Upper GI Disorders: Pathophysiology and Current Therapeutic Approaches.

Symptoms referable to the upper digestive tract are associated with abnormalities of upper gastric neuromuscular function including abnormalities of motility, sensation, and absorption. Of the upper digestive tract, the stomach is of particular importance in its role in symptom generation and is highlighted in this chapter. Gastric symptoms can be associated with alterations in the rates of gastric emptying, impaired accommodation, heightened gastric sensation, or alterations in gastric myoelectrical activity and contractility. Treatment of gastric neuromuscular disorders requires an understanding of pathophysiology of the disorders, the appropriate use and interpretation of diagnostic tests, and the knowledge of effective treatment options. This chapter covers the pathophysiology and current treatment approaches to disorders of the upper gastrointestinal tract, focusing on classic disorders of the stomach, particularly gastroparesis and functional dyspepsia.

Use of Betaine HCl with Pepsin in Esophageal Cancer Patient: A Case Report.

The principal mechanisms surrounding gastrointestinal (GI) side effects due to chemotherapy are unclear, whereas the information regarding symptom management of patients with esophageal cancer post-esophagectomy is lacking. Esophagectomy patients are left with significant anatomical changes to the GI tract, including the cutting of the vagus nerve, which regulates gastric secretions, gastric acid pH, and motility. A 76-year-old male patient self-referred himself to the clinical dietitian for nutritional management of chronic nausea, fatigue, weight loss, and dumping syndrome 9 months post-esophagectomy, which was not responsive to medications. A physical functional nutritional assessment with evaluation of diet history and elimination suggested gastric hypochlorhydria. Gastric acid is needed for the active absorption of iron, zinc, B complex vitamins, especially B12, and digestion of consumed proteins. A digestive supplement, betaine hydrochloric acid with pepsin (BHClP), was introduced, and the patient ingested 1 capsule containing 500 mg betaine hydrochloride and 23.5 mg pepsin prior to protein-containing meals and reported a substantial decrease in GI symptoms while eating a regular diet with no limitations. He gained necessary weight and energy for daily activities. After a few months, the patient discontinued BHClP, and GI symptoms and dumping syndrome returned, leading to a loss of 7.5% of his body weight. The patient reinitiated the supplement and GI symptoms dissipated, and weight was restored. BHClP provided metabolic therapeutic benefit to optimize the patient's oral intake, preventing further complications and malnutrition. The success with BHClP for this patient case suggests that more research is needed to fully realize the mechanisms and clinical usage.

Effect of rikkunshito, a Japanese herbal medicine, on gastrointestinal symptoms and ghrelin levels in gastric cancer patients after gastrectomy.

BACKGROUND: Gastric cancer patients who undergo gastrectomy suffer from a post-gastrectomy syndrome that includes weight loss, dumping syndrome, reflux esophagitis, alkaline gastritis, and finally malnutrition. It is important to ameliorate the post-gastrectomy symptoms to restore postoperative quality of life (QoL). The aim of this study was to investigate the effect of rikkunshito, a Japanese herbal medicine, on postoperative symptoms and ghrelin levels in gastric cancer patients after gastrectomy. METHODS: Twenty-five patients who had undergone gastrectomy received 2.5 g of rikkunshito before every meal for 4 weeks, and a drug withdrawal period was established for the next 4 weeks. Changes in gastrointestinal hormones, including ghrelin, and appetite visual analog scale scores were measured, and QoL was estimated by using the European Organization for Research and Treatment of Cancer core questionnaire QLQ-C30. The Dysfunction After Upper Gastrointestinal Surgery for Cancer (DAUGS) scoring system was used to evaluate gastrointestinal symptoms after gastrectomy. RESULTS: Sixteen men and nine women (mean age 61.9 years) were enrolled in the study. All patients had either stage I (n = 24) or II (n = 1) disease and had undergone either distal gastrectomy (n = 17) or total gastrectomy (n = 8) by a laparoscopy-assisted approach. The mean ratio of the acyl-/total ghrelin concentration increased significantly after rikkunshito administration (Pre: 7.8 ± 2.1, 4 weeks: 10.5 ± 1.7 %, p = 0.0026). The total DAUGS score, as well as the scores reflecting limited activity due to decreased food consumption, reflux symptoms, dumping symptoms, and nausea and vomiting significantly improved after rikkunshito administration. CONCLUSIONS: The present study demonstrated a significant attenuation of gastrointestinal symptoms after gastrectomy by treatment with rikkunshito. Rikkunshito is potentially useful to minimize gastrointestinal symptoms after gastrectomy.

