Comparative study of the effects of ipragliflozin and sitagliptin on multiple metabolic variables in Japanese patients with type 2 diabetes: A multicentre, randomized, prospective, open-label, active-controlled study.

In the present randomized study, we assessed the efficacy of ipragliflozin compared with sitagliptin in 124 Japanese patients with type 2 diabetes. Sodium-glucose co-transporter-2 inhibitor-naïve and incretin-related agent-naïve patients were randomly assigned to receive additional 50 mg ipragliflozin or sitagliptin. The primary endpoint was the proportion of participants with >0.5% decrease in glycated haemoglobin (HbA1c) without body weight gain at 12 weeks. For secondary endpoints, we measured several biomarkers related to metabolic changes. After 12 weeks, 53.9% of participants in the ipragliflozin and 42.9% in the sitagliptin group reached the primary endpoint (P = 0.32). Decreases in homeostatic model assessment of insulin resistance, body fat percentage and skeletal muscle mass index, and increases in free fatty acids, ketone body concentration and HDL cholesterol levels were greater in the ipragliflozin group. Increases in homeostatic model assessment of ß-cell function and decreases in proinsulin-to-insulin ratio were greater in the sitagliptin group. No serious adverse events occurred in either group. In conclusion, ipragliflozin had beneficial effects on fat reduction, insulin resistance and lipid metabolism, while sitagliptin had beneficial effects on ß-cell function.

Establishment of a high sensitivity plasma assay for human pentraxin3 as a marker for unstable angina pectoris.

OBJECTIVE: Plasma pentraxin 3 (PTX3) levels are increased in patients with acute myocardial infarction, yet its involvement in unstable angina pectoris (UAP) remains unclear. To critically evaluate the role of PTX3 in UAP, a sensitive and precise measurement of PTX3 concentration is needed. METHODS AND RESULTS: We established a high sensitive plasma ELISA assay system for the detection of PTX3 using monoclonal antibodies. The lower limit of detection of our ELISA was 0.1 ng/mL, sensitivity far greater than the current commercially available kit. Plasma samples were obtained from 162 consecutive patients treated for hypertension, hyperlipidemia, diabetes mellitus, or cardiovascular disease at a physician's office. PTX3 was not associated with any known coronary risk factors. Additionally, we collected plasma samples from 252 consecutive subjects admitted to a university hospital for coronary artery assessment by coronary angiography. PTX3 was significantly increased in patients in whom coronary intervention was performed. We further analyzed the plasma level of PTX3 in 52 patients with effort angina (EAP) and 16 patients with UAP. Compared with the control group, PTX3 were significantly higher in the UAP group. CONCLUSIONS: The levels of plasma PTX3 were increased in patients with arterial inflammation, especially UAP. This PTX3 detection system will be useful for the prediction of UAP.

Impact of diabetes mellitus on angiographically silent coronary atherosclerosis.

Constrictive remodeling occurs in significant atherosclerotic lesions of the diabetic patient, but the impact of diabetes mellitus (DM) on the angiographically normal coronary artery is still unclear. Morphometric analysis using intravascular ultrasound (IVUS) prior to intervention evaluated 54 sites in 33 DM patients and 106 in 62 non-diabetic patients. Vessel area (VA) and lumen area (LA) were measured at angiographically normal sites in the vessel. Plaque area (PA) was calculated as VA - LA. Percentage plaque area (%PA) was calculated as PA VA. Even in the angiographically normal site, mild coronary atherosclerosis was detected by IVUS in both groups. In the patients with DM, VA and LA were significantly smaller than in the non-diabetic patient (15.5 vs 17.8 mm(2), p<0.01; and 10.1 vs 12.2 mm(2), p<0.01 respectively), whereas % PA was similar (34.5 vs 31.6%). At angiographically normal sites where mild coronary atherosclerosis is detected by IVUS, the coronary artery of diabetic patients is smaller than that of the non-diabetic. These results suggest impaired compensatory enlargement or some other constrictive mechanism has already occurred in the early stages of coronary atherosclerosis in patients with DM.