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Medical nutrition therapy and exercise therapy are the cornerstones of treatment for patients with type 2 diabetes; however, there has not been a nationwide study on the actual dietary intake and physical activity status of patients since the 2000s. We aimed to clarify this in Japanese patients with type 2 diabetes using data from the Japan Diabetes Complication and its Prevention prospective (JDCP) , a nationwide study launched in 2007. A total of 1,992 patients with type 2 diabetes, aged 40-75 years, completed either the Brief-type, self-administered Diet History Questionnaire (1,643 patients) or International Physical Activity Questionnaire (1,834 patients) , and their data were analyzed in this study. Mean daily energy intake for all participants was 1686.8 kcal/day, and the mean proportions of carbohydrate, protein, and fat comprising total energy intake were 60.2, 16.2, and 23.6%, respectively. The patients in this study had similar energy and nutrient intake status to patients in the 1996 Japan Diabetes Complications Study; however, Japanese patients still had higher carbohydrate and lower fat consumption than patients with diabetes in Western countries. Only 10.5 % of the patients had equal to or more than 20 g/day of dietary fiber and 7.5% consumed less than 6 g of salt. Weekly physical activities of male and female patients were 2344.5±2700.9 and 1948.3±2209.3 METs·min/week in women, respectively (p Disclosure C.Horikawa: None. K.Tsuda: None. J.Satoh: None. Y.Hayashino: None. N.Tajima: None. R.Nishimura: Speaker's Bureau; Abbott Diabetes, Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Merck & Co., Inc., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi, Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Terumo Corporation. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. Funding Japan Diabetes Society

Aims/Introduction To explore the factors associated with the glucose‐lowering efficacy of sitagliptin treatment in Japanese patients with type 2 diabetes mellitus. Materials and Methods This was a post‐hoc analysis of pooled data from seven sitagliptin phase II and III clinical studies carried out in Japan. All studies were double‐blind, randomized, placebo‐controlled, parallel‐group and of 12‐week duration. The analysis population consisted of 1,075 type 2 diabetes mellitus patients. In two of the trials, sitagliptin 50 mg and/or 100 mg daily were used as monotherapy; in five others, sitagliptin 50 mg daily was used as add‐on treatment to ongoing pioglitazone, glimepiride, metformin, voglibose or glinides. Efficacy (reduction in hemoglobin A1c [HbA1c]) was evaluated in 12 sets of subgroups defined by demographic, glycemic, pancreatic β‐cell function and insulin resistance parameters. An analysis of covariance model was used to evaluate the interaction between each parameter and efficacy. Results Sitagliptin consistently provided a clinically meaningful reduction in HbA1c relative to placebo across all subgroups. Within subgroups, a greater absolute HbA1c reduction was associated with higher baseline HbA1c, fasting plasma glucose and 2‐h post‐meal glucose. Lower β‐cell function, represented by homeostatic model assessment of β‐cell function and insulinogenic index, was also associated with greater HbA1c reduction. In contrast, age, sex, body mass index, duration of type 2 diabetes mellitus and insulin resistance‐related parameters did not interact with HbA1c changes. Conclusions Sitagliptin treatment was associated with clinically meaningful improvement in glycemic control in all subgroups of Japanese patients with type 2 diabetes mellitus that were evaluated. Higher baseline glycemic status and lower baseline β‐cell function were identified as factors associated with greater HbA1c reduction after sitagliptin treatment., Sitagliptin treatment was associated with clinically meaningful improvement in glycemic control in all subgroups of Japanese patients with type 2 diabetes that were evaluated. Higher baseline glycemic status and lower baseline β‐cell function were identified as factors associated with greater hemoglobin A1c reduction after sitagliptin treatment.

Aim To assess the efficacy and safety of empagliflozin as add‐on to insulin in Japanese patients with type 2 diabetes (T2D). Materials and methods This multicentre, double‐blind, parallel‐group study randomized Japanese patients with T2D insufficiently controlled with insulin (1:1:1) to empagliflozin 10 mg (n=89), empagliflozin 25 mg (n=90) or placebo (n=90) for 52 weeks. The primary endpoint was change from baseline in glycated haemoglobin (HbA1c) at 16 weeks. Results At 16 weeks, empagliflozin 10 mg and 25 mg significantly decreased HbA1c: adjusted mean difference −0.92% (95% confidence interval [CI] −1.11, −0.73) and −1.00% (95% CI −1.18, −0.82; both P

Fibres composed of carbon nanotubes (CNT) can be used to make lightweight materials with high mechanical strength and electrical conductivity. However, the reported properties have been much poorer than those of the individual CNT. To address this discrepancy, it is necessary to elucidate the relationship between the fibres' structure and their properties. Here, we systematically investigated the CNT length and fibre density dependences of the electrical and the mechanical properties of CNT fibres produced by the wet-spinning method. The obtained specific conductivities of the fibres were almost proportional to the effective CNT lengths, whereas such correlations were less apparent for the fracture strengths and Young's moduli.

This study introduces a method to deposit polystyrene latex (PSL) particles on a silicon wafer in a manner that allows their number to be predicted with a high degree of accuracy. A laminar...

