Utility of continuous glucose monitoring following gastrectomy.

BACKGROUND: Glucose fluctuation after gastrectomy represented by dumping syndrome is a well-known post-gastrectomy syndrome that negatively impacts patient quality of life. However, the current methods of post-gastrectomy glucose monitoring do not comprehensively capture the postoperative blood glucose fluctuations that characterize this. METHODS: We used a continuous glucose monitoring (CGM) system to document the glycemic profiles of patients undergoing gastrectomy and compared these between patients undergoing distal gastrectomy (DG) and total gastrectomy (TG). To evaluate post-gastrectomy syndromes, including dumping syndrome, we used the Post-gastrectomy Syndrome Assessment Scale 37-item questionnaire. The glycemic profiles were also compared using this tool. RESULTS: We studied 57 patients who had undergone DG and 13 who had undergone TG between September 2017 and September 2019. Our results revealed larger diurnal glycemic variability and longer periods of nocturnal hypoglycemia after gastrectomy. The dumping score was worse in the TG than in the DG group (TG 2.4 ± 1.4 vs. DG 1.3 ± 1.2, P = 0.0061). Importantly, 30 of 57 DG patients (52.6%) and 5 of 13 TG patients (38.5%) experienced postprandial hypoglycemia following hyperglycemia without hypoglycemic symptoms. There was no correlation between the dumping symptom score and glycemic variability (ρ = 0.0545, P = 0.6662). CONCLUSIONS: CGM demonstrated diurnal glycemic variability and nocturnal hypoglycemia in patients undergoing gastrectomy. Because some hypoglycemic patients did not develop symptoms and glycemic variability was not necessarily associated with dumping symptom, dumping syndrome must only partially explain the postoperative glucose fluctuations.

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.

Rapid gastric and intestinal transit is a major determinant of changes in blood glucose, intestinal hormones, glucose absorption and postprandial symptoms after gastric bypass.

OBJECTIVE: To evaluate the effect of modulating pouch emptying (PE) and SI transit of glucose after Roux-en-Y gastric bypass (RYGB) on blood glucose, incretin hormones, glucose absorption and gastrointestinal (GI) symptoms. METHODS: Ten RYGB patients were studied twice in random order, receiving either a 150 ml glucose drink (200 kcal) or the same solution infused into the proximal Roux-limb at 4 kcal/min. Data were compared with 10 healthy volunteers who received a 4 kcal/min duodenal infusion. PE, cecal arrival time (CAT), blood glucose, plasma 3-O-methylglucose (3-OMG), insulin, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1), and GI symptoms were measured. RESULTS: In RYGB subjects, the glucose drink emptied very rapidly (PE t50 = 3 ± 1 min) and intestinal glucose infusion was associated with higher blood glucose and plasma 3-OMG, but lower plasma GLP-1, GIP, insulin, and GI symptoms than oral glucose (all P < 0.001), and comparable to volunteers. In RYGB subjects, CAT correlated inversely with peak GLP-1 (r = -0.73, P = 0.01), and plasma 3-OMG correlated tightly blood glucose (r = 0.94, P < 0.0001). CONCLUSIONS: After RYGB, reducing intestinal glucose delivery to 4 kcal/min is associated with higher blood glucose, greater glucose absorption, lower incretin responses, and less GI symptoms, supporting rapid transit contribution to the exaggerated incretin responses and "dumping symptoms".

Gut hormones, early dumping and resting energy expenditure in patients with good and poor weight loss response after Roux-en-Y gastric bypass.

OBJECTIVE: To identify factors contributing to the variation in weight loss after Roux-en-Y gastric bypass (RYGB). DESIGN: Cross-sectional study of patients with good (excess body mass index lost (EBL) >60%) and poor weight loss response (EBL <50%) >12 months after RYGB and a lean control group matched for age and gender. MATERIALS AND METHODS: Sixteen patients with good weight loss response, 17 patients with poor weight loss response, and eight control subjects were included in the study. Participants underwent dual energy X-ray absorptiometry scan, indirect calorimetry and a 9 h multiple-meal test with measurements of glucose, insulin, total bile acids (TBA), glucagon-like peptide (GLP)-1, peptide YY3-36 (PYY), cholecystokinin (CCK), ghrelin, neurotensin and pancreatic polypeptide (PP) as well as assessment of early dumping and appetite. RESULTS: Suppression of hunger was more pronounced in the good than the poor responders in response to the multiple-meal test (P=0.006). In addition, the good responders had a larger release of GLP-1 (P=0.009) and a greater suppression of ghrelin (P=0.037) during the test, whereas the postprandial secretion of CCK was highest in the poor responders (P=0.005). PYY, neurotensin, PP and TBA release did not differ between the RYGB-operated groups. Compared with control subjects, patients had exaggerated release of GLP-1 (P<0.001), PYY (P=0.008), CCK (P=0.010) and neurotensin (P<0.001). Early dumping was comparable in the good and poor responders, but more pronounced than in controlled subjects. Differences in resting energy expenditure between the three groups were entirely explained by differences in body composition. CONCLUSION: Favorable meal-induced changes in hunger and gut hormone release in patients with good compared with poor weight loss response support the role of gut hormones in the weight loss after RYGB.

