Severe Diabetic Gastroparesis Research Articles

Metoclopramide Nasal Spray in Women with Symptomatic Diabetic Gastroparesis: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study

Background & AimsMetoclopramide nasal spray (MNS) was developed as an alternative to oral metoclopramide. Prior phase 2 studies demonstrated efficacy in reducing symptoms in women, but not men with diabetic gastroparesis. The aim of this phase 3 study was to further determine the safety and efficacy of MNS compared to placebo in reducing symptoms of diabetic gastroparesis in women. MethodsThis US multi-center, randomized, double-blind, parallel group study enrolled women aged 18 to 75 years with diabetic gastroparesis and delayed gastric emptying. Subjects were randomized 1:1 to receive placebo or MNS 10 mg. The primary efficacy endpoint was change in mean daily Gastroparesis Symptom Assessment (GSA) total score from baseline to week 4. The GSA daily diary is a validated patient-reported outcome instrument that averages scores of nausea, early satiety, prolonged fullness, bloating, and upper abdominal pain on a five-point ordinal scale. ResultsTwo-hundred-five subjects were randomized to receive placebo (n = 103) or MNS (n = 102). Overall, the MNS group did not experience a significant reduction in symptoms compared to the placebo group from baseline to week 4 (P = 0.881). However, subjects with moderate to severe symptoms at baseline had a significant treatment effect from weeks 1 to 3 (P < 0.05) and experienced a significant reduction in nausea and upper abdominal pain for all four weeks versus placebo (P < 0.05). Treatment-emergent adverse events were primarily mild to moderate with headache and abdominal pain reported most frequently. ConclusionsAlthough the primary endpoint was not met using all enrolled patients, treatment with MNS provided significant relief for women with moderate to severe diabetic gastroparesis symptoms. MNS was well tolerated and demonstrated a similar safety profile to placebo. ClinicalTrials.gov identifier: NCT02025725.

S2054 A Low Cost, Novel Treatment Approach for Severe Diabetic Gastroparesis Based on Burkitt’s Fiber Hypothesis: A Case Report

S2054 A Low Cost, Novel Treatment Approach for Severe Diabetic Gastroparesis Based on Burkitt’s Fiber Hypothesis: A Case Report

Severe diabetic gastroparesis - two cases of challenging treatment

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

NICE guidance on gastroelectrical stimulation for gastroparesis

Patients with severe diabetic gastroparesis with intractable bouts of nausea and vomiting are often refractory to drug therapy and have poor quality of life with malnutrition, weight loss, poor glycaemic control and frequent hospital admissions. Such patients may benefit from gastroelectrical stimulation (GES). The NICE guidance on GES for gastroparesis in 2004 did not support its use but since then a considerable amount of new evidence has become available and NICE updated the guidance in May 2014.

Gastric emptying and glycaemia in health and diabetes mellitus.

The rate of gastric emptying is a critical determinant of postprandial glycaemia and, accordingly, is fundamental to maintaining blood glucose homeostasis. Disordered gastric emptying occurs frequently in patients with longstanding type 1 diabetes mellitus and type 2 diabetes mellitus (T2DM). A complex bidirectional relationship exists between gastric emptying and glycaemia--gastric emptying accounts for ∼35% of the variance in peak postprandial blood glucose concentrations in healthy individuals and in patients with diabetes mellitus, and the rate of emptying is itself modulated by acute changes in glycaemia. Clinical implementation of incretin-based therapies for the management of T2DM, which diminish postprandial glycaemia, in part by slowing gastric emptying, is widespread. Other therapies for patients with T2DM, which specifically target gastric emptying include pramlintide and dietary-based treatment approaches. A weak association exists between upper gastrointestinal symptoms and the rate of gastric emptying. In patients with severe diabetic gastroparesis, pathological changes are highly variable and are characterized by loss of interstitial cells of Cajal and an immune infiltrate. Management options for patients with symptomatic gastroparesis remain limited in their efficacy, which probably reflects the heterogeneous nature of the underlying pathophysiology.

