The Treatment of Diabetic Gastroparesis With Botulinum Toxin Injection of the Pylorus

Abstract

OBJECTIVE -Gastroparesis is a disorder of delayed gastric emptying that is often chronic in nature. Up to 50% of type 1 diabetic subjects have symptoms of gastroparesis, which include nausea, vomiting, and early satiety. Elevated pyloric pressures may be responsible for delayed gastric emptying in diabetic subjects. Botulinum toxin inhibits the release of acetylcholine and produces transient paralysis when injected into smooth muscle. The aim of this study was to determine whether injection of the pylorus with botulinum toxin in patients with diabetic gastroparesis improves symptoms of gastroparesis, alters gastric emptying scan time, and/or changes weight and insulin use. RESEARCH DESIGN AND METHODS -This was an open-label trial with age-and sex-matched control subjects from a tertiary care referral center for patients with gastroparesis. Eight type 1 diabetic subjects (six women and two men; mean age 41 years; mean years with diabetes 25.3) who had failed standard therapy were enrolled. Intervention consisted of injection of the pylorus with 200 units of botulinum toxin during upper endoscopy. Symptoms, antropyloric manometry, gastric emptying scan times, weight, and insulin use were all recorded before intervention and during a 12-week follow-up period.RESULTS -Seven of the eight patients completed the full 12-week follow-up period. No complications were noted. Mean symptom scores declined from 27 to 12.1 (P Ͻ 0.01), whereas the SF-36 physical functioning domain also improved (P Ͻ 0.05). Four patients noted an increase in insulin use of Ͼ5 units/day. Six of the seven patients gained weight (P ϭ 0.05). Gastric emptying scan time improved in four patients.CONCLUSIONS -Botulinum toxin injection of the pylorus is safe and improves symptoms in patients with diabetic gastroparesis. These results warrant further investigation with a large, double-blind, placebo-controlled trial. Diabetes Care 27:2341-2347, 2004G astroparesis is a disorder of gastrointestinal motility defined as a delay in gastric emptying in the absence of mechanical obstruction. Common symptoms include early satiety, nausea, vomiting, anorexia, weight loss, and epigastric pain. Gastroparesis is a common problem in type 1 diabetic subjects (1,2), especially in the presence of hyperglycemia (3). Treatment options include erythromycin (4,5), metoclopramide (6), domperidone (7), and cisapride (8), although all of these medications have limitations. Pylorospasm is thought to be a contributing factor in the development of diabetic gastroparesis (9). Reports of intrapyloric botulinum toxin injection to relieve symptoms of gastroparesis (10 -14) prompted us to perform a trial in eight patients with severe diabetic gastroparesis who had failed standard therapy.The hypothesis was that elevated pyloric pressures delay gastric emptying, and thus transient paralysis of the pylorus should accelerate gastric emptying and improve symptoms of nausea and vomiting. Preliminary data from this study was presented in abstract form at the American College of Gastroentero...

Tetrahydrobiopterin (BH4), a cofactor for nNOS, restores gastric emptying and nNOS expression in female diabetic rats

“…We next examined the effects of BH4 deficiency on NO release from pyloric strips in vitro. Gastric muscle strips were incubated with 10 mmol of DAHP, a specific inhibitor of GTPCH1, for 24 (Fig. 2A).…”

Endoscopic Ultrasound-Guided Gastric Botulinum Toxin Injections in Obese Subjects: A Pilot Study

“…BTA injection is used therapeutically to treat human gastrointestinal disorders, including achalasia and anal fissure, at doses ranging from 100 to 300 U of the Botox formulation [21]. Doses of 200 U of Botox injected into the pylorus have been reported to improve symptoms of gastroparesis, without adverse effects [5,22]. Doses of up to 500 U of the lower-potency Dysport formulation of BTA have been injected in the stomach [6], but 500 U of Dysport has an estimated potency equivalent to 125 U of the Botox formulation [23].…”

Endoscopic Botulinum Toxin Injection for the Treatment of Diabetic Gastropathy in Pancreas and Islet-cell Transplant Patients

“…In a case study involving a single patient with type 1 diabetes, Gupta and associates 16 demonstrated a return of normally coordinated peristaltic activity in the antroduodenal region after botulinum injection, with an improvement in the patient's level of nausea and vomiting. Lacy and associates 17 have shown a substantial decrease in symptom scoring in 8 type 1 diabetic patients after a botulinum injection. However, of 2 randomized controlled trials performed to date, neither found a significant difference in either symptom scoring (P = NS; P = .42) or solid or liquid gastric emptying (P = NS) between botulinum toxin and placebo.…”