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.

[Somatostatin and the digestive system. Clinical experiences]. / A szomatosztatin és az emésztorendszer. Klinikai tapasztalatok.

The effect of somatostatin on the gastrointestinal tract is complex; it inhibits the release of gastrointestinal hormones, the exocrine function of the stomach, pancreas and bile, decreases motility and influences absorption as well. Based on these diverse effects there was an increased expectation towards the success of somatostatin therapy in various gastrointestinal disorders. The preconditions for somatostatin treatment was created by the development of long acting somatostatin analogues (octreotide, lanreotide). During the last twenty-five years large trials clarified the role of somatostatin analogues in the treatment of various gastrointestinal diseases. This study summarizes shortly these results. Somatostatin analogue treatment could be effective in various pathological conditions of the gastrointestinal tract, however, this therapeutic modality became a part of the clinical routine only in neuroendocrine tumours and adjuvant treatment of oesophageal variceal bleeding and pancreatic fistulas.

Safety and efficacy of high-dose acarbose treatment for dumping syndrome.

Dumping syndrome (DS) is a complication of Nissen fundoplication. Dietary strategies can ameliorate symptoms, but this approach is not always foolproof. Limited evidence reports the efficacy of acarbose for children who are unresponsive to feeding manipulations. We report 8 patients with DS aged between 7 and 24 months. In 4 of 8 nutritional strategies failed, and acarbose treatment was started. The initial dose was 25 mg for meals, and increased until postprandial glucose was stable. In 3 of 4 children the final dose was higher than previously reported, without adverse effects. Acarbose is useful to treat DS in cases of failure of dietary strategies.

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.

Efficacy of the long-acting repeatable formulation of the somatostatin analogue octreotide in postoperative dumping.

BACKGROUND & AIMS: Several studies have established symptomatic and mechanistic benefits of the somatostatin analogue octreotide in patients with dumping syndrome, but clinical use is hampered by the requirement for subcutaneous administration 3 times daily. We compared the efficacy of subcutaneous octreotide with that of the long-acting repeatable (LAR) octreotide formulation, which is administered monthly, in patients with dumping syndrome. METHODS: The study included 30 consecutive patients with postoperative dumping, evidenced by oral glucose tolerance test (OGTT) results and insufficient response to dietary measures. OGTT, dumping severity score (summary of scores 0-3 for 8 early and 6 late dumping symptoms), and quality-of-life data were evaluated at baseline, after 3 days of subcutaneous administration of octreotide (0.5 mg), and then after 3 monthly intramuscular injections of octreotide LAR (20 mg). RESULTS: Both formulations of octreotide significantly reduced total dumping severity scores (21.7 +/- 1.6 at baseline, 11.2 +/- 1.2 for subcutaneous and 14.0 +/- 1.8 for LAR formulations; P < .05). This reduction was associated with significant improvements in the increase in pulse rate (13.8 +/- 5.8 at baseline vs -0.3 +/- 2.2 and 1.9 +/- 1.7; P < .05) as well as the increase in hematocrit level (4.0 +/- 1.4 at baseline vs 0.3 +/- 0.9. and 0.4 +/- 1.0; P < .05), and the lowest glycemia level in the OGTT (54.1 +/- 6.7 at baseline vs 98.9 +/- 7.1 and 67.8 +/- 5.9; P < .05). LAR octreotide administration significantly improved patients' quality of life. Patients' evaluations of their overall treatment efficacy was higher on LAR compared with the subcutaneous formulation (83% vs 52%; P = .01). Gallbladder stones occurred in 4 patients. CONCLUSIONS: Monthly administration of LAR octreotide improves OGTT results, symptoms, and quality of life in patients with postoperative dumping.

Herbal Medicine for Dumping Syndrome: A Systematic Review and Meta-Analysis.

