Ultrasonographic assessment of gastric motility in diabetic gastroparesis before and after attaining glycemic control

Background Glycemic control is important for maintaining gastric motility in diabetic patients, but gastric motility has not yet been studied ultrasonographically in relation to glycemic control.Methods We made such observations before and after establishing glycemic control in diabetic patients with gastroparesis. We studied 30 diabetic patients with upper abdominal digestive symptoms who were hospitalized for correction of poor blood sugar control and who underwent upper digestive tract endoscopy to rule out structural causes such as gastric/duodenal lesions. Gastric motility was evaluated by transabdominal ultrasonography, using a test meal, before and after attainment of glycemic control (within 3 days after admission and 3 days before discharge). Also, upper abdominal digestive symptoms present on admission and at discharge were compared.Results After glycemic control was established, contractions of the antral region were more frequent than before the attainment of control (8.93 ± 1.17/3 min vs 7.63 ± 2.22/3 min, respectively; P < 0.001). Glycemic control also significantly improved gastric emptying (before glycemic control, 49.2 ± 14.8%; after, 67.1 ± 11.5%; P < 0.001). This was also true for the motility index, concerning antral gastric contractility (before control, 2.97 ± 1.57; after, 3.75 ± 1.09; P < 0.05). Upper abdominal symptom scores were also significantly lower after attainment of control than before (0.47 ± 0.78 vs 3.17 ± 2.00, respectively; P < 0.001).Conclusions These findings suggest that attaining glycemic control improves gastric motility and attainments upper abdominal symptoms in diabetic patients with gastroparesis.     

糖尿病性胃轻瘫的动力学研究

目的研究糖尿病性胃轻瘫患者胃动力学异常的机制．方法非胰岛素依赖性糖尿病（ｎｏｎｉｎｓｕｌｉｎｄｅｐｅｎｄｅｎｔｄｉａｂｅｔｅｓｍｅｌｉｔｕｓ，ＮＩＤＤＭ）患者３２例，正常人２２例作对照．采用同位素方法测定固体液体胃排空．另外，用胃频谱图机做胃频谱分析．结果ＮＩＤＤＭ患者的固体液体胃半排空时间较正常对照组明显延缓／ｍｉｎ．（９１５±２３７ｖｓ４９２±９２及５９１±１１４ｖｓ３３２±１４８，Ｐ＜００１），固体胃排空延迟主要在排空３０ｍｉｎ以后，液体胃排空延迟主要在６０ｍｉｎ以后；ＮＩＤＤＭ患者中糖尿病性胃轻瘫检出率为５６３％；ＮＩＤＤＭ胃轻瘫患者伴有胃动过速者（４４４％）多于ＮＩＤＤＭ不伴胃轻瘫的患者（７１％，Ｐ＜００５）；ＮＩＤＤＭ患者的胃排空延迟与自主神经病变有关（Ｐ＜００１）；ＮＩＤＤＭ患者的胃排空延迟与外周神经病变、肾脏病变、空腹血糖和病程无关（Ｐ＞００５）．结论ＮＩＤＤＭ患者胃固体液体胃排空延迟，胃轻瘫检出率５６３％，其特点：固体液体胃排空延迟和胃节律紊乱．自主神经病变是引起糖尿病性胃轻瘫的重要因素．     

Long-term outcome after gastrectomy for intractable diabetic gastroparesis.

AIMS: To examine the long-term outlook for patients with intractable vomiting from diabetic gastroparesis who underwent major gastric surgery. METHODS: Of 18 patients with problems from vomiting referred to the King's Diabetes Centre during the years 1994-2000, seven were considered to suffer irreversible symptoms not alleviated by protracted periods of medical treatment. They were all Type 1 Caucasian diabetic women, mean age 32 years (range 28-37 years) with multiple symptoms of severe autonomic neuropathy. They underwent major gastric surgery comprising 70% gastric resection including pylorus and antrum, with a 60-cm Roux-en-Y loop of jejunum to prevent reflux gastritis. RESULTS: The vomiting was relieved in six of the seven patients almost immediately after surgery and during review up to more than 6 years post-operatively. There have been no serious relapses, resulting in considerable improvement in quality of life. Unfortunately, three of the patients developed renal failure, two of them needing renal support treatments 2 and 3 years after successful gastrectomy. One patient died suddenly 5 months after successful surgery and one 3 months after starting dialysis. CONCLUSIONS: Major gastric surgery can, after careful patient selection, effectively relieve distressing vomiting from severe gastroparesis and give a greatly improved quality of life to a small group of seriously disadvantaged patients where risk of subsequent renal failure is high and where life expectancy is poor.     

