Effectiveness of beinaglutide in a patient with late dumping syndrome after gastrectomy: A case report.

RATIONALE: Dumping syndrome is a frequent and potentially severe complication after gastric surgery. Beinaglutide, a recombinant human glucagon-like peptide-1 (GLP-1) which shares 100% homology with human GLP-1(7-36), has never been reported in the treatment of dumping syndrome before. PATIENT CONCERNS: The patient had undergone distal gastrectomy for gastric signet ring cell carcinoma 16 months ago. He presented with symptoms of paroxysmal palpitation, sweating, and dizziness for 4 months. DIAGNOSIS: He was diagnosed with late dumping syndrome. INTERVENTIONS AND OUTCOMES: The patient was treated with dietary changes and acarbose for 4 months before admitted to our hospital. The treatment with dietary changes and acarbose did not prevent postprandial hyperinsulinemia and hypoglycemia according to the 75 g oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) on admission.Therefore, the patient was treated with beinaglutide 0.1 mg before breakfast and lunch instead of acarbose. After the treatment of beinaglutide for 1 month, OGTT showed a reduction in postprandial hyperinsulinemia compared with before starting treatment, and the time in the range of 3.9 to 10 mmol/L became 100% in CGM. No side effect was observed in this patient during beinaglutide treatment. LESSONS: These findings suggest that beinaglutide may be effective for treating post-gastrectomy late dumping syndrome.

Diagnostic tools for post-gastric bypass hypoglycaemia.

In spite of its evident success, several late complications can occur after gastric bypass surgery. One of these is post-gastric bypass hypoglycaemia. No evidence-based guidelines exist in the literature on how to confirm the presence of this syndrome. This study aims to describe and compare the tests aimed at making a diagnosis of post-gastric bypass hypoglycaemia and to provide a diagnostic approach based upon the available evidence. A search was conducted in PubMed, Cochrane and Embase. A few questionnaires have been developed to measure the severity of symptoms in post-gastric bypass hypoglycaemia but none has been validated. The gold standard for provocation of a hypoglycaemic event is the oral glucose tolerance test or the liquid mixed meal tolerance test. Both show a high prevalence of hypoglycaemia in post-gastric bypass patients with and without hypoglycaemic complaints as well as in healthy volunteers. No uniformly established cut-off values for glucose concentrations are defined in the literature for the diagnosis of post-gastric bypass hypoglycaemia. For establishing an accurate diagnosis of post-gastric bypass hypoglycaemia, a validated questionnaire, in connection with the diagnostic performance of provocation tests, is the most important thing missing. Given these shortcomings, we provide recommendations based upon the current literature.

Evaluation of an open access software for calculating glucose variability parameters of a continuous glucose monitoring system applied at pediatric intensive care unit.

BACKGROUND: Continuous Glucose Monitoring (CGM) has become an increasingly investigated tool, especially with regards to monitoring of diabetic and critical care patients. The continuous glucose data allows the calculation of several glucose variability parameters, however, without specific application the interpretation of the results is time-consuming, utilizing extreme efforts. Our aim was to create an open access software [Glycemic Variability Analyzer Program (GVAP)], readily available to calculate the most common parameters of the glucose variability and to test its usability. METHODS: The GVAP was developed in MATLAB® 2010b environment. The calculated parameters were the following: average area above/below the target range (Avg. AUC-H/L); Percentage Spent Above/Below the Target Range (PATR/PBTR); Continuous Overall Net Glycemic Action (CONGA); Mean of Daily Differences (MODD); Mean Amplitude of Glycemic Excursions (MAGE). For verification purposes we selected 14 CGM curves of pediatric critical care patients. Medtronic® Guardian® Real-Time with Enlite® sensor was used. The reference values were obtained from Medtronic®(')s own software for Avg. AUC-H/L and PATR/PBTR, from GlyCulator for MODD and CONGA, and using manual calculation for MAGE. RESULTS: The Pearson and Spearman correlation coefficients were above 0.99 for all parameters. The initial execution took 30 minutes, for further analysis with the Windows® Standalone Application approximately 1 minute was needed. CONCLUSIONS: The GVAP is a reliable open access program for analyzing different glycemic variability parameters, hence it could be a useful tool for the study of glycemic control among critically ill patients.

Verification of glycemic profiles using continuous glucose monitoring: cases with steroid use, liver cirrhosis, enteral nutrition, or late dumping syndrome.

