Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue
Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue
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DOI：
10.1530/eje-11-1065
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发表时间：
2012-05-01
影响因子：
5.8
通讯作者：
Finer, N.
中科院分区：
文献类型：
--
作者：
Myint, K. S.;Greenfield, J. R.;Finer, N.
背景：胃旁路手术(GBS)后自发性高胰岛素血症的研究日益受到重视。然而，其病理生理机制仍不清楚。有些病人需要切除胰腺。钙通道阻滞剂、阿卡波糖和二氮卓的药物治疗已被报道是有益的，但有不同的依从性和反应。方法：我们展示了GLP1的作用，逆调节激素，以及随后GLP1对生长抑素类似物治疗的反应，42岁的女性在GBS后6年持续神经性血糖下降。在三种设置下测定血浆GLP1、胰岛素和血糖5h：I)75g口服葡萄糖耐量试验(OGTT)；II)标准液体试餐(LTM)；以及III)S.C.30min后的OGTT。结果：与肥胖的非糖尿病对照组相比，患者在OGTT期间空腹水平升高，GLP1反应明显增强，随后胰岛素反应夸大，随后出现低血糖水平。GLP1对LTM的反应相似，但更大。在口服葡萄糖耐量试验前给予奥曲肽可同时减轻GLP1和胰岛素反应，并消除低血糖。奥曲肽治疗显著改善了患者的神经降糖症状。激素谱在LTM后6个月重新评估，在注射奥曲肽之前。峰值GLP1和胰岛素反应比治疗前反应不明显，且没有低血糖。患者接受了兰瑞肽治疗，4年来一直保持无症状和正常血糖。结论：胃肠道解剖改变后过度的胰岛素反应可能是我们GBS患者低血糖的可能原因。生长抑素成功地在长期内迅速抑制了这种反应，从而避免了胰腺切除术及其后遗症。
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 mu g 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.