PMID- 15356026
OWN - NLM
STAT- MEDLINE
DCOM- 20041007
LR  - 20220309
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 89
IP  - 9
DP  - 2004 Sep
TI  - Effect of pioglitazone on circulating adipocytokine levels and insulin 
      sensitivity in type 2 diabetic patients.
PG  - 4312-9
AB  - 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-(3)H-glucose; determination of 
      fat mass ((3)H(2)O); 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 micromol/liter) and TNFalpha (Delta = 0.7 pg/ml) 
      concentrations decreased (P < 0.05 vs. placebo), whereas adiponectin (Delta = 8.7 
      microg/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 micromol/fat-free mass.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.
FAU - Miyazaki, Yoshinori
AU  - Miyazaki Y
AD  - University of Texas Health Science Center, Diabetes Division, Room 3.380S, 7703 
      Floyd Curl Drive, San Antonio, Texas 78229-3900, USA. albarado@uthscsa.edu
FAU - Mahankali, Archana
AU  - Mahankali A
FAU - Wajcberg, Estela
AU  - Wajcberg E
FAU - Bajaj, Mandeep
AU  - Bajaj M
FAU - Mandarino, Lawrence J
AU  - Mandarino LJ
FAU - DeFronzo, Ralph A
AU  - DeFronzo RA
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Adiponectin)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Leptin)
RN  - 0 (Proteins)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - X4OV71U42S (Pioglitazone)
SB  - IM
MH  - Adiponectin
MH  - Aged
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Double-Blind Method
MH  - Fatty Acids, Nonesterified/*blood
MH  - Female
MH  - Glucose Tolerance Test
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Insulin/*blood
MH  - *Intercellular Signaling Peptides and Proteins
MH  - Leptin/*blood
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - Pioglitazone
MH  - Proteins/*analysis
MH  - Sex Factors
MH  - Thiazolidinediones/pharmacology/*therapeutic use
MH  - Tumor Necrosis Factor-alpha/*analysis
EDAT- 2004/09/10 05:00
MHDA- 2004/10/08 09:00
CRDT- 2004/09/10 05:00
PHST- 2004/09/10 05:00 [pubmed]
PHST- 2004/10/08 09:00 [medline]
PHST- 2004/09/10 05:00 [entrez]
AID - 89/9/4312 [pii]
AID - 10.1210/jc.2004-0190 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2004 Sep;89(9):4312-9. doi: 10.1210/jc.2004-0190.