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Peroxisome proliferator-activated receptor-gamma agonist increases both low-density lipoprotein cholesterol particle size and small high-density lipoprotein cholesterol in patients with type 2 diabetes independent of diabetic control.
- Source :
-
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists [Endocr Pract] 2003 Nov-Dec; Vol. 9 (6), pp. 487-93. - Publication Year :
- 2003
-
Abstract
- Objective: To ascertain whether troglitazone, independent of control of diabetes, increases low-density lipoprotein (LDL) particle size.<br />Methods: We administered 600 mg of troglitazone (a peroxisome proliferator-activated receptor-gamma agonist) daily for 8 weeks to 10 patients with type 2 diabetes (8 of whom completed the study). Then troglitazone therapy was discontinued, and alternative medication for diabetic control was used for another 4 weeks. The LDL, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) concentrations and subpopulations, as well as blood glucose and hemoglobin A1c (HbA1c), were determined at weeks 0, 4, 8, and 12 and analyzed statistically.<br />Results: Small, dense LDL cholesterol is commonly seen in patients with diabetes and is thought to be associated with an increased risk for coronary artery disease. After both 4 and 8 weeks of troglitazone therapy, control of diabetes was significantly improved (mean HbA1c values at baseline, week 4, and week 8 were 8.0 +/- 0.7%, 7.4 +/- 0.5%, and 7.0 +/- 0.7%, respectively; P<0.05). HbA1c (6.5 +/- 0.6% at 12 weeks) and blood glucose levels (126 +/- 19 mg/dL at 8 weeks versus 145 +/- 9 mg/dL at 12 weeks) were not significantly different 4 weeks after troglitazone therapy was discontinued. Troglitazone treatment increased the large LDL particle at 4 and 8 weeks, a change that significantly (P<0.05) enlarged the LDL particle size (20.5 +/- 0.3 nm, 21.2 +/- 0.3 nm, and 21.3 +/- 0.2 nm at baseline, week 4, and week 8, respectively). After 8 weeks of troglitazone therapy, VLDL triglycerides were reduced (195 +/- 37 mg/dL versus 136 +/- 28 mg/dL; P<0.05) and HDL was increased (31.6 +/- 2.4 mg/dL versus 35.5 +/- 2.9 mg/dL; P<0.05). This greater HDL value was due to an increase in the small HDL particles. A decrease in the larger VLDL particles (V5 and V6) resulted in a reduction in the mean VLDL particle size (59 +/- 3 nm versus 46 +/- 2 nm; P<0.05). Despite the fact that control of diabetes remained significantly improved after troglitazone therapy was discontinued, the LDL particle size decreased to the baseline value. This change was due to a reduction in the large LDL cholesterol particle (L3).<br />Conclusion: This study shows that troglitazone therapy increases LDL particle size, reduces VLDL particle size, and increases small HDL particles. These changes may lower the risk for coronary artery disease.
- Subjects :
- Blood Glucose analysis
Diabetes Mellitus, Type 2 drug therapy
Female
Glycated Hemoglobin analysis
Humans
Lipoproteins, VLDL blood
Male
Middle Aged
Particle Size
Troglitazone
Cholesterol, HDL blood
Cholesterol, LDL blood
Chromans administration & dosage
Diabetes Mellitus, Type 2 blood
Hypoglycemic Agents administration & dosage
Receptors, Cytoplasmic and Nuclear agonists
Thiazolidinediones administration & dosage
Transcription Factors agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1530-891X
- Volume :
- 9
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
- Publication Type :
- Academic Journal
- Accession number :
- 14715475
- Full Text :
- https://doi.org/10.4158/EP.9.6.487