Background: Dumping syndrome is a common complication of surgical treatment of gastric cancer, but conventional therapy has limitations related to symptom care due to its structural cause and the decreased quality of life. Objectives: The objective of this review was to assess the clinical evidence for the effectiveness of herbal medicine as a treatment for dumping syndrome. Methods: A literature review was conducted using 16 databases from their inceptions to March 2018. All randomized controlled trials (RCTs) of herbal medicine used to treat dumping syndrome patients were included and meta-analyzed. Methodological quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Results: A total of 174 dumping syndrome patients of 3 trials met all inclusion criteria. Two trials assessed the effectiveness of herbal medicine on the symptom response rate compared with conventional pharmacotherapy. Their results suggested significant effects in favor of herbal medicine (risk ratio [RR] = 1.37, 95% confidence interval [CI] = 1.16-1.63, P = .0003, heterogeneity τ2 = 0, χ2 = 0.02, P = .88, I2 = 0%). One trial assessed its effectiveness on the improvement rate of overall symptoms compared with conventional conservative complex therapy, such as postural management, diet regulation, and counseling (RR = 1.23, 95% CI = 0.96-1.58). Conclusions: Due to the small sample size, scarcity of reported articles, and lack of quality of the current RCTs, it was concluded that the effectiveness of herbal medicine in treating dumping syndrome is unclear.

Efficacy and safety of lanreotide in postoperative dumping syndrome: A Phase II randomised and placebo-controlled study.

Background: Data on the efficacy and safety of the long-acting somatostatin analogue lanreotide (LAN) for postoperative dumping syndrome are lacking. Objective: We performed a double-blind, randomised and placebo-controlled crossover study of LAN Autogel® 90 mg in postoperative dumping. Methods: Adults with a positive prolonged oral glucose tolerance test or spontaneous hypoglycaemia and total dumping score (DS) ≥ 10 despite dietary measures were treated with three monthly injections of LAN or placebo in a randomised crossover fashion with an eight-week wash-out period. Primary outcome was the effect of LAN on total DS versus placebo. Secondary outcomes were the effect on early and late DS, treatment assessment, quality of life and safety. Results: Of 24 included patients (66.7% female; age 49.1 ± 2.1 years), 12 were randomised to LAN first. Pooled DS after three injections were lower compared to baseline after LAN (median=14 (interquartile range (IQR) 11.5-23) vs. median = 22 (IQR 16-27); p = 0.03) but not placebo (median = 20 (IQR 15-27) vs. median = 23 (IQR 13-29); p = 0.15). Improvement of early (median = 7.5 (IQR 4.5-13) vs. median = 12 (IQR 9-16); p = 0.03) but not late (median = 7 (IQR 6-10.3) vs. median = 9 (IQR 6-13); p = 0.26) DS was seen. Overall treatment assessment correlated with change in DS (r = -0.69, p = 0.004). Symptom improvement was not associated with changes in quality of life. Of the 81 reported adverse events, 44 occurred on LAN compared to 37 on placebo (p > 0.05), with seven serious adverse events on LAN. Conclusions: LAN is effective for treating early postoperative dumping symptoms, although side effects are common and quality of life is not significantly affected.

Post-prandial hypoglycemia after bariatric surgery: pharmacological treatment with verapamil and acarbose.

Postprandial hypoglycemia is a common complication of bariatric surgery. It is usually caused by late dumping syndrome, but a few other causes have already been described, including insulinoma and noninsulinoma pancreatogenous hypoglycemic syndrome (NIPHS). Considering that NIPHS is a recently described syndrome and is also very rare, therapeutic approaches are still not consensual. We report the case of a 26-year-old woman who was submitted to bariatric surgery and presented episodic postprandial hypoglycemic episodes after 16 months. Fasting C-peptide, insulin, and glucose were normal. Because of the possibility of NIPHS, clinical treatment was initiated with verapamil and acarbose, leading to a significant reduction of hypoglycemic episodes and also their severity. Surgery is the most common approach to NIPHS. However, in cases of mild or moderate symptoms, it is important to consider the possibility of pharmacological treatment. This approach may result, at least for some time, in an amelioration of symptoms without the need of an aggressive procedure.

Safety and efficacy of pasireotide in dumping syndrome-results from a phase 2, multicentre study.

