Davies M J, Metcalfe J, Day J L, Grenfell A, Hales C N, Gray I P
Ipswich Diabetes Centre, Ipswich Hospital, UK.
Diabet Med. 1994 Apr;11(3):293-8. doi: 10.1111/j.1464-5491.1994.tb00274.x.
This study was undertaken to clarify the effect of sulphonylurea therapy on beta cell function in 27 subjects with newly diagnosed Type 2 diabetes mellitus. Plasma glucose, insulin, intact and 32/33 split proinsulin were measured at diagnostic OGTT. After 8-12 weeks on a conventional diet, subjects with a fasting glucose > 9 mmol l-1 (n = 12) were commenced on sulphonylurea therapy. At diagnosis, the sulphonylurea requiring group were more hyperglycaemic (p < 0.0001), less obese (p < 0.05) and more insulin deficient with a lower 30 min insulin (p < 0.0002) than the diet group. Following dietary intervention in the sulphonylurea group, weight remained unchanged but there was a reduction in fasting glucose (p < 0.009). Fasting insulin, intact proinsulin, and 32/33 split proinsulin remained unchanged. After 12 weeks of sulphonylurea therapy there was a weight gain of 1.5 kg (p < 0.01), but a reduction in fasting glucose (p < 0.0001). Fasting insulin and intact proinsulin increased (p < 0.004) but 32/33 split proinsulin remained unchanged. There was a significant increase in both the fasting insulin to glucose ratio (p < 0.005), and intact to 32/33 split proinsulin ratio (p < 0.02). Final fasting glucose following sulphonylurea therapy was positively correlated with the initial intact and 32/33 split proinsulin and the fasting glucose following dietary treatment. It is clear from this work that sulphonylureas have a complex effect on beta cell physiology and as well as stimulating release of insulin they increase the release of intact proinsulin but not that of 32/33 split proinsulin, hence they increase the intact to 32/33 split proinsulin ratio.
本研究旨在阐明磺脲类药物治疗对27例新诊断的2型糖尿病患者β细胞功能的影响。在诊断性口服葡萄糖耐量试验（OGTT）时测定血浆葡萄糖、胰岛素、完整胰岛素原和32/33裂解胰岛素原。在常规饮食8 - 12周后，空腹血糖>9 mmol/L的患者（n = 12）开始接受磺脲类药物治疗。诊断时，与饮食治疗组相比，需要使用磺脲类药物的患者血糖更高（p < 0.0001），肥胖程度更低（p < 0.05），胰岛素缺乏更严重，30分钟胰岛素水平更低（p < 0.0002）。在磺脲类药物治疗组进行饮食干预后，体重保持不变，但空腹血糖有所降低（p < 0.009）。空腹胰岛素、完整胰岛素原和32/33裂解胰岛素原保持不变。磺脲类药物治疗12周后，体重增加了1.5 kg（p < 0.01），但空腹血糖降低（p < 0.0001）。空腹胰岛素和完整胰岛素原增加（p < 0.004），但32/33裂解胰岛素原保持不变。空腹胰岛素与血糖比值（p < 0.005）以及完整胰岛素原与32/33裂解胰岛素原比值（p < 0.02）均显著增加。磺脲类药物治疗后的最终空腹血糖与初始完整胰岛素原和32/33裂解胰岛素原以及饮食治疗后的空腹血糖呈正相关。从这项研究可以清楚地看出，磺脲类药物对β细胞生理功能有复杂的影响，除了刺激胰岛素释放外，它们还增加完整胰岛素原的释放，但不增加32/33裂解胰岛素原的释放，因此它们增加了完整胰岛素原与32/33裂解胰岛素原的比值。