Glycemic control is often difficult to achieve in patients with diabetes, especially in the presence of comorbid diseases or conditions such as steroid-use or liver cirrhosis, or in patients receiving enteral nutrition. Moreover, reactive hypoglycemia due to late dumping syndrome in people having undergone gastrectomy is also a matter of concern. Empirically and theoretically, the typical glycemic profiles associated with these conditions have been determined; however, what actually happens during a 24-h span is still somewhat obscure. In order to verify and provide information about the 24-h glycemic profiles associated with these conditions, 8 patients with the 4 above-mentioned conditions were monitored using a continuous glucose monitoring system (CGMS). For all 8 patients, CGMS provided detailed information regarding the 24-h glycemic profiles. The CGM results showed typical glycemic patterns for each condition, and we were moreover able to observe the effects of various practical treatments. Based on these cases, we conclude that the CGMS is highly useful for determining the glycemic patterns of patients with the aforementioned conditions in a practical setting; and this system may be used to monitor the treatment success of such cases.

Continuous glucose monitoring for suspected dumping syndrome in infants after Nissen fundoplication.

Dumping syndrome is infrequently reported, but known to occur after Nissen fundoplication in children. However, it may be difficult both to diagnose and manage. Here we presented four infants who received Nissen fundoplication for severe gastroesophageal reflux disease, two of whom developed dumping syndrome whilst the other two did not. Continuous glucose monitoring (CGM) was very useful to clearly detect large glycemic fluctuation around each feeding. CGM was also helpful to prove the effect of treatment to avoid abnormal glucose levels. We believe that dumping syndrome in children may be underdiagnosed if clinicians rely solely on the recognition of symptoms or limited frequency of blood samplings. CGM might be the most sensitive diagnostic tool.

Octreotide improves early dumping syndrome potentially through incretins: a case report.

Dumping syndrome, or rapid gastric emptying, is a frequent complication after gastric surgery. In this case, the patient was a 47-year-old woman who 10 years previously had undergone distal gastrectomy with Billroth I reconstruction for early-stage gastric cancer. She presented with symptoms of weakness, headache, palpitation, sweating, dizziness and significant fatigue between one and two hours after a meal. Because a 75 g oral glucose tolerance test (75 g-OGTT) induced both acute postprandial tachycardia (within 1 hour) and postprandial hypoglycemia, we diagnosed this patient with early and late dumping syndrome. Dietary measures and acarbose improved symptoms of late dumping syndrome but did not prevent the symptoms of early dumping syndrome such as postprandial tachycardia, weakness, headache, palpitation, and dizziness. We therefore used the somatostatin analogue octreotide, which has been reported as an effective therapy for early dumping syndrome. Octreotide prevented the symptoms of early dumping syndrome, especially postprandial tachycardia, but caused postprandial hyperglycemia. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were completely suppressed during the 75 g-OGTT following subcutaneous injection of octreotide. No change was observed in vasoactive intestinal polypeptide (VIP), which is the gastrointestinal peptide hormone generally responsible for early dumping syndrome, suggesting possible contribution of incretins in early dumping syndrome of this patient.

Abnormal glucose tolerance testing after gastric bypass.

BACKGROUND: Symptoms secondary to dumping have been suggested to help patients refrain from simple carbohydrate ingestion after Roux-en-Y gastric bypass (RYGB). During follow-up examinations, we noted many patients with weight regain complaining of fatigue shortly after eating. Thus, we decided to study the glucose tolerance test (GTT) results in a cohort of post-RYGB patients. METHODS: A total of 63 RYGB patients, >6 months postoperatively, were studied with a GTT and measurement of insulin levels. The mean age was 48.5 ± 10.8 years, mean preoperative body mass index was 49.0 ± 6.5 kg/m(2), mean percentage of excess body mass index lost was 64.5% ± 29.0%, mean weight regain at follow-up was 11.6 ± 12.4 lb, and mean follow-up period was 47.9 months. RESULTS: Of the 63 patients, 49 had abnormal GTT results. Of the 63 patients, 6 were diabetic; however, only 1 of these patients had an elevated fasting glucose level. All 6 patients were diabetic preoperatively. Of the 63 patients, 43 had evidence of reactive hypoglycemia at 1-2 hours after the glucose load. Of these patients, 22 had a maximum/minimum glucose ratio >3:1, including 7 with a ratio >4:1. CONCLUSION: The results of the present study have demonstrated that an abnormal GTT result is a common finding after RYGB. Reactive hypoglycemia was found in 43 of 63 patients, with insulin values that do not support nesidioblastosis. It is our hypothesis, that rather than preventing simple carbohydrate ingestion, the induced hypoglycemia that occurs might contribute to weight regain and maladaptive eating in certain post-RYGB patients.

Usefulness of acarbose and dietary modifications to limit glycemic variability following Roux-en-Y gastric bypass as assessed by continuous glucose monitoring.

