Improved glycemic control and enhanced insulin sensitivity in type 2 diabetic subjects treated with pioglitazone.
OBJECTIVE
To elucidate the effects of pioglitazone treatment on glucose and lipid metabolism in patients with type 2 diabetes.


METHODS
A total of 23 diabetic patients (age 30-70 years BMI < 36 kg/m2) who being treated with a stable dose of sulfonylurea were randomly assigned to receive either placebo (n = 11) or pioglitazone (45 mg/day) (n = 12) for 16 weeks. Before and after 16 weeks of treatment, all subjects received a 75-g oral glucose tolerance test (OGTT) and hepatic peripheral insulin sensitivity was measured with a two-step euglycemic insulin (40 and 160 mU x min(-1) x m(-2) clamp performed with 3-[3H]glucose and indirect calorimetry HbA1c measured monthly throughout the study period.


RESULTS
After 16 weeks of pioglitazone treatment, the fasting plasma glucose (FPG; 184 +/- 15 to 135 +/- 11 mg/dl, P < 0.01), mean plasma glucose during OGTT(293 +/- 12 to 225 +/- 14 mg/dl, P < 0.01), and HbA1c (8.9 +/- 0.3 to 7.2 +/- 0.5%, P < 0.01 ) decreased significantly without change in fasting or glucose-stimulated insulin/C-peptide concentrations. Fasting plasma free fatty acid (FFA; 647 +/- 39 to 478 +/- 49) microEq/l, P < 0.01) and mean plasma FFA during OGTT (485 +/- 30 to 347 +/- 33 microEq/l, P < 0.01) decreased significantly after pioglitazone treatment. Before and after pioglitazone treatment, basal endogenous glucose prodution (EGP) and FPG were strongly correlated (r = 0.67, P < 0.01). EGP during the first insulin clamp step was significantly decreased after pioglitazone treatment (P < 0.05) whereas insulin-stimulated total and nonoxidative glucose disposal during the second insulin clamp was increased (P < 0.01). The change in FPG was related to the change in basal EGP, EGP during the first insulin clamp step, and total glucose disposal during the second insulin clamp step. The change in mean plasma glucose concentration during the OGGTT was strongly related to the change in total body glucose disposl during the second insulin clamp step.


CONCLUSIONS
These results suggest that pioglitazone therapy in type 2 diabetic patients decreases lasting and postprandial plasma glucose levels by improving hepatic and peripheral (muscle) tissue sensitivity to insulin.
Miyazaki
Y
Y
University of Texas Health Science Center and Texas Diabetes Institute, San Antonio 78284-7886, USA.
Mahankali
A
A
Matsuda
M
M
Glass
L
L
Mahankali
S
S
Ferrannini
E
E
Cusi
K
K
Mandarino
L J
LJ
DeFronzo
R A
RA
D000273:Adipose Tissue / Q000503:physiopathology; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D008875:Middle Aged; D000077205:Pioglitazone; D010919:Placebos; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002096:C-Peptide; D002784:Cholesterol; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000077205:Pioglitazone; D010919:Placebos; D013453:Sulfonylurea Compounds; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides