Fajans S S, Brown M B
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
Diabetes Care. 1993 Sep;16(9):1254-61. doi: 10.2337/diacare.16.9.1254.
To ascertain whether the effect of sulfonylureas on glucose-mediated insulin release persists for years to decades in patients with maturity-onset diabetes of the young.
The effect of sulfonylurea treatment on glucose-induced insulin secretion was ascertained prospectively for up to 33 yr in 12 diabetic patients of the maturity-onset diabetes of the young RW pedigree, who are genetically homogeneous because they share DNA markers on chromosome 20q. In 7 of these patients, paired glucose tolerance tests, given while the patients were on and off sulfonylureas, were performed after 7-31 yr.
Glucose-induced insulin secretion showed an average increase of 68% in diabetic patients who remained responsive to chlorpropamide after having been on and off the drug for decades. In most patients, however, glucose-induced insulin secretion declines over time (1-4%/yr). Some patients become unresponsive to sulfonylureas after 3-25 yr and then have very small or no increases in glucose-induced insulin secretion and require treatment with insulin to normalize fasting hyperglycemia.
Increase in glucose-induced insulin secretion remains the most important mechanism of the action of sulfonylureas during long-term administration.
确定磺脲类药物对年轻的成年发病型糖尿病患者葡萄糖介导的胰岛素释放的影响是否会持续数年至数十年。
前瞻性地确定了12名年轻的成年发病型糖尿病RW家系糖尿病患者长达33年的磺脲类药物治疗对葡萄糖诱导的胰岛素分泌的影响，这些患者在基因上是同质的，因为他们在20号染色体上共享DNA标记。在其中7名患者中，在停药和用药7 - 31年后进行了配对葡萄糖耐量试验。
在停药和用药几十年后仍对氯磺丙脲有反应的糖尿病患者中，葡萄糖诱导的胰岛素分泌平均增加了68%。然而，在大多数患者中，葡萄糖诱导的胰岛素分泌随时间下降（每年1 - 4%）。一些患者在3 - 25年后对磺脲类药物无反应，然后葡萄糖诱导的胰岛素分泌很少增加或不增加，需要用胰岛素治疗以使空腹高血糖正常化。
在长期给药期间，葡萄糖诱导的胰岛素分泌增加仍然是磺脲类药物作用的最重要机制。
