Brain glucose uptake and unawareness of hypoglycemia in patients with insulin-dependent diabetes mellitus
Brain glucose uptake and unawareness of hypoglycemia in patients with insulin-dependent diabetes mellitus
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DOI：
10.1056/nejm199512283332602
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发表时间：
1995-12-28
影响因子：
158.5
通讯作者：
Nagy, RJ
中科院分区：
文献类型：
--
作者：
Boyle, PJ;Kempers, SF;Nagy, RJ
背景在治疗导致平均血糖浓度接近正常的胰岛素依赖型糖尿病（IDDM）患者中，可能会发生无意识的低血糖，此类患者发生癫痫发作和昏迷的风险增加。我们检验了这一假设，即在低血糖期间，这些患者的大脑葡萄糖摄取正常，因此没有交感肾上腺激活将开始，导致对低血糖的无意识。我们测量了血浆葡萄糖浓度为105和54毫克/分升时大脑的葡萄糖摄取（5.8和3.0 mmol/L），根据糖化血红蛋白值分为三组（平均[+/-SD]值，7.2 +/- 0.5，8.5 +/- 0.4，和10.2 +/-1.3%），并将脑葡萄糖摄取值与15名血浆葡萄糖浓度为85和55 mg/dl的正常受试者的脑葡萄糖摄取值进行比较（4.2和3.1 mmol/L）。我们还记录了受试者的低血糖症状评分，并测量了他们的血浆反调节物质浓度。在糖基化血红蛋白值最低（每分钟每100 g脑组织+0.6 +/- 2.0 mg [3.3 +/- 11.1 μ mol]，P = 0.39）的IDDM患者中，脑中葡萄糖摄取量（计算为低血糖时的摄取量减去血糖正常时的摄取量）无显著变化。相反，在两个中间值组中，（每100 g每分钟减少1.3 +/- 1.0 mg [7.2 +/- 5.6 μ mol]，P = 0.009）和具有最高值的组（每100 g/min减少1.8 +/- 1.6 mg [10.0 +/- 9.0 μ mol]，P = 0.01），与正常受试者相同（每100 g/min减少1.6 +/- 1.8 mg [9.0 +/- 10.1 μ mol]，P = 0.003）。糖化血红蛋白值最低组的血浆肾上腺素和胰多肽反应以及低血糖症状发生率最低。在低血糖期间，具有接近正常的糖化血红蛋白值的IDDM患者在大脑中具有正常的葡萄糖摄取，这保持了大脑代谢，减少了反调节激素的反应，并导致对低血糖的无意识。
Background. In patients with insulin-dependent diabetes mellitus (IDDM) whose treatment results in nearly normal mean plasma glucose concentrations, an unawareness of hypoglycemia can develop, and such patients are at increased risk for seizures and coma. We tested the hypothesis that during hypoglycemia, these patients would have normal glucose uptake in the brain and that consequently no sympathoadrenal activation would begin, resulting in an unawareness of hypoglycemia.Methods. We measured glucose uptake in the brain at plasma glucose concentrations of 105 and 54 mg per deciliter (5.8 and 3.0 mmol per liter) in 24 patients with IDDM, stratified into three groups according to their glycosylated hemoglobin values (mean [+/-SD] values, 7.2 +/- 0.5, 8.5 +/- 0.4, and 10.2 +/- 1.3 percent) and compared the values for brain glucose uptake with those measured in 15 normal subjects at plasma glucose concentrations of 85 and 55 mg per deciliter (4.2 and 3.1 mmol per liter). We also recorded the subjects' hypoglycemic-symptom scores and measured their plasma concentrations of counterregulatory hormones.Results. There was no significant change in the uptake of glucose in the brain (calculated as the uptake during hypoglycemia minus the uptake during normoglycemia) among the patients with IDDM who had the lowest glycosylated hemoglobin values (+0.6 +/- 2.0, mg [3.3 +/- 11.1 mu mol] per 100 g of brain tissue per minute, P = 0.39). Conversely, glucose uptake in the brain fell in both the group with intermediate values (a decrease of 1.3 +/- 1.0 mg [7.2 +/- 5.6 mu mol] per 100 g per minute, P = 0.009) and the group with the highest values (a decrease of 1.8 +/- 1.6 mg [10.0 +/- 9.0, mu mol] per 100 g per minute, P = 0.01), as it did in the normal subjects (a decrease of 1.6 +/- 1.8 mg [9.0 +/- 10.1 mu mol] per 100 g per minute, P = 0.003). The responses of plasma epinephrine and pancreatic polypeptide and the frequency of symptoms of hypoglycemia were lowest in the group with the lowest glycosylated hemoglobin values.Conclusions. During hypoglycemia, patients with IDDM who have nearly normal glycosylated hemoglobin values have normal glucose uptake in the brain, which preserves cerebral metabolism, reduces the responses of counter-regulatory hormones, and causes an unawareness of hypoglycemia.