A Novel Approach to Glycemic Control in Type 2 Diabetes Mellitus, Partial Jejunal Diversion: Pre-clinical to Clinical Pathway

Overview

Journal BMJ Open Diabetes Res Care

Specialty Endocrinology

Date 2017 Dec 12

PMID 29225893

Citations 4

Authors

Martin Fried

Karin Dolezalova

Adam P Chambers

Elliott J Fegelman

Robin Scamuffa

Michael L Schwiers

Jason R Waggoner

Martin Haluzik

Randy J Seeley

Affiliations

Soon will be listed here.

Abstract

Objective: To explore partial jejunal diversion (PJD) via a side-to-side jejuno-jejunostomy for improved glycemic control in type 2 diabetes mellitus (T2DM). PJD is an anatomy-sparing, technically simple surgery in comparison to the predominate metabolic procedures, Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). Positive results in a rodent model prompted a human proof-of-concept study.

Research Design And Methods: Pre-clinically, 71 rats were studied in a model of metabolic dysfunction induced by a high-fat diet; 33 animals undergoing one of two lengths of PJD were compared with 18 undergoing sham, 10 RYGB and 10 jejuno-ileal bypass. Clinically, 15 adult subjects with treated but inadequately controlled T2DM (hemoglobin A1c (HbA1c) of 8.0%-11.0%), body mass index of 27.0-40.0 kg/m, and C peptide ≥3 ng/mL were studied. Follow-up was at 2 weeks, and 3, 6, 9, and 12 months post-PJD.

Results: Pre-clinically, positive impacts with PJD on glucose homeostasis, cholesterol, and body composition versus sham control were demonstrated. Clinically, PJD was performed successfully without serious complications. Twelve months post-surgery, the mean (SD) reduction from baseline in HbA1c was 2.3% (1.3) (p<0.01).

Conclusions: PJD may provide an anatomy sparing, low-risk, intervention for poorly controlled T2DM without significant alteration of the patient's lifestyle. The proof-of-concept study is limited by a small sample size and advanced disease, with 80% of participants on insulin and a mean time since diagnosis of over 10 years. Further study is warranted.

Trial Registration Number: NCT02283632; Pre-results.

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A rodent model of partial intestinal diversion: a novel metabolic operation.

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