Metoclopramide for the treatment of diabetic gastroparesis

ABSTRACT

Introduction: Gastroparesis is a chronic disorder of the stomach characterized by delayed gastric emptying without mechanical obstruction. Diabetes is the most commonly known cause of gastroparesis. Management of diabetic gastroparesis involves lifestyle modifications, glycemic control, pharmacological drugs, and for refractory cases surgical treatments. Metoclopramide remains the only drug approved by the Food and Drug Administration for diabetic gastroparesis. The aim of this article is to provide a concise review of the pharmacology, clinical efficacy and tolerability of metoclopramide.

Areas covered: We searched PubMed using the key words ‘metoclopramide’, ‘diabetic gastroparesis’, and ‘gastric emptying’. The relevant articles and their bibliography were reviewed. Metoclopramide acts on several different receptors; primarily as a dopamine receptor antagonist, both peripherally improving gastric emptying, and centrally resulting in an anti-emetic effect. Metoclopramide side effects, mostly related to its ability to cross the blood-brain barrier, include drowsiness, restlessness, hyperprolactinemia, and tardive dyskinesia (TD), a movement disorder that may be irreversible.

Expert opinion: Metoclopramide carries a black box warning for use >12 weeks due to the risk of TD. However, gastroparesis patients experience chronic symptoms often requiring prolonged treatments. Physicians and patients look forward to FDA approval of new agents for gastroparesis with better efficacy and safety profile.     

Gastric electrical stimulation in patients with gastroparesis

Abstract As in the heart, there is a pacemaker in the human stomach and it generates myoelectrical activity with a frequency of approximately three cycles per minute. Abnormalities in gastric myoelectrical activity may result in gastric motility disorders, such as gastroparesis. Electrical stimulation of the stomach is achieved by delivering electrical currents via electrodes attached to the smooth muscle of the stomach. Recently, a number of studies on electrical stimulation of the stomach in both humans and dogs have indicated that gastric electrical stimulation with appropriate parameters is able to entrain gastric slow waves and normalize gastric dysrhythmias. This has led some investigators to use gastric electrical stimulation to treat patients with gastroparesis. Previous studies and the current state of the field in gastric electrical stimulation in treatment of gastroparesis will be discussed and summarized.     

Novel surgical treatment and gastric pathology in diabetic gastroparesis.

AIMS: Observations are made on four Type 1 diabetic patients with the rare syndrome of intractable vomiting from confirmed gastroparesis, to determine whether radical surgery would alleviate their symptoms and subsequently to examine in detail the gastric histopathology. METHODS: The surgical approach consisted of an approximate 70% resection of the stomach, including the antrum and pylorus, with closure of the duodenum and restoration of gastrointestinal continuity with a 60-cm Roux-en-Y jejunal loop. Four longstanding Type 1 diabetic patients were examined and treated as described. They were all women in the age range 2741 years with grossly abnormal autonomic function tests in whom other causes for gastric paresis had been excluded. RESULTS: Vomiting episodes leading to multiple hospital admissions (6-8) in the year preceding surgery were eliminated in three of the four patients, while in the fourth initial success was followed by the need for dialysis for renal failure. Gastric histopathology showed evidence of smooth muscle degeneration and fibrosis, with eosinophilic inclusion bodies (M-bodies) which appear to be unique to this condition. The findings suggest the presence of a gastromyopathy. CONCLUSIONS: Satisfactory relief of intractable vomiting from diabetic gastroparesis was achieved by a novel radical surgical procedure. Histopathological findings suggest that gastromyopathy may contribute to the production of this syndrome.     