Cellulose nanofibers (CNFs) with different degrees of fibrillation are prepared by the mechanical fibrillation of kraft pulp using wet disk milling, and dispersions of the prepared CNFs were subjected to differential centrifugal sedimentation (DCS) in order to estimate the diameter distributions of the CNFs. The low-fibrillated CNFs (fiber diameter (d):10 μm) had a weak reinforcing effect on natural rubber (NR), while the medium-fibrillated CNFs (d: 0.1-10 μm) dramatically improve the initial modulus and decrease the elongation at break. The high-fibrillated CNFs (d:0.1 μm) enhanced the tensile strength even further while maintaining the elongation at break. The reinforcing mechanism of the NR composites reinforced by the CNFs (NR-CNFs) was confirmed by field-emission scanning electron microscopy imaging, dynamic mechanical analysis, and toluene uptake measurements. It was concluded that these characteristic mechanical properties of the NR-CNFs were determined by the morphologies of the CNFs. The branching structure of the medium-fibrillated CNFs affected high improvement of the initial modulus, and the network formed by the high-fibrillated CNFs were involved in enhancement of the tensile strength without compromising viscoelastic properties. Understanding the effect of their diameter distribution can potentially reduce the production cost of CNFs and thus expand their applicability.

Background No case definition of Type 1 diabetes (T1D) for the claims data has been proposed in Japan yet. This study aimed to evaluate the performance of candidate case definitions for T1D using Electronic health care records (EHR) and claims data in a University Hospital in Japan. Methods The EHR and claims data for all the visiting patients in a University Hospital were used. As the candidate case definitions for claims data, we constructed 11 definitions by combinations of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. (ICD 10) code of T1D, the claims code of insulin needles for T1D patients, basal insulin, and syringe pump for continuous subcutaneous insulin infusion (CSII). We constructed a predictive model for T1D patients using disease names, medical practices, and medications as explanatory variables. The predictive model was applied to patients of test group (validation data), and performances of candidate case definitions were evaluated. Results As a result of performance evaluation, the sensitivity of the confirmed disease name of T1D was 32.9 (95% CI: 28.4, 37.2), and positive predictive value (PPV) was 33.3 (95% CI: 38.0, 38.4). By using the case definition of both the confirmed diagnosis of T1D and either of the claims code of the two insulin treatment methods (i.e., syringe pump for CSII and insulin needles), PPV improved to 90.2 (95% CI: 85.2, 94.4). Conclusions We have established a case definition with high PPV, and the case definition can be used for precisely detecting T1D patients from claims data in Japan.

Most risk calculators that predict future cardiovascular disease (CVD) by baseline profiles are originally developed for primary prevention, but some studies applied the calculators to secondary prevention. We compared the impact of baseline profiles on the future CVD risk between patients with diabetes with and without a CVD history. We analyzed a multicenter prospective cohort of 6338 Japanese patients with diabetes aged 40–74 years, including those with (n = 634) and without a CVD history (n = 5704). The future risk of CVD was investigated using the competing risk model, with adjustment for non-cardiovascular mortality. During the median follow-up of 6.9 years, 413 CVD events were observed. The 8-year cumulative incidence rates of CVD were 21.5% and 7.2% in patients with and without a CVD history, respectively. A higher systolic blood pressure and lower high-density lipoprotein cholesterol levels were independently associated with a future CVD risk in patients without a CVD history (both P

Japan Diabetes Complication and Prevention prospective (JDCP) study was conducted to examine the association between glycemic control and oral conditions in a large database of Japanese patients with diabetes. It included a total of 6099 patients with diabetes (range, 40–75 years) who had been treated as outpatients between 2007 and 2009. The mean number of present teeth at baseline was 19.8 and women with type 2 diabetes had fewer teeth than men with type 2 diabetes. Within the previous year, 17% of all patients had lost teeth. At baseline, 32% had experienced gingival swelling, 69% had brushed more than twice a day, 37% had used interdental cleaning aids, and 43% had undergone regular dental checkups. Multiple logistic regression analysis indicated that type 1 patients with HbA1c ≥ 7.0% were at higher risk of having fewer than 20 teeth (odds ratio [OR] 2.38; 95% confidence interval [CI] 1.25–4.78), and type 2 patients with HbA1c ≥ 8.0% also were at high risk of having fewer than 20 teeth (OR 1.16; 95% CI 1.00–1.34), after adjustment for nine possible confounding factors. In conclusion, patients with diabetes were found to be at high risk of tooth loss, and the poorer the glycemic control, the higher the risk of tooth loss in these patients.

Background It is not clear whether resistin, adiponectin and leptin are as closely associated with cardiovascular disease risk in childhood as in adulthood. Methods A survey was performed on elementary school 4 th graders aged 9 to 10 years in Ina-machi, Saitama, Japan to investigate whether resistin, adiponectin and leptin in these children might be associated with cardiovascular risk factors (atherosclerosis index: AI, waist-to-height ratio: W/H ratio, body mass index: BMI), and how the presence of obesity might affect their association. Results A total of 204 boys and 176 girls participated in the survey. Leptin and the leptin-to-adiponectin ratio (L/A ratio) were significantly correlated with the cardiovascular risk factors except AI, and adiponectin was shown to be negatively correlated with all the cardiovascular risk factors examined in the entire study population. While the serum resistin concentration was not found to be significantly different among the boys and girls with or without obesity, the resistin-to-adiponectin ratio (R/A ratio) was found to be significantly different between the obese and non-obese boys but not between the obese and non-obese girls. Among the obese boys, there was a significant correlation between resistin and AI and between the R/A ratio and the cardiovascular risk factors, neither of which was noted among the entire boy population or the non-obese boys. Whereas the R/A ratio was significantly correlated with all the cardiovascular risk factors only in the obese boys. (AI: 0.426, p

