Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated type 2 diabetic patients
Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated type 2 diabetic patients
复制标题
DOI：
10.1210/jc.2003-031315
复制
发表时间：
2004-01-01
影响因子：
5.8
通讯作者：
Defronzo, RA
中科院分区：
文献类型：
--
作者：
Bajaj, M;Suraamornkul, S;Defronzo, RA
在11例2型糖尿病患者中研究了吡格列酮（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（年龄52 ± 2岁;体重指数29.6 ± 1.1 kg/m2; HbA1c 7.8 ± 0.4%）。分别于PIO（45 mg/d）治疗16 wk前后测定HFC（磁共振波谱）和基础血浆脂联素浓度。受试者在PIO前后接受3小时正葡萄糖胰岛素（100 mU/m2. min）钳夹结合3-[H-3]葡萄糖输注，以测定EGP和组织葡萄糖消失率（Rd）。PIO降低空腹血糖（10.0 +/-0.7至7.2 +/-0.6 mmol/L，P <0.01）和HbA（1c）（7.8 +/-0.4至6.5 +/-0.3%，P <0.01），尽管体重增加（83.0 +/-3.0至86.4 +/-3.0 kg，P <0.01）。PIO改善了Rd（6.6 +/-0.6 vs. 5.2 +/-0.5 mg/kg中心点min，P <0.005）并降低了EGP（0.23 +/-0.04至0.05 +/-0.02 mg/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 +/-1增至21 +/-2 μ g/ml（P <0.0001）。血浆脂联素浓度与HFC呈负相关（r =-0.60，P <0.05）与EGP（r =-0.80，P <0.004），与术前Rd呈正相关吡格列酮组（r = 0.68，P <0.02）;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）呈相似的相关性。吡格列酮治疗后EGP几乎完全被抑制，总体而言，吡格列酮治疗前后血浆脂联素浓度与胰岛素钳夹期间EGP仍呈负相关（r =-0.65，P <0.001）。总之，PIO治疗2型糖尿病导致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。
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-[H-3] 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 center dot 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 mug/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.