Lack of an effect of pioglitazone or glipizide on lipoprotein-associated phospholipase A2 in type 2 diabetes.
OBJECTIVE
To study the effects of pioglitazone, a peroxisome proliferator-activated receptor-y agonist with vascular beneficial effects, and glipizide, an insulin secretagogue, on novel inflammatory vascular risk markers in subjects with and without type 2 diabetes.


METHODS
We studied 11 subjects without diabetes and 19 matched subjects with diabetes. The subjects with diabetes were randomly assigned to receive either 45 mg daily of pioglitazone (N = 8) or 10 mg daily of glipizide (N = 11) (median dose) for 12 weeks. Lipoprotein-associated phospholipase A2 (LpPLA2), vascular cell adhesion molecule (VCAM-1), intracellular adhesion molecule (ICAM-1), and e-selectin were measured by established techniques before and after therapy with either agent. The subjects without diabetes were studied only once.


RESULTS
The study subjects with diabetes had higher (P<0.05) LpPLA2, e-selectin, and VCAM-1 levels than did those without diabetes. ICAM-1 levels tended to be higher (P = 0.07) in the study subjects with than in those without diabetes. Neither pioglitazone nor glipizide therapy significantly altered LpPLA2 or VCAM-1 concentrations. While pioglitazone therapy reduced (P<0.05) eselectin concentrations, glipizide therapy reduced (P<0.03) ICAM-1 concentrations.


CONCLUSIONS
Type 2 diabetes is associated with elevated concentrations of the novel vascular risk marker LpPLA2 and inflammatory risk markers e-selectin and VCAM-1. Neither pioglitazone nor glipizide significantly altered LpPLA2, VCAM-1, or highly sensitive C-reactive protein levels after 12 weeks of therapy. In study subjects with type 2 diabetes, e-selectin concentrations declined significantly with pioglitazone therapy, whereas ICAM-1 concentrations decreased significantly with glipizide therapy.
Basu
Ananda
A
Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Jensen
Michael D
MD
McCann
Frances
F
Nandy
Debashis
D
Mukhopadhyay
Debabrata
D
McConnell
Joseph P
JP
Rizza
Robert A
RA
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D019040:E-Selectin / Q000097:blood; D005260:Female; D005913:Glipizide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D054467:Phospholipases A2; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D001786:Blood Glucose; D019040:E-Selectin; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000077205:Pioglitazone; D005913:Glipizide