AIMS: This study aims to identify associations of non-proliferative diabetic retinopathy (NPDR) in the Japan Diabetes Complication and its Prevention prospective (JDCP) study, a nation-wide study capturing real-world practice for diabetes in Japan. METHODS: We recruited patients with type 1 and type 2 diabetes mellitus aged between 40 and 75 years from 464 hospitals and clinics. Seven thousand and seven hundred patients fulfilled the inclusion criteria, and 5852 patients were included for this specific analysis. Multiple logistic regression models were used to identify associated factors of NPDR. RESULTS: Of the 363 patients with type 1 diabetes, 83 patients (22.8%) had NPDR; there were significant associations of duration of diabetes and high-density lipoprotein cholesterol with the presence of NPDR. Of the 5489 patients with type 2 diabetes, 1515 (27.6%) had NPDR. Female, duration of diabetes, lifetime maximum body weight, treatment types, systolic blood pressure, and the number of oral hypoglycemic agents (OHA) and antihypertensive drug were associated with increased odds of having NPDR. Diastolic BP, body mass index, alcohol intake, and the number of lipid-lowering drugs were associated with lower odds of having NPDR. Statin and fibrate use was associated with lower odds of having NPDR; this association was confirmed in the model adjusting for the propensity score for taking fibrate or statin (odds ratio 0.80, 95% confidence interval 0.70–0.92; p = 0.002). CONCLUSIONS: There was a potential protective association of lipid-lowering medication (statin or fibrate) and statin use and the presence of NPDR in patients with type 2 diabetes in the JDCP study. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13340-018-0357-z) contains supplementary material, which is available to authorized users.

Quantification of the cellular uptake of nanomaterials is crucial for studies of their toxicity and medical applications. However, our knowledge of the behaviors of carbon nanotubes (CNTs) in cells or tissues remains incomplete due to the lack of appropriate methods for quantitative analysis. Here, we present a unique methodology for quantitatively assessing the cellular uptake of CNTs, taking advantage of their absorption of light in the near-infrared region. Measurement of CNT concentration in cell lysates by monitoring absorbance at 750 nm enabled highly accurate quantification of CNTs accumulated within cells. In a comparative study of eight commercially available CNTs with dynamic size ranging from 30 to 400 nm, we obtained the first quantitative evidence that cellular uptake of CNTs by RAW264.7 macrophages depends on their sizes, specifically on the widths of their bundles in dispersion, regardless of type or manufacturer. Specifically, uptake of CNTs increased linearly with dynamic size, and cytotoxicity increased along with uptake.

Executive Summary This document updates the 1999 World Health Organization (WHO) classification of diabetes. It prioritizes clinical care and guides health professionals in choosing appropriate treatments at the time of diabetes diagnosis, and provides practical guidance to clinicians in assigning a type of diabetes to individuals at the time of diagnosis. It is a compromise between clinical and aetiological classification because there remain gaps in knowledge of the aetiology and pathophysiology of diabetes. While acknowledging the progress that is being made towards a more precise categorization of diabetes subtypes, the aim of this document is to recommend a classification that is feasible to implement in different settings throughout the world. The revised classification is presented in Table 1. Unlike the previous classification, this classification does not recognize subtypes of type 1 diabetes and type 2 diabetes and includes new types of diabetes ("hybrid types of diabetes" and "unclassified diabetes").

Aims/Introduction Little information is available regarding the status of insulin resistance (IR) and insulin deficiency (ID), as well as their relationship with obesity in children using the homeostasis model assessment (HOMA) in a population-based setting. Materials and Methods The study included a total of 445 ninth-grade children participating in health check-up programs implemented in Tsunan Town, Niigata, Japan (boys/girls, 252/193 [participation rates: 98.1/95.5%]). HOMA of insulin resistance ≥2.5 was defined as IR, and HOMA of β-cell function

In 169 Japanese patients with type 2 diabetes mellitus with blood glucose levels that were inadequately controlled with diet and exercise therapy alone, or with diet and exercise therapy plus a sulfonylurea (SU) drug, we evaluated the safety and efficacy of global standard dose metformin given up to a maximum daily dose of 2250 mg for 54 weeks. The changes in HbA1c from baseline to the final evaluation visit were -1.32 ± 0.76% for metformin monotherapy and -1.29 ± 0.81% for metformin plus SU, both significantly lower than baseline. The incidences of adverse events and adverse drug reactions were 91.1% (154/169 patients) and 67.5% (114/169 patients), respectively. The most common adverse events were gastrointestinal symptoms, and most of the gastrointestinal symptoms were considered by investigators to be related to metformin treatment. An increased blood lactic acid level was observed in three subjects (1.8%); however, no clinical symptoms were reported, and there was no increase in mean lactic acid concentration throughout the evaluation period. Symptoms of hypoglycemia were reported in 16 patients, all receiving metformin plus SU, but none received metformin monotherapy. There was a decrease in mean body weight. Global standard dose metformin may be useful for maintaining good blood glucose control over the long term in the treatment of type 2 diabetes mellitus in Japanese patients.

