选择更安全的降糖之路.ppt

* Key message: Multiple risk factors can lead to hypoglycaemia in patients with diabetes. * 我们验证了这样一个理论，在胰岛素严重缺乏的2型糖尿病患者中，胰高血糖素对低血糖的敏感性下降，对于先前发生了低血糖的2型糖尿病患者，机体的血糖反馈调节机制下降，降低了对低血糖的反应。将实验分为3组，第一组为应用口服药治疗，HbA1c 8.6的2型糖尿病患者（7名），第二组为接受胰岛素治疗5年以上的，糖化血红蛋白为7.5%的糖尿病患者（6名），第三组为非糖尿病对照组（15名）。在第一天下午先行对13名2型糖尿病患者给予持续2小时的低血糖刺激，然后第二天对各组分别进行逐级低血糖钳夹试验低血糖钳夹试验的血糖级别为 85, 75, 65, 55, and 45 mg/dl），当第二天再次发生低血糖时，各组胰高血糖素的反应有明显的差别。在胰岛素治疗组，最终胰高血糖素水平为5216，而非糖尿病对照组为9315，口服药组为9816. 第1天刚刚发生了低血糖的患者，在第2天，再次遭遇低血糖时，肾上腺能的反应减弱，神经反馈调节减弱，胰高血糖素水平相对减少。这些低血血糖反应并非消失了，而是他们低血糖阈值发生了改变。他们的低血糖阈值比在第一天时发生低血糖的阈值升高。第一天的低血糖使机体低血糖发生时，血糖反馈调节的阈值升高。即低血糖时，缺乏相应自主神经症状及反调节激素水平降低发动上述神经内分泌反应的血糖阚值明显升高，即需更低血糖浓度才能发动上述反应。 We tested the hypotheses that the glucagon response to hypoglycemia is reduced in patients who are approaching the insulin-deficient end of the spectrum of type 2 diabetes and that recent antecedent hypoglycemia shifts the glycemic thresholds for autonomic (including adrenomedullary epinephrine) and symptomatic responses to hypoglycemia to lower plasma glucose concentrations in type 2 diabetes. Hyperinsulinemic stepped hypoglycemic clamps (85, 75, 65, 55, and 45 mg/dl steps) were performed on two consecutive days, with an additional 2 h of hypoglycemia (50 mg/dl) in the afternoon of the first day, in 13 patients with type 2 diabetes—7 treated with oral hypoglycemic agents (OHA RX; mean [SD] HbA1c 8.6 1.1%) and 6 requiring therapy with insulin for an average of 5 years and with reduced C-peptide levels (insulin RX, HbA1c 7.5 0.7%)—and 15 nondiabetic control subjects. The glucagon response to hypoglycemia was virtually absent (P 0.0252) in the insulin-deficient type 2 diabetic patients (insulin RX mean [SE] final values of 52 16 vs. 93 15 pg/ml in control subjects and 98 16 pg/ml in type 2 diabetic patients, OHA RX on day 1). Glucagon (P 0.0015), epinephrine (P 0.0002), and norepinephrine (P 0.0138) responses and neurogenic (P 0.0149) and neuroglycopenic (P 0.0015) symptom responses to hypoglycemia were