Bajaj Mandeep, Suraamornkul Swangjit, Piper Paul, Hardies Lou J, Glass Leonard, Cersosimo Eugenio, Pratipanawatr Thongchai, Miyazaki Yoshinori, DeFronzo Ralph A
Diabetes Division, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7886, USA.
J Clin Endocrinol Metab. 2004 Jan;89(1):200-6. doi: 10.1210/jc.2003-031315.
The effect of pioglitazone (PIO) on plasma adiponectin concentration, endogenous glucose production (EGP), and hepatic fat content (HFC) was studied in 11 type 2 diabetic patients (age, 52 +/- 2 yr; body mass index, 29.6 +/- 1.1 kg/m(2); HbA(1c), 7.8 +/- 0.4%). HFC (magnetic resonance spectroscopy) and basal plasma adiponectin concentration were quantitated before and after PIO (45 mg/d) for 16 wk. Subjects received a 3-h euglycemic insulin (100 mU/m(2).min) clamp combined with 3-[(3)H] glucose infusion to determine rates of EGP and tissue glucose disappearance (Rd) before and after PIO. PIO reduced fasting plasma glucose (10.0 +/- 0.7 to 7.2 +/- 0.6 mmol/liter, P < 0.01) and HbA(1c) (7.8 +/- 0.4 to 6.5 +/- 0.3%, P < 0.01) despite increased body weight (83.0 +/- 3.0 to 86.4 +/- 3.0 kg, P < 0.01). PIO improved Rd (6.6 +/- 0.6 vs. 5.2 +/- 0.5 mg/kg.min, P < 0.005) and reduced EGP (0.23 +/- 0.04 to 0.05 +/- 0.02 mg/kg.min, P < 0.01) during the 3-h insulin clamp. After PIO treatment, HFC decreased from 21.3 +/- 4.2 to 11.0 +/- 2.4% (P < 0.01), and plasma adiponectin increased from 7 +/- 1 to 21 +/- 2 micro g/ml (P < 0.0001). Plasma adiponectin concentration correlated negatively with HFC (r = -0.60, P < 0.05) and EGP (r = -0.80, P < 0.004) and positively with Rd before (r = 0.68, P < 0.02) pioglitazone treatment; similar correlations were observed between plasma adiponectin levels and HFC (r = -0.65, P < 0.03) and Rd after (r = 0.70, P = 0.01) pioglitazone treatment. EGP was almost completely suppressed after pioglitazone treatment; taken collectively, plasma adiponectin concentration, before and after pioglitazone treatment, still correlated negatively with EGP during the insulin clamp (r = -0.65, P < 0.001). In conclusion, PIO treatment in type 2 diabetes causes a 3-fold increase in plasma adiponectin concentration. The increase in plasma adiponectin is strongly associated with a decrease in hepatic fat content and improvements in hepatic and peripheral insulin sensitivity. The increase in plasma adiponectin concentration after thiazolidinedione therapy may play an important role in reversing the abnormality in hepatic fat mobilization and the hepatic/muscle insulin resistance in patients with type 2 diabetes.
在11例2型糖尿病患者（年龄52±2岁；体重指数29.6±1.1kg/m²；糖化血红蛋白7.8±0.4%）中研究了吡格列酮（PIO）对血浆脂联素浓度、内源性葡萄糖生成（EGP）和肝脏脂肪含量（HFC）的影响。在使用PIO（45mg/d）治疗16周前后，通过磁共振波谱法测定HFC，并对基础血浆脂联素浓度进行定量。受试者接受3小时的正常血糖胰岛素钳夹试验（100mU/m²·min），同时输注3-[(3)H]葡萄糖，以测定PIO治疗前后的EGP和组织葡萄糖消失率（Rd）。尽管体重增加（83.0±3.0kg增至86.4±3.0kg，P<0.01），但PIO仍降低了空腹血糖（从10.0±0.7mmol/L降至7.2±0.6mmol/L，P<0.01）和糖化血红蛋白（从7.8±0.4%降至6.5±0.3%，P<0.01）。在3小时胰岛素钳夹试验期间，PIO改善了Rd（6.6±0.6对5.2±0.5mg/kg·min，P<0.005）并降低了EGP（从0.23±0.04降至0.05±0.02mg/kg·min，P<0.01）。PIO治疗后，HFC从21.3±4.2%降至11.0±2.4%（P<0.01），血浆脂联素从7±1μg/ml增至21±2μg/ml（P<0.0001）。在吡格列酮治疗前，血浆脂联素浓度与HFC（r=-0.60，P<0.05）和EGP（r=-0.80，P<0.004）呈负相关，与Rd呈正相关（r=0.68，P<0.02）；在吡格列酮治疗后，血浆脂联素水平与HFC（r=-0.65，P<0.03）和Rd（r=0.70，P=0.01）之间也观察到类似的相关性。吡格列酮治疗后EGP几乎完全被抑制；总体而言，吡格列酮治疗前后的血浆脂联素浓度在胰岛素钳夹试验期间仍与EGP呈负相关（r=-0.65，P<0.001）。总之，2型糖尿病患者接受PIO治疗可使血浆脂联素浓度增加3倍。血浆脂联素的增加与肝脏脂肪含量的降低以及肝脏和外周胰岛素敏感性的改善密切相关。噻唑烷二酮类药物治疗后血浆脂联素浓度的增加可能在逆转2型糖尿病患者肝脏脂肪动员异常和肝脏/肌肉胰岛素抵抗中起重要作用。
