Page Kathleen A, Williamson Anne, Yu Namyi, McNay Ewan C, Dzuira James, McCrimmon Rory J, Sherwin Robert S
Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut, USA.
Diabetes. 2009 May;58(5):1237-44. doi: 10.2337/db08-1557. Epub 2009 Feb 17.
We examined whether ingestion of medium-chain triglycerides could improve cognition during hypoglycemia in subjects with intensively treated type 1 diabetes and assessed potential underlying mechanisms by testing the effect of beta-hydroxybutyrate and octanoate on rat hippocampal synaptic transmission during exposure to low glucose.
A total of 11 intensively treated type 1 diabetic subjects participated in stepped hyperinsulinemic- (2 mU x kg(-1) x min(-1)) euglycemic- (glucose approximately 5.5 mmol/l) hypoglycemic (glucose approximately 2.8 mmol/l) clamp studies. During two separate sessions, they randomly received either medium-chain triglycerides or placebo drinks and performed a battery of cognitive tests. In vitro rat hippocampal slice preparations were used to assess the ability of beta-hydroxybutyrate and octanoate to support neuronal activity when glucose levels are reduced.
Hypoglycemia impaired cognitive performance in tests of verbal memory, digit symbol coding, digit span backwards, and map searching. Ingestion of medium-chain triglycerides reversed these effects. Medium-chain triglycerides also produced higher free fatty acids and beta-hydroxybutyrate levels compared with placebo. However, the increase in catecholamines and symptoms during hypoglycemia was not altered. In hippocampal slices beta-hydroxybutyrate supported synaptic transmission under low-glucose conditions, whereas octanoate could not. Nevertheless, octanoate improved the rate of recovery of synaptic function upon restoration of control glucose concentrations.
Medium-chain triglyceride ingestion improves cognition without adversely affecting adrenergic or symptomatic responses to hypoglycemia in intensively treated type 1 diabetic subjects. Medium-chain triglycerides offer the therapeutic advantage of preserving brain function under hypoglycemic conditions without causing deleterious hyperglycemia.
我们研究了摄入中链甘油三酯是否能改善强化治疗的1型糖尿病患者低血糖期间的认知功能,并通过测试β-羟基丁酸酯和辛酸酯对暴露于低血糖状态下大鼠海马突触传递的影响,评估其潜在的作用机制。
共有11名强化治疗的1型糖尿病患者参与了逐步高胰岛素(2 mU·kg⁻¹·min⁻¹)-正常血糖(葡萄糖约5.5 mmol/L)-低血糖(葡萄糖约2.8 mmol/L)钳夹研究。在两个独立的时间段内,他们随机饮用中链甘油三酯饮料或安慰剂饮料,并进行一系列认知测试。采用体外大鼠海马脑片制备技术,评估葡萄糖水平降低时β-羟基丁酸酯和辛酸酯支持神经元活动的能力。
低血糖损害了言语记忆、数字符号编码、倒背数字跨度和地图搜索测试中的认知表现。摄入中链甘油三酯可逆转这些影响。与安慰剂相比,中链甘油三酯还产生了更高的游离脂肪酸和β-羟基丁酸酯水平。然而,低血糖期间儿茶酚胺的增加和症状并未改变。在海马脑片中,β-羟基丁酸酯在低葡萄糖条件下支持突触传递,而辛酸酯则不能。尽管如此,辛酸酯可改善恢复对照葡萄糖浓度后突触功能的恢复速率。
摄入中链甘油三酯可改善认知功能,且不会对强化治疗的1型糖尿病患者低血糖时的肾上腺素能反应或症状性反应产生不利影响。中链甘油三酯具有在低血糖条件下保护脑功能而不引起有害高血糖的治疗优势。