Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue
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 mug 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.
|ISBN||1479-683X (Electronic) 0804-4643 (Linking)|
|Authors||Myint, K. S.; Greenfield, J. R.; Farooqi, I. S.; Henning, E.; Holst, J. J.; Finer, N.;|
|Publisher Name||EUROPEAN JOURNAL OF ENDOCRINOLOGY|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/22408121|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/11563|