The treatment of diabetic gastroparesis with botulinum toxin injection of the pylorus

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 < 0.01), whereas the SF-36 physical functioning domain also improved (P < 0.05). Four patients noted an increase in insulin use of >5 units/day. Six of the seven patients gained weight (P = 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.     

非胃手术后胃排空障碍的肠内营养支持

目的:探讨肠内营养在非胃手术后功能性胃排空障碍治疗中的作用。方法:40例非胃手术后胃排空障碍患者随机分为肠内营养组(EN组)及肠外营养组(PN组)各15例,常规输液组(对照组)10例,比较各组胃肠减压量和胃排空障碍恢复时间。结果:EN组胃排空恢复时间明显短于PN组和对照组(P<0.01),胃肠减压量在治疗7和14d后明显少于PN组和对照组(P<0.05)。结论:肠内营养对胃排空功能的恢复有明显促进作用,对非胃手术后功能性胃排空障碍患者应尽量采用肠内营养支持。     

Pilot study on gastric electrical stimulation on surgery-associated gastroparesis: long-term outcome

OBJECTIVES: Patients with postgastric surgery gastroparesis are often unresponsive to conventional medical therapy. Gastric electrical stimulation (GES) with the use of high-frequency and low-energy neural stimulation is an approved technique for patients with idiopathic and diabetic gastroparesis. METHODS: We hypothesized that GES would improve symptoms, health resource utilization, and gastric emptying in six patients with postsurgical gastroparesis from a variety of surgical procedures. Patients were evaluated by means of the following criteria: symptoms, health-related quality of life, and gastric emptying tests at baseline over time. RESULTS: All patients noted improvements after device implantation for up to 46 months: the frequency score for weekly vomiting went from a baseline of 3.2 down to 0.4 immediately after treatment before settling at 1.4 by the long-term follow up. Total gastrointestinal symptom score went from 36.5 at baseline down to 12.3 before settling at 20.5 at long-term follow up. Improvements were also seen in health-related quality of life and solid and liquid gastric emptying. CONCLUSIONS: We conclude that GES is associated with clinical improvements in this group of patients with either postsurgical or surgery-associated gastroparesis. This pilot study with long-term outcomes offers evidence for a new therapy for otherwise refractory patients with gastroparesis associated with previous surgery.     

Gastroparesis: approach, diagnostic evaluation, and management

Gastroparesis is a chronic motility disorder of the stomach that involves delayed emptying of solids and liquids, without evidence of mechanical obstruction. Although no cause can be determined for the majority of cases, the disease often develops as a complication of abdominal surgeries or because of other underlying disorders, such as diabetes mellitus or scleroderma. The pathophysiology behind delayed gastric emptying is still not well-understood, but encompasses abnormalities at 3 levels--autonomic nervous system, smooth muscle cells, and enteric neurons. Patients will often cite nausea, vomiting, postprandial fullness, and early satiety as their most bothersome symptoms on history and physical examination. Those that present with severe disease may already have developed complications, such as the formation of bezoars or masses of undigested food. In patients suspected of gastroparesis, diagnostic evaluation requires an initial upper endoscopy to rule out mechanical causes, followed by a gastric-emptying scintigraphy for diagnosis. Other diagnostic alternatives would be wireless capsule motility, antroduodenal manometry, and breath testing. Once gastroparesis is diagnosed, dietary modifications, such as the recommendation of more frequent and more liquid-based meals, are encouraged. Promotility medications like erythromycin and antiemetics like prochlorperazine are offered for symptomatic relief. These agents may be frequently changed, as the right combination of effective medications will vary with each individual. In patients who are refractory to pharmacologic treatment, more invasive options, such as intrapyloric botulinum toxin injections, placement of a jejunostomy tube, or implantation of a gastric stimulator, are considered. Future areas of research are based on current findings from clinical studies. New medications, such as hemin therapy, are emerging because of a better understanding of the pathophysiology behind gastroparesis, and present treatment options, such as gastric electric stimulation, are evolving to be more effective. Regenerative medicine and stem cell-based therapies also hold promise for gastroparesis in the near future.     

The Investigation and Treatment of Diabetic Gastroparesis

Purpose

This review provides an update on the investigations and treatment options for gastroparesis.

