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Shosaku Nomura,1 Takehito Taniura,2 Akira Shouzu,3 Seitaro Omoto,4 Masahiko Suzuki,5 Yoshinori Okuda,6 Tomoki Ito1 1First Department of Internal Medicine, Kansai Medical University, Hirakata, 2Division of Internal Medicine, Daiwa Hospital, Suita, 3Division of Internal Medicine, Saiseikai Izuo Hospital, Osaka, 4Division of Internal Medicine, Korigaoka Yukeikai Hospital, Hirakata, 5Division of Internal Medicine, Katano Hospital, Katano, 6Division of Internal Medicine, Meisei Memorial Hospital, Osaka, Japan Background: The aim was to evaluate the significance of arteriosclerosis obliterans-related biomarkers in patients with type 2 diabetes mellitus (T2DM), and to compare the effects of sarpogrelate, eicosapentaenoic acid (EPA) and pitavastatin on these markers. Patients and methods: Seventy-two arteriosclerosis obliterans patients with T2DM were classified into two groups, pitavastatin with either sarpogrelate (PS) or EPA (PE). We observed no differences in all biomarkers between the PS and PE groups before treatments. Results: The levels of body mass index, hemoglobin A1c, soluble E-selectin, soluble vascular cell adhesion molecule 1, plasminogen activator inhibitor-1 and platelet-derived microparticle in the PE group decreased significantly after treatment. The ankle branchial pressure index and adiponectin levels significantly increased in the PE group after treatment compared with the PS group. Conclusion: These results suggest that combination therapy using pitavastatin and EPA possesses an antiatherosclerotic effect and may be beneficial for prevention of vascular complications in patients with T2DM. Keywords: T2DM, pitavastatin, sarpogrelate, eicosapentaenoic acid, EPA, adiponectin, platelet-derived microparticle, PDMP

Yoshinori Okuda,1 Seitaro Omoto,2 Takehito Taniura,3 Akira Shouzu,4 Shosaku Nomura,51Division of Internal Medicine, Meisei Memorial Hospital, 2Division of Internal Medicine, Kohrigaoka Yukeikai Hospital, 3Division of Internal Medicine, Daiwa Hospital, 4Division of Internal Medicine, Saiseikai Izuo Hospital, 5First Department of Internal Medicine, Kansai Medical University, Osaka, Japan Background: Cardiovascular disease (CVD) is the main cause of death among hemodialysis (HD) patients. The effects of the dipeptidyl peptidase-4 inhibitor teneligliptin on CVD-related biomarkers in patients with type 2 diabetes mellitus (T2DM) receiving HD treatment are poorly understood. To determine whether teneligliptin has anti-CVD properties, we assessed its effects on soluble P-selectin (sP-selectin), platelet-derived microparticles (PDMPs), plasminogen activator inhibitor 1 (PAI-1), soluble E-selectin (sE-selectin), soluble vascular adhesion molecule 1 (sVCAM-1), and adiponectin plasma levels in HD and non-HD patients with T2DM. Methods: Patients with T2DM eligible for teneligliptin monotherapy or combination therapy (eg, teneligliptin plus a sulfonylurea) were administered teneligliptin (20 mg/d) once daily for 6 months. Plasma levels of sP-selectin, PDMPs, PAI-1, sE-selectin, sVCAM-1, and adiponectin were measured by enzyme-linked immunosorbent assay at baseline and after 3 months and 6 months of treatment. Results: Teneligliptin therapy significantly reduced plasma levels of sP-selectin, PDMPs, and PAI-1 compared with baseline levels, while significantly increasing adiponectin levels. sE-selectin and sVCAM-1 levels were significantly decreased only at 6 months. The reduction in sP-selectin, PDMPs, and PAI-1 was more significant in HD patients than in non-HD patients. However, the improvement in adiponectin levels was unchanged with HD treatment. Conclusion: By modulating PDMPs or PAI-1, teneligliptin shows an antiatherothrombotic effect that may be beneficial in the primary prevention of CVD in patients with T2DM on HD.Keywords: type 2 diabetes mellitus, teneligliptin, hemodialysis, PDMP, PAI-1&nbsp

Seitaro Omoto,1 Takehito Taniura,2 Tohru Nishizawa,3 Takeshi Tamaki,3 Akira Shouzu,4 Shosaku Nomura3 1Division of Internal Medicine, Korigaoka Yukeikai Hospital, 2Division of Internal Medicine, Daiwa Hospital, 3First Department of Internal Medicine, Kansai Medical University, 4Division of Internal Medicine, Saiseikai Izuo Hospital, Osaka, Japan Background: Advanced glycation end products, selectins, and adiponectin play important roles in the development of atherosclerosis in individuals with diabetes. Sitagliptin has been shown to reduce the concentration of glycated hemoglobin in diabetic patients. However, its effects on soluble receptor for advanced glycation end products (sRAGEs), selectins, and adiponectin in these patients are poorly understood. This study was conducted to assess the effects of sitagliptin on the circulating levels of sRAGEs, monocyte chemoattractant protein-1 (MCP-1), selectins, and adiponectin in patients with type 2 diabetes. Methods: Diabetic patients eligible for sitagliptin monotherapy or combination therapy (eg, sitagliptin plus a sulfonylurea) were administered sitagliptin (50 mg/day) for 6 months. Levels of soluble P-selectin (sP-selectin), soluble E-selectin (sE-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), MCP-1, sRAGEs, and adiponectin were measured by ELISA at baseline and after 3 and 6 months of treatment. Results: At baseline, the levels of MCP-1, sP-selectin, sE-selectin, and sVCAM-1 were higher and the level of adiponectin was lower in diabetic patients than in nondiabetic patients. Sitagliptin therapy for 3 and 6 months significantly reduced plasma levels of sP-selectin, sE-selectin, sVCAM-1, and MCP-1 relative to baseline, while significantly increasing adiponectin levels. sRAGEs did not exhibit a statistical significance, although there was an increasing tendency. Furthermore, the reductions in sP-selectin, sE-selectin, sVCAM-1, and MCP-1 during sitagliptin therapy were significantly greater in responders, defined as patients with a significant increase in adiponectin levels, than in nonresponders. In contrast, responders showed a significant increase in the plasma concentration of sRAGEs. Conclusion: Sitagliptin shows an adiponectin-dependent anti-atherothrombotic effect, which may be beneficial for primary prevention of atherothrombosis, in patients with type 2 diabetes. Keywords: type 2 diabetes mellitus, sitagliptin, sRAGE, selectins, sVCAM-1, adiponectin