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Hiroyuki Konya,1 Yuzo Yano,1 Satoshi Matsutani,1 Taku Tsunoda,2 Takashi Ikawa,2 Yoshiki Kusunoki,2 Toshihiro Matsuo,2 Masayuki Miuchi,2 Tomoyuki Katsuno,3 Tomoya Hamaguchi,4 Jun-ichiro Miyagawa,2 Mitsuyoshi Namba21Department of Internal Medicine, Ashiya Municipal Hospital, Ashiya, 2Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, 3Division of Innovative Diabetes Treatment, Hyogo College of Medicine, Nishinomiya, 4Division of Diabetes, Department of Internal Medicine, Itami City Hospital, Itami, Hyogo, JapanAbstract: Saxagliptin is a selective and potent dipeptidyl peptidase (DPP)-4 inhibitor, approved as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus (T2DM) in the USA on July 2009, and had been launched globally in over 86 countries by September 2013. In patients with T2DM, once-daily administration of saxagliptin before breakfast achieves sustained inhibition of plasma DPP-4 activity and reduction of postprandial hyperglycemia, including after dinner, associated with an increase in plasma glucagon-like peptide-1 levels. This paper reviews the safety and efficacy of saxagliptin in Japanese patients with T2DM. The clinical development study in Japan supported its usefulness for the disease. Saxagliptin 1, 2.5, and 5 mg led to significant improvements in glycated hemoglobin (HbA1c), and was generally well tolerated. Treatment with saxagliptin 5 mg induced a sustained reduction in HbA1c over 52 weeks. Long-term combination therapy with saxagliptin and other oral hypoglycemic agents also provided sustained glycemic control and was well tolerated for up to 52 weeks. Saxagliptin as add-on to sulfonylureas or glinides has a tendency to increase hypoglycemia, but not with other oral antidiabetic agents, such as α-glucosidase inhibitors, metformin, or thiazolidinediones. The results of clinical trials have confirmed the long-term efficacy and safety of saxagliptin monotherapy as well as its use as add-on combination therapy, and support its usefulness as a therapeutic agent for T2DM. Saxagliptin has less concern for hypoglycemia and weight gain, which often becomes problematic in routine care of T2DM. Meta-analysis of clinical trials in the USA showed no evidence of increased risk of cardiovascular events associated with saxagliptin, suggesting the superior of saxagliptin in terms of safety. Recently, investigators in the SAVOR-TIMI (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction) 53 study suggested that DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events, although the rate of hospitalization for heart failure was increased. Although saxagliptin improves glycemic control, other approaches are necessary to reduce cardiovascular risk in patients with diabetes. Saxagliptin is applicable for various pathological conditions, and is considered to be clinically significant as a new therapeutic option for Japanese patients with T2DM.Keywords: dipeptidyl peptidase-4, incretin hormones, saxagliptin, type 2 diabetes mellitus, Japan, efficacy, safety, patient acceptability

Hiroyuki Konya,1 Tomoyuki Katsuno,2 Taku Tsunoda,1 Yuzo Yano,1 Mai Kamitani,1 Masayuki Miuchi,2 Tomoya Hamaguchi,3 Jun-Ichiro Miyagawa,2 Mitsuyoshi Namba2 1Department of Internal Medicine, Ashiya Municipal Hospital, Ashiya, Hyogo, Japan; 2Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; 3Division of Innovative Diabetes Treatment, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan Abstract: Patients with diabetes mellitus are at increased risk from cardiovascular-related morbidity and mortality as compared with healthy individuals. An association between the postprandial metabolic state and atherogenesis has been observed in patients with diabetes mellitus. In the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM), treatment with an α-glucosidase inhibitor (α-GI) in patients with impaired glucose tolerance not only reduced the rate of conversion from impaired glucose tolerance to type 2 diabetes mellitus (T2DM), but was also associated with a reduction in the risk of cardiovascular events. These results suggested the importance of treating postprandial hyperglycemia in the early stages of T2DM. Glinides are rapid and short-acting insulin secretagogues that bind to the sulfonylurea receptors on pancreatic β-cells to facilitate rapid insulin secretion, restore postprandial early insulin secretion, and reduce the postprandial glucose spike. Moreover, α-GIs reduce postprandial hyperglycemia and insulin secretion by delaying the digestion of carbohydrates and polysaccharides in the small intestine. Then, both glinides and α-GI have beneficial effects for treating patients with T2DM and impaired glucose tolerance. Considering the ameliorating effects of these drugs on postprandial metabolic disorders, combinations of glinides and α-GI might constitute a promising therapeutic strategy for managing patients with T2DM, and also appear to be suitable for Japanese people, who consume more carbohydrates, such as polished rice, than Caucasians. It has recently been reported that combined use of mitiglinide and voglibose reduces postprandial insulin secretion and blunts diurnal glycemic changes in T2DM patients. This therapy can thus be regarded as being suitable for achieving strict postprandial glycemic control. In this report, we outline the effects of this combination therapy on postprandial plasma glucose and assess its safety. Keywords: mitiglinide, voglibose, combination therapy, type 2 diabetes mellitus, postprandial hyperglycemia

Gamma-ray transition edge sensors (TESs) are intensively studied not only to measure isotopic composition of nuclear materials but to monitor transuranic radionuclides inside the human body. We have recently proposed a thick-trilayer membrane as an alternative to silicon-nitride (Si x N y ) single-layer ones. It consists of silicon dioxide (SiO 2 ), Si x N y , and SiO 2 layers. Their total thickness is 6.9 μ m and exhibits almost the same thermal conductance as conventional Si x N y ones with 1- μ m thickness. The thick-trilayer membrane is expected to have better mechanical strength against implementing heavy-bulk absorbers. In this paper, the gamma-ray TES with the thick-trilayer membrane is used to carry out the spectroscopy for the nuclear radiation source. Neptunium-237 and its decay product Protactinium-233 emit 86.5 and 86.6-keV lines, respectively, and they are clearly resolved by four pixels with the full-width-half-maximum (FWHM) resolution of ( 43.7 ± 0.9 ) eV. Furthermore, their intensity ratio agrees with the radioactive equilibrium between the two nuclides. Our experimental results predict that a vast array of pixel formats will reduce the statistical uncertainty in less measuring time. [ABSTRACT FROM AUTHOR]

In regards to servo-writing with perpendicular recording, we investigated servo-write quality and servo performance, and found that the premagnetization conditions, the magnetic-flux flow mechanism, and head structure strongly affect the servo-write quality. In response to these findings, we clarified that the flux flows through the writer to the reader are one of the root causes of servo-signal deterioration. In addition, we found that the flux amount is related to the magnetization switching ratio (MSR)--a one sided magnetization pole per writer-pole area. On the other hand, the reader can absorb flux even if it is far from the flux source. This means that not only the reader element but also the adjacent structure can absorb flux from the flux source. Index Terms--Magnetic flux, NRRO, perpendicular recording, RRO, self-servo-write, servo signal quality, servo-track-write.