Development of hypertension within 2 weeks of initiation of sorafenib for advanced hepatocellular carcinoma is a predictor of efficacy.

Background: Sorafenib is an agent that inhibits vascular endothelial growth factor and is associated with onset or worsening of hypertension in some patients. We conducted a retrospective analysis of whether the development of hypertension during sorafenib treatment of advanced hepatocellular carcinoma could be a predictor of anti-cancer efficacy.

Methods: The study included 38 patients with advanced hepatocellular carcinoma who had received sorafenib for at least 1 month between January 2010 and December 2012.

Efficacy and safety of 10-mg azilsartan compared with 8-mg candesartan cilexetil in Japanese patients with hypertension: a randomized crossover non-inferiority trial.

We investigated whether 10 mg per day of azilsartan, one-half of the normal dosage, would be non-inferior to 8 mg per day of candesartan cilexetil for controlling blood pressure in Japanese patients with hypertension. In this open-label, randomized, crossover trial, 309 hypertensive Japanese adults treated with 8-mg candesartan cilexetil were randomized into two arms and received either 10-mg azilsartan or 8-mg candesartan cilexetil in a crossover manner. The primary efficacy outcome was systolic blood pressure, and the margin of non-inferiority was set to be 2.

Rationale, design, and baseline characteristics of a clinical trial for prevention of atherosclerosis in patients with insulin-treated type 2 diabetes mellitus using DPP-4 inhibitor: the Sitagliptin Preventive study of Intima-media thickness Evaluation (SPIKE).

Background: Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is currently used to achieve glycemic targets in patients with type 2 diabetes mellitus (T2DM). The addition of DPP-4 inhibitors to ongoing insulin therapy is expected to reduce insulin dosage, leading to a reduction in the frequency of hypoglycaemia and/or weight gain. Recent studies have demonstrated potential anti-atherosclerotic effects for DPP-4 inhibitors.

Efficacy of adding once- and thrice-daily voglibose in Japanese type 2 diabetic patients treated with alogliptin.

We investigated the efficacy of once- and thrice-daily voglibose, an alpha-glucosidase inhibitor, as an add-on therapy to alogliptin, a dipeptidyl peptidase-4 inhibitor, on glycemic control in Japanese type 2 diabetic patients. In this 12-week, parallel-group, randomized, open-label, three-arm trial, 151 participants treated with alogliptin were randomly allocated to the following three arms; one was the group to initiate once-daily voglibose, another was to initiate thrice daily voglibose, and the other was the control group. The primary endpoint was the change of hemoglobin A1c levels at the end of the study, which was revealed to be significantly different among groups (p < 0.

Contribution of visceral fat accumulation and adiponectin to the clustering of metabolic abnormalities in a Japanese population.

Aim: The clustering of metabolic abnormalities occurs not only due to abdominal obesity but also other etiologies. We investigated the contribution of visceral fat accumulation and the circulating adiponectin level to the clustering of metabolic abnormalities in a Japanese population.

Methods: We used the data for 1,989 Japanese employees to perform a structural equation modeling analysis.

Sequential introduction and dosage balance of defined transcription factors affect reprogramming efficiency from pancreatic duct cells into insulin-producing cells.

While the exogenous expression of a combination of transcription factors have been shown to induce the conversion of non-β cells into insulin-producing cells, the reprogramming efficiency remains still low. In order to develop an in vitro screening system for an optimized reprogramming protocol, we generated the reporter cell line mPac-MIP-RFP in which the reprogramming efficiency can be quantified with red fluorescent protein expressed under the control of the insulin promoter. Analysis with mPac-MIP-RFP cells sequentially infected with adenoviruses expressing Pdx1, Neurog3, and Mafa revealed that expression of Pdx1 prior to Neurog3 or Mafa augments the reprogramming efficiency.

Aniridia with a heterozygous PAX6 mutation in which the pituitary function was partially impaired.

We herein report the case of a woman with aniridia and with a heterozygous PAX6 mutation. Pax6 is a transcription factor involved in the development of several organs, including the eye, pancreas and pituitary. The patient had been diagnosed with aniridia in childhood and was found to have impaired glucose tolerance with a heterozygous PAX6 mutation 12 years prior to the current admission.

