Section of Diabetes, Endocrinology and Metabolism, VA San Diego Healthcare System and University of California San Diego, San Diego, CA 92161, USA.
Diabetes Obes Metab. 2012 Jan;14(1):40-6. doi: 10.1111/j.1463-1326.2011.01486.x. Epub 2011 Nov 21.
Colesevelam lowers glucose and low-density lipoprotein cholesterol levels in patients with type 2 diabetes mellitus. This study examined the mechanisms by which colesevelam might affect glucose control.
In this 12-week, randomized, double-blind, placebo-controlled study, subjects with type 2 diabetes and haemoglobin A(1c) (HbA(1c)) ≥7.5% on either stable diet and exercise or sulphonylurea therapy were randomized to colesevelam 3.75 g/day (n = 16) or placebo (n = 14). Hepatic/peripheral insulin sensitivity was evaluated at baseline and at week 12 by infusion of (3) H-labelled glucose followed by a 2-step hyperinsulinemic-euglycemic clamp. Two 75-g oral glucose tolerance tests (OGTTs) were conducted at baseline, one with and one without co-administration of colesevelam. A final OGTT was conducted at week 12. HbA(1c) and fasting plasma glucose (FPG) levels were evaluated pre- and post-treatment.
Treatment with colesevelam, compared to placebo, had no significant effects on basal endogenous glucose output, response to insulin or on maximal steady-state glucose disposal rate. At baseline, co-administration of colesevelam with oral glucose reduced total area under the glucose curve (AUC(g)) but not incremental AUC(g). At week 12, neither total AUC(g) nor incremental AUC(g) were changed from pre-treatment values in either group. Post-load insulin levels increased with colesevelam at 30 and 120 min, but these changes in total area under the insulin curve (AUC(i)) and incremental AUC(i) did not differ between groups. Both HbA(1c) and FPG improved with colesevelam, but treatment differences were not significant.
Colesevelam does not affect hepatic or peripheral insulin sensitivity and does not directly affect glucose absorption.
考来烯胺可降低 2 型糖尿病患者的血糖和低密度脂蛋白胆固醇水平。本研究探讨了考来烯胺影响血糖控制的机制。
在这项为期 12 周、随机、双盲、安慰剂对照的研究中，2 型糖尿病患者的糖化血红蛋白（HbA1c）≥7.5%，无论其基础治疗是稳定饮食和运动，还是磺脲类药物治疗，均随机分为考来烯胺 3.75g/天组（n=16）或安慰剂组（n=14）。在基线和第 12 周时，通过输注（3）H 标记的葡萄糖，然后进行两步高胰岛素-正常血糖钳夹，评估肝/外周胰岛素敏感性。在基线时进行了两次 75g 口服葡萄糖耐量试验（OGTT），一次与考来烯胺合用，一次不用。在第 12 周时进行了最后一次 OGTT。治疗前后评估 HbA1c 和空腹血浆葡萄糖（FPG）水平。
与安慰剂相比，考来烯胺治疗对基础内源性葡萄糖输出、胰岛素反应或最大稳态葡萄糖摄取率均无显著影响。基线时，考来烯胺与口服葡萄糖合用可降低总葡萄糖曲线下面积（AUCg），但不增加增量 AUCg。在第 12 周时，两组的总 AUCg 和增量 AUCg 均未较治疗前发生变化。负荷后胰岛素水平在 30 和 120 分钟时随考来烯胺而升高，但两组间胰岛素曲线下总面积（AUCi）和增量 AUCi 的变化无差异。HbA1c 和 FPG 均随考来烯胺而改善，但治疗差异无统计学意义。
考来烯胺不影响肝或外周胰岛素敏感性，也不直接影响葡萄糖吸收。
