Endoscopic bariatric therapies and the effect of duodenal exclusionusing a duodenal-jejunal bypass liner (EndoBarrier®) on insulin sensitivity and blood lipid profile in patients with obesityand type 2 diabetes.

Abstract

Background: The Endobarrier® duodenal-jejunal bypass liner (DJBL) shows promise as a safe and effective therapeutic option for patients with obesity and type 2 diabetes (T2DM) by reducing weight and improving glycaemic control. Objective: Effectiveness of the Endobarrier® DJBL compared with intensive medical therapy, diet and exercise in the treatment of patients with obesity and T2DM. Design, setting and participants: Multicentre randomised controlled, open-label, trial at two University hospitals in England. 170 patients, aged 18 – 65 years, BMI 30–50 kg/m2 , with inadequately controlled T2DM (HbA1c 58 – 97 mmol/mol) on oral anti-hyperglycaemic medications, were randomised at a ratio of 1:1 by a centralised computer system. Trial Registration: ClinicalTrials.gov Identifier NCT02459561. Intervention: 12 months of intensive medical therapy with (n = 85) vs without (n = 85) the DJBL. Follow-up for 12 months. Outcome Measures: Primary outcome was the percentage of participants (using Intention to Treat) achieving a glycated haemoglobin (HbA1c) reduction of ≥20% at 12 months (reported elsewhere). Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months. Nested mechanistic studies examined alterations in insulin sensitivity, ß-cell function, lipid profile and blood concentrations of polyunsaturated fatty acids (PUFAs). Results: DJBL treatment resulted in significantly greater weight loss (DJBL -10.6 ± 6.2% vs. control -5.4 ± 5.8%, p<0.0001) and significantly more DJBL-treated patients achieved a ≥ 15% weight loss at 12 months (DJBL 24.2% vs. control 3.7% (OR 8.3, 95% CI: 1.8, 39.0; p=0.0071)). At 24 months there were no significant differences in weight loss between the two groups. Hepatic glucose production and fasting plasma glucose (FPG) concentrations significantly reduced within both groups at 10 days but were not significantly different between groups at any time-point. Peripheral insulin sensitivity increased significantly within both groups at 10 days and was significantly higher in the DJBL group at 6 months (rate of peripheral glucose disposal: DJBL 39.5 ± 15.8 µmol/kg/min vs. control 26.4 ± 11.1 µmol/kg/min (mean difference [95% CI] = 12.9 [5.0, 20.7], p = 0.002) and 11.5 months (HOMA2-%S, median (range): 90.4 (70.6 – 114.0) vs. 66.6 (50.4 -106.6), p = 0.02). Early improvements in beta cell function (HOMA2-%B) were observed but there were no differences between groups. Absolute concentrations of long-chain PUFAs, total serum cholesterol and LDLcholesterol were significantly lower in DJBL-treated patients after 1 year compared to controls (p<0.05). After the Endobarrier was removed, patients regained weight, insulin sensitivity decreased and insulin resistance, FPG and insulin concentrations increased. At 24 months, all values remained significantly improved from baseline but were not statistically different from control arm participants. Conclusions: One year of therapy with the Endobarrier DJBL in patients with obesity and T2DM resulted in superior weight loss, greater late improvements in peripheral insulin sensitivity and significant reductions in total serum cholesterol and LDL-C concentrations when compared to intensive medical therapy, diet and lifestyle advice alone. Early reductions in FPG may be as a consequence of improvements in hepatic insulin sensitivity but the DJBL provided no additional improvements to early changes in glucose homeostasis above that achieved through calorie restriction alone. Absolute blood concentrations of essential fatty acids and their long chain derivatives are depleted during 1 year of Endobarrier therapy and should be offset by maintaining an adequate dietary intake of PUFAs or by supplementation.

More information

Identifiers

ORCID for Philip Calder: orcid.org/0000-0002-6038-710X

Catalogue record

Export record