Fanelli C, Pampanelli S, Lalli C, Del Sindaco P, Ciofetta M, Lepore M, Porcellati F, Bottini P, Di Vincenzo A, Brunetti P, Bolli G B
Dipartimento di Medicina Interna e Scienze Endocrine e Metaboliche, Università degli Studi di Perugia, Italy.
Diabetes. 1997 Jul;46(7):1172-81. doi: 10.2337/diab.46.7.1172.
To test the hypothesis that hypoglycemia unawareness and impaired counterregulation are reversible after meticulous prevention of hypoglycemia in IDDM patients with diabetic autonomic neuropathy (DAN), 21 patients (8 without DAN [DAN-]; 13 with DAN [DAN+]; of the latter, 7 had orthostatic hypotension [DAN+PH+] and 6 did not [DAN+PH-]) and 15 nondiabetic subjects were studied during stepped hypoglycemia (plateau plasma glucose decrements from 5.0 to 2.2 mmol/l) before and 6 months after prevention of hypoglycemia (intensive therapy). After 6 months, frequency of mild hypoglycemia decreased from approximately 20 to approximately 2 episodes/patient-month while HbA1c increased from 6.2 +/- 0.3 to 6.9 +/- 0.2% (P < 0.05). Responses of adrenaline improved more in DAN- patients (from 1.17 +/- 0.12 to 2.4 +/- 0.22 nmol/l) than in DAN+PH- (from 0.75 +/- 0.25 to 1.56 +/- 0.23 nmol/l) and DAN+PH+ patients (from 0.80 +/- 0.24 to 1.15 +/- 0.27 nmol/l, P < 0.05) but remained lower than in nondiabetic subjects (4.9 +/- 0.37 nmol/l, P < 0.05), whereas glycemic thresholds normalized only in DAN-, not DAN+. Autonomic symptoms of hypoglycemia improved but remained lower in DAN- (6.2 +/- 0.6) than in nondiabetic subjects (8.1 +/- 1.1) and lower in DAN+PH+ (4 +/- 0.8) than in DAN+PH- subjects (5.1 +/- 0.8, P < 0.05), whereas neuroglycopenic symptoms normalized (NS). Cognitive function deteriorated less before than after prevention of hypoglycemia (P < 0.05). Thus, intensive therapy with emphasis on preventing hypoglycemia reverses hypoglycemia unawareness in DAN+ patients despite marginal improvement of adrenaline responses, results in low frequency of hypoglycemia despite impaired counterregulation, and maintains HbA1c in the range of intensive therapy. We conclude that DAN, long IDDM duration per se, and antecedent recent hypoglycemia contribute to different extents to impaired adrenaline responses and hypoglycemia unawareness.
在对患有糖尿病自主神经病变（DAN）的胰岛素依赖型糖尿病（IDDM）患者进行精心的低血糖预防后，低血糖无意识症和反调节功能受损是可逆的，我们对21例患者（8例无DAN [DAN-]；13例有DAN [DAN+]；其中后者7例有体位性低血压 [DAN+PH+]，6例无 [DAN+PH-]）和15名非糖尿病受试者在低血糖阶梯试验（血浆葡萄糖平台期从5.0降至2.2 mmol/l）期间进行了研究，分别在预防低血糖（强化治疗）前和6个月后进行。6个月后，轻度低血糖的发生率从大约20次/患者月降至大约2次/患者月，而糖化血红蛋白（HbA1c）从6.2±0.3%升至6.9±0.2%（P<0.05）。DAN-患者的肾上腺素反应改善程度更大（从1.17±0.12升至2.4±0.22 nmol/l），高于DAN+PH-患者（从0.75±0.25升至1.56±0.23 nmol/l）和DAN+PH+患者（从0.80±0.24升至1.15±0.27 nmol/l，P<0.05），但仍低于非糖尿病受试者（4.9±0.37 nmol/l，P<0.05），而血糖阈值仅在DAN-患者中恢复正常，DAN+患者未恢复。低血糖的自主神经症状有所改善，但DAN-患者（6.2±0.6）仍低于非糖尿病受试者（8.1±1.1），DAN+PH+患者（4±0.8）低于DAN+PH-受试者（5.1±0.8，P<0.05），而神经低血糖症状恢复正常（无显著性差异）。预防低血糖前认知功能的恶化程度低于预防后（P<0.05）。因此，强调预防低血糖的强化治疗可使DAN+患者的低血糖无意识症得到逆转，尽管肾上腺素反应仅略有改善，尽管反调节功能受损，但仍能使低血糖发生率较低，并使HbA1c维持在强化治疗范围内。我们得出结论，DAN、IDDM的长病程本身以及先前近期的低血糖在不同程度上导致了肾上腺素反应受损和低血糖无意识症。
