Pioglitazone-Mediated Changes in Lipoprotein Particle Composition Are Predicted by Changes in Adiponectin Level in Type 2 Diabetes

Abstract

In animal and observational studies, adiponectin is associated with lipoprotein risk factors for cardiovascular disease. We analyzed data from a randomized clinical trial to evaluate the relationship between changes in adiponectin to changes in lipoprotein risk factors after an intervention that alters adiponectin levels. Adiponectin levels were measured at baseline and follow-up, as were lipoprotein risk factors for cardiovascular disease, at academic medical centers and ambulatory care centers. Participants included 361 men and women with type 2 diabetes. Intervention included randomization to treatment with glimepiride or pioglitazone for 72 wk. The relationship of treatment-related differences in adiponectin level to treatment-related differences in lipoprotein cardiovascular risk factors at 72 wk was evaluated. Pioglitazone led to an increase in adiponectin compared with glimepiride. Compared with baseline, pioglitazone treatment at 72 wk led to an increase in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle size and a decrease in very-low-density lipoprotein (VLDL) particle size and LDL particle number. Glimepiride treatment more modestly decreased LDL particle number and increased LDL particle size. At 72 wk, there were significant treatment group differences for HDL, LDL, and VLDL particle size, and triglyceride and HDL cholesterol level. The increase in adiponectin predicted treatment-related improvement for triglyceride and HDL cholesterol level and LDL and HDL particle size. Increased adiponectin contributed to treatment-related benefit in lipoprotein cardiovascular disease risk factors in obese diabetic subjects treated with pioglitazone. These results provide support for a model that mechanistically links changes in adiponectin level to changes in lipoprotein composition in humans.