BACKGROUND: About 70% of the patients operated on for a gastric bypass (Roux-en-Y gastric bypass [RYGB]) suffer from dumping syndrome. In these patients, previous studies have demonstrated a high glycemic variability with hypoglycemia and with altered continuous glucose monitoring (CGM) profiles. The aim of this study was to evaluate the effect of treatment with dietary counseling plus acarbose administration on the symptoms and on the characteristics of the CGM profile. SUBJECTS AND METHODS: Eight consecutive patients with dumping syndrome were given dietary counseling for 6 weeks and also treated with acarbose (50-100 mg three times a day). Their symptoms and the features of the CGM were compared before and after treatment. RESULTS: The symptoms disappeared in seven patients. There was a significant increase in the time to the interstitial glucose (IG) peak and a reduction in the rate of the IG increase after a meal and in the rate of the IG decrease following the peak. The time below 60 mg/dL was significantly decreased, and the minimal IG value was significantly increased. The maximum and mean IG levels and the time above 140 mg/dL were decreased, but not significantly. Six patients spent more than 1% of the time with IG values below 60 mg/dL before treatment, but after treatment this was reduced to one patient. Before treatment only one patient had an IG level neither below 60 or above 140 mg/dL, and after treatment four patients were in this category. CONCLUSIONS: Dietary counseling and acarbose treatment eliminated the symptoms and improved the CGM profile of patients suffering from dumping syndrome after RYGB.

Acarbose improves hypoglycaemia following gastric bypass surgery without increasing glucagon-like peptide 1 levels.

BACKGROUND: Postprandial hypoglycaemia is a severe complication of Roux-en-Y gastric bypass (RYGBP). Acarbose, an α-glucosidase inhibitor (AGI), is employed in its treatment. Several studies have shown that AGIs increase the postprandial levels of glucagon-like peptide 1 (GLP-1). However, an excessive level of GLP-1 is one of the factors involved in the physiopathology of this condition. We analysed the effect of acarbose oral administration in eight RYBGP patients with clinically significant hypoglycaemia or dumping syndrome. METHODS: Glucose, insulin and GLP-1 plasma levels in fasting and after ingestion of a standard meal (Ensure Plus®; 13 g protein, 50 g carbohydrate, 11 g fat) were measured. The test was repeated the following week with the oral administration of 100 mg of acarbose 15 min prior to the meal. RESULTS: Five patients developed asymptomatic hypoglycaemia during the test (glucose level <50 mg/dl) with inappropriately high insulin levels and exaggerated GLP-1 response. Acarbose ingestion avoided hypoglycaemia in all of the patients and increased the lowest plasma glucose level (46.4 ± 4.8 vs. 59.0 ± 2.6 mg/dl, p < 0.01). Acarbose ingestion decreased the area under the curve for serum insulin and GLP-1 levels at 15 min after the meal. CONCLUSIONS: Acarbose avoided postprandial hypoglycaemia following RYGBP by decreasing the hyperinsulinemic response. This was associated with a decrease in early GLP-1 secretion, in contrast to that observed in non-surgical subjects. This finding could be explained by the reduction of glucose load in the jejunum produced by the α-glucosidase inhibition, which is the main stimulus for GLP-1 secretion.

[Modifications of the glucose curves and gastric voiding of children with Dumping syndrome after laparoscopic Nissen surgery]. / Modificaciones de las curvas de glucemia y vaciamiento gástrico de los niños con síndrome de dumping tras cirugía de nissen laparoscópico.

