Kennedy F P, Bolli G B, Go V L, Cryer P E, Gerich J E
J Clin Endocrinol Metab. 1987 Mar;64(3):602-8. doi: 10.1210/jcem-64-3-602.
The impaired epinephrine and glucagon responses to hypoglycemia often found in patients with insulin-dependent diabetes mellitus (IDDM) may be due to autonomic neuropathy. Since the pancreatic polypeptide response to hypoglycemia is mediated by cholinergic mechanisms, we used this response as an indicator of autonomic neuropathy to determine whether deficient epinephrine and glucagon responses in IDDM could be ascribed to an autonomic defect. The relationships between pancreatic polypeptide, epinephrine, and glucagon responses during insulin-induced hypoglycemia were assessed in 18 patients with IDDM who had no overt evidence of autonomic neuropathy, including normal standard cardiovascular reflex tests, and 11 age-matched nondiabetic subjects. All of the diabetic patients had impaired glucagon responses [19 +/- 3 (SEM) vs. 96 +/- 11 pg/ml, peak increment, P less than 0.001]. Ten of the 18 diabetic patients had either impairment of plasma epinephrine or plasma pancreatic polypeptide responses or both to hypoglycemia. Moreover, pancreatic polypeptide responses were significantly correlated with epinephrine responses (r = 0.53, P less than 0.003). There was no association between the plasma glucagon response and the epinephrine (r = 0.02, NS), norepinephrine (r = 0.03, NS), or pancreatic polypeptide (r = 0.35, NS) response. Last, there was no correlation between the plasma hormone responses and the cardiovascular reflex test results. Therefore, the association of impaired plasma pancreatic polypeptide responses with impaired plasma epinephrine responses suggests that the impaired epinephrine responses are due to autonomic neuropathy, whereas the dissociation of plasma glucagon responses with both plasma pancreatic polypeptide and epinephrine responses suggests that the impaired pancreatic alpha-cell response to hypoglycemia is not due to autonomic neuropathy. In addition, the plasma pancreatic polypeptide and epinephrine responses to hypoglycemia appear to be an earlier indicator of underlying autonomic dysfunction than standard cardiovascular reflex tests. Thus, the responses of plasma pancreatic polypeptide and epinephrine to insulin-induced hypoglycemia may be a useful test for the identification of early autonomic neuropathy in IDDM.
胰岛素依赖型糖尿病（IDDM）患者中常发现的对低血糖的肾上腺素和胰高血糖素反应受损可能归因于自主神经病变。由于胰腺多肽对低血糖的反应是由胆碱能机制介导的，我们将此反应用作自主神经病变的指标，以确定IDDM中肾上腺素和胰高血糖素反应不足是否可归因于自主神经缺陷。在18例无明显自主神经病变证据（包括正常标准心血管反射试验）的IDDM患者和11例年龄匹配的非糖尿病受试者中，评估了胰岛素诱导低血糖期间胰腺多肽、肾上腺素和胰高血糖素反应之间的关系。所有糖尿病患者的胰高血糖素反应均受损[峰值增量为19±3（SEM）对96±11 pg/ml，P<0.001]。18例糖尿病患者中有10例对低血糖的血浆肾上腺素或血浆胰腺多肽反应或两者均受损。此外，胰腺多肽反应与肾上腺素反应显著相关（r = 0.53，P<0.003）。血浆胰高血糖素反应与肾上腺素（r = 0.02，无显著性差异）、去甲肾上腺素（r = 0.03，无显著性差异）或胰腺多肽（r = 0.35，无显著性差异）反应之间无关联。最后，血浆激素反应与心血管反射试验结果之间无相关性。因此，血浆胰腺多肽反应受损与血浆肾上腺素反应受损相关，提示肾上腺素反应受损是由于自主神经病变，而血浆胰高血糖素反应与血浆胰腺多肽和肾上腺素反应均无关，提示胰腺α细胞对低血糖的反应受损并非由于自主神经病变。此外，血浆胰腺多肽和肾上腺素对低血糖的反应似乎比标准心血管反射试验更能早期提示潜在的自主神经功能障碍。因此，血浆胰腺多肽和肾上腺素对胰岛素诱导低血糖的反应可能是识别IDDM早期自主神经病变的有用试验。