胃大部切除术后胃排空障碍的病因及诊治分析

目的：探讨胃大部切除术后胃排空障碍（FDGE）发生的病因、诊断方法及治疗手段。方法：对2007年5月—2011年5月因胃大部切除术后出现胃排空障碍的患者的临床资料进行回顾性分析。结果：观察期间行胃大部切除术的134例患者中,8例出现胃排空障碍,发生率为6%。术前流出道梗阻和胃肠手术吻合方式是诱发本病的危险因素。X线口服造影、胃镜是诊断FDGE的重要手段。8例经对症保守治疗13~35 d后均治愈。结论：胃大部切除术后功能性胃排空障碍在临床上的发生率并不少见,准确诊断及积极治疗十分重要。     

Update on gastroparesis.

Gastroparesis is a manifestation of diabetic autonomic neuropathy. Gastrointestinal autonomic neuropathy contributes to morbidity, mortality, reduced quality of life, and increased healthcare costs of a patient with diabetes mellitus. Complications from gastroparesis include ketoacidosis, infection, and bezoar formation. The gold standard for the diagnosis of gastroparesis is a gastric emptying study. Other tests and procedures may also be performed to eliminate other causes of the symptoms. In general, treatment involves dietary and lifestyle adjustment as well as pharmacological interventions. Gastric electrical stimulation has recently emerged as an effective strategy in the management of these patients. Research is evolving in this area to include the use of botulinum toxin to control symptoms of gastroparesis. Patients with gastroparesis can be frustrated with the symptoms they experience, the intensive treatment regimens they must follow, as well as the medical procedures they undergo during the course of their treatment. Quality of life is an important factor to consider when caring for and supporting these patients. This article will provide an overview of gastroparesis and the latest treatments available to improve gastric motility and prevent further complications.     

Understanding diabetic gastroparesis: a case study.

The purpose of this article is to present an overview of diabetic gastroparesis, defined as delayed gastric emptying in the absence of mechanical obstruction. Diabetic gastroparesis is a substantial and unrecognized problem. Failure to treat may result in a decreased quality of life and a potential increase for morbidity. The treatment protocol for diabetic gastroparesis combines dietary and pharmacologic measures. This article will discuss normal physiology of gastric emptying along with the pathogenesis of delayed emptying in patients with diabetes. Nursing implications for the care of the patient with diabetic gastroparesis is also presented along with commonly used pharmacologic agents.     

Delayed gastric emptying and gastric autoimmunity in type 1 diabetes

OBJECTIVE: Delayed gastric emptying and/or gastrointestinal symptoms occur in 30-50% of diabetic patients. Known contributing factors are autonomic neuropathy and acute hyperglycemia, but the role of gastric autoimmunity has never been investigated, although 15-20% of type 1 diabetic patients exhibit parietal cell antibodies (PCAs). We studied gastric motility in diabetes in relation to PCA status, autonomic nerve function, HbA(1c), thyroid-stimulating hormone (TSH), Helicobacter pylori (HP), acid production, and gastric histology. RESEARCH DESIGN AND METHODS: Gastric emptying of solids and liquids (measured by (13)C-octanoic acid and (13)C-glycine breath tests, respectively) was tested in euglycemic conditions in 42 type 1 diabetic patients (male/female: 29/13; 15 PCA+; mean age 40 +/- 15 years; mean HbA(1c) 7.8 +/- 0.9%). Gastrointestinal symptoms, autonomic nerve function (Ewing tests), PCA status (indirect immunofluorescence), gastric histology, and acid secretion (pentagastrin) were assessed. RESULTS: Solid gastric emptying was delayed in 40% and liquid emptying in 36% of patients. Gastric motility did not correlate with symptoms. PCA status, gastric morphology, and acid secretion were similar in those with and without gastroparesis. HbA(1c) level (beta = 1.34, P = 0.011) was the only risk factor for delayed solid emptying in a logistic regression model testing HbA(1c), autonomic nerve function, PCA, HP status, age, sex, diabetes duration, and TSH. Half-emptying time for liquids correlated with TSH level (r = 0.83, P < 0.0001) and autonomic neuropathy score (r = -0.79, P = 0.001). CONCLUSIONS: We found that approximately 50% of type 1 diabetic patients studied had delayed gastric emptying that did not correlate with symptoms. Gastric autoimmunity did not contribute to diabetic gastroparesis. Metabolic control was worse in patients with delayed solid emptying.     