INTRODUCTION: There has been an important evolution of surgical treatment in recent years due to the progressive generalization of laparoscopic surgery. All of the available techniques can be done laparoscopically with similar results to those of open surgery. In 1978, Villet et al. described the Dumping syndrome (DS) as a frequent complication of Nissen fundoplication. DS is a group of signs and symptoms that appear shortly after surgery, including abdominal pain, paleness, sweating, diarrhea, nausea, even weight loss. These symptoms can be differentiated into early dumping that occurs between 30 to 60 minutes after eating and late dumping that occurs 92-240 minutes after the postprandial period. MATERIAL AND METHODS: A total of 8 patients (3 boys and 5 girls) have been studied. Their ages ranged from 3 to 12 years (mean 9 years), and they were diagnosed of dumping syndrome after performing the laparoscopic Nissen-Rossetti. All underwent a gastric voiding study by scintigraphy after administration of a volume of milk adjusted to their weight labeled with 99Tc-DTPA and oral glucose overload test with 1.75 g/kg of glucose, determining the baseline glycemia and every 30 minutes post-intake, at 0, 30 and 90 minutes. Insulin was also measured to obtain the glucose/insulin ratio. This study was conducted for all patient diagnosed of dumping syndrome before and after laparoscopic Nissen-Rossetti surgery. RESULTS: The following results were obtained: Glucose Curve: 1. Maximum glycemia. PreNissen. The mean of the maximum glycemia values before surgery was 133.9+/-32.11 mg/dl. Post-Nissen. Mean maximum glycemias after surgery was 208.5 +/- 45.07 mg/dl with a range of 147-276 mg/dl. These differences of maximum glycemia were clearly significant with a p <0.002. Minimum glycemia. The mean value of the minimum glycemias after the surgery, compared with the previous value, did not show significant differences: 62.6+/- 11.51 mg/dl versus 71.8 +/- 28.04 mg/dl. Glucose/insulin ratio. The hyperinsulinism values after the intervention studied by means of the glucose/insulin ratio were abnormal in 70.5% (defined as ratio under 3). The mean value was also characteristic of hyperinsulinism (2.3 +/- 1.62). The mean value of the coefficient prior to the surgery was 4.6 with a deviation of 3.04, the differences not being statistically significant with a p= 0.097. Measurement of gastric voiding: The T1/2 (decay) value in post-Nissen patients was significantly lower than in pre-Nissen patients. The postsurgical mean and standard deviation was 29.74 +/- 7.92 min, while in the presurgical group, the mean and standard deviation was 73.75 +/- 28.34 min with p< 0.011; statistically significant. CONCLUSIONS: From the values obtained, we can state that a significant increase in maximum glycemia has been found in all children after surgery who were diagnosed of dumping syndrome and a significant decrease in the mean time of gastric voiding and therefore an increase in the acceleration of gastric voiding after the performance of the Nissen regarding the previous values. The dumping syndrome is a frequent side effect that we must keep in mind in patients who have been previously operated for anti-reflex surgery, the symptoms being greater in most of the transitory cases. Furthermore, it is important to keep in mind because it has an easy treatment that reverts the symptoms in a short time

A possible role of GLP-1 in the pathophysiology of early dumping syndrome.

Exaggerated plasma concentrations of GLP-1 precede reactive hypoglycemia after oral glucose in gastrectomy patients, resulting in late dumping syndrome. Recently, we showed that GLP-1 elicits the activation of sympathetic outflow. Because sympathetic activation is thought to be a cause of early dumping, we hypothesized that exaggerated GLP-1 may contribute to the pathophysiology of early dumping syndrome. In 11 patients after gastrectomy and 14 controls, blood pressure, heart rate, and plasma concentrations of norepinephrine, epinephrine, GLP-1, glucagon, insulin, and glucose were measured after oral glucose. In gastrectomy patients, GLP-1, norepinephrine, and heart rate peaked 15 to 30 min after oral glucose. Significant positive correlations were found among GLP-1, norepinephrine, and heart rate at 30 min, and these parameters at 30 min were significantly higher in patients with early dumping syndrome. These results suggest that GLP-1 is involved in the pathophysiology of early dumping syndrome.

Sympathoadrenal activation and the dumping syndrome after gastric surgery.

Dumping symptoms suggest concomitant sympathoadrenal activation. To evaluate the relation between dumping symptoms and postprandial plasma catecholamine changes, standardized dumping-provocation tests with use of oral glucose were performed for 16 gastric surgery patients with dumping, for 14 gastric surgery patients without dumping, and for 14 healthy control patients. Early dumping symptoms were present for all patients with dumping, and late symptoms developed in three patients with dumping after glucose ingestion. Patients without dumping and healthy control patients had slight complaints or no complaints. Systolic and diastolic blood pressure remained unaffected for the three groups. Positive breath-hydrogen tests, heart rate increments, and reactive plasma glucose decrements were present for patients with dumping and for patients without dumping, but not for control patients. Plasma noradrenaline and adrenaline increased for patients with dumping and for patients without dumping, but not for control patients. The noradrenaline increment was higher for patients with dumping (98%) than for patients without dumping (78%; p <0.05). The noradrenaline increment was related to the dumping score and to the heart rate increment for the first hour after glucose ingestion, whereas the adrenaline increment was related to the plasma glucose decrement for the third hour. Therefore, dumping symptoms clearly are accompanied by postprandial sympathoadrenal activation, but sympathoadrenal activation cannot account completely for development of dumping symptoms.

Long-term results of octreotide-therapy in severe dumping syndrome.