BACKGROUND: Dumping syndrome is a prevalent complication of oesophageal and gastric surgery characterised by early (postprandial tachycardia) and late (hypoglycaemia) postprandial symptoms. AIM: To evaluate efficacy and safety of the somatostatin analogue, pasireotide in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery. METHODS: A single-arm, open-label, multicentre, intrapatient dose-escalation, phase 2 study with 4 phases: screening, 3-month SC (subcutaneous), 3-month IM (intramuscular) and 6-month optional extension IM phase. Primary endpoint was the proportion of patients without hypoglycaemia (plasma glucose <3.3 mmol/L [60 mg/dL] during an oral glucose tolerance test, OGTT) at the end of 3-month SC phase. A ≥50% response rate was considered clinically relevant. RESULTS: Forty-three patients with late dumping were enrolled; 33 completed the 3-month SC phase and 23 completed the 12-month study. The proportion of patients without hypoglycaemia at month 3 (primary endpoint) was 60.5% (26 of 43; 95% confidence interval, 44.4%-75.0%). Improvement in quality of life was observed during SC phase, which was maintained in the IM phase. The proportion of patients with a rise in pulse rate of ≥10 beats/min during OGTT reduced from baseline (60.5%) to month 3 (18.6%) and month 12 (27.3%). Overall (month 0-12), the most frequent (>20% of patients) adverse events were headache (34.9%); diarrhoea, hypoglycaemia (27.9% each); fatigue, nausea (23.3% each); and abdominal pain (20.9%). CONCLUSION: These results suggest that pasireotide is a promising option in patients with dumping syndrome after bariatric or upper gastrointestinal cancer surgery.

Effectiveness of sitagliptin in a patient with late dumping syndrome after total gastrectomy.

An 83-year-old man developed hypoglycemia after undergoing total gastrectomy for gastric cancer in 200X-4. The patient was admitted to our hospital in May 200X and placed on continuous glucose monitoring (CGM). Glycemic excursions were examined while on 3-meal/day (1700kcal) and 6-meal/day (1800kcal) diets. Oxyhyperglycemia followed about 2h later by a sudden drop in glucose levels was seen with both regimens. These findings were consistent with late dumping syndrome. CGM was continued, oral miglitol at 150mg/day or sitagliptin at 50mg/day was started, and glycemic excursions were compared. Results were similar for both drugs, with reductions in postprandial glucose elevations. Meal tolerance testing 3 months after oral sitagliptin, compared to before starting treatment, showed reductions in both early postprandial hyperglycemia and insulin hypersecretion. These findings suggest that DPP-4 inhibitors such as sitagliptin may be effective for treating post-gastrectomy late dumping syndrome.

Applications of peptide hormone ligands for the treatment of dumping and short bowel syndrome.

Dumping syndrome is a common and debilitating complication of upper gastrointestinal surgery. Accelerated gastric emptying and dysregulated secretion of gastrointestinal (GI) hormones are involved in its pathophysiology. Pasireotide, a novel somatostatin analogue, improved dumping in a phase-2 study. Preliminary data suggest that the glucagon-like peptide-1 (GLP-1) analogue liraglutide can also improve dumping. Short bowel syndrome is the most common cause of intestinal failure and involves not only a loss of mucosal absorptive area but also hypersecretion and accelerated transit. GLP-2 is the best studied hormone involved in intestinal adaptation. An increasing body of evidence demonstrates that the GLP-2 analogue teduglutide reduces parenteral support needs. New GLP-2 analogues and analogues of other GI hormones such as liraglutide are being investigated as promising treatments in short bowel syndrome.

Efficacy of depot long-acting release octreotide therapy in severe dumping syndrome.