Down-regulation of pancreatic transcription factors and incretin receptors in type 2 diabetes.

Type 2 diabetes is one of the most prevalent and serious metabolic diseases. Under diabetic conditions, chronic hyperglycemia and subsequent induction of oxidative stress deteriorate pancreatic β-cell function, which leads to the aggravation of type 2 diabetes. Although such phenomena are well known as glucose toxicity, its molecular mechanism remains unclear.

Painful diabetic neuropathy in Japanese diabetic patients is common but underrecognized.

Although chronic pain due to diabetic neuropathy, defined as painful diabetic neuropathy (PDN), is a debilitating and distressing complication of diabetes, epidemiological data on PDN has been scarce, especially in Asia. We evaluated the prevalence of Japanese PDN and its impact on their quality of life (QOL) and metnal state. In addition, we examined to which extent physicians are aware of patients' PDN.

Pharyngeal cancer surveillance using narrow band imaging during conventional upper gastrointestinal endoscopy.

Background: Recent studies have suggested that narrow band imaging (NBI) is useful for detecting superficial pharyngeal cancer. Nevertheless, pharyngeal observation is not a routine practice during upper gastrointestinal (GI) endoscopy. Two aims of this study were to evaluate the feasibility of pharyngeal observation during upper GI endoscopy and to determine the prevalence of pharyngeal cancer in asymptomatic high-risk patients.

The utility of ultrasonic tissue characterization of carotid plaque in the prediction of cardiovascular events in diabetic patients.

Objective: The aim of this study was to evaluate whether non-invasive ultrasonic tissue characterization of carotid plaque using gray-scale median (GSM) can be a predictor of future cardiovascular disease (CVD) events in type 2 diabetic patients.

Methods: A total of 287 type 2 diabetic patients with carotid plaque but without CVD were enrolled (male 72%, mean age 65 ± 7 years). We prospectively evaluated the association between GSM, a quantitative parameter of the plaque echogenicity, and CVD.

Prediction of the presence of insulin resistance using general health checkup data in Japanese employees with metabolic risk factors.

Aim: The aim of the current study was to develop a predictive model of insulin resistance using general health checkup data in Japanese employees with one or more metabolic risk factors.

Methods: We used a database of 846 Japanese employees with one or more metabolic risk factors who underwent general health checkup and a 75-g oral glucose tolerance test (OGTT). Logistic regression models were developed to predict existing insulin resistance evaluated using the Matsuda index.

Juxtaglomerular cell tumor that was preoperatively diagnosed using selective renal venous sampling.

We herein report the case of a patient with a juxtaglomerular cell tumor (JCT). Dynamic enhanced computed tomography revealed a small nodule on the surface of the lower pole of the right kidney. Selective renal venous sampling showed an elevated level of plasma renin activity (PRA) in the right lower pole renal vein only.

Rationale, design, and baseline characteristics of a trial for the prevention of diabetic atherosclerosis using a DPP-4 inhibitor: the Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A).

Aim: Alogliptin, an efficacious inhibitor of DPP-4 that improves glycemic control, as well as the pancreatic beta-cell function, is now increasingly used to accomplish glycemic targets in type 2 diabetic patients. Interestingly, recent experimental studies have shown that alogliptin exerts anti-atherosclerotic effects in GLP-1-dependent and -independent manners. The aim of the present ongoing study is to investigate the preventive effects of alogliptin on the progression of atherosclerosis in type 2 diabetic subjects using the carotid intima-media thickness (IMT), an established marker of cardiovascular disease.

A novel function of Onecut1 protein as a negative regulator of MafA gene expression.

The transcription factor MafA is a key regulator of insulin gene expression and maturation of islet β cells. Despite its importance, the regulatory mechanism of MafA gene expression is still unclear. To identify the transcriptional regulators of MafA, we examined various transcription factors, which are potentially involved in β cell differentiation.

Evaluation of a minimally invasive system for measuring glucose area under the curve during oral glucose tolerance tests: usefulness of sweat monitoring for precise measurement.

Aims: We developed a system for measuring glucose area under the curve (AUC) using minimally invasive interstitial fluid extraction technology (MIET). Sweat contamination during interstitial fluid glucose (IG) extraction affects the accuracy of glucose AUC measurement, because this technology uses extracted sodium ion levels as an internal standard. Therefore, we developed a sweat monitoring patch to reduce this effect and investigated its efficacy in volunteers undergoing oral glucose tolerance tests (OGTTs).