Diabetic gastroparesis: recent insights into pathophysiology and implications for management

Delayed gastric emptying affects a substantial proportion of patients with long-standing diabetes, and when associated with symptoms and/or disordered glycemic control, affects quality of life adversely. Important clinicopathological insights have recently been gained by the systematic analysis of gastric biopsies from patients with severe diabetic gastroparesis, which may stimulate the development of new therapies in the coming decade. Experience with prokinetic therapies and treatments, such as pyloric botulinum toxin injection and gastric electrical stimulation, has established that relief of symptoms does not correlate closely with acceleration of delayed gastric emptying, and that well-designed controlled trials are essential to determine the efficacy of emerging therapies.

Two‐channel gastric pacing in patients with diabetic gastroparesis

Our primary goals were to investigate the effects of two-channel gastric pacing on gastric myoelectrical activity, and energy consumption with the secondary intent to monitor gastric emptying and symptoms in patients with severe diabetic gastroparesis. Four pairs of temporary pacing wires were inserted on the serosa of the stomach at the time of laparotomy to place the Enterra™ System in 19 patients with severe gastroparesis not responding to standard medical therapies. Two of the pairs were for electrical stimulation and the other two for recording. Five days after surgery the optimal pacing parameters for the entrainment of gastric slow waves in each patient were identified by serosal recordings. Two-channel gastric pacing was then initiated for 6 weeks using a newly developed external multi-channel pulse generator. Electrogastrogram (EGG), Total Symptom Score (TSS), and a 4-h gastric emptying test were assessed at baseline and after 6 weeks of active gastric pacing. Enterra™ device was turned OFF during the duration of this study. Two-channel gastric pacing at 1.1 times the intrinsic frequency entrained gastric slow waves and normalized gastric dysrhythmia. After 6 weeks of gastric pacing, tachygastria was decreased from 15 ± 3 to 5 ± 1% in the fasting state and from 10 ± 2 to 5 ± 1% postprandially (P < 0.05), mean TSS was reduced from 21.3 ± 1.1 to 7.0 ± 1.5 (P < 0.05) and mean 4-h gastric retention improved from 42 to 28% (P = 0.05). Two-channel gastric pacing is a novel treatment approach which is able to normalize and enhance gastric slow wave activity as well as accelerate gastric emptying in patients with diabetic gastroparesis with a goal safety profile.

A Most Unusual Pacemaker

We present a case of pacemaker artifact on 12-lead electrocardiogram that was initially interpreted as malfunction of the patient's dual-chamber cardiac pacemaker. It was ultimately determined to arise from an extracardiac gastric pacemaker, which had been inserted for refractory, severe diabetic gastroparesis. Proper functioning of both devices was confirmed, and settings were adjusted to test for interdevice interference. This is a report of a patient with both cardiac pacemaker and a gastric pacemaker. We review the literature on patients with multiple pacemaker devices, and conclude with several practical considerations for their care.

A Combination of Gastric Pacing and Neurostimulation as Effective Therapy for Severe Diabetic Gastroparesis

A Combination of Gastric Pacing and Neurostimulation as Effective Therapy for Severe Diabetic Gastroparesis

W2047 The Results of Two-Channel, Synchronized, Multipoint Gastric Electrical Pacing Effect On Gastric Emptying in Patients with Severe Diabetic Gastroparesis

W2047 The Results of Two-Channel, Synchronized, Multipoint Gastric Electrical Pacing Effect On Gastric Emptying in Patients with Severe Diabetic Gastroparesis

A case of severe, refractory diabetic gastroparesis managed by prolonged use of aprepitant