胃轻瘫犬固体胃排空特征的超声评价

目的 探讨清醒状态下胃轻瘫比格犬的固体胃排空特征。方法 采用双侧迷走神经干切断术联合胰高血糖素复制胃轻瘫犬动物模型,运用超声成像技术评价比格犬正常和胃轻瘫状态下固体胃排空功能,并与核素SPECT闪烁成像结果进行比较。结果 比格犬的固体胃排空过程符合改良的指数模型：Y=1-(1-e-k1)β,胃轻瘫比格犬的胃半排时间较正常显著延长,差异具有统计学意义(P＜0.05)。结论 胃轻瘫比格犬的固体胃排空特征具有稳定的数学表达方式。     

三黄脂消饮对糖尿病胃轻瘫大鼠血糖和胃排空率的改变

[摘要] 目的 研究三黄脂消饮对糖尿病胃轻瘫大鼠血糖和胃排空率的改变。方法 以三黄脂消饮治疗糖尿病胃轻瘫模型大鼠，并与正常组及模型组比较。结果 中药治疗后血糖下降，胃排空率增加。 结论 三黄脂消饮不仅可以降低糖尿病血糖水平，而且增加了并发症胃轻瘫的胃排空率，明显地改善了胃排空延迟，所以三黄脂消饮是治疗糖尿病胃轻瘫的有效药物。     

Predictors of delayed gastric emptying in diabetes.

OBJECTIVE: To define the predictors of the rate of gastric emptying in patients with diabetes. RESEARCH DESIGN AND METHODS: A total of 101 outpatients with diabetes (79 type 1 and 22 type 2) underwent measurements of gastric emptying of a solid/liquid meal (scintigraphy), upper gastrointestinal symptoms (questionnaire), glycemic control (blood glucose concentrations during gastric emptying measurement), and autonomic nerve function (cardiovascular reflexes). RESULTS: The gastric emptying of solid and/or liquid was delayed in 66 (65%) patients. Solid (retention at 100 min 64 +/- 3.2 vs. 50.2 +/- 3.6%, P < 0.005) and liquid (retention at 100 min 22.7 +/- 1.7 vs. 16.0 +/- 1.8%, P < 0.001) gastric emptying was slower in women than in men. Of all upper gastrointestinal symptoms (including nausea and vomiting), only abdominal bloating/fullness was associated with slower gastric emptying (P < 0.005). A multiple regression analysis demonstrated that both abdominal bloating/fullness and female sex were predictors of slower gastric emptying of both solids and liquids. CONCLUSIONS: We conclude that the presence of abdominal bloating/fullness but not any other upper gastrointestinal symptom is associated with diabetic gastroparesis and that gastric emptying is slower in diabetic women than in diabetic men.     

Laparoscopic and open placement of electronic implants for Gastric Electrical Stimulation (GES): technique and results

Gastric Electrical Stimulation (GES) with a fully implantable device including two electrodes to the gastric wall has proven to be an effective treatment of symptoms in patients with gastroparesis and therapy of refractory nausea and vomiting. Stimulation is given continuously with 12 imp/min at 5?mA. Multicentre studies have shown effectiveness in most patients with diabetic and idiopathic gastroperesis but results are promising also for postsurgical gastroparesis. The long-term clinical outcome seems to be similar for the two implantation techniques, laparoscopy and open surgery, but the postoperative hospital stay is shorter after laparoscopy. The improvement in symptoms is not directly related to an improvement in gastric emptying. The mechanisms for relief of symptoms by GES are still unknown.     

Novel Soy Germ Pasta Enriched in Isoflavones Ameliorates Gastroparesis in Type 2 Diabetes: A pilot study

OBJECTIVE

To determine the effect of soy germ pasta enriched in biologically active isoflavone aglycons on gastric emptying in type 2 diabetic patients with gastroparesis.

RESEARCH DESIGN AND METHODS

This randomized double-blind, placebo-controlled study compared soy germ pasta with conventional pasta for effects on gastric emptying. Patients (n = 10) with delayed gastric emptying consumed one serving per day of each pasta for 8 weeks, with a 4-week washout. Gastric emptying time (t_1/2) was measured using the [¹³C]octanoic acid breath test at baseline and after each period, and blood glucose and insulin concentrations were determined after oral glucose load.

RESULTS

Soy germ pasta significantly accelerated the t_1/2 in these patients (161.2 ± 17.5 min at baseline vs. 112.6 ± 11.2 min after treatment, P = 0.009). Such change differed significantly (P = 0.009) from that for conventional pasta (153.6 ± 24.2 vs. 156.2 ± 27.4 min), without affecting glucose or insulin concentrations.

