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Plasma Phospholipid Transfer Protein Activity Is Decreased in Type 2 Diabetes During Treatment With Atorvastatin

A Role for Apolipoprotein E?

¹ Department of Internal Medicine, Vascular and Metabolic Diseases, Erasmus Medical Center, Rotterdam, the Netherlands
² Department of Cell Biology and Genetics, Erasmus Medical Center, Rotterdam, the Netherlands
³ Department of Endocrinology and Metabolism, University Medical Center Groningen, Groningen, the Netherlands
⁴ Advanced Medical Technology and Development, BML, Saitama, Japan
⁵ Departments of General Internal Medicine, Endocrinology and Metabolism, Leiden University Medical Center, Leiden, the Netherlands

Address correspondence and reprint requests to G.M. Dallinga-Thie, Department of Internal Medicine, Vascular and Metabolic Diseases, Bd 277, Erasmus Medical Center, Dr Molewaterplein 40, 3015GD Rotterdam, PO Box 2040, 3000 CA, Rotterdam, Netherlands. E-mail: g.dallinga{at}erasmusmc.nl

Abbreviations: apo, apolipoprotein; DALI, Diabetes Atorvastatin Lipid Intervention; PLTP, phospholipid transfer protein

Plasma phospholipid transfer protein (PLTP) plays an important role in lipoprotein metabolism. PLTP activity is elevated in patients with diabetes, a condition with strongly elevated risk for coronary heart disease. The aim of this study was to test the hypothesis that statins reduce PLTP activity and to examine the potential role of apolipoprotein E (apoE). PLTP activity and apoE were measured in patients with type 2 diabetes from the DALI (Diabetes Atorvastatin Lipid Intervention) Study, a 30-week randomized double-blind placebo-controlled trial with atorvastatin (10 and 80 mg daily). At baseline, PLTP activity was positively correlated with waist circumference, HbA_1c, glucose, and apoE (all P < 0.05). Atorvastatin treatment resulted in decreased PLTP activity (10 mg atorvastatin: –8.3%, P < 0.05; 80 mg atorvastatin: –12.1%, P < 0.002). Plasma apoE decreased by 28 and 36%, respectively (P < 0.001). The decrease in apoE was strongly related to the decrease in PLTP activity (r = 0.565, P < 0.001). The change in apoE remained the sole determinant of the change in PLTP activity in a multivariate model. The activity of PLTP in type 2 diabetes is decreased by atorvastatin. The association between the decrease in PLTP activity and apoE during statin treatment supports the hypothesis that apoE may prevent PLTP inactivation.

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