Dumping syndrome, a cause of acquired glycogenic hepatopathy.

A 2-year-old boy, having undergone fundoplication for gastroesophageal reflux disease and fed by gastrostomy, presented with recurrent emesis, syncope with hypoglycemia, and persistently elevated serum liver transaminase levels. Liver biopsy revealed hepatocellular glycogenosis by light and electron microscopy. Further evaluation showed no evidence of diabetes mellitus, glycogen storage disease, or corticosteroid use. Since the hyperglycemic-hyperinsulinemic state of dumping syndrome would provide a mechanism for hepatocellular glycogenosis, the biopsy findings prompted consideration of dumping syndrome. Metabolic evaluation confirmed the diagnosis of dumping syndrome, and appropriate dietary management led to sustained resolution of symptomatology and hypertransaminasemia. Dumping syndrome is proposed to be a cause of hepatocellular glycogenosis, the latter representing a form of acquired glycogenic hepatopathy.

Bariatric surgery for diabetes management.

PURPOSE OF REVIEW: To review the role of bariatric surgery in the treatment of patients with type 2 diabetes. RECENT FINDINGS: Multiple studies demonstrate that bariatric surgical approaches to obesity lead to substantial and sustained weight loss. Patients with diabetes have remission of hyperglycemia or require reduced medications. Surgical intervention for patients with more recent diabetes onset may have higher rates of resolution than patients with longer duration disease. In addition, dyslipidemia and hypertension improve. A short-term randomized clinical trial comparing laparoscopic banding with optimal medical management suggests surgery leads to more improvement in multiple metabolic measures. Perioperative risk is low and observational studies suggest long-term survival is favorable for obese patients following bariatric surgery. Metabolic risks of bariatric procedures are reviewed. SUMMARY: Although there are several surgical approaches for weight management, improvements in diabetes, including achievement of near normal glycemia without medication or reduced medications, are realized in many patients. Early surgical intervention for overweight type 2 diabetes may be clinically appropriate in patients for in whom operative risks are acceptable.

[A new view on pathogenesis of dumping-syndrome].

Clinical-laboratory investigations in 58 patients with peptic ulcer have shown that increased production of the intestinal hormones of the chromophine system of the gastrointestinal tract is of great significance in pathogenesis of dumping syndrome after Billroth-II resection of the stomach.

[Neurohumoral regulation of gastric secretion in postvagotomy syndromes]. / Neirogumoralnaia reguliatsiia sekretornoi deiatelnosti zheludka pri postvagotomicheskikh sindromakh.

The secretion of hormones stimulating and inhibiting gastric secretory activity was studied in 85 patients with postvagotomy syndromes. The somatropin level was found to increase significantly in gastrostasis. The lower values of the blood insulin and C-peptide content in patients with recurrent ulcers was evidently associated either with insufficiency of the pancreatic insular apparatus or with partial vagal denervation, increased STH level, and plausible inhibiting effect of glucagon. Increased somatostatin secretion in the dumping syndrome, gastrostasis, and peptic ulcers may be due to the encountered hypergastrinemia.

The effect of somatostatin in dumping syndrome after gastric surgery.

The effect of somatostatin on early and late dumping syndrome was studied in 12 patients with gastric resection. Each patient underwent two glucose challenges with 75 gram of glucose administered orally. In the control study isotonic sodium chloride was given, while in the other study cyclic somatostatin in a dose of 80 ng/kg/min was given for a period of 270 minutes. In the control study all patients showed subjective symptoms of the early dumping syndrome with significant (p < 0.001) increases in pulse rate, hematocrit, and vasoactive intestinal polypeptide. Ten patients showed asymptomatic hypoglycemia, as a sign of the late dumping syndrome associated with a significant (p < 0.001) increase of insulin, gastric inhibitory peptide and glucagon levels. During the administration of somatostatin these changes failed to develop. The difference between the results of the two challenges are significant. These results indicate that somatostatin alleviates the symptoms both of early and late dumping syndrome partly by inhibiting the vasoactive intestinal polypeptide, gastric inhibitory peptide and insulin release, which are increased in dumping syndrome and may, therefore, be implicated as to have an etiological role.

Nutritional manipulation in the management of dumping syndrome.

Two children with Nissen's fundoplication and either gastrocystoplasty or pyloroplasty developed dumping syndrome. Correction of their blood glucose abnormalities, resolution of symptoms, and weight gain were effectively achieved by addition of fats and uncooked corn starch (50 g/l) to their feeds.

Control of dumping symptoms by somatostatin analogue in patients after gastric surgery.

