DUMPING - Hypo -Research ....good news (1)

[gutlesswonder]

I post below an excerpt from a recent published and peer reviewed paper concerning investigations into certain after-effects of bariatric obesity surgery.

This text is pretty indigestible but it serves to illustrate that big guns are starting to be deployed on the problem, which is identical to and due to the same mechanisms as our own syndrome.

Realistically, time and money is at last being expended by medical researchers because of the expanded patient universe generated by slimming/diabetic therapy procedures.

We can look forward to the day when this,arguably the worst and most dangerous legacy of our carcinoma is fully and properly understood and remedies are available.

I will post further positive news shortly.

Gastric bypass surgery and postprandial hypoglycemia

Six patients with hyperinsulinemic hypoglycemia following meal ingestion were detected 0.5-8 years following Roux-en-Y gastric bypass surgery were found to have histological evidence for nesidioblastosis following resection of pancreatic tissue-one patient was found to have multiple insulinomas as described in the July 21 2005 New England Journal of Medicine Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery. N Engl J Med. 2005 Jul 21;353(3):249-54. The authors speculated, as further discussed in an accompanying editorial, that excessive secretion of gut hormones such as GLP-1 may have contributed to the development of islet proliferation in these human subjects. Indeed, many of the patients presenting with hypoglycemia post bypass have increased GLP-1 levels and enhanced beta cell sensitivity to GLP-1 action Exaggerated release and preserved insulinotropic action of glucagon-like peptide-1 underlie insulin hypersecretion in glucose-tolerant individuals after Roux-en-Y gastric bypass Diabetologia. 2013 Dec;56(12):2679-87

A similar clinical picture was reported in 3 subjects following gastric bypass, and plasma levels of GLP-1 were markedly elevated in these studies Severe hypoglycaemia post-gastric bypass requiring partial pancreatectomy: evidence for inappropriate insulin secretion and pancreatic islet hyperplasia. Diabetologia. 2005 Sep 30; [Epub ahead of print]. However, a subsequent re-analysis of the pancreas histology, together with control slides obtained from 31 obese subjects and 16 lean control subjects, yielded somewhat modified conclusions. Meier and colleagues reported that b-cell area was not increased in the subjects with gastric bypass-associated hypoglycemia and no evidence of increased islet neogenesis or b-cell proliferation was detected in this group. These findings further emphasis the importance of functional defects, namely changes in gut motility and the acute b-cell response to nutrients/gut hormones in the pathogenesis of the hyperinsulinemic hypoglycemia syndrome seen in some subjects. See Hyperinsulinemic hypoglycemia after gastric bypass surgery is not accompanied by islet hyperplasia or increased beta-cell turnover. Diabetes Care. 2006 Jul;29(7):1554-9. Indeed, many of the patients presenting with hypoglycemia have increased GLP-1 levels and enhanced beta cell sensitivity to GLP-1 action Exaggerated release and preserved insulinotropic action of glucagon-like peptide-1 underlie insulin hypersecretion in glucose-tolerant individuals after Roux-en-Y gastric bypass Diabetologia. 2013 Dec;56(12):2679-87

Salehi and colleagues examined the importance of GLP-1/the GLP-1R in glucose-stimulated insulin secretion in asymptomatic subjects after gastric bypass (GB) and in subjects with recurrent hypoglycemia using acute administration of the GLP-1R antagonist, exendin(9-39). Fasting blood glucose and insulin levels were comparable in the two groups. The insulin response to IV glucose and insulin sensitivity was also similar between groups. Administration of Ex9 produced a comparatively greater suppression of postprandial insulin levels in the GB groups however the rate of gastric emptying was not modified by Ex9. The postmeal rise in plasma GLP-1 was significantly higher in the patients experiencing hypoglycemia. Intriguingly, Ex9 infusion produced a further rise in plasma GLP-1 levels, consistent with a negative feedback loop. The control of glucagon secretion was also abnormal and increased in GB patients fater meal ingestion. Whether increased levels of GLP-1 are the predominant factor producing hypoglycemia in these subjects remains uncertain. Gastric Bypass Surgery Enhances Glucagon-Like Peptide 1-Stimulated Postprandial Insulin Secretion in Humans Diabetes. 2011 Sep;60(9):2308-2314

In a subsequent study, Salehi studied 24 subjects, 9 (2 with prior diabetes) with recurrent hypoglycemia (recurrent episodes with symptoms of neuroglycopenia) and 7 individuals (2 with prior diabetes) without hypoglycemia after gastric bypass, and 8 control subjects who did not undergo previous bariatric surgery. The magnitude of peak GLP-1 levels correlated inversely with the glucose in hypoglycemic subjects. Complaints compatible with dumping syndrome were common in subjects after GBS. Total weight loss and time since surgery were comparable across groups. Subjects were studied with a mixed meal, tracer infusion, with and without an intravenous infusion of the GLP-1R antagonist Ex9. Blockade of the GLP-1R with Ex9 increased both fasting and postprandial glucose levels in all three groups, however the increase in glucose was greater in subjects with hypoglycemia and infusion of Ex9 largely prevented the previously demonstrated meal-related hypoglycemia in this cohort. Insulin responses were more rapid and greater in the hypoglycemia group, and Ex9 attenuated in the insulin responses to meal ingestion in all groups. Glucagon levels were higher after meals in the GBS groups and increased further after Ex9. The authors conclude that accelerated glucose absorption together with increased GLP-1 secretion substantially contribute to hypoglycemia after bariatric surgery in susceptible individuals Blockade of Glucagon-like Peptide 1 Receptor Corrects Post-prandial Hypoglycemia After Gastric Bypass Gastroenterology. 2013 Dec 3. doi:pii: S0016-5085(13)01725-3

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I do not understand the text, but one lining on the cloud is that medical people are starting to talk about 'dumping syndrome' using different terms - ie post prandial hypoglycaemia or 'an insulin spike after taking food'. There are more than enough people suffering from this to provide a good database for research, and I entirely agree that it is one thing from which long-suffering people who visit this site would really welcome some relief.