Differential effect of pioglitazone (PGZ) and rosiglitazone (RGZ) on postprandial glucose and lipid metabolism in patients with type 2 diabetes mellitus: a prospective, randomized crossover study.
BACKGROUND
Postprandial metabolism is impaired in patients with type 2 diabetes (T2Dm). Two thiazolidinediones pioglitazone (PGZ) and rosiglitazone (RGZ) have similar effects on glycaemic control but differ in their effects on fasting lipids. This study investigated the effects of RGZ and PGZ on postprandial metabolism in a prospective, randomized crossover trial.


METHODS
Seventeen patients with T2Dm were randomized to RGZ or PGZ for 12 weeks, with an 8-week wash-out period. Fasting blood samples were taken for glucose (FPG), insulin, HbA(1c), lipids, apolipoproteins (apo), lipoprotein (LPL) and hepatic lipase (HL), and cholesterol ester transfer protein (CETP) activity. A standardized breakfast was served and postprandial glucose, insulin, and lipid subfraction profiles were determined.


RESULTS
RGZ and PGZ treatment resulted in a similar improvement in FPG, HbA(1c) and homeostasis model assessment. Fasting and postprandial triglyceride (TG) levels were significantly lower following PGZ therapy (fasting: -0.35 vs 0.44 mmol/L; p < 0.04; postprandial AUC-TG: -195.6 vs 127.9 mmol/L/min; p < 0.02) associated with changes in VLDL-2-TG (-0.10 vs 0.21 mmol/L; p = 0.23) and VLDL-3-TG (0.0 vs 0.34 mmol/L; p < 0.04). Fasting cholesterol increased with RGZ compared to PGZ (0.06 vs 0.59 mmol/L; p < 0.04), particularly in VLDL-2-C (-0.30 vs 0.59 mmol/L; p < 0.03) and VLDL-3-C (-0.85 vs 2.11 mmol/L; p < 0.02). Postprandial VLDL lipid and protein content increased after RGZ and decreased after PGZ. Fasting apoB, apoA-I, apoC-II/C-III-ratio, and LPL activity did not differ. CETP activity decreased after RGZ and increased after PGZ (-6.2 vs 4.2 p/mol/mL/min; p < 0.002).


CONCLUSIONS
Both the glitazones had similar effects on glucose metabolism. The additional beneficial effect of PGZ on lipid metabolism may be related to its effects on insulin-independent VLDL production and CETP activity.
Chappuis
Bernard
B
Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital of Berne, Inselspital, CH-3010 Bern, Switzerland.
Braun
Monika
M
Stettler
Christoph
C
Allemann
Sabine
S
Diem
Peter
P
Lumb
Peter J
PJ
Wierzbicki
Anthony S
AS
James
Richard
R
Christ
Emanuel R
ER
D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005215:Fasting; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood / Q000187:drug effects; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D000077205:Pioglitazone; D019518:Postprandial Period; D011446:Prospective Studies; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002784:Cholesterol; D053480:Cholesterol Ester Transfer Proteins; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008055:Lipids; D008074:Lipoproteins; D008687:Metformin; D000077205:Pioglitazone; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D014280:Triglycerides; C506642:CETP protein, human