In individuals with type 2 diabetes, metabolic syndrome, and the combined dyslipidemia, cardiovascular risk is increased by a clustering of risk factors such as abdominal obesity, impaired fasting glucose, increased blood pressure, low HDL-cholesterol (HDL-C), increased triglycerides (TGs), and an increase in small, dense LDL particles. The current increase in the incidence of type 2 diabetes in the population perhaps poses the most urgent cardiovascular risk (1). Although insulin resistance is crucial to the pathogenesis of the disease, the associated atherogenic lipoprotein phenotype considerably enhances the risk. Hence there is an ongoing intense search for a medication capable of modifying the atherogenic lipid profile as well as lowering glucose. Medications of the thiazolidinedione class traditionally used for glycemic control in patients with type 2 diabetes seem to hold promise in this respect. In this issue of Clinical Chemistry , Tan et al. (2) studied the effect of pioglitazone, a thiazolidinedione that reduces insulin resistance, on the atherogenic lipoprotein profile in individuals with type 2 diabetes. Data were obtained from four randomized, placebo-controlled dose–response clinical trials examining the efficacy of therapy with pioglitazone when added to sulfonylurea, metformin, or insulin therapy. To evaluate changes in the lipoprotein profile induced by their therapy, Tan et al. (2) used the atherogenic index of plasma (AIP), calculated as log(TG/HDL-C), with TG and HDL-C expressed in molar concentrations (3). Changes in the AIP of pioglitazone-treated patients were evaluated by a statistical model of single-slope analysis of covariance, and each of the pioglitazone treatments was compared with placebo. All pioglitazone treatment groups had a high AIP at baseline, and pioglitazone treatment significantly decreased the AIP in each study group. Pioglitazone treatment groups had significantly lower AIP than did their respective placebo controls. AIP correlated inversely with insulin sensitivity measures, i.e., the homeostasis model measurement (HOMA-S) and …