Octreotide acetate is a long-acting analogue of the naturally occurring inhibitory gastrointestinal peptide, somatostatin. We tested the efficacy of octreotide in controlling the symptoms of dumping syndrome in response to a provocative meal in a randomized, double-blinded, crossover trial in nine severely affected patients. Pretreatment with octreotide acetate (100 micrograms injected subcutaneously) reduced postprandial dumping symptoms from a mean +/- SEM score of 15.7 +/- 1.6 (placebo treatment day) to 4.6 +/- 1.7. With placebo treatment, all nine patients became symptomatic in response to the meal, whereas with octreotide treatment, symptoms occurred in only two of nine patients. Similarly, all placebo-treated patients showed a postprandial increase in pulse rate to a mean +/- SEM of 105 +/- 6 beats per minute, whereas only one of nine octreotide-treated patients showed an increase in pulse rate (mean +/- SEM, 80 +/- 3 beats per minute). These differences were also statistically significant. While no significant changes were observed in postprandial hematocrit values or osmolality between placebo and octreotide treatments, octreotide prevented hypoglycemia in four affected patients and significantly inhibited insulin release. We conclude that octreotide is a useful tool in the treatment of patients with severe, refractory dumping syndrome.

[Atrial natriuretic peptide in dumping syndrome]. / Pitvari nátriuretikus peptid dumping szindrómában.

The significance of atrial natriuretic factor (ANF) was investigated in the maintenance of the fluid volume in hypovolemia associated with dumping syndrome following gastric resection. The study was performed on 10 patients with Billroth II procedure. Ten age and sex matched patients--without previous gastric surgery served as controls. Each patient underwent oral glucose challenge. The patients following gastric resection underwent an other glucose challenge with intravenous infusion for the maintenance of the fluid volume. All patients with gastric resection showed subjective symptoms of the early dumping syndrome with significant (p less than 0.001) increases in heart rate and in hematocrit, while plasma ANF level decreased significantly (p less than 0.01). Significant negative correlation was found between the changes in hematocrit and the changes in plasma ANF level (r = -0.89; p less than 0.001). Neither the subjective symptoms characteristic for early dumping syndrome, nor changes in the laboratory parameters were noted in the patients during the challenge with infusion. The results show that the hypovolemia in dumping syndrome is associated with significant decreased ANF activity, and in the regulation of ANF release besides the well known stimulating effect of hypervolemia, there exists an inhibition of secretion in volume depleted states.

The 15-minute dumping provocation test.

Following gastric surgery, the diagnosis of the dumping syndrome (DS) has never been precise. The importance of diagnosis is not only in deciding management, but also in comparing series of incidences. The mainstay of diagnosis has been the gastric emptying and dumping provocation test (DPT); however it requires expensive equipment and the interpretation of the results is subjective and therefore variable. In 38 DPTs the percentage plasma volume and pulse rate changes, 15 min after the ingestion of 150 ml of hypertonic glucose, were expressed as percentages of the maximum values encountered and summed to form a score. The tests were independently interpreted by the authors and where they disagreed the result was defined as equivocal. The score was used with the symptoms provoked to follow a simple algorithm to divide the patients into those with and those without DS. There were six suffering from DS on our current interpretation; the new method identified all of these. Three tests were positive on the scoring scheme only and on review the interpreters agreed that all of these patients were suffering from the dumping syndrome. An accurate test using only the baseline and 15 min samples is simple, cheap and has definite rules of interpretation; the only laboratory measurement needed is the haematocrit estimation of three blood samples.

Plasma peptide YY (PYY) in dumping syndrome.

The newly isolated hormonal peptide PYY is mainly localized to endocrine cells of the lower intestinal mucosa. The release of PYY by oral glucose was studied in six patients with the dumping syndrome to ascertain the effect of this condition on PYY release. Plasma PYY concentrations were greatly increased following oral glucose in patients with the dumping syndrome compared with healthy controls. In a separate series of experiments, the effect of somatostatin infusion on the PYY release by glucose in these patients was investigated. The release of PYY was completely blocked by infusion of somatostatin, and its release from the bowel in normal subjects may therefore be modulated by local somatostatin in the gut. PYY has been shown to inhibit gastric acid secretion and emptying, at plasma concentrations similar to those seen after glucose, in patients with the dumping syndrome. PYY may therefore be a factor involved in the pathophysiological changes associated with this condition.

Effect of acarbose on biochemical responses and clinical symptoms in dumping syndrome.

A dose of 50 mg of acarbose was administered with a standard breakfast to 13 subjects with dumping syndrome. Significant attenuation of hyperglycaemia (p less than 0.01) was observed, and rises in plasma gastric inhibitory polypeptide, insulin and enteroglycagon were reduced (p less than 0.05). Plasma levels of neurotensin, vasoactive intestinal polypeptide and somatostatin were not affected. Dumping score was reduced, but this did not achieve statistical significance. In a longer-term study, 9 patients took acarbose, 50 mg t.i.d., for 1 month. No significant reduction in the number or severity of dumping attacks was observed, but a majority expressed a preference for the drug and some individuals experienced a marked improvement of symptoms.