Effect of pioglitazone on the metabolic and hormonal response to a mixed meal in type II diabetes
Effect of pioglitazone on the metabolic and hormonal response to a mixed meal in type II diabetes
复制标题
DOI：
10.1038/sj.clpt.6100034
复制
发表时间：
2007-02-01
影响因子：
6.7
通讯作者：
Ferrannini, E.
中科院分区：
文献类型：
--
作者：
Gastaldelli, A.;Casolaro, A.;Ferrannini, E.
我们探讨了4个月的安慰剂对照吡格列酮治疗（45 mg/天）改善II型糖尿病患者的血糖控制（T2 D，n = 27）使用生理学测试（6小时混合餐）和三重示踪技术（[6，6-H-2（2）]葡萄糖输注，（H2O）-H-2和[6-H-3]葡萄糖摄取），以测量内源性葡萄糖产生（EGP），葡萄糖生成（GNG），胰岛素介导的葡萄糖清除和β细胞葡萄糖敏感性（通过C肽建模）。与性别/年龄/体重匹配的非糖尿病对照组相比，T2 D患者显示不适当的（对于普遍的胰岛素血症）增加葡萄糖的产生（1.05[0.53] vs 0.71[0.36]mmol min（-1）kg（ffm）（-1）pm，P = 0.03），因为GNG增强（73.1 +/-2.4% vs 59.5 +/-3.6%，P < 0.01）在整个膳食中持续存在，胰岛素介导的葡萄糖清除率降低（6[5] vs 12[13]ml min（-1）kg（ffm）（-1）nM（-1），P < 0.005），β细胞葡萄糖敏感性受损（27[38] vs 71[37]pmol min（-1）m（-2）mM（-1），P=0.002）。与安慰剂相比，吡格列酮改善了葡萄糖过度生产（P = 0.0001）、GNG和葡萄糖利用不足（P = 0.05），尽管胰岛素血症较低。GNG的改善与脂联素的升高在数量上相关。β-细胞葡萄糖敏感性不变。在轻度至中度T2 D中，吡格列酮单药治疗主要通过抑制胰岛素生成降低空腹和餐后胰岛素水平，改善肝脏和外周胰岛素抵抗。
We explored the mechanisms by which a 4-month, placebo-controlled pioglitazone treatment (45 mg/day) improves glycemic control in type II diabetic patients (T2D, n = 27) using physiological testing (6-h mixed meal) and a triple tracer technique ([6,6-H-2(2)]glucose infusion, (H2O)-H-2 and [6-H-3]glucose ingestion) to measure endogenous glucose production (EGP), gluconeogenesis (GNG), insulin-mediated glucose clearance and beta-cell glucose sensitivity (by c-peptide modeling). Compared to sex/age/weight-matched non-diabetic controls, T2D patients showed inappropriately (for prevailing insulinemia) raised glucose production (1.05[0.53] vs 0.71[0.36]mmol min(-1) kg(ffm)(-1) pm, P = 0.03) because of enhanced GNG (73.1 +/- 2.4 vs 59.5 +/- 3.6%, P < 0.01) persisting throughout the meal, reduced insulin-mediated glucose clearance (6[5] vs 12[13]ml min(-1) kg(ffm)(-1) nM(-1), P < 0.005), and impaired beta-cell glucose-sensitivity (27[38] vs 71[37]pmol min(-1) m(-2) mM(-1), P=0.002). Compared to placebo, pioglitazone improved glucose overproduction (P = 0.0001), GNG and glucose underutilization (P = 0.05) despite lower insulinemia. GNG improvement was quantitatively related to raised adiponectin. beta-cell glucose sensitivity was unchanged. In mild-to-moderate T2D, pioglitazone monotherapy decreased fasting and post-prandial glycemia, principally via inhibition of gluconeogenesis, improved hepatic and peripheral insulin resistance.