Abnormal gastric myoelectrical activity and delayed gastric emptying in patients with symptoms suggestive of gastroparesis

Gastric myoelectrical activity modulates gastric motor activity. Abnormalities in gastric myoelectrical activity may be associated with gastric motility disorders. The aim of this study was to investigate the correlation of gastric myoelectrical activity with gastric emptying in symptomatic patients with and without gastroparesis. Ninety-seven patients with symptoms suggestive of gastroparesis participated in the study. Gastric myoelectrical activity was recorded using surface electrogastrography. The electrogastrogram (EGG) was recorded for 30 min in the fasting state and for 120 min after a solid test meal. Gastric emptying of the solid meal was simultaneously monitored for 120 min. Patients with delayed gastric emptying showed a significantly lower percentage of normal gastric slow waves (P<0.03) and a significantly reduced increase of the dominant power in the postprandial EGG (P<0.02). Postprandial EGG parameters were found to be able to predict delayed emptying of the stomach. Postprandial gastric dysrhythmia predicts delayed gastric emptying with an accuracy of 78%, while the abnormality in postprandial EGG power predicts delayed gastric emptying with an accuracy of 75%. All patients with abnormalities in both the rhythmicity and the power had delayed gastric emptying. Patients with delayed gastric emptying have a lower percentage of normal gastric slow waves in the EGG and a lower postprandial increase in the dominant power. Abnormalities in the postprandial EGG seem to be able to predict delayed emptying of the stomach. However, a normal EGG does not seem to guarantee normal emptying of the stomach.     

2型糖尿病患者胃动力学与植物神经病变关系的探讨

目的研究胃动力障碍及植物神经病变与2型糖尿病(DM2)的关系。方法采用半流质核素胃排空试验对129例DM2患者的胃动力进行了研究,同时还用Ewing法对心血管植物神经功能、用B超对膀胱残余尿量、用神经病星对外周神经进行定量测定。结果糖尿病胃排空延迟发生率为62.02％。植物神经病变呈弥漫性分布,随病程延长而加重。胃动力异常者,其植物神经病变发生率较胃动力正常者显著增高。结论DM2胃动力异常及植物神经病变发生率均明显增高,二者显著相关。故早期进行胃排空试验,并同时对其它植物神经功能进行测定,对糖尿病胃及神经并发症的早期防治有重要意义。     

[13C]0ctanoic acid breath test for non-invasive assessment of gastric emptying in diabetic patients: Validation and relationship to gastric symptoms and cardiovascular autonomic function

Summary Since there is a need for a widely applicable non-invasive test to assess gastric emptying in diabetic patients, we evaluated the sensitivity, specificity, and reproducibility of the [¹³C]octanoic acid breath test as compared with scintigraphy. Moreover, we examined the relationship between the breath test indices and gastric symptoms, cardiovascular autonomic function, and metabolic parameters. Forty healthy control subjects and 34 diabetic patients were studied. Three indices of gastric emptying, assessed by the breath test, were computed: half-emptying time (t_1/2breath), gastric emptying coefficient (GEC), and lag phase. Furthermore, the half-emptying time, measured by scintigraphy (t_1/2scint), was calculated and gastric symptoms and cardiovascular autonomic neuropathy (CAN) were scored. The coefficients of variation of day-to-day reproducibility in 10 healthy subjects were 29.6 % for t_1/2breath, 7.4 % for GEC, and 46.5 % for lag phase. An abnormal delay for t_1/2scint (> 100 min) or t_1/2breath (> 200 min) was noted in 12 patients. Based on the results for t_1/2scint, the sensitivity of t_1/2breath and GEC was 75 % and the specificity was 86 %. Both t_1/2breath (r _s = 0.523; p < 0.05) and GEC (r ₂ = − 0.594; p < 0.05) were significantly associated with the gastric symptom score. A significant relationship to the CAN score was demonstrated for t_1/2breath (r _s = 0.448; p < 0.05), GEC (r _s = − 0.467; p < 0.05), and t_1/2scint (r _s = 0.602; p < 0.05). There were no significant associations of the breath test indices with the blood glucose levels during the test, HbA_1c, age, and duration of diabetes. In patients with abnormal t_1/2scint (n = 12) not only was t_1/2breath significantly prolonged and GEC reduced, but also the scores of CAN and gastric symptoms were significantly increased as compared with those who had a normal t_1/2scint (n = 22). We conclude that the [¹³C]octanoic acid breath test represents a suitable measure of delayed gastric emptying in diabetic patients which is associated with the severity of gastric symptoms and CAN but not affected by the blood glucose level. [Diabetologia (1996) 39: 823–830]     