OBJECTIVE: Little is known about the long-term results of octreotide therapy in dumping syndrome. We report the results of an open study including 20 patients with severe dumping symptoms after gastric surgery treated with octreotide between 1987 and 1997 at the Leiden University Medical Centre. DESIGN: Patient selection was based on (1) the results of a dumping provocation test and (2) symptoms that were refractory to other therapeutic measures. At regular intervals the presence of dumping symptoms was evaluated together with measurement of body weight and faecal fat excretion. RESULTS: Mean follow-up was 37 +/- 9 months (range 1-107 months). Doses of octreotide ranged from 25 to 200 microg/day. Initial relief of symptoms was achieved in all subjects, but after three months of therapy symptom relief persisted in 80% of patients. Mean body weight increased by 2.4 +/- 1.2 kg despite a significant increase in faecal fat excretion from 10 +/- 2 g/24 h to 24 +/- 3 g/24 h. Reasons for discontinuation of therapy were diminished efficacy in the longer term in 4 patients and side-effects in 7 patients. Biliary complications were encountered in 3 patients. CONCLUSIONS: Self-administration of octreotide proves an effective symptomatic treatment of severe dumping, even on the long-term. Its use is frequently limited by the occurrence of side-effects.

[The correction of the hormonal response during the treatment of the dumping syndrome with potable mineral waters]. / Korrektsiia gormonal'nogo otveta pri lechenii demping-sindroma pit'evymi mineral'nymi vodami.

Glucose tolerance test (40 g/lm2 b.s.) in patients with stomach resected for gastroduodenal ulcer provoked dumping-syndrome seen 15-30 min after glucose introduction. There was also a rise in blood sugar (by 77%), ACTH (by > 400%), STH (by > 400%), hydrocortisone (by 56%). Aldosterone levels fell by 68%. There was also a marked fall in activity of early insulin pool changed for elevation of its secretion by the test minute 60. 65 patients with dumping-syndrome following a course of drinking mineral water demonstrated improvement in clinical symptoms of the disease and changed hormonal response to glucose which manifested with activation of insulin secretion early phase and reduced rise of hydrocortisone levels.

Hypoglycemia unawareness in a patient with dumping syndrome: report of a case.

We report the case of a 49-yr-old man affected by coma and hypoglycemia unawareness following repetitive hypoglycemic episodes due to dumping syndrome. The dumping syndrome, which was due to partial gastrectomy and vagotomy performed for recurrent peptic ulcer, was responsible for reactive hyperinsulinemia as demonstrated by an oral glucose tolerance test. While the glucose counterregulatory hormones were all normally sensitive to specific stimulation tests, insulin-induced hypoglycemia failed to induce an adequate counterregulatory response, causing no response in plasma norepinephrine, a slight and short increase in plasma cortisol, ACTH and glucagon and an insufficient increase in plasma epinephrine and GH. This case demonstrates that hypoglycemia unawareness has to be taken into account not only in patients affected by IDDM or insulinoma but also in any case of reactive hypoglycemia.

Vasoactive substances in early dumping syndrome: effects of dumping provocation with and without octreotide.

In patients after gastric surgery, early dumping symptoms can be provoked by oral glucose challenge. Octreotide effectively prevents the occurrence of dumping symptoms. We have studied plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (ANP) concentrations in nine patients with early dumping, 10 surgical control subjects and nine healthy control subjects after an oral glucose challenge preceded by either placebo or 25 micrograms of octreotide subcutaneously (s.c.). In the dumping group, basal PRA was significantly (P < 0.01) higher (3.9 +/- 0.6 micrograms L-1 h-1) than in either surgical or healthy control subjects (1.1 +/- 0.3 micrograms L-1 h-1 and 1.1 +/- 0.2 micrograms L-1 h-1 respectively) and showed a significant rise after glucose ingestion to 5.4 +/- 0.9 micrograms L-1 h-1 that did not occur in control subjects. Aldosterone concentration showed a concomitant rise. In dumping patients, plasma ANP decreased after glucose ingestion from 31 +/- 6 ngL-1 to 21 +/- 5 ngL-1 (P < 0.05). This decrease did not occur in control subjects. Early dumping is associated with an activation of the renin-aldosterone axis and a decrease in plasma ANP, reflecting a hypovolaemic state. Octreotide prevents the occurrence of these changes.

Dumping syndrome in a young child.

UNLABELLED: We describe a 17-month-old child with dumping syndrome after plication of the right diaphragm. He presented with periods of abdominal distension and pallor, recurrent convulsions, glucosuria and refusal of feeding. After changing the diet the symptoms disappeared. CONCLUSION: Although dumping syndrome in children is rare, early recognition is important. Serial determination of blood glucose after bolus feeding can lead to the diagnosis. Treatment should consist of dietary changes.