HYPOGLYCEMIA-ASSOCIATED AUTONOMIC FAILURE IN INSULIN-DEPENDENT DIABETES-MELLITUS - RECENT ANTECEDENT HYPOGLYCEMIA REDUCES AUTONOMIC RESPONSES TO, SYMPTOMS OF, AND DEFENSE AGAINST SUBSEQUENT HYPOGLYCEMIA
HYPOGLYCEMIA-ASSOCIATED AUTONOMIC FAILURE IN INSULIN-DEPENDENT DIABETES-MELLITUS - RECENT ANTECEDENT HYPOGLYCEMIA REDUCES AUTONOMIC RESPONSES TO, SYMPTOMS OF, AND DEFENSE AGAINST SUBSEQUENT HYPOGLYCEMIA
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DOI：
10.1172/jci116302
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发表时间：
1993-03-01
影响因子：
15.9
通讯作者：
CRYER, PE
中科院分区：
文献类型：
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作者：
DAGOGOJACK, SE;CRAFT, S;CRYER, PE
我们假设，在胰岛素依赖型糖尿病（IDDM）患者中，近期发生的医源性低血糖是低血糖相关自主神经功能衰竭的主要原因，低血糖相关自主神经功能衰竭是一种与经典糖尿病自主神经病变（CDAN）不同的疾病，低血糖相关自主神经功能衰竭通过减少低血糖的症状和对低血糖的防御，导致复发性医源性低血糖，从而形成恶性循环。我们使用高胰岛素（12.0 pmol. kg-1.min-1）阶梯式低血糖钳夹技术评估IDDM患者对低血糖的自主神经和症状反应，并使用胰岛素输注试验（4.0 pmol. kg-1.min-1）评估IDDM患者在钳夹下午低血糖（约2.8 mmol/L）和高血糖（约11.1 mmol/L）之前和之后对低血糖的防御。与非糖尿病受试者相比，伴或不伴CDAN的IDDM对低血糖的肾上腺素（P = 0.0222和0.0040）和胰多肽（P = 0.0083和0.0056）反应降低。下午低血糖后，在无CDAN的患者中，需要较低的血糖浓度才能在早晨低血糖钳夹期间引起自主神经和症状反应。在2.8 mmol/L的步进下，平均（+/-SE）肾上腺素水平为1，160 +/-270和2，040 +/-270 pmol/L（P = 0.0060），胰多肽水平分别为14 +/-2和49 +/-11 pmol/L（P = 0.0275），下午低血糖和高血糖后总症状评分分别为22 +/-3和41 +/-7（P = 0.0475）。在下午低血糖后的早晨胰岛素输注试验中，最低血糖浓度为2.6 +/-0.2 mmol/L，而3.3 +/-0.3 mmol/L（P
We hypothesize that in patients with insulin-dependent diabetes mellitus (IDDM), recent antecedent iatrogenic hypoglycemia is a major cause of hypoglycemia-associated autonomic failure, a disorder distinct from classical diabetic autonomic neuropathy (CDAN), and that hypoglycemia-associated autonomic failure, by reducing both symptoms of and defense against developing hypoglycemia, results in recurrent iatrogenic hypoglycemia, thus creating a vicious cycle. We used the hyperinsulinemic (12.0 pmol.kg-1.min-1) stepped hypoglycemic clamp technique to assess autonomic and symptomatic responses to hypoglycemia and the insulin infusion test (4.0 pmol.kg-1.min-1) to assess defense against hypoglycemia on mornings before and after clamped afternoon hypoglycemia (approximately 2.8 mmol/liter) and hyperglycemia (approximately 11.1 mmol/liter) in patients with IDDM. Compared with nondiabetic subjects, IDDM with or without CDAN exhibited reduced epinephrine (P = 0.0222 and 0.0040) and pancreatic polypeptide (P = 0.0083 and 0.0056) responses to hypoglycemia. After afternoon hypoglycemia, lower plasma glucose concentrations were required to elicit autonomic and symptomatic responses during morning hypoglycemic clamps in patients without CDAN. At the 2.8 mmol/liter step, mean (+/-SE) epinephrine levels were 1,160+/-270 and 2,040+/-270 pmol/liter (P = 0.0060), pancreatic polypeptide levels were 14+/-2 and 49+/-11 pmol/liter (P = 0.0275), and total symptom scores were 22+/-3 and 41+/-7 (P = 0.0475) after afternoon hypoglycemia and hyperglycemia, respectively. During morning insulin infusion tests after afternoon hypoglycemia, nadir plasma glucose concentrations were 2.6+/-0.2 mmol/liter compared with 3.3+/-0.3 mmol/liter (P