Idiopathic gastroparesis in patients with unexplained nausea and vomiting

Nausea and vomiting are symptoms sometimes associated with motor dysfunction. We compared a group of young patients suffering from chronic nausea and/or vomiting and normal upper gastrointestinal x-ray series with a control group. The members of both groups underwent isotopic examinations of their stomachs. The aim of the study was to find a simple method of checking the stomach and proving a motor dysfunction in a group of patients with chronic, inexplicable nausea and vomiting. Patients and controls fasted for an least 6 hr were given 0.5 mCI of [^99mTc] diethylene triaminopentaacetic acid orally in 150 cc milk with 50 g cornflakes. A time-activity curve was obtained and radioactivity over the stomach was recorded exponentially. The parameter of theT1/2 emptying time was used. In normal controlsT1/2 emptying time ranged from 18 to 26 min. Twenty-five symptomatic patients were examined, three of whom achieved normal values, but 22 patients showed pathologic results ranging from 36 to 184 min. In patients with chronic nausea and/or vomiting an isotopic examination of the stomach may provide a simple and rapid diagnostic method of evaluation.     

Novel insights into the effects of diabetes on gastric motility

Recent data from the Diabetes Control and Complications Trial/Epidemiology of Diabetic Interventions and Complications cohort indicate that the disease burden of gastroparesis in diabetes remains high, consistent with the outcome of cross-sectional studies in type 1 and 2 diabetes. An improved understanding of the pathogenesis of diabetic gastroparesis at the cellular level has emerged in the last decade, particularly as a result of initiatives such as the National Institute of Health funded Gastroparesis Clinical Research Consortium in the US. Management of diabetic gastroparesis involves dietary and psychological support, attention to glycaemic control, and the use of prokinetic agents. Given that the relationship between upper gastrointestinal symptoms and the rate of gastric emptying is weak, therapies targeted specifically at symptoms, such as nausea or pain, are important. The relationship between gastric emptying and postprandial glycaemia is complex and inter-dependent. Short-acting glucagon-like peptide-1 agonists, that slow gastric emptying, can be used to reduce postprandial glycaemic excursions and, in combination with basal insulin, result in substantial reductions in glycated haemoglobin in type 2 patients.     

Effects of percutaneous endoscopic gastrostomy tube placement on gastric antral motility and gastric emptying

Background Percutaneous endoscopic gastrostomy (PEG) is the preferred method for providing enteral nutritional support in patients with dysphagia. We examined gastric antral myoelectrical activity and gastric emptying before and after PEG tube placement to evaluate the effects of PEG on gastric motility.Methods PEG was performed in 41 patients; 21 fed by total parenteral nutrition (TPN) and 20 who received nasogastric tube feeding (NGF). Antral myoelectrical activity and gastric emptying were examined before and 4 weeks after PEG tube placement.Results The percentage of normal-range electrogastrograms (EGGs) was significantly lower in the TPN group than in the NGF group in both the pre- and postprandial periods before PEG tube placement. Enteral feeding after PEG tube placement improved gastric motility in the patients with TPN. The percentage of normal-range EGGs increased significantly after PEG tube placement in both the pre- and postprandial periods, and plasma concentrations of paracetamol increased significantly after PEG tube placement in patients with TPN. A total of 7.3% of the patients developed the complication of gastroesophageal reflux (GER) after PEG tube placement. Gastric myoelectrical activity and gastric emptying were improved in these patients with GER after PEG tube placement. In contrast, the prevalence of esophageal hiatus hernia was significantly higher in patients with GER after PEG tube placement than in patients without GER after PEG tube placement.Conclusions Prolonged TPN with bowel rest induces physiological dysfunction of gastric motility. Enteral nutrition is the preferable physiological nutritional route. GER after PEG tube placement is not related to gastric motility. Esophageal hiatus hernia seems to be a major risk factor for GER complications after PEG tube placement.     

