REVERSIBILITY OF UNAWARENESS OF HYPOGLYCEMIA IN PATIENTS WITH INSULINOMAS
REVERSIBILITY OF UNAWARENESS OF HYPOGLYCEMIA IN PATIENTS WITH INSULINOMAS
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DOI：
10.1056/nejm199309163291203
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发表时间：
1993-09-16
影响因子：
158.5
通讯作者：
BOLLI, G
中科院分区：
文献类型：
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作者：
MITRAKOU, A;FANELLI, C;BOLLI, G
背景糖尿病患者在神经性低血糖症发生前缺乏适当的自主神经警告症状是常见的。这种现象的发病机制尚不清楚，但它与强化胰岛素治疗、糖尿病持续时间延长、低血糖频繁发作和葡萄糖反调节受损有关。最近，有人提出，反复发作的低血糖可能本身引起的现象。为了验证这一假设并确定这一现象是否可逆，我们对6例胰岛素瘤患者在根治性手术前和手术后约6个月以及14例年龄、体重和性别相匹配的正常受试者进行了阶梯式降糖钳夹研究，评估了自主神经和神经性血糖减少症状、反调节激素反应和认知功能。手术前，胰岛素瘤患者的自主神经症状评分（平均值[+/-SD]，3.5+/-0.8 vs. 9.6+/-4.5）和神经低血糖症状评分（2.8+/-1.5 vs. 8.9+/-5.3）低于正常受试者。这些患者也有受损的反调节激素反应（手术前他们的血浆肾上腺素、去甲肾上腺素、胰高血糖素、生长激素和皮质醇反应分别为187+/-227 pg/ml [1.03+/-1.25 nmol/L]，223+/-85 pg/ml [1.32+/-0.50 nmol/L]，86+/-21 ng/L，7.4+/-5.2 mug/L和12.1+/-1.5 mug/dl [334+/-41 nmol/L]，相比之下，842+/-439 pg/ml [4.63+/-2.41 nmol/L]，519+/-150 pg/ml [3.07+/-0.89 nmol/L]，201+/-58 ng/L，25.3+/-13.7 mug/L和26.3+/-1.2 mug/dl [正常受试者为726+/-33 nmol/L]，低血糖期间认知功能的恶化程度低于正常受试者（7项认知功能测试的z评分总和，1.7+/-1.9 vs. 8.9+/-3.5）（P
Background. A lack of appropriate autonomic warning symptoms before the development of neuroglycopenia occurs frequently in patients with diabetes mellitus. The pathogenesis of this phenomenon is unclear, but it is associated with intensive insulin therapy, prolonged duration of diabetes, frequent episodes of hypoglycemia, and impaired glucose counterregulation. Recently, it has been proposed that repeated episodes of hypoglycemia may themselves induce the phenomenon.Methods. To test this hypothesis and to determine whether the phenomenon is reversible, we assessed autonomic and neuroglycopenic symptoms, counterregulatory hormonal responses, and cognitive function during stepped hypoglycemic-clamp studies in 6 patients with insulinomas before and approximately six months after curative surgery and in 14 normal subjects matched for age, weight, and sex.Results. Before surgery, the patients with insulinomas had lower scores than the normal subjects for autonomic symptoms (mean [+/-SD], 3.5+/-0.8 vs. 9.6+/-4.5) and neuroglycopenic symptoms (2.8+/-1.5 vs. 8.9+/-5.3). The patients also had impaired counterregulatory hormonal responses (their plasma epinephrine, norepinephrine, glucagon, growth hormone, and cortisol responses before surgery were 187+/-227 pg per milliliter [1.03+/-1.25 nmol per liter], 223+/-85 pg per milliliter [1.32+/-0.50 nmol per liter], 86+/-21 ng per liter, 7.4+/-5.2 mug per liter, and 12.1+/-1.5 mug per deciliter [334+/-41 nmol per liter], respectively, as compared with 842+/-439 pg per milliliter [4.63+/-2.41 nmol per liter], 519+/-150 pg per milliliter [3.07+/-0.89 nmol per liter], 201+/-58 ng per liter, 25.3+/-13.7 mug per liter, and 26.3+/-1.2 mug per deciliter [726+/-33 nmol per liter in the normal subjects) and less deterioration in cognitive function than the normal subjects during hypoglycemia (sum of z scores for seven tests of cognitive function, 1.7+/-1.9 vs. 8.9+/-3,5) (P