Activation of mineralocorticoid receptor (MR) is shown in resistant hypertension including diabetes mellitus. Although protein kinase C (PKC) signaling is involved in the pathogenesis of diabetic complications, an association between PKC and MR is not known. Activation of PKCα and PKCβ by TPA (12-O-Tetradecanoylphorbol 13-acetate) increased MR proteins and its transcriptional activities in HEK293-MR cells. In contrast, a high glucose condition resulted in PKCβ but not PKCα activation, which is associated with elevation of MR protein levels and MR transcriptional activities. Reduction of endogenous PKCβ by siRNA decreased those levels. Interestingly, high glucose did not affect MR mRNA levels, but rather decreased ubiquitination of MR proteins. In db/db mice kidneys, levels of phosphorylated PKCβ2, MR and Sgk-1 proteins were elevated, and the administration of PKC inhibitor reversed these changes compared to db/+ mice. These data suggest that high glucose stimulates PKCβ signaling, which leads to MR stabilization and its transcriptional activities.

The JDCP study is a large-scale, prospective observational study designed to elucidate risk factors for diabetic complications as they become manifest in Japanese type 1 and 2 diabetic patients in the course of their observation and follow-up. Of the 6338 patients enrolled in the study, all patients with type 1 diabetes (n = 394) were examined for baseline clinical characteristics, which were summarized as follows: men, n = 174 (44 %); mean age (men/women), 55.3/56.8 years; duration of diabetes, 11.9/11.1 years; and those with a family history of diabetes, 27.7 %/35.6 %; BMI, 22.4/21.8 kg/m2 (P = 0.048); HbA1c, 7.9/7.7 %; those with HbA1c

This study aims to investigate the prevalence and characteristics of diabetic polyneuropathy (DPN) in type 2 diabetic patients registered in the Japan Diabetes Complication and its Prevention Prospective (JDCP) study. In the JDCP study, 6,338 diabetic patients who had been treated by diabetes specialists were registered in 2007-9. Of these, 5,451 patients with type 2 diabetes (61.4 years-old, duration of diabetes 10. 8 years, BMI 24.5 and HbA1c 7.42%) who could be evaluated for DPN were analyzed by using t-test, chi-square test and logistic regression analysis. The diagnosis of DPN was performed by using simple diagnostic criterion for diabetic polyneuropathy proposed by Diabetic Neuropathy Study Group in Japan. This criterion should meet two or more of the following three items: 1) sensory symptoms (SS) considered to be due to DPN, 2) bilaterally decreased or absent Achilles tendon reflex (ATR) and 3) decreased vibratory perception threshold (VPT) in bilateral medical malleoli. The prevalence of positive SS, bilaterally decreased/absent ATR and symmetric decrease in VPT were 25.8%, 40.9% and 48.1%, respectively. Based on simple diagnostic criterion, DPN was observed in 35.8% of the total. The decrease/absence of bilateral ATR showed high sensitivity (87.2%) and specificity (84.8%) in the diagnosis of DPN. In the group with DPN, we investigated the odds ratio (OR) of covariates for neuropathy and found that the age (OR 1.58, p Disclosure H. Kamiya: Other Relationship; Self; MSD K.K., Ono Pharmaceutical Co., Ltd., Sanofi K.K., AstraZeneca, Astellas Pharma KK, Eli Lilly and Company, Novartis Pharma K.K., Dainippon Sumitomo Pharma Co., Ltd, Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd.. A. Watarai: None. M. Baba: None. R. Nishimura: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Astellas Pharma US, Inc., Eli Lilly and Company, Abbott, Medtronic, MSD K.K., Novo Nordisk A/S, Sanofi, Takeda Development Center Asia, Pte. Ltd., Kissei Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd.. N. Tajima: None. J. Nakamura: Other Relationship; Self; Astellas Pharma US, Inc., AstraZeneca, Ono Pharmaceutical Co., Ltd., MSD K.K., Kyowa Hakko Kirin Co., Ltd., Kowa Pharmaceuticals America, Inc., Sanofi K.K., Taisho Pharmaceutical Co., Ltd., Takeda Development Center Asia, Pte. Ltd., Mitsubishi Tanabe Pharma Corporation, Eli Lilly and Company, Novartis Pharma K.K., Pfizer Inc..

The Japan Diabetes Complication and its Prevention prospective (JDCP) study is a large-scale observational study conducted to investigate the current status of the management of people with diabetes, and to clarify the risk factors for the onset and progression of diabetes complications. The study includes 6338 patients aged 40 to

To investigate the causes of death and how they changed over time in patients with childhood-onset type 1 diabetes who were receiving dialysis.Of the 1384 patients who were diagnosed with type 1 diabetes at18 years of age between 1965 and 1979, 113 who were subsequently confirmed as having received dialysis and having died as of January 1, 2008 were found eligible for the study. The cause of death trends were expressed according to the duration of dialysis.The leading causes of death were end-stage renal disease (ESRD) (36.3%), cardiovascular disease (CVD) (31.9%), and infections (20.3%). Among CVD, cerebral hemorrhage was the most frequent (38.9%) and showed a significant trend for an increase in the duration of dialysis (P=0.01, the Cochran-Armitage trend test). The mortality from ESRD concentrated within 5 years of dialysis and that from CVD increased after 10 years of dialysis, while the mortality from infections peaked during 5 to 10 years from initiation of dialysis.The leading causes of death in dialysis patients with type 1 diabetes were ESRD, CVD, and infections. As the duration of dialysis increased, however, CVD contributed more to mortality. Special attention should be paid to CVD, particularly cerebral hemorrhage, to improve the long-term prognosis of patients.