Gastrobiliary motility is not coordinated in patients with non-ulcer dyspepsia of normal gastric emptying time: simultaneous sonographic study

BACKGROUND: Disorders of the motor function of the upper gastrointestinal tract have been implicated in the pathogenesis of non-ulcer dyspepsia. Approximately 50% of patients with abdominal symptoms (without ulcer) have normal gastric emptying. Apart from gastric emptying, other mechanisms are very important in the etiology of non-ulcer dyspepsia. METHODS: Gastric emptying and gallbladder motility were simultaneously investigated in 16 patients with non-ulcer dyspepsia and in 15 healthy controls. Fasting blood samples were taken, and pepsinogen levels were assayed. RESULTS: Gastric emptying time, fasting antral diameter, and post-prandial antral diameter were not significantly different between the patients with non-ulcer dyspepsia and the controls. Fasting gallbladder volume, the time required to reach minimal gallbladder residual volume, minimal gallbladder residual volume, and the serum levels of pepsinogen were not significantly different. Simple linear regression was used to summarize the relationship between gastric emptying time and time required to reach minimal gallbladder residual volume. In the controls, the gastric emptying time and time required to reach minimal gallbladder residual volume were linearly related. However, in the patients with non-ulcer dyspepsia, they were not related. CONCLUSIONS: These observations suggest that disturbance of coordination between gastric emptying and gallbladder emptying is a cause of the symptoms of non-ulcer dyspepsia.     

Upper abdominal symptoms in patients with Type 1 diabetes: unrelated to impairment in gastric emptying caused by autonomic neuropathy

Aims Diabetic gastroparesis is a common condition occurring in some 30–50% of patients with long-term diabetes. Some studies have found a relationship between autonomic neuropathy and diabetic gastroparesis. In addition to autonomic neuropathy, acute changes in plasma glucose concentration can also affect gastric emptying. The objective was to examine the relationship between autonomic nerve function, glucose concentration, gastric emptying, and upper abdominal symptoms in Type 1 diabetic patients. Methods Gastric emptying of solids and liquids was measured with scintigraphy in 27 patients with longstanding Type 1 diabetes with upper abdominal symptoms. Autonomic nerve function was examined by standardized cardiovascular tests, and plasma glucose concentrations were measured during scintigraphy. Severity of abdominal symptoms and quality of life were explored by validated questionnaires. Results Seven patients (26%) had delayed gastric emptying of solids and three (11%) of liquids. Mean gastric half-emptying time of solids was 128 ± 116 min and of liquids 42 ± 30 min. Of the 26 patients undergoing tests, 16 (62%) had autonomic nerve dysfunction. Autonomic neuropathy score (1.6 ± 1.7) correlated positively with the gastric emptying rate of solids (P = 0.006), a rate unrelated to symptom scores or plasma glucose concentrations during scintigraphy. Quality of life in patients with abdominal symptoms was lower than in the normal Finnish population. Conclusions Impaired gastric emptying of solids in patients with Type 1 diabetes is related to autonomic neuropathy, but not to actual glycaemic control. The upper abdominal symptoms observed in these patients cannot be explained, however, by impaired gastric emptying.     

Integration of canine proximal gastric,antral, pyloric,and proximal duodenal motility during fasting and after a liquid meal

The aim was to investigate the integration of proximal gastric, antral, pyloric, and duodenal motility during fasting and after feeding. Using a proximal gastric barostat and a manometric assembly with an array of side holes astride the gastroduodenal junction, the gastrointestinal interdigestive migrating motor complex was detected in five of seven conscious fasting dogs. During phase III of the complex, which lasted a mean ± SEM of 13 ± 0.5 min, 9.6 ± 0.9 volume waves were present in the proximal stomach. The volume waves were coordinated with clusters of antral waves 64 ± 11% of the time and with inhibition of duodenal waves 91±3% of the time. A 300-ml calorie-dense liquid meal abolished the complex and promptly increased proximal gastric volume in five of six dogs. Volume waves were nearly completely suppressed, while antral waves decreased from 24 ±3.0 waves/10 min to 10±2.8 waves/10 min (P<0.05) and isolated pyloric pressure waves increased from 7.2±2.8 waves/10 min to 22±3.3 waves/10 min (P<0.005). In summary, proximal gastric motility was integrated with antral, pyloric, and duodenal motility under both fasting and fed conditions. The integrated patterns likely account for the efficient clearance of indigestible solids during fasting and the controlled emptying of nutrients with feeding.Supported in part by USPHS NIH Grants DK 18278, DK34988, and DK07198, the Winthrop Travelling Fellowship of the Royal Australasian College of Physicians, the S.K.F. (Australia) Travelling Fellowship, and the Mayo Foundation.This work was presented in part before the World Congress of Gastroenterology, Sydney, Australia, August 30, 1990     

