Lerche Susanne, Soendergaard Liselotte, Rungby Joergen, Moeller Niels, Holst Jens Juul, Schmitz Ole E, Brock Birgitte
Institute of Pharmacology, University of Aarhus, University Park 1240, Aarhus C, Denmark.
Clin Endocrinol (Oxf). 2009 Oct;71(4):500-6. doi: 10.1111/j.1365-2265.2008.03510.x. Epub 2008 Dec 15.
It is uncertain whether the ability to avoid hypoglycaemia during fasting is preserved, and the risk of reactive hypoglycaemia after an oral glucose stimulus following a prolonged fasting period is increased at augmented glucagon-like peptide-1 (GLP-1) levels.
A randomized, double-blind placebo-controlled cross-over study in eight healthy men to assess the safety, in terms of hypoglycaemia, of a continuously infused pharmacological dose of native GLP-1 during long-term fasting. After an overnight fast the fasting period continued for 48 h and was followed by a 3-h oral glucose tolerance test (OGTT). GLP-1(7-36 amide) or placebo was continuously infused subcutaneously and titrated to a dose of 4.8 pmol/kg per min.
Two subjects in the GLP-1 group and one subject in the placebo group were withdrawn due to protocol specified plasma glucose (PG) < or = 2.8 mm and neuroglycopaenic symptoms. The infusion of GLP-1 resulted in pharmacological levels of intact GLP-1. During the fasting period PG, insulin and C-peptide levels declined and glucagon, GH and free fatty acid (FFA) levels increased with no differences between GLP-1 and placebo. During OGTT circulating levels of insulin and C-peptide were higher with GLP-1 infusion. However, PG was similar during GLP-1 vs. placebo infusions. GLP-1 infusion increased norepinephrine and cortisol levels during OGTT.
The counter-regulatory response during 48 h of subcutaneous GLP-1 infusion was preserved despite long-term fasting with no apparent increased risk of hypoglycaemic episodes. No reactive hypoglycaemia was observed when the fast was followed by an OGTT. Thus use of long-acting GLP-1 analogues may not increase the risk of hypoglycaemia.
尚不确定禁食期间避免低血糖的能力是否得以保留，且在长期禁食后口服葡萄糖刺激后，胰高血糖素样肽-1（GLP-1）水平升高时发生反应性低血糖的风险会增加。
一项针对8名健康男性的随机、双盲、安慰剂对照交叉研究，以评估长期禁食期间持续输注药理剂量的天然GLP-1在低血糖方面的安全性。经过一夜禁食后，禁食期持续48小时，随后进行3小时口服葡萄糖耐量试验（OGTT）。皮下持续输注GLP-1（7-36酰胺）或安慰剂，并滴定至4.8 pmol/kg每分钟的剂量。
GLP-1组的两名受试者和安慰剂组的一名受试者因方案规定的血浆葡萄糖（PG）≤2.8 mmol/L和神经低血糖症状而退出。GLP-1的输注导致完整GLP-1达到药理水平。在禁食期间，PG、胰岛素和C肽水平下降，胰高血糖素、生长激素和游离脂肪酸（FFA）水平升高，GLP-1组和安慰剂组之间无差异。在OGTT期间，输注GLP-1时胰岛素和C肽的循环水平较高。然而，GLP-1输注与安慰剂输注期间的PG相似。GLP-1输注在OGTT期间增加了去甲肾上腺素和皮质醇水平。
尽管长期禁食，但皮下输注GLP-1 48小时期间的对抗调节反应得以保留，低血糖发作风险无明显增加。禁食后进行OGTT时未观察到反应性低血糖。因此，使用长效GLP-1类似物可能不会增加低血糖风险。