The safety and efficacy of sitagliptin as add-on therapy to glinides, rapid-acting insulin secretagogues, were evaluated for Japanese patients with type 2 diabetes mellitus. This 52-week study consisted of a 12-week double-blind period, followed by a 40-week open-label period. During the double-blind period, patients were randomized to sitagliptin 50 mg q.d. (S/S group) or placebo (P/S group) as add-on therapy to glinide monotherapy. During the open-label period, all patients in both groups were administered sitagliptin 50 mg q.d. (or 100 mg q.d. after up-titration). During the double-blind period, the overall occurrence of adverse experiences (AE) was similar in both treatment groups. The frequency of reported AE of hypoglycemia in both groups was low and not notably different. The nature of clinical AE during the open-label period for both groups was not notably different from that of clinical AE in the sitagliptin group during the double-blind period. The between-group difference in HbA1c least squares (LS) mean of change from baseline (95 % CI) at Week 12 was −1.1 % (−1.3, −0.8) in favor of sitagliptin (P

Background We investigated the prevalence and trends of underweight and overweight/obesity in a population-based sample of Japanese schoolchildren from 2003 to 2012, defined by body mass index (BMI) and percentage overweight (POW). Methods Subjects comprised fourth and seventh graders from the town of Ina, Japan, from 2003 to 2012. The height and weight of each subject were measured. Children were classified as underweight, normal weight, or overweight/obese using two criteria: BMI cutoff points proposed by the International Obesity Task Force and cutoffs based on POW in Japan. Results Data from 4367 fourth graders and 3724 seventh graders were analyzed. The prevalence of underweight and overweight as defined by POW criteria were lower than those based on BMI criteria. There was a decrease in the prevalence of overweight among fourth-grade boys and girls and seventh-grade girls according to BMI; this decrease was also observed when POW criteria were used for the definition of overweight. Conclusions The prevalence and trends of both underweight and overweight as defined by POW were underestimated among Japanese schoolchildren compared to those determined using BMI. The results of this study also suggest that trends in underweight and overweight/obesity using POW criteria are similar to those based on BMI criteria among schoolchildren in Japan.

The Japan Diabetes Society/Japanese Cancer Association Joint Committee on Diabetes and Cancer published its first report in July 2013 on the epidemiological assessment of the associations of diabetes with cancer risk/prognosis, the common risk factors for diabetes and cancer, and cancer risk associated with diabetes treatment. The Joint Committee continued its work to assess the role of glycemic control in the development of cancer in patients with diabetes. This review shows that high‐quality evidence examining the association between glycemic control and cancer risk is lacking. In 2014, the Japan Diabetes Society (JDS) and the Japanese Cancer Association (JCA) restarted the JDS/JCA Joint Committee on Diabetes and Cancer, which published the second committee report in Japanese [1]. This is the English version of that report. This article has been jointly published in Diabetology International (doi:10.1007/s13340‐016‐0257‐z) and Cancer Science by the Japan Diabetes Society and the Japanese Cancer Association. Members of the JDS/JCA Joint Committee on Diabetes and Cancer. JDS: Mitsuhiko Noda, Kohjiro Ueki, Masato Kasuga, Naoko Tajima, and Ken Ohashi; Editorial collaborators: Atsushi Goto and Hiroshi Noto; JCA: Ryuichi Sakai, Shoichiro Tsugane, Nobuyuki Hamajima, Kazuo Tajima, Kohzoh Imai, and Hitoshi Nakagama.

Summary Background Limited evidence suggests that multifactorial interventions for control of glucose, blood pressure, and lipids reduce macrovascular complications and mortality in patients with type 2 diabetes. However, safe and effective treatment targets for these risk factors have not been determined for such interventions. Methods In this multicentre, open-label, randomised, parallel-group trial, undertaken at 81 clinical sites in Japan, we randomly assigned (1:1) patients with type 2 diabetes aged 45–69 years with hypertension, dyslipidaemia, or both, and an HbA 1c of 6·9% (52·0 mmol/mol) or higher, to receive conventional therapy for glucose, blood pressure, and lipid control (targets: HbA 1c 1c 1c , and history of cardiovascular disease. Neither patients nor investigators were masked to group assignment. The primary outcome was occurrence of any of a composite of myocardial infarction, stroke, revascularisation (coronary artery bypass surgery, percutaneous transluminal coronary angioplasty, carotid endarterectomy, percutaneous transluminal cerebral angioplasty, and carotid artery stenting), and all-cause mortality. The primary analysis was done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00300976. Findings Between June 16, 2006, and March 31, 2009, 2542 eligible patients were randomly assigned to intensive therapy or conventional therapy (1271 in each group) and followed up for a median of 8·5 years (IQR 7·3–9·0). Two patients in the intensive therapy group were found to be ineligible after randomisation and were excluded from the analyses. During the intervention period, mean HbA 1c , systolic blood pressure, diastolic blood pressure, and LDL cholesterol concentrations were significantly lower in the intensive therapy group than in the conventional therapy group (6·8% [51·0 mmol/mol] vs 7·2% [55·2 mmol/mol]; 123 mm Hg vs 129 mm Hg; 71 mm Hg vs 74 mm Hg; and 85 mg/dL vs 104 mg/dL, respectively; all p vs 283 [22%] in the conventional therapy group, p vs 129 [10%], p=0·0001), the frequencies of major adverse events did not differ between groups. Interpretation Our results do not fully support the efficacy of further intensified multifactorial intervention compared with current standard care for the prevention of a composite of coronary events, cerebrovascular events, and all-cause mortality. Nevertheless, our findings suggest a potential benefit of an intensified intervention for the prevention of cerebrovascular events in patients with type 2 diabetes. Funding Ministry of Health, Labour and Welfare of Japan, Asahi Kasei Pharma, Astellas Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Kissei Pharmaceutical, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Novartis Pharma, Novo Nordisk, Ono Pharmaceutical, Pfizer, Sanwa Kagaku Kenkyusho, Shionogi, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, and Takeda.

