Ryder R E, Owens D R, Hayes T M, Ghatei M A, Bloom S R
Diabetic Research Unit, University Hospital of Wales and University of Cardiff.
BMJ. 1990 Oct 6;301(6755):783-7. doi: 10.1136/bmj.301.6755.783.
To examine the traditional view that unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation in insulin dependent diabetes mellitus are manifestations of autonomic neuropathy.
Perspective assessment of unawareness of hypoglycaemia and detailed assessment of autonomic neuropathy in patients with insulin dependent diabetes according to the adequacy of their hypoglycaemic counterregulation.
One routine diabetic unit in a university teaching hospital.
23 Patients aged 21-52 with insulin dependent diabetes mellitus (seven with symptoms suggesting autonomic neuropathy, nine with a serious clinical problem with hypoglycaemia, and seven without symptoms of autonomic neuropathy and without problems with hypoglycaemia) and 10 controls with a similar age distribution, without a personal or family history of diabetes.
Presence of autonomic neuropathy as assessed with a test of the longest sympathetic fibres (acetylcholine sweatspot test), a pupil test, and a battery of seven cardiovascular autonomic function tests; adequacy of hypoglycaemic glucose counterregulation during a 40 mU/kg/h insulin infusion test; history of unawareness of hypoglycaemia; and response of plasma pancreatic polypeptide during hypoglycaemia, which depends on an intact and responding autonomic innervation of the pancreas.
There was little evidence of autonomic neuropathy in either the 12 diabetic patients with a history of unawareness of hypoglycaemia or the seven patients with inadequate hypoglycaemic counterregulation. By contrast, in all seven patients with clear evidence of autonomic neuropathy there was no history of unawareness of hypoglycaemia and in six out of seven there was adequate hypoglycaemic counterregulation. Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation were significantly associated (p less than 0.01). The response of plasma pancreatic polypeptide in the diabetic patients with adequate counterregulation but without autonomic neuropathy was not significantly different from that of the controls (change in plasma pancreatic polypeptide 226.8 v 414 pmol/l). The patients with autonomic neuropathy had a negligible plasma pancreatic polypeptide response (3.7 pmol/l), but this response was also blunted in the patients with inadequate hypoglycaemic counterregulation (72.4 pmol/l) compared with that of the controls (p less than 0.05).
Unawareness of hypoglycaemia and inadequate glucose counterregulation during hypoglycaemia are related to each other but are not due to autonomic neuropathy. The blunted plasma pancreatic polypeptide responses of the patients with inadequate hypoglycaemic counterregulation may reflect diminished autonomic activity consequent upon reduced responsiveness of a central glucoregulatory centre, rather than classical autonomic neuropathy.
检验传统观点，即胰岛素依赖型糖尿病患者对低血糖症无察觉及低血糖对抗调节不足是自主神经病变的表现。
根据低血糖对抗调节的充分程度，对胰岛素依赖型糖尿病患者低血糖症无察觉情况进行前瞻性评估，并对自主神经病变进行详细评估。
一所大学教学医院的一个常规糖尿病科室。
23例年龄在21至52岁的胰岛素依赖型糖尿病患者（7例有提示自主神经病变的症状，9例有严重的低血糖临床问题，7例无自主神经病变症状且无低血糖问题）以及10名年龄分布相似、无糖尿病个人或家族史的对照者。
通过最长交感神经纤维测试（乙酰胆碱汗斑试验）、瞳孔测试以及一系列七项心血管自主功能测试评估自主神经病变的存在；在40 mU/kg/h胰岛素输注试验期间低血糖葡萄糖对抗调节的充分程度；低血糖症无察觉史；以及低血糖期间血浆胰多肽的反应，这取决于胰腺完整且有反应的自主神经支配。
在12例有低血糖症无察觉史的糖尿病患者或7例低血糖对抗调节不足的患者中，几乎没有自主神经病变的证据。相比之下，在所有7例有明确自主神经病变证据的患者中，无低血糖症无察觉史，且7例中有6例低血糖对抗调节充分。低血糖症无察觉与低血糖对抗调节不足显著相关（p<0.01）。低血糖对抗调节充分但无自主神经病变的糖尿病患者血浆胰多肽的反应与对照者无显著差异（血浆胰多肽变化为226.8对414 pmol/l）。有自主神经病变的患者血浆胰多肽反应可忽略不计（3.7 pmol/l），但与对照者相比，低血糖对抗调节不足的患者该反应也减弱（72.4 pmol/l）（p<0.05）。
低血糖症无察觉与低血糖期间葡萄糖对抗调节不足相互关联，但并非由自主神经病变所致。低血糖对抗调节不足的患者血浆胰多肽反应减弱可能反映了中枢葡萄糖调节中心反应性降低导致的自主神经活动减弱，而非典型的自主神经病变。
