ABSTRACT
The effects of troglitazone 400 or 600 mg/d on the glycemic control, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) subclass concentrations and plasminogen-activator inhibitor 1 (PAI-1) levels were assessed in patients with type 2 diabetes that had not been controlled with dietary treatment. This was a multicenter, open-label, parallel-groups study. It included a run-in 4-week diet period and a 24-week randomized treatment. Fifty one patients received 400 mg/d and 55 patients 600 mg. The mean HbA(1c) concentration at the end of the study was similar for both doses. Troglitazone, regardless of dose, significantly improved insulin sensitivity assessed by the homeostasis model (HOMA). PAI-1 levels were significantly decreased in both groups by 13%. Higher HDL cholesterol concentrations and lower triglycerides levels were observed at the end of treatment. Triglyceride contents were reduced only in the lighter VLDL1. The change in HDL cholesterol concentration resulted from a combination of increased HDL3 cholesterol and lower HDL2 cholesterol levels. No differences were found in the effects of both treatment groups on the evaluated parameters. Our data provide new information about the actions of the drug on the lipid profile. Troglitazone reduces triglyceride levels by lowering the triglycerides content of the VLDL1 particles and increases HDL cholesterol concentrations by increasing HDL3 cholesterol levels.
Subject(s)
Blood Glucose/analysis , Chromans/administration & dosage , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin Resistance/physiology , Lipoproteins, HDL/blood , Lipoproteins, VLDL/blood , Thiazoles/administration & dosage , Thiazolidinediones , Aged , Chromans/adverse effects , Chromans/therapeutic use , Dose-Response Relationship, Drug , Fatty Acids, Nonesterified/blood , Female , Fibrinogen/metabolism , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Insulin/metabolism , Insulin Secretion , Lipoproteins/blood , Male , Middle Aged , Plasminogen Activator Inhibitor 1/blood , Thiazoles/adverse effects , Thiazoles/therapeutic use , TroglitazoneABSTRACT
Objetivo. Evaluar la respuesta a bezafibrato en la dieta de sujetos con hipertensión arterial, hiperinsulinemia, hiperlipidemia mixta e hiperfibrinogenemia. Métodos. Se usó un diseño comparativo, doble ciego de placebo (N = 13) ó 400 mg/día de bezafibrato (N = 15) añadidos a una dieta hipolipémica pobre en azúcares refinados durante 90 días de tratamiento. Al inicio y al final del tratamiento se midieron fibrinógeno, lípidos, insulina y péotido C y se hizo una curva de tolerancia a la glucosa. Resultados. Los grupos fueron similares en edad, presión arterial e IMC. Al final de tratamiento hubo disminución de fibrinógeno, colesterol, triglicéridos y LDL-C en ambos grupos, pero sólo en el grupo de bezafibrato hubo: a) una disminución significativa de triglicéridos (64 mg/dL, p 0.01); y b) cambios marginales en fibrinógeno (disminuyó 35 mg/dL, p = 0.09), colesterol (disminuyó 26 mg/dL, p= 0.10) y en la relación glucosa/insulina (aumentó de 4.4 a 5.2, p= 0.09). El bezafibrato disminuyó ligeramente los niveles de insulina pero no afectó al péptido C. La correlación de los cambios de nivel de fibrinógeno versus la insulina de 60 min de la curva de tolerancia fue mayor en el grupo de bezafibrato (r = 0.61) que en el de placebo (r = 0.23). Conclusiones. En pacientes resistentes a insulina y con riesgo cardiovascular elevado, el bezafibrato y el placebo añadidos a una dieta hipolipémica disminuyeron el fibrinógeno plasmático. El bezafibrato bajó significativamente los niveles de triglicéridos en estos pacientes