Background: While triglycerides (TGs) and diabetes increase the risk of cardiovascular disease (CVD), their combined effects have not been quantified. We explored the combined effect of elevated TGs and glucose on CVD in a post hoc analysis of the large-scale Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA) Study. Material and Methods: In the MEGA Study, 8214 patients with mild to moderate hypercholesterolemia were randomly allocated to the diet alone group or diet plus pravastatin group and followed for 5 years. Of those, 7832 patients included in the intention-to-treat analysis were stratified into 4 groups: abnormal fasting glucose (AFG) plus high TGs, high TGs alone, AFG alone, and normal fasting glucose plus normal TGs (reference). Cox proportional hazard models were used to compare the incidence of and mortality from CVD in the 4 groups. Results: Incidence of CVD and coronary heart disease was significantly higher in the groups with AFG alone (hazard ratio [HR], 2.02 and 3.38; P < .01, respectively) and AFG plus high TGs (HR, 2.87 and 3.87; P < .01, respectively) than the reference group. A similar relation was found in models adjusting for high-density lipoprotein cholesterol (HDL-C). Although the incidence of cerebral infarction was significantly higher only in the group with AFG plus high TGs (HR, 2.16; P = .01), it was marginally significantly higher than the reference group after adjustment for HDL-C (HR, 1.86; P = .06). Diet plus pravastatin treatment reduced the risk of cerebral infarction by 66% in the group with AFG plus high TGs ( P = .03). Conclusions: Our findings contribute to the formulation of the hypothesis that patients with hypercholesterolemia having AFG plus high TGs have an increased risk of cerebral infarction. These are compatible with the result from the main study that patients with hypercholesterolemia randomized to diet plus pravastatin had a reduced risk of cerebral infarction.

To better understand patient resistance to initiation of insulin therapy, this study examined the perception gap concerning initiation of insulin therapy between individuals with type 2 diabetes and their physicians by using data from the DAWN Japan study.The DAWN Japan study is a multi-center, questionnaire-based survey, conducted between 2004-2005. Patients recommended to start insulin therapy (n = 148) answered a questionnaire by rating degree of agreement with 16 statements concerning insulin therapy on a 5-point scale (1: strongly disagree to 5: strongly agree). Ratings of 1 and 2 were categorized as 'disagree' with a statement, and 3, 4, and 5 as 'agree'. Their attending physicians (n = 68) selected statements which could be associated with patient's concerns about insulin therapy.Nearly all the patients agreed with the statements 'I don't want to inject myself for the rest of my life' (95%), and 'I don't want to be bothered with doing injections' (90%); fewer than half agreed with 'My friendships may suffer' (46%), and 'I don't understand why insulin is necessary for me' (45%). Estimation by the physicians and the actual perceptions patients reported differed significantly for 13 statements. Physicians seemed to particularly under-estimate the impact associated with social aspects of insulin use (e.g., 'I don't want to be different from others', 55% patients vs 7% physicians). On the contrary, the statement 'Injections are painful' was the only concern over-estimated by the physicians.It was demonstrated that differences in perceptions regarding insulin therapy exist between physicians and patients, particularly in terms of social impacts. The data, obtained in 2004, may not precisely reflect the present situation, but still represents a barrier to insulin therapy widely held by patients and physicians. These results suggest that appropriate understanding of patients' concerns about insulin therapy is important to encourage timely insulin initiation.

A compact aerosol particle mass analyzer (APM) of which the size of the classifier was significantly reduced than that of the first commercial model (Kanomax Model 3600) was developed. Firstly, requirements for desired performance in classifying particle mass were set forth. Secondly, a theoretical framework for the design parameters of an APM that satisfies the requirements was formulated. Thirdly, the design parameters were determined that satisfies the requirements while reducing the instrument size. The requirements include the condition that the classification range covers from 0.001 to 1000 fg (approximately 12 to 1200 nm in size for spherical particles having the density of 1 g/cm3), and the condition that both the classification resolution and particle penetration in this mass range are higher than certain specified values. A prototype having the design parameters determined according to this theoretical framework was constructed, and its performance was evaluated experimentally. The external dime...