Seasonal variation in critical limb ischemia requiring endovascular therapy: an analysis of a multicenter database of Japanese patients with critical limb ischemia undergoing endovascular therapy.

Aim: We investigated whether any seasonal variation is observed in the incidence, severity and prognosis of critical limb ischemia (CLI) requiring endovascular therapy.

Methods: We analyzed a multicenter database of 1,568 consecutive CLI cases undergoing primary endovascular therapy for infrainguinal lesions between July 2004 and June 2011. The monthly incidence was assessed according to the cumulative number of cases in each month, using a simple moving average.

A Case of Hypocalcemia with Severe Vitamin D Deficiency following Treatment for Graves' Disease with Methimazole.

We herein report the case of a 41-year-old Japanese female office worker who developed symptomatic hypocalcemia with severe vitamin D deficiency following treatment for Graves' disease with methimazole. The patient's hypocalcemia was mainly caused by vitamin D deficiency due to unbalanced diets and inadequate exposure to sunlight in addition to the resolution of hyperthyroidism. Vitamin D deficiency is increasing worldwide, and it has been more recently shown to relate to the pathogenesis of Graves' disease.

Predictive impact of adiponectin for detecting dysglycemia in non-fasting Japanese employees with metabolic risk factors.

The screening of dysglycemia in the non-fasting state is a challenging issue in healthcare practice. We investigated whether the additional measurement of circulating adiponectin levels could improve screening performance. We used a database of 1190 Japanese employees with metabolic risk factors, who underwent a 75-g oral glucose tolerance test (OGTT), following non-fasting health check-ups.

Evaluation of hypertriglyceridemia using non-fasting health checkup data in a Japanese population.

Aim: Some employees have difficulty undergoing health checkups in the workplace in a fasting state. However, hypertriglyceridemia is usually diagnosed based on fasting triglyceride (TG) measurements. The current study investigated the performance of non-fasting health checkup data for predicting hypertriglyceridemia in a Japanese population.

Cancer detection by ubiquitin carboxyl-terminal esterase L1 methylation in pancreatobiliary fluids.

Aim: To evaluate the utility of measuring epigenetic alterations in pancreatic and biliary fluids in determining molecular markers for pancreatobiliary cancers.

Methods: DNA was extracted from undiluted pancreatic and biliary fluids. As a surrogate for a genome-wide hypomethylation assay, levels of long interspersed nuclear element-1 (LINE-1) methylation were analyzed using bisulfite pyrosequencing.

Pancreatic beta cell function in lean and obese Japanese with various degrees of glucose tolerance.

The aim of the current study was to investigate whether obese subjects have different insulin secretory capacity compared to lean subjects with the same glucose tolerance in a Japanese population. We included a total of 1749 Japanese employees who underwent 75-g oral glucose tolerance test (OGTT). The study population was divided into deciles of 120-min glucose levels and the indices of insulin secretion and insulin sensitivity in each decile were compared between the subjects with and without obesity (body mass index ≥ 25 kg/m2).

Dipeptidyl peptidase-4 inhibitors are effective in Japanese type 2 diabetic patients with sustained endogenous insulin-secreting capacity, a higher body mass index and insulin resistance.

Aims/introduction: Recently, dipeptidyl peptidase-4 (DPP-4) inhibitors have become available in Japan. It has not yet been clarified what clinical parameters could discriminate DPP-4 inhibitor-effective patients from DPP-4 inhibitor-ineffective patients.

Materials And Methods: We reviewed 33 consecutive patients with type 2 diabetes admitted to Osaka University Hospital for glycemic control.

Effect of sarpogrelate treatment on the prognosis after endovascular therapy for critical limb ischemia.

5-Hydroxytryptamine type 2 antagonists are used to treat symptomatic peripheral arterial disease. However, it remains unknown as to whether the administration of sarpogrelate, a 5-hydroxytryptamine type 2 antagonist, improves the prognosis after endovascular therapy for critical limb ischemia (CLI). We performed a retrospective analysis using a database of 386 Japanese patients undergoing endovascular therapy for CLI.