LISBON – Improved glucose parameters, substantial weight loss, and increased incretin hormone levels can be achieved by the insertion of a novel, minimally invasive, intestinal device in obese patients with type 2 diabetes.
The use of a duodenal-jejunal bypass liner (DJBL) not only improves hemoglobin A1c and aids weight loss, but also appears to increase levels of glucagon-like peptide (GLP)-1 and peptide YY while in place, according to the findings of a small study presented at the annual meeting of the European Society for the Study of Diabetes.
Although the effects may be temporary, they could offer patients a reversible alternative to bariatric surgery that helps to kick-start weight loss and self-management of diabetes, said study author Dr. Charlotte de Jonge of Maastricht University Medical Centre in the Netherlands. "Not all patients want [bariatric] surgery, as it is permanent."
She added that the DJBL was perhaps "an easy first step" and that patients could perhaps still opt for weight-loss surgery later on or be retreated with the device to the point that medication was again sufficient to help manage their diabetes.
The DJBL (EndoBarrier) is a 60-cm impermeable sleeve that is inserted and removed endoscopically, and which effectively blocks the duodenum and proximal jejunum in a manner similar to the Roux-en-Y-gastric bypass procedure. It is thought to work by creating a physical barrier between ingested food and the intestinal wall, and perhaps alters the activation of incretin hormones in the gut. On average, the device can be inserted in 20 minutes and removed in 10 minutes, under conscious sedation, which allows the patient to go home the same day as the procedure.
The aim of the 17-patient study was to investigate the possible mechanisms for the improvement in diabetic parameters after insertion of the DJBL seen in previous studies. Fourteen men and three women participated, all of whom had type 2 diabetes and a body mass index in excess of 30 kg/m2. All ate a low-calorie diet during the study, which restricted their intake to around 1,200-1,500 kcal per day. Participants consulted a nutritionist every month, but the diet was not prescriptive.
Before implantation of the device, subjects underwent a meal tolerance test that involved a 12-hour fast, then ingestion of a 500-kcal liquid meal and blood sampling at baseline and at 10-, 20-, 30-, 60-, 90-, and 120-minute intervals. HbA1c, glucose, insulin, GLP-1, and PYY concentrations were measured. Measurements were repeated before removal of the device, and again 1 week after removal of the device.
The DJBL was left in place for 24 weeks, although Dr. de Jonge noted that the device could be used for up to 2 years in some patients. Around 500 patients have received the device in clinical studies, she said in an interview. It has received approval for use in a few European countries and Australia. It remains investigational in the United States.
Within 1 week after implantation, fasting and area under the curve (AUC) glucose concentrations were improved (11.4±0.5 mmol/L vs. 8.9±0.4 mmol/L and 1,999±88 vs. 1,535±53), respectively. In addition, AUC concentrations of GLP-1 increased from 2,584 at baseline to 4,112 at removal and PYY from 4,440 to 6,448 (P less than .01 for all comparisons with baseline).
When the device was removed at 6 months, a significant mean weight loss of 13 kg (P less than .001) had been recorded, with a mean loss of excess weight of 30% (P less than .001), said Dr. de Jonge. Importantly, mean HbA1c decreased from 8.4% at baseline to 7.0% at removal (P less than .001) and there was a reduction in the use of antidiabetic medication in all but one of the study participants.
"Interestingly, GLP-1 and GIP [glucose-dependent insulinotropic peptide] not only have an effect on insulin, but they also affect glucagon as well," Dr. de Jonge reported during her presentation. There was a normalization of the glucagon response during treatment with the DJBL to a more physiological response.
Almost all patients reported increased satiety, she added.
Commenting on the presentation, Dr. Roy Taylor, professor of medicine and metabolism at the University of Newcastle in England, noted that it would be useful to know what the effects of diet alone were and to see the relationship to the other changes in parameters shown.
In an interview, Dr. de Jonge noted that other data had suggested the weight loss achieved by diet alone was around 4-5 kg, so there did appear to be a greater weight loss effect when the DJBL was inserted.
With regard to side effects, the most common adverse events were abdominal discomfort, including epigastric pain and nausea. Such events were more common in the first 1-2 weeks, but tended to resolve with longer duration of use. There was no withdrawal of the device, and Dr. de Jonge noted that even when patients reported side effects, they were loath to have it removed.