Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue

Abstract

Background: Spontaneous hyperinsulinaemic hypoglycaemia following gastric bypass surgery (GBS) is increasingly recognised. However, its pathophysiology remains unclear. Some patients require pancreatectomy. Medical therapy with calcium channel blockers, acarbose and diazoxide has been reported to be beneficial but has variable adherence and response. Method: We demonstrate the role of GLP1, counter-regulatory hormones and the subsequent response of GLP1 to somatostatin analogue therapy in a 42-year-old woman with persistent neuroglycopaenia 6 years after GBS. Plasma GLP1, insulin and glucose were measured for 5 h on three settings: i) a 75 g oral glucose tolerance test (OGTT); ii) a standard liquid test meal (LTM); and iii) an OGTT 30 min after a s.c. injection of 100 mg octreotide. Results: In comparison with obese non-diabetic controls, the patient had an elevated fasting and a markedly enhanced GLP1 response during the OGTT, followed by an exaggerated insulin response and a subsequent low glucose level. The GLP1 response to a LTM was similar but greater. Octreotide given prior to the OGTT attenuated both the GLP1 and insulin responses and abolished hypoglycaemia. Octreotide therapy significantly improved the patient's neuroglycopaenic symptoms. The hormone profile was reassessed after 6 months following the LTM preceded by octreotide injection. Peak GLP1 and insulin responses were less pronounced than pretreatment responses and without hypoglycaemia. The patient was treated with lanreotide and had remained symptom-free and euglycaemic for 4 years. Conclusion: An exaggerated incretin response following altered gastrointestinal anatomy was the likely cause of hypoglycaemia in our GBS patient. Somatostatin successfully suppressed this response acutely and in the long term, thereby avoiding pancreatectomy and its sequelae.

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

“…Octreotide is significantly effective for early dumping syndrome, although it may be less effective in the long term than in the short term [16]. Recently, Myint et al reported a 42 year old woman with hyperinsulinaemic hypoglycaemia after gastric bypass [17]. In their report, octreotide therapy significantly improved the patient's symptoms and GLP-1 response.…”

“…Somatostatin receptors exist as five isoforms (SSTR1-SSTR5), of which sst5 is expressed by the rat L-cell and the rodent K-cell [18,19]. Somatostatin inhibits GIP and GLP-1 secretion from small intestinal cultures through SSTR5 [17]. Peripheral GLP-1 receptor ligand administration caused tachycardia [20,21], but exendin-(9-39), the GLP-1 receptor antagonist, blocked the response in rats [22].…”

Hypoglycemia in everyday life after gastric bypass and duodenal switch

“…Several treatments have been proposed in the literature; these involve acarbose (24,25), calcium channel antagonists (nifedipine and verapamil) (26), the somatostatin analogues octreotide (27) and pasireotide (28), the b-cell inhibitor diazoxide (29), and finally and ultimately, partial pancreatectomy (30). Glucagon has been tried as infusion but has not been proven to be useful perhaps because of its concomitantly high levels of insulin (31).…”

Using miglitol at 30 min before meal is effective in hyperinsulinemic hypoglycemia after a total gastrectomy

“…However, the occurrence of adverse effects necessitated its discontinuation of the drug. Octreotide reportedly suppresses plasma GLP-1 and GIP levels and improves early dumping syndrome [9,19]. Recently, Smith et al reported that the incretin effect of GLP-1 is not mediated by the GLP-1 receptor of the pancreatic β cells under normoglycemic conditions [20].…”