The Rho/Rho-kinase signaling pathway has been shown to be involved in the complications of diabetes. In this study, we found that fasudil, a specific Rho-kinase inhibitor, had a beneficial effect on the motor nerve conduction velocity (MNCV), which is delayed in rats with streptozotocin (STZ)-induced diabetes. Cadherin-dependent adherens junctions (AJs) in myelinating Schwann cells, necessary for proper myelin formation and rapid propagation of action potentials, are regulated by Rho/Rho-kinase signaling. These AJ structures are maintained by E-cadherin and catenin complexes such as β-catenin and p120 catenin. To elucidate the mechanism underlying the effect of fasudil on MNCV, we examined alterations in AJ structure in the peripheral nerves of the experimental rats. Our results showed that the activities of Rho and Rho-kinase increased simultaneously in the sciatic nerves of the diabetic rats. Fasudil restored the MNCV by suppressing the up-regulation of the Rho-kinase. In the diabetic state, enhanced Rho and Rho-kinase activity reduced p120 catenin expression and altered the distribution of p120 catenin and E-cadherin, which are normally localized in the paranodal compartment of the nodes of Ranvier and Schmidt-Lanterman incisures where autotypic AJs stabilize myelin structure. Fasudil restored normal p120 catenin expression and the distribution of p120 catenin and E-cadherin in the myelin sheath. In conclusion, reduced expression and altered distribution of the adhesion molecules in the myelin sheath might contribute to the slowing of the MNCV in the diabetic rats. Fasudil, through its effect on the distribution of the adhesion-related molecules, might prevent slowing of the MNCV.

Background: Because most studies about the relationship between eating quickly and overweight/obesity have been cross-sectional, it is necessary to investigate prospectively the influence of eating quickly on anthropometric variables in order to examine the causal relationship. The aim of the present study was to investigate the impact of eating quickly on anthropometric variables among schoolgirls in a prospective cohort study. Methods: We investigated 427 non-overweight/obese schoolgirls from fourth grade (aged 9 or 10 years) in Ina-town, Japan from 2004 to 2006. Physical examinations and a questionnaire survey were conducted in fourth grade and 3 years later (in seventh grade). Height, weight, percent body fat (%BF) and waist circumference (WC) were measured in physical examinations, and information on eating speed was collected in a questionnaire survey. Results: The differences in anthropometric variables (body mass index, %BF, WC and waist-to-height ratio) between fourth and seventh grade were significantly greater in girls who continued to eat quickly from fourth to seventh grade than in those who did not continue to eat quickly during this 3-year period. In contrast, these differences were not statistically significant in girls who ate quickly in fourth grade but not in seventh grade compared with those who did not continue to eat quickly during the 3-year period. Conclusion: Eating quickly was associated with excess gains in anthropometric variables. The present study also suggested that stopping a habit of eating quickly prevents these excess gains in non-overweight/obese girls, which could contribute to the prevention of childhood overweight and obesity.

Aims/Introduction Type 2 diabetes mellitus is a progressive disease that frequently requires patients to use more than one oral antihyperglycemic agent to achieve adequate glycemic control. The present multicenter, randomized study assessed the efficacy and safety of the addition of sitagliptin to ongoing voglibose monotherapy (0.2–0.3 mg three times daily) in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control (glycated hemoglobin ≥6.9% and

In recent years, diabetes has been shown to be associated with cancer risk, and this has led to a joint committee being formed, enlisting experts from the Japan Diabetes Society (JDS) and the Japanese Cancer Association (JCA) to address this issue. Epidemiological data in Japan provides evidence to demonstrate that diabetes is associated with increased risk for cancers, especially colorectal, liver, and pancreatic cancers. The mechanisms through which diabetes is assumed to promote oncogenesis include insulin resistance and associated hyperinsulinemia, hyperglycemia and inflammation. Common risk factors for type 2 diabetes and cancer include aging, male sex, obesity, physical inactivity, inappropriate diet (excessive red/processed meat intake, inadequate vegetable/fruit/dietary fiber intake), excessive alcohol drinking, and smoking. Given that inappropriate diet/exercise, smoking and excessive alcohol drinking are common risk factors for diabetes and cancer, diet/exercise therapy, smoking cessation and alcohol moderation may be associated with decreased risk for cancer in diabetic patients. There is as yet limited evidence as to whether any particular anti-diabetic agents may influence cancer risk.

This multicenter, randomized study assessed the efficacy and safety of the dipeptidyl peptidase 4 inhibitor sitagliptin added to insulin monotherapy in Japanese patients with type 2 diabetes mellitus (T2DM). This study had an initial 16-week, double-blind treatment period in which 266 patients on diet/exercise and insulin monotherapy for ≥12 weeks were randomized (1:1) to sitagliptin 50 mg q.d. (N = 129; mean baseline HbA1c = 8.9 %) or placebo (N = 137; mean baseline HbA1c = 8.9 %). It was followed by a 36-week, open-label treatment period in which all patients received sitagliptin 50 mg q.d., which could have been increased to 100 mg q.d. for patients meeting predefined glycemic criteria. After 16 weeks, treatment with sitagliptin resulted in significant placebo-adjusted mean decreases from baseline in HbA1c, fasting plasma glucose, and 2-h postmeal glucose of −0.9 % (p

