Kong M F, Stubbs T A, King P, Macdonald I A, Lambourne J E, Blackshaw P E, Perkins A C, Tattersall R B
Department of Diabetes, University Hospital, Queen's Medical Centre, Nottingham, UK.
Diabetologia. 1998 May;41(5):577-83. doi: 10.1007/s001250050949.
In a previous study we have shown that an intravenous infusion of pramlintide (an analogue of human amylin) delayed gastric emptying, but the dose of pramlintide was supraphysiological in relation to the amylin response to food in non-diabetic subjects. The purpose of this study was to examine the dose response relationship of subcutaneous injections of pramlintide on gastric emptying and to determine whether administration of the drug before one meal has an impact on the subsequent meal. Eleven men with insulin-dependent diabetes mellitus were studied in a double-blind, randomised, four-way crossover design. None had autonomic neuropathy. Euglycaemia was maintained overnight before the study day. At -30 min the patients self-injected their usual morning insulin and at -15 min they injected the study drug (either placebo or 30, 60 or 90 microg pramlintide) subcutaneously. At 0 min they ate a standard meal consisting of a pancake, labelled with 99mTc, and a milkshake containing 3-ortho-methylglucose (3-OMG). Gastric emptying images were obtained for the next 8 h. At 240 min the subjects ate a similar meal, but on this occasion the pancake was labelled with (111)In. All three doses of pramlintide delayed emptying of the solid component of the first meal (p < 0.004) with no significant difference between the drug doses. There were no differences between placebo and pramlintide after the second meal. All three doses of pramlintide resulted in a prolongation in the time to peak plasma 3-OMG level (p < 0.0001) after the first meal but there was no difference after the second meal.
在之前的一项研究中，我们已经表明静脉输注普兰林肽（一种人胰淀素类似物）会延迟胃排空，但相对于非糖尿病受试者对食物的胰淀素反应而言，普兰林肽的剂量是超生理剂量。本研究的目的是研究皮下注射普兰林肽对胃排空的剂量反应关系，并确定在一餐前给药是否会对随后一餐产生影响。我们采用双盲、随机、四交叉设计对11名胰岛素依赖型糖尿病男性患者进行了研究。所有患者均无自主神经病变。在研究日之前的夜间维持血糖正常。在 -30分钟时，患者自行皮下注射其常规的早晨胰岛素，在 -15分钟时，他们皮下注射研究药物（安慰剂或30、60或90微克普兰林肽）。在0分钟时，他们进食一顿标准餐，包括用99mTc标记的薄煎饼和含有3-邻甲基葡萄糖（3-OMG）的奶昔。在接下来的8小时内获取胃排空图像。在240分钟时，受试者进食类似的一餐，但此次薄煎饼用（111）In标记。所有三种剂量的普兰林肽均延迟了第一餐固体成分的排空（p < 0.004），各药物剂量之间无显著差异。第二餐后安慰剂和普兰林肽之间没有差异。所有三种剂量的普兰林肽在第一餐后均导致血浆3-OMG水平达到峰值的时间延长（p < 0.0001），但第二餐后没有差异。