CONCLUSIONS

These findings suggest that soy germ pasta may offer a simple dietary approach to managing diabetic gastropathy.Gastroparesis is a symptomatic chronic debilitating disorder of the stomach, characterized by delayed gastric emptying of solid and semisolid foods in the absence of mechanical obstruction. It affects 30–50% of patients with long-standing type 2 diabetes (T2D) (1,2) and is associated with upper gastrointestinal symptoms. It compromises the pharmacokinetics of orally administered drugs by altering rates of absorption and can also alter glycemia control. The withdrawal of the prokinetic cisapride (3) has compromised therapeutic options (4,5). Interestingly, dietary modifications have been suggested to potentially represent an alternative to drugs for diabetic gastroparesis (2). Our objective was to evaluate a novel soy germ pasta containing biologically active isoflavone aglycons (6,7) for effects on gastric emptying in T2D patients with gastroparesis.     

New therapeutic approaches to diabetic gastroparesis.]

CASE HISTORY AND PHYSICAL EXAMINATION: A 24-year-old man with type 1 diabetes, nonresponding to standard treatment for severe gastroparesis, was admitted to hospital due to persisting nausea and vomiting. Further known complications included diabetic retinopathy, diabetic nephropathy with mild renal impairment, diabetic peripheral and cardiac autonomic neuropathy, and arterial hypertension. EXAMINATIONS: Gastric motility parameters were evaluated by functional scintigraphy. Gastric emptying was severely delayed showing first appearance of food in duodenum after 25 min. After 60 min, technetium activity in the stomach was still detected in considerable amounts. The 50% emptying time was 58 min (normal time 10-20 min). A detailed symptom score for gastroparesis, prospectively investigated by a standardized patient diary, showed a severe and complex clinical disturbance: the frequency of daily attacks of impulsive vomiting ranged from 2 to 21 and the mean daily duration of nausea was 7.5 h. A value of 3.4 on the scale for a premature feeling of satiety (range 0-4, normal = 0) was determined, as well as scores of 2.5 for symptoms of abdominal bloating (range 0-3, normal = 0) and 3.7 for general well-being (range 0-4, normal = 0). COURSE OF DISEASE AND TREATMENT: Pharmacological interventions with antibiotics, prokinetics, antiemetics and, as a second step, percutaneous gastrostomy (first invervention) and jejunostomy (second intervention) were not long-term effective in reducing the clinical symptoms described above. Therefore, a single intrapyloric injection with 100 U of botulinum toxin was performed leading to a prompt and significant improvement of symptoms and an adequate oral nutrient intake the day after the procedure. Determined by gastric scintigraphy 1 week later, this led to a significant reduction of the 50% emptying time (36 min) and to an improvement of the symptom score for gastroparesis as determined 4 weeks later: frequency of daily attacks of impulsive vomiting ranged from 0 to 1, mean daily duration of nausea was 1 h, premature feeling of satiety (score 1.9), symptoms of abdominal bloating (1.1), and general well-being (2.1). The beneficial effect of the botulinum toxin injection was unchanged over 3 months, slightly diminishing by 4.5 months. After a second round of botulinum toxin injection, again, prompt relief of most of the symptoms was achieved. Percutaneous jejunostomy was then revised. CONCLUSION: Intrapyloric injection of botulinum toxin is effective in improving the complex symptoms and clinical syndrome associated with diabetic gastroparesis resistant to conventional treatment. Upon waning of the therapeutic effect over time, the procedure can be repeated with success.     

Natural history of diabetic gastroparesis

OBJECTIVE: The major aim of this study was to evaluate the prognosis of diabetic gastroparesis. RESEARCH DESIGN AND METHODS: Between 1984 and 1989, 86 outpatients with diabetes (66 type 1, 20 type 2; 40 male, 46 female) underwent assessment of solid and liquid gastric emptying and esophageal transit (by scintigraphy), gastrointestinal symptoms (by questionnaire), autonomic nerve function (by cardiovascular reflex tests), and glycemic control (by HbAlc and blood glucose concentrations during gastric emptying measurement). These patients were followed up in 1998. RESULTS: Of the 86 patients, solid gastric emptying (percentage of retention at 100 min) was delayed in 48 (56%) patients and liquid emptying (50% emptying time) was delayed in 24 (28%) patients. At follow-up in 1998, 62 patients were known to be alive, 21 had died, and 3 were lost to follow-up. In the group who had died, duration of diabetes (P = 0.048), score for autonomic neuropathy (P = 0.046), and esophageal transit (P = 0.032) were greater than in those patients who were alive, but there were no differences in gastric emptying between the two groups. Of the 83 patients who could be followed up, 32 of the 45 patients (71%) with delayed solid emptying and 18 of the 24 patients (75%) with delay in liquid emptying were alive. After adjustment for the effects of other factors that showed a relationship with the risk of dying, there was no significant relationship between either gastric emptying or esophageal transit and death. CONCLUSIONS: In this relatively large cohort of outpatients with diabetes, there was no evidence that gastroparesis was associated with a poor prognosis.     