BACKGROUND: Dumping syndrome is a serious complication occurring in 10% of patients after gastric surgery. Dumping symptoms are effectively reduced by subcutaneous application of the somatostatin analogue octreotide, but side-effects limit its use. AIM: To evaluate the efficacy of depot long-acting release octreotide (Sandostatin-LAR) vs. octreotide subcutaneous on dumping symptoms, quality of life and side-effects. METHODS: Twelve patients (five females, age 58 +/- 3 years) with severe dumping symptoms, requiring daily use of octreotide subcutaneous, were included in an open study and changed from octreotide subcutaneous after a 2 weeks washout to Sandostatin-LAR 10 mg i.m., every 4 weeks for 6 months. Symptoms (diary), body weight, fat excretion, food intake and Gastrointestinal Specific Quality of Life Index were evaluated. RESULTS: Gastrointestinal Specific Quality of Life Index increased significantly (P < 0.05) during Sandostatin-LAR treatment (88 +/- 4) compared with octreotide (74 +/- 4) and washout (75 +/- 6). During Sandostatin-LAR treatment, abdominal symptom score was lower compared with octreotide and washout, but not significantly. During Sandostatin-LAR treatment, body weight increased (66 +/- 4 to 70 +/- 3 kg; P = 0.19). CONCLUSIONS: Sandostatin-LAR is at least as effective as octreotide subcutaneous in suppressing symptoms in patients with severe dumping syndrome and is more effective than octreotide subcutaneous in increasing body weight and quality of life.

Acarbose. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential.

Acarbose delays the production of monosaccharides (notably glucose) by inhibiting the alpha-glucosidases associated with the brush-border membrane of the small intestine which are responsible for the digestion of complex polysaccharides and sucrose. In healthy subjects acarbose 100 to 200 mg significantly inhibits postprandial glucose, insulin and triglyceride responses, with some evidence of carbohydrate malabsorption with the higher dose. Clinical trials in patients with non-insulin-dependent diabetes mellitus showed that acarbose improved diabetic control, especially postprandial blood glucose levels, independent of whether the patients were receiving concomitant oral antidiabetic drugs in addition to dietary management. In comparative studies acarbose was significantly superior to placebo, and comparable to biguanides, when used alone or as an adjuvant to sulphonylurea therapy. Trials in patients requiring insulin to control their diabetes demonstrated that acarbose significantly reduced postprandial blood glucose concentrations, resulting in a smoother diurnal blood glucose-time curve and improved symptoms associated with nocturnal hypoglycaemia. Daily insulin requirements were sometimes reduced. In large multicentre trials acarbose up to 600 mg/day for 3 to 12 months improved glycaemic control in approximately 55% of patients with non-insulin-dependent or insulin-dependent diabetes mellitus. Apart from its use in diabetes, encouraging preliminary results have been obtained with acarbose in other therapeutic areas such as dumping syndrome, reactive hypoglycaemia, and types IIb and IV hyperlipoproteinaemias--however, further clinical experience is needed in these settings before clear conclusions can be drawn. No serious side effects have been reported during treatment with acarbose, although it is associated with a high incidence of troublesome gastrointestinal symptoms such as flatulence, abdominal distension, borborygmus and diarrhoea. The incidence of these reactions usually decreases with time. Thus, acarbose represents the first of a new class of oral antidiabetic drugs--the alpha-glucosidase inhibitors. It has proven useful for improving glycaemic control when used as an adjunct to standard therapy involving dietary restriction, oral antidiabetic drugs and/or subcutaneous insulin. That being the case, acarbose should provide the clinician with an interesting treatment option which can be used in a broad range of patients with diabetes mellitus in whom 'traditional' management approaches produce suboptimal glycaemic control.

The effect of somatostatin on dumping after gastric surgery: a preliminary report.

Many of the features of the dumping syndrome may be manifestations of hypovolemia and mechanical distension of the gut, resulting from abnormal fluid secretion in the upper gastrointestinal tract. The object of the present study was to assess the effect of somatostatin, an inhibitor of upper gastrointestinal secretions, on the response to a dumping provocation test, using a double-blind, placebo-controlled method. Four patients were studied; two had undergone total gastrectomy for gastric carcinoma and two had undergone gastric bypass for morbid obesity. Each subject received, on two separate occasions, a challenge of 200 ml of 50% glucose administered orally after an overnight fast. Somatostatin in 150 mm of NaCl (250 micrograms bolus followed by 300 micrograms/hr infusion) was given intravenously during one dumping provocation test and placebo (150 mm of NaCl) during the other according to a Latin square design. When the subjects received the placebo there were significant increases in pulse rate and packed cell volume after oral glucose (p less than 0.05, paired t test), which did not occur when they received somatostatin. The glucose challenge also produced a more rapid increase in serum osmolality and blood glucose during administration of placebo than when somatostatin was given. Marked diarrhea developed in all placebo-treated subjects but in none when they received somatostatin; however, three of the subjects developed marked abdominal pain during dumping provocation tests when treated with somatostatin, which did not occur when placebo was given. Although somatostatin appears to suppress some of the objective responses to a dumping provocation test, it may not prove particularly useful in the treatment of dumping symptoms.

