TY - JOUR
T1 - Plasma resistin concentration, hepatic fat content, and hepatic and peripheral insulin resistance in pioglitazone-treated type II diabetic patients
AU - Bajaj, M.
AU - Suraamornkul, S.
AU - Hardies, L. J.
AU - Pratipanawatr, T.
AU - DeFronzo, R. A.
N1 - Funding Information:
We thank the nurses on the GCRC for their diligent care of our patients and especially Patrcia Wolff RN, Norma Diaz BSN, James King RN and John Kincade RN for carrying out the insulin clamp studies. We gratefully acknowledge the technical assistance of Richard Castillo, Kathy Camp, Cindy Munoz, and Sheila Taylor. Ms Lorrie Albarado and Ms Elva Chapa provided skilled secretarial support in the preparation of the manuscript. This work was supported in part by grants from Takeda America, NIH Grant DK-24092, a VA Merit Award, and GCRC Grant MO1-RR01346.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/6
Y1 - 2004/6
N2 - OBJECTIVES: To study the effect of pioglitazone (PIO) on plasma resistin concentration, endogenous glucose production (EGP), and hepatic fat content (HFC) in patients with type II diabetes (T2DM). SUBJECTS: A total of 13 T2DM patients (age = 51 ± 2y, BMI = 29.7 ± 1.1 kg/m2, HbA1c = 8.0 ± 0.5%). METHODS: HFC (magnetic resonance spectroscopy) and basal plasma resistin concentration were quantitated before and after PIO treatment (45 mg/day) for 16 weeks. Subjects received a 3 h euglycemic insulin (100 mU/m2/min) clamp with 3-[3H] glucose to determine rates of EGP and tissue glucose disappearance (Rd) before and after PIO. RESULTS: PIO reduced fasting plasma glucose (10.3 ± 0.7 to 7.6 ±0.6 mmol/l, P < 0.001) and HbA1c (8.0 + 0.4 to 6.8 + 0.3%, P < 0.001) despite increased body weight (83.2 ± 3.4 to 86.3 ± 3.4 kg, P < 0.001). PIO improved Rd (4.9 ± 0.4 to 6.6 ± 0.5 mg/ kg/min, P < 0.005) and reduced ECP (0.22 ± 0.04 to 0.06 ± 0.02 mg/kg/min, P < 0.01) during the insulin clamp. Following PIO, HFC decreased from 21.1 ± 3.5 to 11.2 ± 2.1% (P < 0.005), and plasma resistin decreased from 5.3 ± 0.6 to 3.5 ± 0.3 ng/ml (P < 0.01). Plasma resistin concentration correlated positively with HFC before (r=0.58, P < 0.05) and after (r = 0.55, P < 0.05) PIO treatment. Taken collectively, plasma resistin concentration, before and after PIO treatment, correlated positively with hepatic fat content (r = 0.66, P < 0.001) and EGP during the insulin clamp (r = 0.41, P < 0.05). However, the plasma resistin concentration did not correlate with whole body glucose disposal (Rd) during the insulin clamp either before (r = -0.18, P = NS) or after (r = -0.13, P = NS) PIO treatment. CONCLUSIONS: PIO treatment in T2DM causes a significant decrease in plasma resistin concentration. The decrease in plasma resistin is positively correlated with the decrease in hepatic fat content and improvement in hepatic insulin sensitivity.
AB - OBJECTIVES: To study the effect of pioglitazone (PIO) on plasma resistin concentration, endogenous glucose production (EGP), and hepatic fat content (HFC) in patients with type II diabetes (T2DM). SUBJECTS: A total of 13 T2DM patients (age = 51 ± 2y, BMI = 29.7 ± 1.1 kg/m2, HbA1c = 8.0 ± 0.5%). METHODS: HFC (magnetic resonance spectroscopy) and basal plasma resistin concentration were quantitated before and after PIO treatment (45 mg/day) for 16 weeks. Subjects received a 3 h euglycemic insulin (100 mU/m2/min) clamp with 3-[3H] glucose to determine rates of EGP and tissue glucose disappearance (Rd) before and after PIO. RESULTS: PIO reduced fasting plasma glucose (10.3 ± 0.7 to 7.6 ±0.6 mmol/l, P < 0.001) and HbA1c (8.0 + 0.4 to 6.8 + 0.3%, P < 0.001) despite increased body weight (83.2 ± 3.4 to 86.3 ± 3.4 kg, P < 0.001). PIO improved Rd (4.9 ± 0.4 to 6.6 ± 0.5 mg/ kg/min, P < 0.005) and reduced ECP (0.22 ± 0.04 to 0.06 ± 0.02 mg/kg/min, P < 0.01) during the insulin clamp. Following PIO, HFC decreased from 21.1 ± 3.5 to 11.2 ± 2.1% (P < 0.005), and plasma resistin decreased from 5.3 ± 0.6 to 3.5 ± 0.3 ng/ml (P < 0.01). Plasma resistin concentration correlated positively with HFC before (r=0.58, P < 0.05) and after (r = 0.55, P < 0.05) PIO treatment. Taken collectively, plasma resistin concentration, before and after PIO treatment, correlated positively with hepatic fat content (r = 0.66, P < 0.001) and EGP during the insulin clamp (r = 0.41, P < 0.05). However, the plasma resistin concentration did not correlate with whole body glucose disposal (Rd) during the insulin clamp either before (r = -0.18, P = NS) or after (r = -0.13, P = NS) PIO treatment. CONCLUSIONS: PIO treatment in T2DM causes a significant decrease in plasma resistin concentration. The decrease in plasma resistin is positively correlated with the decrease in hepatic fat content and improvement in hepatic insulin sensitivity.
KW - Hepatic fat content
KW - Hepatic insulin resistance
KW - Pioglitazone
KW - Resistin
KW - Type II diabetes mellitus
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U2 - 10.1038/sj.ijo.0802625
DO - 10.1038/sj.ijo.0802625
M3 - Article
C2 - 15024400
AN - SCOPUS:2942515930
SN - 0307-0565
VL - 28
SP - 783
EP - 789
JO - International Journal of Obesity
JF - International Journal of Obesity
IS - 6
ER -