Case Report of gastroparesis healing: 16 years of a chronic syndrome resolved after proximal intercessory prayer

A male infant at two weeks of age was hospitalized vomiting forcefully. He had a pyloromyotomy. He did not improve with medical therapy. The diagnosis of gastroparesis was made after a nuclear medicine gastric emptying study and intestinal manometry. He required a gastrostomy tube (g-tube) and a jejunostomy tube (j-tube) for feeding. At 11 months of age, the j-tube was converted into a feeding jejunostomy with Roux-en-Y limb. For 16 years he was completely dependent on j-tube feeding. In November 2011, he experienced proximal-intercessory-prayer (PIP) at a church and felt an electric shock starting from his shoulder and going through his stomach. After the prayer experience, he was unexpectedly able to tolerate oral feedings. The g- and j-tube were removed four months later and he did not require any further special treatments for his condition as all symptoms had resolved. Over seven years later, he has been free from symptoms. This article investigates a case of PIP as an alternative intervention for resolving severe idiopathic gastroparesis when maximal medical management is not effective.     

Gastroparesis after a presumed viral illness: clinical and laboratory features and natural history

Gastroparesis after a viral infection has rarely been reported. In this article, we describe the clinical features and long-term outcome of 7 patients who had gastroparesis after a presumed viral illness and who were identified in a retrospective review of 103 consecutive cases of gastroparesis seen at our institution from 1977 through 1988. The three male and four female patients with gastroparesis after a suspected viral illness were young (mean age, 26.9 years) and healthy before the onset of the illness, which manifested as low-grade fever, fatigue, and myalgia with or without diarrhea. A mean of 4.5 days after spontaneous resolution of the viral illness, persistent nausea, vomiting, and epigastric pain developed in these patients. In all seven patients, delayed emptying of the gastric contents was substantiated. Autonomic neuropathy was found in all three patients who underwent autonomic function tests. During a mean follow-up of 32.3 months, five of the seven patients had complete resolution of gastroparetic symptoms, and the other two had considerable improvement of their condition. We conclude that postviral gastroparesis is uncommon, is frequently associated with autonomic dysfunction, and is associated with an apparently excellent prognosis.     

糖尿病性胃轻瘫发病特点及其对患者影响的调查研究

目的:探讨糖尿病性胃轻瘫的发病特点及对患者的影响。方法:对2019年8月就诊的517例糖尿病患者进行横断面调查,调查对象填写人口统计学问卷、胃轻瘫主要症状指数问卷、胃轻瘫对糖尿病相关症状和血糖控制影响的调查问卷,统计胃轻瘫总体患病率,1型、2型糖尿病患者胃轻瘫患病率,分析影响2型糖尿病患者并发胃轻瘫的相关因素,胃轻瘫对患者血糖控制的影响。结果:本研究糖尿病患者胃轻瘫总体患病率为6.8%(35/517),其中1型糖尿病患者胃轻瘫患病率(13.1%,8/61)显著高于2型糖尿病患者(5.9%,27/456),差异有统计学意义(P0.05)。2型糖尿病患者中,使用二甲双胍控制血糖者发生胃轻瘫的比例更高[7.4%(23/310)比2.7%(4/146)],差异有统计学意义(P0.05)。与2型糖尿病患者相比,1型糖尿病患者并发胃轻瘫后对血糖控制的不利影响更大,更容易导致血糖过高、低血糖发作频繁(P0.05)。结论:糖尿病尤其是1型糖尿病患者胃轻瘫患病率较高,二甲双胍可增加胃轻瘫发病风险或者引起胃轻瘫的相似症状,胃轻瘫对1型糖尿病患者血糖控制的不良影响较大。     

Gastroparesis

Gastroparesis is a symptomatic disorder of the stomach characterized by slow or delayed gastric emptying. Diabetes and idiopathic factors account for over 60% of gastroparesis cases. Symptoms associated with delayed gastric emptying include nausea, vomiting, abdominal bloating and early satiety. Delayed gastric emptying due to gastroparesis is managed by dietary adjustments, prokinetic medications, avoidance of medications that retard gastric motor activity and optimizing glycemic control in diabetic patients. Electrical stimulation and gastric pacing are an evolving treatment option for patients who do not respond to standard medical therapy. This article provides a review of gastric motility, the etiologies of gastroparesis and therapeutic approaches to this disorder.