Effect of simvastatin and/or pioglitazone on insulin resistance, insulin secretion, adiponectin, and proinsulin levels in nondiabetic patients at cardiovascular risk--the PIOSTAT Study.
We investigated the effect of pioglitazone in comparison with and in combination with simvastatin on insulin resistance, plasma adiponectin, postprandial plasma glucose, insulin, and intact proinsulin levels in a nondiabetic population at cardiovascular risk. One hundred twenty-five nondiabetic patients at cardiovascular risk were randomized to pioglitazone (PIO), pioglitazone and simvastatin (PIO/SIM), or simvastatin (SIM) treatments. Blood samples were taken for the measurement of adiponectin and lipid levels. In addition, an oral glucose load with the measurements of glucose, insulin, and intact proinsulin levels was performed. Adiponectin levels increased from 14.0+/-8.2 to 27.6+/-14.5 microg/mL (P<.0001) during PIO treatment and from 11.7+/-10.0 to 26.7+/-15.7 microg/mL (P<.0001) during PIO/SIM treatment. A decrease in adiponectin levels from 15.5+/-12.7 to 11.6+/-7.0 microg/mL (P<.05) was observed during SIM treatment. Although fasting intact proinsulin levels remained unchanged, the increase in postprandial intact proinsulin levels could be reduced from 29.5+/-21.4 to 22.1+/-17.5 pmol/L (P<.01) during PIO treatment and from 24.3+/-27.4 to 21.1+/-16.5 mmol/L (P<.05) during PIO/SIM treatment. Lipid parameters improved during SIM treatment but not during PIO treatment. Combined treatment with PIO/SIM was superior in improving overall cardiovascular risk profile than every single drug.
Forst
Thomas
T
Institute for Clinical Research and Development, Medical Department, D-55116 Mainz, Germany. thomasf@ikfe.de
Pfützner
Andreas
A
Lübben
Georg
G
Weber
Matthias
M
Marx
Nikolaus
N
Karagiannis
Efstrathios
E
Koehler
Carsta
C
Baurecht
Werner
W
Hohberg
Cloth
C
Hanefeld
Markolf
M
D052242:Adiponectin / Q000097:blood*; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D004311:Double-Blind Method; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D000077205:Pioglitazone; D011384:Proinsulin / Q000097:blood*; D011446:Prospective Studies; D012307:Risk Factors; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*
D052242:Adiponectin; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D011384:Proinsulin; D019821:Simvastatin; D000077205:Pioglitazone