A 31-year-old woman with an 11-year history of poorly controlled type 1 diabetes mellitus was admitted with severe vomiting and ketoacidosis. The patient had been admitted to hospital on 14 occasions in the past 3 years for diabetic ketoacidosis precipitated by intractable vomiting, and she had been diagnosed with gastroparesis 2 years previously. Assessment of the patient's response to standard treatments for diabetic gastroparesis. These approaches involved tight glycemic control that included subcutaneous insulin infusion via a pump, correction of electrolyte disturbances, use of standard antiemetic and promotility agents, somatostatin-analog treatment, intrapyloric injection of botulinum toxin, and insertion of a percutaneous jejunal feeding tube. Severe diabetic gastroparesis refractory to standard treatments. The neurokinin-receptor antagonist aprepitant was started and her vomiting stopped within 24 h. This treatment was successfully continued for 4 months until a gastric electrical stimulation device was inserted, which enabled aprepitant treatment to be withdrawn and the percutaneous jejunostomy feeding tube to be removed. This successful treatment led to a substantial improvement in the patient's quality of life and overall glycemic control.

Is Two-Channel Synchronized, Multipoint Gastric Electrical Pacing (MGP) Able to Control Upper GI Symptoms and Improve Gastric Emptying in Patients with Severe Diabetic Gastroparesis?

Is Two-Channel Synchronized, Multipoint Gastric Electrical Pacing (MGP) Able to Control Upper GI Symptoms and Improve Gastric Emptying in Patients with Severe Diabetic Gastroparesis?

Gastric electrical stimulation for intractable vomiting in patients with chronic intestinal pseudoobstruction

Gastric electrical stimulation (GES) is effective for medically refractory nausea and vomiting in patients with idiopathic or diabetic gastroparesis (DGP). We studied whether GES has similar effects in chronic intestinal pseudoobstruction (CIP). Patients referred for chronic small bowel (SB) motor dysfunction requiring parenteral nutrition and having a weekly vomiting frequency (WVF) >/=7 refractory to prokinetics and antiemetics were included. Patients were implanted for high-frequency GES 12 stimuli min(-1), laparoscopy being the first-line implantation procedure. Results were compared with those obtained in 11 DGP patients. Three patients with familial CIP and one patient with postsurgical CIP fulfilled the criteria. Gastric emptying was delayed in two and was normal in two patients. SB transit time was markedly delayed. Laparoscopy was used in three patients, one patient required laparotomy. During GES, WVF decreased from 24 (mean) before GES to 6.9 at 12 months and 7.5 at last visit. Vomiting reduction was 50-90% at last visit. For the DGP patients, WVF decreased from 23 before GES to 3.5 at 12 months and 3.5 (P < 0.01) at last visit. In patients with CIP and medically refractory vomiting, GES seems to have an anti-vomiting effect comparable to that seen in patients with severe DGP. GES should be considered as a therapeutic option for these patients.

43 Gastric Electrical Stimulation in Severe Gastroparesis – The Scottish Experience

Introduction: Gastroparesis (GP) is a common complication of type 1 and 2 diabetes affecting up to 50% of the diabetic population. In severe cases diabetic gastroparesis (DGP) may be profoundly disabling with severe GI symptoms, prolonged hospital stay and potentially life‐threatening metabolic upset. Standard management of DGP with dietary changes or drug treatment is unsatisfactory in many patients. The development of gastric electrical stimulation (GES) in drug refractory DGP has been shown to be beneficial in this difficult group of patients. In Scotland GES has only recently been available as a treatment option and we report here our initial experience in both diabetic and idiopathic gastroparesis patients. We have treated 7 patients (5 female), age 30 (21–73) (median, range) over a 3 years period. Of the 7 patients 5 were type 1 diabetics and 2 had idiopathic gastroparesis. All had severe drug refractory GP and 6/7 had required enteral feeding prior to GES implantation. All 7 patients had GES initiated with the Enterra (Medtronic) neural stimulator placed at mini‐laparotomy. No peri‐operative complications were noted. One patient died of unrelated sepsis 6 month post‐implant. GES was initiated with standard parameters (frequency 14 Hz, intensity 5 mA, pulse width 330 μs; cycle on 0.1 s; cycle off 5 s).All 6 patients who had required enteral feeding pre‐GES had their feeding tubes removed at surgery and have had normal nutritional intake without supplemental feeding after GES [follow‐up 24 month (11–34)].Gastric emptying as assessed by dual phase solid/liquid labeled meals improved in 50% of our patients.Conclusions: GES significantly improves the weekly vomiting frequency in patients with GP and avoids the need for enteral feeding. Long‐term GES should be considered as a treatment option in all drug refractory GP patients. Results (6 months) PRE POST GES Median (range) Weekly vomiting frequency 25 (15–35) 4 (1–6) *p &lt; 0.001 Weight (kg) 49 (44–70) 54 (50–89) p = ns

