Plasma resistin concentration, hepatic fat content, and hepatic and peripheral insulin resistance in pioglitazone-treated type II diabetic patients.
OBJECTIVE
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).


METHODS
A total of 13 T2DM patients (age=51+/-2 y, BMI=29.7+/-1.1 kg/m(2), HbA(1c)=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/m(2)/min) clamp with 3-[(3)H] 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 HbA(1c) (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 EGP (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.
Bajaj
M
M
Diabetes Division, Department of Medicine, University of Texas Health Science Center at San Antonio, Texas, USA. mandeepbajaj@hotmail.com
Suraamornkul
S
S
Hardies
L J
LJ
Pratipanawatr
T
T
DeFronzo
R A
RA
D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D006729:Hormones, Ectopic / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000032:analysis*; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D052243:Resistin; D045162:Thiazolidinediones / Q000627:therapeutic use*; D015430:Weight Gain / Q000502:physiology
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006729:Hormones, Ectopic; D007004:Hypoglycemic Agents; D008055:Lipids; C499624:RETN protein, human; D052243:Resistin; D045162:Thiazolidinediones; D005947:Glucose; D000077205:Pioglitazone