Treatment of gastroparesis with electrical stimulation

Electrically stimulating the stomach to treat gastroparesis has been proposed by investigators for decades. With the development of techniques of implantable pacing devices and electrodes and promising preliminary results in chronic pacing studies, gastric electrical stimulation (GES) has received increasing attention recently among researchers and clinicians. A number of studies have been performed to investigate the effects of GES on gastric motility, gastric emptying, and gastrointestinal symptoms in both dogs and humans. Based on the frequency of the electrical stimulus used for chronic treatment of gastroparesis, gastric electrical stimulation can be classified into low-frequency stimulation (LFS) and high-frequency stimulation (HFS). Although some of the results are still controversial, the majority of these studies seem to indicate that LFS is able to normalize gastric dysrhythmias and entrain gastric slow waves and accelerate gastric emptying. On the other hand, HFS has no effect on gastric emptying but is able to significantly reduce symptoms of nausea and vomiting in gastroparetic patients. GES has provided an exciting new advance in the treatment of gastroparesis and management of upper gastrointestinal symptoms. This paper will review the available studies of GES in the treatment of gastroparesis and current status of this field.     

养阴和胃法和益气健脾法对糖尿病胃轻瘫大鼠胃动力及Cajal间质细胞影响的比较研究

[目的]探讨并比较养阴和胃法和益气健脾法对糖尿病胃轻瘫(DGP)大鼠胃动力及Cajal间质细胞(ICC)的影响.[方法]SD大鼠随机均分为正常对照组、DGP模型组、养阴组及益气组.静脉注射链脲佐菌素(STZ)建立大鼠DGP模型,正常对照组和DGP模型组注射等量蒸馏水,养阴组及益气组分别用养阴和胃中药与益气健脾中药灌胃.酚红灌胃实验测定胃排空率,免疫组化法检测胃窦肌间c-kit阳性ICC的含量.[结果]DGP模型组大鼠的胃排空率、胃血流量、胃窦ICC含量均显著低于正常对照组(P＜0.05),表明DGP大鼠模型建立成功.各给药组大鼠的胃排空率、胃血流量、胃窦ICC含量均优于DGP模型组(P＜0.05),其中养阴组大鼠的胃排空率、胃血流量、胃窦ICC含量较益气高剂量组略有增高,但差异无统计学意义.[结论]养阴和胃与益气健脾中药均可通过调节ICC的数量,改善PGP大鼠的胃肠起搏功能,促进胃动力,且养阴和胃法作用优于益气健脾法.     

Effects of nutrients on gastrointestinal motility and gastric emptying after Billroth-I gastrectomy in dogs

We wanted to clarify the way in which nutrients influence gastrointestinal motility and gastric emptying following distal gastrectomy with Billroth-I gastroduodenostomy. Four gastrectomized dogs were equipped with extraluminal strain gauge transducers. Gastric emptying was measured radiographically. Four intact dogs were used as controls for emptying studies. Following gastrectomy, gastric emptying of both acaloric and nutrient meals was rapid in the initial period of the experiments. Gastric outflow was supported by propagating duodenal contractions. Compared with control dogs, the early emptying of nutrient meals was accelerated. In the following period, nutrients markedly slowed gastric emptying compared with acaloric meals due to a segmenting contractile pattern of the duodenum and a significant diminution of gastrointestinal motility. Results suggest that after Billroth-I gastrectomy (1) the control of gastric emptying by nutrients acts too late to slow the initial enhanced gastric outflow, and (2) the duodenal contractile patterns influence gastric emptying.The study was supported by the Deutsche Forschungsgemeinschaft, grant Eh 64/3-1.