An Insulin-dependent Diabetic Patient with Severe Diabetic Gastroparesis Successfully Treated with Domperidone Suppository

An Insulin-dependent Diabetic Patient with Severe Diabetic Gastroparesis Successfully Treated with Domperidone Suppository

Interstitial cells of Cajal in the gastric body in severe diabetic gastroparesis

Interstitial cells of Cajal in the gastric body in severe diabetic gastroparesis

Diabetic gastroparesis

AbstractWe describe the case of a man with chronic poor glycaemic control who developed multiple complications. Gastroparesis was proven on radio‐nucleotide scanning and failed to respond to therapeutic interventions. Despite his glycaemic control being optimised he was admitted frequently with intractable vomiting and abdominal pain and did not respond to conventional treatment. A percutaneous endoscopic feeding gastro‐jejunos‐tomy was inserted under local anaesthesia. The double lumen system allowed easy drainage of retained gastric content while facilitating jejunal feeding via a soft biliary tube. The technique we have described may be of benefit in the management of severe diabetic gastroparesis.

Severe refractory diabetic gastroparesis. What is the utility of jejunostomy tube placement? A long-term retrospective review of the 26 patients: [formula omitted], J.L. Barnett. Dept of Internal Medicine, University of Michigan, Ann Arbor, MI

Severe refractory diabetic gastroparesis. What is the utility of jejunostomy tube placement? A long-term retrospective review of the 26 patients: [formula omitted], J.L. Barnett. Dept of Internal Medicine, University of Michigan, Ann Arbor, MI

Conservative treatment with alternative routes of drug administration

There seems little doubt that this unfortunate young person has unusually severe diabetic gastroparesis, a condition thought to be due to vagal denervation of the stomach. It is important, however, to identify and correct factors that may be aggravating the gastroparesis to cause such a difficult problem that required admission to hospital for one whole year. Swings in blood sugar concentrations, in particular hyperglycaemia, and fluctuation in serum potassium concentrations, may slow gastric emptying. Also dietary fat is known to impair gastric motility. Certain drugs may worsen the situation. With severe gastric …

Effect of motilin on gastric emptying in patients with diabetic gastroparesis

Erythromycin markedly accelerates gastric emptying, possibly because it acts as a motilin agonist. In the present study, the effect of an equipotent dose of motilin was tested. In six patients with severe diabetic gastroparesis, gastric emptying of liquids and solids was examined scintigraphically after motilin or placebo in a double-blind crossover study. Motilin (10 pmol · kg−1 · min−1) or saline was infused over a 90-minute period starting 5 minutes before breakfast. Motilin markedly accelerated emptying. For liquids, the half-emptying time was reduced from 51 ± 6 to 22 ± 11 minutes (P < 0.01) and for solids from 111 ± 4 to 51 ± 12 minutes (P < 0.01). The mean increase in plasma motilin levels was 1315 ± 342 pg/mL, corresponding to an effective infusion rate of about 4 pmol · kg−1 · min−1. In the control experiments, basal motilin levels (173 ± 17 pg/ mL) were within the normal range but increased steadily postprandially, reaching 321 ± 25 pg/mL at the end of the study period, probably reflecting gastric distension. The postprandial increase in pancreatic polypeptide level was blunted compared with accepted normal values but was more pronounced during motilin infusion, i.e., 650 ± 217 vs. 279 ± 66 pg/mL (P < 0.01), probably because of the improved emptying. Our data show that motilin accelerates gastric emptying in diabetic gastroparesis and support the hypothesis that erythromycin's effect is mediated through motilin receptors.