Platinum-deposited titanium nitride (Pt/TiN) nanoparticle aggregates with high porosities were successfully prepared via a self-assembly-assisted spray pyrolysis method. The addition of formic acid (HCOOH) had a significant influence on the process, promoting the simultaneous formation of metallic Pt and reduction on the surface of the TiN support material. Complete reduction of the Pt/TiN nanoparticle aggregates improved the catalytic activity. The electrochemical surface area (ECSA) of Pt/TiN with HCOOH (Pt/TiNw/HCOOH) was 87.15 m2/g-Pt, which was higher than that of Pt/TiN without HCOOH (Pt/TiNw/o-HCOOH). The catalytic durability of Pt/TiNw/HCOOH was twice that of Pt/TiNw/o-HCOOH. An effective strategy for obtaining carbon-free catalysts with high activities and durabilities was identified. © 2013 American Institute of Chemical Engineers AIChE J, 59: 2753–2760, 2013

Aims/Introduction To analyze the association between the duration of diabetes and selection of diabetes therapy in a large database of Japanese patients with type 2 diabetes. Materials and Methods We used the data of 5,844 patients with type 2 diabetes to evaluate the association between the duration of diabetes and types of diabetes therapy. The logistic regression model was used to analyze the association between duration of diabetes and selection of diabetes therapy, and restricted cubic spline curves were used to represent the schematic association. Results Overall, clinical characteristics of the patients were women, 39.9%; mean age, 61.4 years; median duration of diabetes, 9 years; mean glycated hemoglobin, 7.4% (57.0 mmol/mol); and mean body mass index, 24.5 kg/m2. Compared with the first quartile of diabetes duration, the multivariable‐adjusted odds of any antidiabetic therapy (oral hypoglycemic agents or insulin) for the second, third and fourth quartiles were 2.17 (95% confidence interval [CI] 1.68–2.80; 3.39, 95% CI 2.53–4.54; 4.99, 95% CI 3.64–6.84), respectively (P for trend

Objective As a part of the Diabetes Attitudes, Wishes and Needs (DAWN) Japan study, a multi-center, questionnaire-based survey conducted between 2004 and 2005, this analysis aimed to (1) explore patients' attitudes and beliefs contributing to their decision to start insulin therapy, and (2) assess the changes in their attitudes and beliefs after actual initiation. Methods Insulin-naive patients with type 2 diabetes who were recommended to start insulin therapy (n = 149) were invited to answer a 21-item questionnaire consisting of five clusters assessing their attitudes and beliefs toward insulin therapy. The questionnaire was administered twice: first upon insulin recommendation, and then 1 month after insulin initiation for those who started and 4 months after for those who did not. Results Of 130 patients included in the analysis, 74 patients (56.9%) started insulin therapy. 'Negative image of injections' and 'Positive image toward insulin therapy' were significantly associated with patient decision to start insulin therapy (odds ratios [95% CI]: 0.49 [0.32-0.76] and 2.58 [1.51-4.42], respectively). After insulin initiation, 'Negative image of injections', 'Positive image toward insulin therapy', 'Feelings of guilt regarding diabetes self-management', and 'Negative image toward insulin therapy' decreased significantly (P

Aims/Introduction The efficacy and safety of sitagliptin, a highly selective dipeptidyl peptidase-4 inhibitor, when added to metformin monotherapy was examined in Japanese patients with type 2 diabetes. Materials and Methods In this 52-week, add-on to metformin study, 149 patients were randomly assigned to receive sitagliptin 50 mg or placebo once daily in a double-blind fashion for 12 weeks. Thereafter, all patients who completed the double-blind period of the study received open-label sitagliptin 50 mg once daily for 40 weeks, with the investigator option of increasing sitagliptin to 100 mg once daily for patients who met predefined glycemic thresholds. Results After 12 weeks of treatment, the mean change from baseline in glycated hemoglobin (HbA1c) significantly decreased with sitagliptin relative to placebo (between-group difference [95% confidence interval] = −0.7% [−0.9 to −0.5] P

BACKGROUND Monitoring secular trends in blood pressure (BP) among children is important in predicting subsequent hypertension and cardiovascular disease. We investigated secular trends in BP using data from population-based annual screenings of Japanese schoolchildren. METHODS The participants were 10 894 children (all fourth graders between 1994 and 2010 and all seventh graders between 1997 and 2010) living in the town of Ina in Saitama Prefecture, Japan. Body height, weight, and BP were measured, after which children were classified as non-overweight, overweight, or obese. Trends in variables relative to calendar year were analyzed using regression models. RESULTS Systolic BP was significantly associated with calendar year among fourth- and seventh-grade boys (-0.350 and -0.434 mm Hg/year, respectively) and fourth- and seventh-grade girls (-0.513 and -0.473 mm Hg/year, respectively) (all P < 0.001), respectively, over time. Systolic BP and calendar year were significantly negatively correlated regardless of physique or sex among all fourth graders, but not among obese seventh-grade girls. In addition, diastolic BP and calendar year did not significantly correlate among seventh-grade overweight or obese boys or obese seventh-grade girls. CONCLUSIONS BP decreased among fourth-grade schoolchildren in Ina during the past 17 years, regardless of sex or physique. However, BP and calendar year did not significantly correlate among obese seventh graders.