Burge M R, Schmitz-Fiorentino K, Fischette C, Qualls C R, Schade D S
Department of Medicine/Endocrinology, University of New Mexico School of Medicine, Albuquerque 87131, USA.
JAMA. 1998 Jan 14;279(2):137-43. doi: 10.1001/jama.279.2.137.
Retrospective studies have identified oral sulfonylureas, age, and fasting as major risk factors for hypoglycemia in patients with type 2 diabetes. Sulfonylureas may be withheld from elderly patients out of concern for hypoglycemia.
To evaluate the hypoglycemic effects of maximum doses of once-daily second-generation sulfonylureas administered to fasting elderly patients.
A prospective, randomized, double-blind clinical trial.
The University of New Mexico General Clinical Research Center.
Fifty-two sulfonylurea-treated subjects with type 2 diabetes with a mean (SD) age of 65.1 (5.7) years.
Subjects were randomly assigned to glyburide or glipizide gastrointestinal therapeutic system (GITS). Each subject participated in three 23-hour fasting studies after the sequential administration of 1 week of placebo and 1 week of 10 mg and 1 week of 20 mg of the assigned sulfonylurea.
Occurrence of hypoglycemia (defined as plasma glucose level <3.33 mmol/L [60 mg/dL]) and hormonal parameters during the final 9 hours of the 23-hour fast in patients who had taken sulfonylureas vs placebo.
No hypoglycemia was observed during 156 fasting studies. Plasma glucose level was decreased (nadir, 4.9 mmol/L [88 mg/dL] for a 20-mg dose of glyburide vs 8.3 mmol/L [150 mg/dL] for placebo; nadir, 5.8 mmol/L [105 mg/dL] for a 20-mg dose of glipizide GITS vs 8.7 mmol/L [157 mg/dL] for placebo), and serum insulin was increased in the sulfonylurea studies compared with placebo (P<.001). Plasma glucose parameters did not differ between the 2 sulfonylureas, but C peptide concentrations were increased in the glyburide group compared with glipizide GITS in the 20-mg study (P=.05). Concentrations of epinephrine were increased in the sulfonylurea studies compared with placebo (P<.001). Epinephrine secretion increased when glucose concentration fell below the mean (SD) level of 9.10 (2.66) mmol/L (164 [48] mg/dL) in the 10-mg study and 8.77 (2.83) mmol/L (158 [51] mg/ dL) in the 20-mg study.
Fasting was well tolerated among these elderly patients with type 2 diabetes treated with sulfonylureas. Older age should not be considered a contraindication to sulfonylurea treatment for diabetes. Stimulation of epinephrine secretion at normal or elevated plasma glucose levels appears to be the primary mechanism of protection against hypoglycemia in this study.
回顾性研究已确定口服磺脲类药物、年龄和禁食是2型糖尿病患者发生低血糖的主要危险因素。出于对低血糖的担忧，老年患者可能不使用磺脲类药物。
评估给予禁食老年患者最大剂量的每日一次第二代磺脲类药物的降血糖效果。
一项前瞻性、随机、双盲临床试验。
新墨西哥大学综合临床研究中心。
52例接受磺脲类药物治疗的2型糖尿病患者，平均（标准差）年龄为65.1（5.7）岁。
受试者被随机分配至格列本脲或格列吡嗪胃肠治疗系统（GITS）组。在依次服用1周安慰剂、1周10 mg和1周20 mg指定磺脲类药物后，每位受试者参与三项23小时禁食研究。
服用磺脲类药物与安慰剂的患者在23小时禁食的最后9小时内低血糖（定义为血浆葡萄糖水平<3.33 mmol/L [60 mg/dL]）的发生情况及激素参数。
在156项禁食研究中未观察到低血糖。血浆葡萄糖水平降低（20 mg剂量格列本脲组最低点为4.9 mmol/L [88 mg/dL]，而安慰剂组为8.3 mmol/L [150 mg/dL]；20 mg剂量格列吡嗪GITS组最低点为5.8 mmol/L [105 mg/dL]，而安慰剂组为8.7 mmol/L [157 mg/dL]），与安慰剂相比，磺脲类药物研究中血清胰岛素升高（P<0.001）。两种磺脲类药物之间的血浆葡萄糖参数无差异，但在20 mg研究中，格列本脲组的C肽浓度高于格列吡嗪GITS组（P = 0.05）。与安慰剂相比，磺脲类药物研究中肾上腺素浓度升高（P<0.001）。在10 mg研究中，当葡萄糖浓度降至平均（标准差）水平9.10（2.66）mmol/L（164 [48] mg/dL）以下时，肾上腺素分泌增加；在20 mg研究中，当葡萄糖浓度降至8.77（2.83）mmol/L（158 [51] mg/dL）以下时，肾上腺素分泌增加。
这些接受磺脲类药物治疗的老年2型糖尿病患者对禁食耐受性良好。年龄较大不应被视为糖尿病磺脲类药物治疗的禁忌证。在本研究中，正常或升高的血浆葡萄糖水平下刺激肾上腺素分泌似乎是预防低血糖的主要机制。
