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Pioglitazone Reduces Atherogenic Index of Plasma in Patients with Type 2 Diabetes

¹ Eli Lilly and Company, Indianapolis, IN. ² Takeda Pharmaceuticals of North America, Lincolnshire, IL.

^aAddress correspondence to this author at: Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285. Fax 317-277-5458; e-mail tan_meng{at}lilly.com.

Background: Insulin resistance is often associated with increased triglyceride (TG) and decreased HDL-cholesterol (HDL-C) concentrations and increased small LDL particles. The Atherogenic Index of Plasma (AIP), defined as log(TG/HDL-C), has recently been proposed as a marker of plasma atherogenicity because it is increased in people at higher risk for coronary heart disease and is inversely correlated with LDL particle size. We studied the effect of pioglitazone, a thiazolidinedione that reduces insulin resistance, on the AIP of patients with type 2 diabetes.

Methods: The data for the analysis of AIP in this report were obtained from four randomized, double-blind, multicenter, parallel-group, placebo-controlled clinical trials. Pioglitazone was used as monotherapy in one study and in combination therapy in three studies. Fasting glucose, insulin, HDL-C, and TGs plus glycohemoglobin (HbA_1C) were measured at baseline and various points during each study.

Results: Patients in this study population with type 2 diabetes had high AIP values at baseline. Pioglitazone treatment significantly decreased AIP from baseline in each of the study groups. Pioglitazone treatment groups had a significantly lower AIP compared with their respective placebo controls. Finally, AIP was inversely and significantly correlated with measures of insulin sensitivity, such as the homeostasis model assessment and quantitative insulin sensitivity check index. In contrast, AIP was not significantly correlated with HbA_1C.

Conclusions: Pioglitazone reduced AIP when used as monotherapy or in combination therapy with sulfonylurea, metformin, or insulin. AIP was inversely correlated with measures of insulin sensitivity.

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