the incretin effect on insulin secretion after sleeve gastrectomy remains unexplored.We are aware of four ongoing randomised controlled trials comparing the effect of gastric bypass and sleeve gastrectomy on several endpoints including weight and comorbidities (ClinicalTrial.gov identifiers: NCT00722995, NCT00356213, NCT00793143, and NCT00667706). However, these studies include both subjects with and with-out type 2 diabetes and are therefore not powered to detect between-group differences in HbA1c and beta-cell function in the diabetic patients. In conclusion, the effect of gastric bypass and sleeve gastrectomy on glycaemia is not fully elucidated. Moreover, the impact of altered beta-cell function post surgery needs to be explored. We hypothesise that greater improvement in beta-cell function after gastric bypass than after sleeve gastrectomy translates into better glycaemic control in subjects with type 2 diabetes one year after surgery.

Official Title
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Glycaemia, Insulin Secretion and Action in Morbidly Obese Subjects With Type 2 Diabetes After Sleeve Gastrectomy and Roux-en-Y Gastric Bypass: A Randomised Single Centre Study

Conditions
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Type 2 Diabetes, Morbid Obesity

Intervention / Treatment
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* Procedure: Bariatric surgery, either gastric bypass surgery or sleeve gastrectomy
* Procedure: Sleeve gastrecomy
* Procedure: Bastric bypass


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Previously verified BMI ≥35.0 kg/m2 and current BMI ≥33.0 kg/m2 HbA1c ≥6.5 % or use of anti-diabetic medications with HbA1c ≥6.1 % Age ≥18 years Exclusion criteria Not able to give informed consent Previously major abdominal surgery (appendectomy, laparoscopic cholecystectomy or gynaecological procedures not included) Severe endocrine-, heart-, lung-, liver- and kidney disease, cancer and other medical conditions associated with significantly increased risk of peri- and postoperative complications Drug or alcohol addiction Reduced compliance due to severe mental and psychiatric conditions Pregnancy Serum autoantibodies against glutamic acid decarboxylase (GAD) or tyrosine phosphatase (IA2) Regular use (a total of 3 months cumulative use in the last 12 months) or treatment the past two months with systemic corticosteroids Severe gastroesophageal reflux disease defined as Los Angeles classification grade > B, Barrett's oesophagus and/or hiatus hernia >5 cm Elevated esophageal pressure (DCI >5000 mmHg*sec*cm) and symptoms of dysphagia and/or painful swallowing.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sleeve gastrectomy<br>Sleeve gastrectomy. | Procedure: Bariatric surgery, either gastric bypass surgery or sleeve gastrectomy<br>* Vertical sleeve gastrectomy or a gastric bypass surgery in morbidly obese individuals with type 2 diabetes. Random allocation to surgical intervention<br>Procedure: Sleeve gastrecomy<br>* Vertical sleeve gastrectomy<br>|
| Experimental: Gastric bypass<br>Gastric bypass surgery. | Procedure: Bariatric surgery, either gastric bypass surgery or sleeve gastrectomy<br>* Vertical sleeve gastrectomy or a gastric bypass surgery in morbidly obese individuals with type 2 diabetes. Random allocation to surgical intervention<br>Procedure: Bastric bypass<br>* Gastric bypass surgery<br>|
| No Intervention: Control group<br>This is an extra control group without diabetes. All subjects are morbidly obese patients recruited from the Morbid Obesity Centre. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission of type 2 diabetes. | HbA1c below or equal to 6.0 % in the absence of glucose lowering drug therapy | One year | 
| Beta-cell function | Disposition index calculated using glucose and insulin data obtained from a frequently sampled intravenous glucose tolerance test. | One Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycaemic control | HbA1c | Five weeks to five years | 
| Insulin secretion | Fasting and stimulated levels of glucose, insulin, C-peptide and proinsulin after an oral glucose load will be used for the calculation of insulin secretion. | Five weeks to five years | 
| Insulin sensitivity | Fasting and stimulated levels of glucose, insulin and C-peptide after an oral glucose load will be used for the calculation of insulin sensitivity. | Five weeks to five years | 
| Anti-diabetic medication | Use of glucose lowering agents | Five weeks to five years | 
| Body weight | Body weight (kg and kg/m2) | Five weeks to five years | 
| Body composition | Measured by DEXA and bioelectrical impedance analysis | Five weeks to five years | 
| Blood pressure | Resting and 24-h ambulatory systolic and diastolic blood pressure | Five weeks to five years | 
| Pulse wave velocity | The Sphygmocor system (Artcor, Sidney, Australia) and a single high-fidelity applanation tonometer (Millar®) will be used to measure pulse wave velocity. | Five weeks to five years | 
| Lipidemia | Cholesterol and triglyceride levels | Five weeks to five years | 
| Obstructive sleep apnoea | The ApneaLink Plus was used for the calculation of apnoeas and hypopnoeas during sleep. | Five weeks to five years | 
| Proteinuria | Urine protein-to-creatinine and albumin-to-creatinine ratios | Five weeks to five years | 
| Gastroesophageal reflux disease | Gastroesophageal reflux disease will be diagnosed using upper endoscopy, 24 hour intra-oesophageal pH monitoring and symptom scores. | One to five years | 
| Gastroesophageal motility disorders | High-resolution manometry | One to five years | 
| Fatty liver disease | MRI (Siemens Aera 1.5 T) and Chemical Shift Imaging18 will be used to quantify the fat-fraction content of the liver. | One to five years | 
| Gut microbiota | Microbial composition and diversity and quantification of organic acids and DNA extraction and metagenome data analysis. | One to five years | 
| Physical activity | Measured and self-reported physical activity | Five weeks to five years | 
| Energy intake and eating behaviour | Food frequency questionnaire, food tolerance questionnaire, power of food scale and binge eating scale | Five weeks to five years | 
| Health related quality of life | Short Form Quality of Life questionnaire (SF-36) v. 2.0 | Five weeks to five years | 
| Obesity-related symptoms | Impact on Weight Questionnaire IWQOL-Lite and Weight-Related Symptom Measure (WRSM) | Five weeks to five years | 
| Psychological distress | Beck Depression Inventory | Five weeks to five years | 
| Bone mineral density | DEXA scan | Five weeks to five years | 
| Dumping syndrome | Arts' questionnaire | Five weeks to five years | 
| Vitamin and mineral deficiencies | Vitamin (B1, B9, B12, D) and mineral (calcium, iron) levels in blood. | Five weeks to five years |