Clinical trial NCT01778738: Type 2 Diabetes After Sleeve Gastrectomy and Roux-en-Y Gastric Bypass: A Randomised Single Centre Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes
Morbid Obesity
Lead sponsor: Sykehuset i Vestfold HF
Sponsor class: OTHER
First posted: 2013-01-29
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Remission of type 2 diabetes.
timeFrame: One year
measure: Beta-cell function
timeFrame: One Year
Secondary outcomes:
measure: Glycaemic control
timeFrame: Five weeks to five years
measure: Insulin secretion
timeFrame: Five weeks to five years
measure: Insulin sensitivity
timeFrame: Five weeks to five years
measure: Anti-diabetic medication
timeFrame: Five weeks to five years
measure: Body weight
timeFrame: Five weeks to five years
measure: Body composition
timeFrame: Five weeks to five years
measure: Blood pressure
timeFrame: Five weeks to five years
measure: Pulse wave velocity
timeFrame: Five weeks to five years
measure: Lipidemia
timeFrame: Five weeks to five years
measure: Obstructive sleep apnoea
timeFrame: Five weeks to five years
measure: Proteinuria
timeFrame: Five weeks to five years
measure: Gastroesophageal reflux disease
timeFrame: One to five years
measure: Gastroesophageal motility disorders
timeFrame: One to five years
measure: Fatty liver disease
timeFrame: One to five years
measure: Gut microbiota
timeFrame: One to five years
measure: Physical activity
timeFrame: Five weeks to five years
measure: Energy intake and eating behaviour
timeFrame: Five weeks to five years
measure: Health related quality of life
timeFrame: Five weeks to five years
measure: Obesity-related symptoms
timeFrame: Five weeks to five years
measure: Psychological distress
timeFrame: Five weeks to five years
measure: Bone mineral density
timeFrame: Five weeks to five years
measure: Dumping syndrome
timeFrame: Five weeks to five years
measure: Vitamin and mineral deficiencies
timeFrame: Five weeks to five years
Other outcomes:
Locations:
city: Tønsberg
country: Norway
facility: The Morbid Obesity Center, Vestfold Hospital Trust
state: Vestfold
Study officials:
affiliation: Head of the Morbid Obesity Centre
name: Jøran Hjelmesæth, Professor
role: STUDY_CHAIR
References:
citation: Hofso D, Fatima F, Borgeraas H, Birkeland KI, Gulseth HL, Hertel JK, Johnson LK, Lindberg M, Nordstrand N, Cvancarova Smastuen M, Stefanovski D, Svanevik M, Gretland Valderhaug T, Sandbu R, Hjelmesaeth J. Gastric bypass versus sleeve gastrectomy in patients with type 2 diabetes (Oseberg): a single-centre, triple-blind, randomised controlled trial. Lancet Diabetes Endocrinol. 2019 Dec;7(12):912-924. doi: 10.1016/S2213-8587(19)30344-4. Epub 2019 Oct 31.
citation: Borgeraas H, Hjelmesaeth J, Birkeland KI, Fatima F, Grimnes JO, Gulseth HL, Halvorsen E, Hertel JK, Hillestad TOW, Johnson LK, Karlsen TI, Kolotkin RL, Kvan NP, Lindberg M, Lorentzen J, Nordstrand N, Sandbu R, Seeberg KA, Seip B, Svanevik M, Valderhaug TG, Hofso D. Single-centre, triple-blinded, randomised, 1-year, parallel-group, superiority study to compare the effects of Roux-en-Y gastric bypass and sleeve gastrectomy on remission of type 2 diabetes and beta-cell function in subjects with morbid obesity: a protocol for the Obesity surgery in Tonsberg (Oseberg) study. BMJ Open. 2019 Jun 4;9(6):e024573. doi: 10.1136/bmjopen-2018-024573.
citation: Lorentzen J, Medhus AW, Hertel JK, Borgeraas H, Karlsen TI, Kolotkin RL, Sandbu R, Sifrim D, Svanevik M, Hofso D, Seip B, Hjelmesaeth J. Erosive Esophagitis and Symptoms of Gastroesophageal Reflux Disease in Patients with Morbid Obesity with and without Type 2 Diabetes: a Cross-sectional Study. Obes Surg. 2020 Jul;30(7):2667-2675. doi: 10.1007/s11695-020-04545-w.
citation: Hofso D, Hillestad TOW, Halvorsen E, Fatima F, Johnson LK, Lindberg M, Svanevik M, Sandbu R, Hjelmesaeth J. Bone Mineral Density and Turnover After Sleeve Gastrectomy and Gastric Bypass: A Randomized Controlled Trial (Oseberg). J Clin Endocrinol Metab. 2021 Jan 23;106(2):501-511. doi: 10.1210/clinem/dgaa808.
citation: Fatima F, Hjelmesaeth J, Hertel JK, Svanevik M, Sandbu R, Smastuen MC, Hofso D. Validation of Ad-DiaRem and ABCD Diabetes Remission Prediction Scores at 1-Year After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy in the Randomized Controlled Oseberg Trial. Obes Surg. 2022 Mar;32(3):801-809. doi: 10.1007/s11695-021-05856-2. Epub 2022 Jan 4.
citation: Fatima F, Hjelmesaeth J, Birkeland KI, Gulseth HL, Hertel JK, Svanevik M, Sandbu R, Smastuen MC, Hartmann B, Holst JJ, Hofso D. Gastrointestinal Hormones and beta-Cell Function After Gastric Bypass and Sleeve Gastrectomy: A Randomized Controlled Trial (Oseberg). J Clin Endocrinol Metab. 2022 Jan 18;107(2):e756-e766. doi: 10.1210/clinem/dgab643.
citation: Seeberg KA, Borgeraas H, Hofso D, Smastuen MC, Kvan NP, Grimnes JO, Lindberg M, Fatima F, Seeberg LT, Sandbu R, Hjelmesaeth J, Hertel JK. Gastric Bypass Versus Sleeve Gastrectomy in Type 2 Diabetes: Effects on Hepatic Steatosis and Fibrosis : A Randomized Controlled Trial. Ann Intern Med. 2022 Jan;175(1):74-83. doi: 10.7326/M21-1962. Epub 2021 Nov 30.
citation: Lorentzen J, Medhus AW, Hofso D, Svanevik M, Seip B, Hjelmesaeth J. Sleeve Gastrectomy Confers Higher Risk of Gastroesophageal Reflux Disease Than Gastric Bypass: A Randomized Controlled Trial From the Oseberg Reflux Working Group. Gastroenterology. 2021 Dec;161(6):2044-2046.e4. doi: 10.1053/j.gastro.2021.08.021. Epub 2021 Aug 20. No abstract available.
citation: Seeberg KA, Hofso D, Borgeraas H, Grimnes JO, Fatima F, Seeberg LT, Kvan NP, Svanevik M, Hertel JK, Hjelmesaeth J. Association between hepatic steatosis and fibrosis with measures of insulin sensitivity in patients with severe obesity and type 2 diabetes - a cross-sectional study. BMC Gastroenterol. 2022 Nov 7;22(1):448. doi: 10.1186/s12876-022-02550-0.