Treatment of nonendocrine gastrointestinal disorders with octreotide acetate.

Somatostatin and its longer-acting analog, octreotide acetate, can be used effectively for the treatment of nonendocrine gastrointestinal disorders. Octreotide has been shown to decrease pancreatic fistula output by suppressing exocrine pancreatic function. We believe that octreotide acetate may be useful to prophylaxis against the development of pancreatic fistulas following pancreatic resection and may reduce the enzymatic and volume output of established pancreatic fistulas. We also have shown that administration of octreotide acetate 2 hours before a high carbohydrate test meal reduces gut peptide levels, which increase following meal ingestion in patients with the dumping syndrome. Reduction of circulating peptides in these patients may slow gut motility and improve glucose regulation, thus, providing relief of postvagotomy dumping symptoms.

Reactive hypoglycaemia due to late dumping syndrome: successful treatment with acarbose.

Reactive hypoglycaemia is a rare disease which occurs postprandially in everyday life involving blood glucose levels below 2.5 to 2.8 mmol/l. We report on a 66-year-old patient who developed symptomatic reactive hypoglycaemia due to late dumping syndrome 10 years after oesophagectomy with cervical anastomosis. A 75 g sucrose load revealed a plasma glucose level of 9.4 mmol/l after one hour, followed by symptomatic hypoglycaemia with a plasma glucose level of 1.8 mmol/l after three hours. Concomitantly, high concentrations of insulin (3216 pmol/l at a glucose level of 9.4 mmol/l and 335 pmol/l at a glucose level of 1.8 mmol/l) and glucagon-like peptide 1 (GLP-1) (375 pmol/l at a glucose level of 9.4 mmol/l and 85 pmol/l at a glucose level of 1.8 mmol/l) were measured. While the patient was under treatment with acarbose, another sucrose load did not provoke symptomatic hypoglycaemia (plasma glucose nadir of 4.6 mmol/l after two hours). Insulin and GLP-1 levels increased much less, to peak levels of 375 pmol/l and 75 pmol/l respectively, after one hour when plasma glucose was 6.8 mmol/l. We conclude that in patients with reactive hypoglycaemia due to gastrointestinal surgery, acarbose decreases rapid glucose absorption associated with hyperglycaemia and GLP-1 secretion, and thus diminishes excessive insulin release. Acarbose is therefore a successful treatment modality for reactive hypoglycaemia due to late dumping syndrome.

Acarbose treatment of infant dumping syndrome: extensive study of glucose dynamics and long-term follow-up.

Dumping syndrome is a sequel of gastric surgery in adults and Nissen fundoplication in children. The syndrome is characterized by various gastrointestinal symptoms as well as irritability, diaphoresis and lethargy. Shortly after a meal, symptoms are associated with hyperglycemia (early dumping), followed by late dumping symptoms associated with reactive hypoglycemia. Several therapeutic and dietary manipulations failed to control these symptoms in previous reports as well as in an infant we have followed after Nissen fundoplication. Acarbose, an alpha-glucosidase inhibitor, has been used sporadically in adults after gastric surgery, but only once in children. In most of these studies, the effect of acarbose (on reactive hypoglycemia) was evaluated over several hours postprandially or after oral glucose load. In our study, we recorded glucose dynamics by a continuous glucose monitor system over 2 to 3 days before and during acarbose treatment, while the patient was on a well-controlled diet. These measurements (720 before and 832 on therapy) suggested that both early and late dumping symptoms are causally related to the rate of glucose elevation and decline, rather than to glucose peak and nadir, respectively. Acarbose attenuated both postprandial glucose hyperglycemia and reactive hypoglycemia, which subsequently led to a significant reduction in dumping symptoms. In a follow-up of 14 months, acarbose was well tolerated and the frequency of dumping symptoms was remarkably reduced.