Rossetti Paolo, Porcellati Francesca, Ricci Natalia Busciantella, Candeloro Paola, Cioli Patrizia, Bolli Geremia B, Fanelli Carmine G
Department of Internal Medicine, Endocrinology, and Metabolism, University of Perugia, Via E. Dal Pozzo, 06126 Perugia, Italy.
Diabetes. 2008 Mar;57(3):746-56. doi: 10.2337/db07-1433. Epub 2007 Dec 14.
The acylated long-acting insulin analog detemir is more lipophilic than human insulin and likely crosses the blood-to-brain barrier more easily than does human insulin. The aim of these studies was to assess the brain/hypothalamus responses to euglycemia and hypoglycemia in humans during intravenous infusion of equipotent doses of detemir and human insulin.
Ten normal, nondiabetic subjects (six men, age 36+/-7 years, and BMI 22.9+/-2.6 kg/m(2)) were studied on four occasions at random during intravenous infusion of either detemir or human insulin in euglycemia (plasma glucose 90 mg/dl) or during stepped hypoglycemia (plasma glucose 90, 78, 66, 54, and 42 mg/dl steps).
Plasma counterregulatory hormone response to hypoglycemia did not differ between detemir and human insulin. The glycemic thresholds for adrenergic symptoms were higher with detemir (51 +/- 7.7 mg/dl) versus human insulin (56 +/- 7.8 mg/dl) (P = 0.029). However, maximal responses were greater with detemir versus human insulin for adrenergic (3 +/- 2.5 vs. 2.4 +/- 1.8) and neuroglycopenic (4 +/- 3.9 vs. 2.7+/-2.5) symptoms (score, P < 0.05). Glycemic thresholds for onset of cognitive dysfunction were lower with detemir versus human insulin (51 +/- 8.1 vs. 47 +/- 3.6 mg/dl, P = 0.031), and cognitive function was more deteriorated with detemir versus human insulin (P < 0.05).
Compared with human insulin, responses to hypoglycemia with detemir resulted in higher glycemic thresholds for adrenergic symptoms and greater maximal responses for adrenergic and neuroglycopenic symptoms, with an earlier and greater impairment of cognitive function. Additional studies are needed to establish the effects of detemir on responses to hypoglycemia in subjects with diabetes.
酰化长效胰岛素类似物德谷胰岛素比人胰岛素更具亲脂性，可能比人胰岛素更容易穿过血脑屏障。这些研究的目的是评估在静脉输注等效剂量的德谷胰岛素和人胰岛素期间，人体大脑/下丘脑对正常血糖和低血糖的反应。
10名正常、非糖尿病受试者（6名男性，年龄36±7岁，体重指数22.9±2.6kg/m²）在随机的四个时间段接受研究，分别是在正常血糖（血浆葡萄糖90mg/dl）时静脉输注德谷胰岛素或人胰岛素，以及在逐步低血糖（血浆葡萄糖分别为90、78、66、54和42mg/dl阶段）时静脉输注德谷胰岛素或人胰岛素。
德谷胰岛素和人胰岛素对低血糖的血浆反调节激素反应没有差异。德谷胰岛素引起肾上腺素能症状的血糖阈值（51±7.7mg/dl）高于人胰岛素（56±7.8mg/dl）（P = 0.029）。然而，德谷胰岛素引起的肾上腺素能（3±2.5对2.4±1.8）和神经低血糖性（4±3.9对2.7±2.5）症状的最大反应比人胰岛素更大（评分，P<0.05）。德谷胰岛素引起认知功能障碍的血糖阈值低于人胰岛素（51±8.1对47±3.6mg/dl，P = 0.031），且德谷胰岛素比人胰岛素导致的认知功能恶化更严重（P<0.05）。
与人类胰岛素相比，德谷胰岛素对低血糖的反应导致肾上腺素能症状的血糖阈值更高，肾上腺素能和神经低血糖性症状的最大反应更大，且认知功能受损更早、更严重。需要进一步研究以确定德谷胰岛素对糖尿病患者低血糖反应的影响。
