Effect of pioglitazone on circulating adipocytokine levels and insulin sensitivity in type 2 diabetic patients
Effect of pioglitazone on circulating adipocytokine levels and insulin sensitivity in type 2 diabetic patients
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DOI：
10.1210/jc.2004-0190
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发表时间：
2004-09-01
影响因子：
5.8
通讯作者：
DeFronzo, RA
中科院分区：
文献类型：
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作者：
Miyazaki, Y;Mahankali, A;DeFronzo, RA
我们研究了吡格列酮（PIO）对循环脂肪细胞因子水平的影响，以阐明噻唑烷二酮类药物改善2型糖尿病（T2 DM）胰岛素抵抗的机制。23例T2 DM受试者（年龄54 ± 2岁，体重指数29 ± 1 kg/m2）被随机分配接受安慰剂（n = 11）或PIO，45 mg/d（n = 12），持续4个月。在治疗前后，受试者接受75 g口服葡萄糖耐量试验（OGTT）;正常血糖胰岛素钳夹（40 mU/m2）。min）;测定脂肪量（（H2O）-H-3）;以及测量空腹血糖、游离脂肪酸（FFA）、瘦素、脂联素和TNF α浓度。PIO 4个月后，空腹血糖浓度（Delta=-2.7 mol/L）、OGTT期间平均血糖（Delta =-3.8 mol/L）和血红蛋白A（1c）（Delta = 1.7%）降低（与安慰剂相比P < 0.05），空腹或OGTT后血浆胰岛素水平无变化。空腹FFA（Delta = 168 μ mol/L）和TNF α（Delta = 0.7 pg/ml）浓度降低（与安慰剂相比P < 0.05），而脂联素（Delta = 8.7 μ g/ml）升高（与安慰剂相比P < 0.01）。尽管PIO后体脂量增加（Delta = 3.4 kg），但血浆瘦素浓度没有显著变化。在安慰剂治疗的受试者中未观察到血糖、FFAs或脂肪细胞因子水平的变化。在胰岛素钳夹过程中，内源性（肝脏）葡萄糖产生减少（Delta = -2.67 μ mol/无脂肪质量中心点分，P < 0.05 vs.安慰剂），而葡萄糖代谢清除率（MCR）增加（Delta = 0.58 ml/无脂肪质量）。min，P < 0.05 vs.安慰剂）。在所有受试者中，PIO前后，血浆FFA浓度的降低与内源性（肝）葡萄糖生成（r = 0.47，P < 0.05）与MCR血浆脂联素水平的升高与内源性脂联素水平的变化相关（r =-0.41，P < 0.05）。（肝）葡萄糖生成（r =-0.70，P < 0.01）和MCR（r = 0.49，P < 0.05）。这些结果表明，PIO对脂肪组织的直接影响，降低血浆FFA水平和增加血浆脂联素有助于改善肝脏和外周胰岛素敏感性和葡萄糖耐量的T2 DM患者。
We examined the effect of pioglitazone (PIO) on circulating adipocytokine levels to elucidate the mechanisms by which thiazolidinediones improve insulin resistance in type 2 diabetes mellitus (T2DM). Twenty-three subjects with T2DM (age 54 +/- 2 yr, body mass index 29 +/- 1 kg/m(2)) were randomly assigned to receive placebo (n = 11) or PIO, 45 mg/d (n = 12), for 4 months. Before and after treatment, subjects received a 75-g oral glucose tolerance test (OGTT); euglycemic insulin clamp (40 mU/m(2) . min) with 3-H-3-glucose; determination of fat mass ((H2O)-H-3); and measurement of fasting glucose, free fatty acids (FFAs), leptin, adiponectin, and TNFalpha concentrations. After 4 months of PIO, fasting plasma glucose concentration (Delta= - 2.7 mol/liter), mean plasma glucose during OGTT (Delta = - 3.8 mol/ liter), and hemoglobin A(1c) (Delta = 1.7%) decreased (P < 0.05 vs. placebo) without change in fasting or post-OGTT plasma insulin levels. Fasting FFAs (Delta = 168 mu mol/liter) and TNF alpha (Delta = 0.7 pg/ml) concentrations decreased (P < 0.05 vs. placebo), whereas adiponectin (Delta = 8.7 mug/ml) increased (P < 0.01 vs. placebo). Despite the increase in body fat mass (Delta = 3.4 kg) after PIO, plasma leptin concentration did not change significantly. No changes in plasma glucose, FFAs, or adipocytokine levels were observed in placebo-treated subjects. During the insulin clamp, endogenous ( hepatic) glucose production decreased (Delta = -2.67 mu mol/fat-free mass center dot min, P < 0.05 vs. placebo), whereas metabolic clearance rate of glucose (MCR) increased (Delta = 0.58 ml/fat-free mass . min, P < 0.05 vs. placebo) after PIO. In all subjects, before and after PIO, the decrease in plasma FFA concentration was correlated with the changes in both endogenous ( hepatic) glucose production (r = 0.47, P < 0.05) and MCR ( r = -0.41, P < 0.05), whereas the increase in plasma adiponectin concentration was correlated with the change in endogenous ( hepatic) glucose production ( r = -0.70, P < 0.01) and MCR ( r = 0.49, P < 0.05). These results suggest that the direct effects of PIO on adipose tissue to decrease plasma FFA levels and increase plasma adiponectin contribute to the improvements in hepatic and peripheral insulin sensitivity and glucose tolerance in patients with T2DM.