Hirokazu Kakuda

The effect of anagliptin treatment on glucose metabolism and lipid metabolism, and oxidative stress in fasting and postprandial states using a test meal in Japanese men with type 2 diabetes

Keywords Anagliptin Test meal Adiponectin Remnant Renal function 8-OHdGIt has been generally recognized that postprandial hyper-glycemia and hyperlipidemia are highly related to thedevelopment of atherosclerosis [1, 2]. Hyperglycemia isknown to damage vascular endothelial cells, increase oxi-dative stress, promote the expression of adhesion moleculeand inhibit nitric oxide (NO) production [3]. Remnantlipoprotein, an important component of postprandialhyperlipidemia, promotes foam cell formation of macro-phages and proliferation of smooth muscle cells [4].Dipeptidyl peptidase 4 (DPP-4) inhibitors have attractedattention as a new class of anti-diabetic agents for thetreatment of type 2 diabetes [5]. Anagliptin, a member ofthe medication class of DPP-4 inhibitors, has been recentlyavailable in the market in Japan. Animal studies suggestthat anagliptin treatment is associated with improvement ofglucose tolerance either by amelioration of insulin resis-tance or enhancing insulin secretion [6] and the decrease inthe development of atherosclerosis [7]. However, to ourknowledge, there has been no clinical study. In this back-ground, we investigated the effect of anagliptin treatmenton glucose and lipoprotein metabolism in fasting andpostprandial state using a test meal (JANEF E460F18 ,Q.P. Co., Tokyo, Japan).Ten Japanese men with type 2 diabetes (age66.3 ±9.5 years; body mass index (BMI) 26.6 2.2 kg/m

Short-Term Effect of Pitavastatin Treatment on Glucose and Lipid Metabolism and Oxidative Stress in Fasting and Postprandial State Using a Test Meal in Japanese Men

Introduction. The objective of this study was to clarify how pitavastatin affects glucose and lipid metabolism, renal function, and oxidative stress. Methods. Ten Japanese men (average age of 33.9 years) were orally administered 2 mg of pitavastatin for 4 weeks. Postprandial glucose, lipoprotein metabolism, and oxidative stress markers were evaluated at 0 and 4 weeks of pitavastatin treatment (2 mg once daily) with a test meal consisting of total calories: 460 kcal, carbohydrates: 56.5 g (226 kcal), protein: 18 g (72 kcal), lipids: 18 g (162 kcal), and NaCl: 1.6 g. Metabolic parameters were measured at 0, 60, and 120 minutes after test meal ingestion. Results. After administration of pitavastatin, serum total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, arachidonic acid, insulin, and adjusted urinary excretion of uric acid decreased, whereas creatinine clearance (C Cr) and uric acid clearance (C UA) increased. And postprandial versus fasting urine 8-hydroxydeoxyguanosine remained unchanged, while postprandial versus fasting isoprostane decreased after pitavastatin treatment. Next, we compared postprandial glucose and lipid metabolism after test meal ingestion before and after pitavastatin administration. Incremental areas under the curve significantly decreased for triglycerides (P < 0.05) and remnant-like particle cholesterol (P < 0.01), while those for apolipoprotein E (apoE), glucose, insulin, and high-sensitivity C-reactive protein remained unchanged. Conclusion. Pitavastatin improves postprandial oxidative stress along with hyperlipidemia.

Comparison of atorvastatin, pitavastatin and rosuvastatin for residual cardiovascular risk using non-fasting blood sampling.

Abstract Background: Low-density lipoprotein cholesterol (LDL-C) is a major cardiovascular risk. However, some patients show symptoms of coronary heart disease (CHD) even though their LDL-C is strictly controlled. Therefore, it is important to treat other risk factors. Methods: Some 129 outpatients with dyslipidemia who were treated with either atorvastatin 10 mg/day (ATO), pitavastatin 2 mg/day (PIT), or rosuvastatin 2.5 mg/day (ROS) were enrolled. After informed consent was obtained, these patients were switched to another statin. Lipid profiles and lipoprotein fraction by polyacrylamide gel electrophoresis (PAGE) were compared between before and after 3 months of treatment with non-fasting blood sample. Results: LDL-C did not show any significant changes after switching and was maintained around 2.59 mmol/L in all groups. High-density lipoprotein cholesterol (HDL-C) was significantly increased in group ATO→PIT (1.43→1.54 mmol/L, p = 0.0010) and ROS→PIT (1.46→1.57 mmol/L, p = 0.0004), and was significantly decreased in group PIT→ATO (1.44→1.36 mmol/L, p = 0.0290). Apolipoprotein A-I (Apo A-I) and preheparin lipoprotein lipase (LPL) mass showed similar changes in HDL-C. Changes in HDL-C showed a significant positive correlation with those in Apo A-I and preheparin LPL mass, and a little but significant negative correlation with changes in Lp(a) and intermediate density lipoprotein (IDL) fraction. Conclusions: ATO, PIT, and ROS have comparable effect on LDL-C lowering. Changes in HDL-C were similar to those in Apo A-I and preheparin LPL mass, and PIT was the most effective treatment in increasing HDL-C, Apo A-I, and preheparin LPL mass.

Effects of change in high-density lipoprotein cholesterol by statin switching on glucose metabolism and renal function in hypercholesterolemia

BACKGROUND Recent reports have suggested that high-density lipoprotein (HDL) is metabolically related to glucose metabolism and renal function. Statin administration clinically increases HDL cholesterol (HDL-C). OBJECTIVE To confirm that change in HDL-C by statin switching is associated with glucose metabolism and renal function in hypercholesterolemic patients. METHODS In hypercholesterolemic outpatients (n = 129) who had taken either statin, as atorvastatin, pitavastatin, or rosuvastatin and switched to another statin, the relationship of change in HDL-C to glycated hemoglobin and estimated glomerular filtration rate (eGFR) was assessed. RESULTS Change in HDL-C did not significantly correlate with change in HbA1c, eGFR calculated from creatinine (eGFRcre), and eGFR calculated from cystatin C (eGFRcys). The subjects were then divided into 2 groups by change in HDL-C: no change or decrease in HDL-C (HD group) and increase in HDL-C (HI group). In the HI group, apolipoprotein A-1 (Apo A-1) and eGFRs were significantly increased by statin switching. There were significant differences in changes in HDL-C, Apo A-1, lipoprotein lipase, glycated hemoglobin, and eGFR calculated from creatinine between the groups. In the patients with impaired glucose tolerance or diabetes, change in HbA1c was also significant between the groups. CONCLUSIONS Our data suggest that an increase in HDL-C due to statin switching is associated with improvement in glucose metabolism and renal function.