Lifestyle behaviour patterns in the prevention of type 2 diabetes mellitus: the Fukushima Health Database 2015-2020.

OBJECTIVES: Lifestyle behaviours associated with the incidence of type 2 diabetes mellitus (T2DM) need further clarification using health insurance data. STUDY DESIGN: This is a cohort study. METHODS: In 2015, 193,246 participants aged 40-74 years attended the specific health checkups and were observed up to 2020 in Fukushima, Japan. Using the principal component analysis, we identified two patterns from ten lifestyle behaviour questions, namely, the "diet-smoking" pattern (including smoking, alcohol drinking, skipping breakfast, eating fast, late dinner, and snacking) and the "physical activity-sleep" pattern (including physical exercise, walking equivalent activity, walking fast, and sufficient sleep). Then, individual pattern scores were calculated; the higher the scores, the healthier the behaviours. RESULTS: The accumulative incidence rate of T2DM was 630.5 in men and 391.9 in women per 100,000 person-years in an average of 4 years of follow-up. Adjusted for the demographic and cardiometabolic factors at the baseline, the hazard ratio (95% confidence interval) of the highest versus lowest quartile scores of the "diet-smoking" pattern for T2DM risk was 0.82 (0.72, 0.92; P for trend = 0.002) in men and 0.87 (0.76, 1·00; P for trend = 0.034) in women; that of the "physical activity-sleep" pattern was 0.92 (0.82, 1·04; P for trend = 0.0996) in men and 0.92 (0.80, 1·06; P for trend = 0.372) in women. The "physical activity-sleep" pattern showed a significant inverse association in non-overweight men. CONCLUSIONS: Lifestyle behaviour associated with a healthy diet and lack of smoking may significantly lower the risk of T2DM in middle-aged Japanese adults.

Prevalence trends of metabolic syndrome in residents of postdisaster Fukushima: a longitudinal analysis of Fukushima Health Database 2012-2019.

OBJECTIVES: The study aimed to evaluate the long-term metabolic risk profiles of Fukushima residents after the Great East Japan Earthquake of March 2011. STUDY DESIGN: This was a cross-sectional and a longitudinal design. METHODS: The Fukushima Health Database (FDB) contains 2,331,319 annual health checkup records of participants aged 40-74 years between 2012 and 2019. We checked the validity of the FDB by comparing the prevalence of metabolic factors with the National Database of Health Insurance Claims and Specific Health Checkups (NDB). We applied a regression analysis to determine the changes and project the trends of metabolic factors over the years. RESULTS: Compared to the NDB, the prevalence of metabolic factors in Fukushima was higher than the country average from 2013 to 2018, and they showed the same trends as those from the FDB. The prevalence of metabolic syndrome (MetS) increased from 18.9% in 2012 to 21.4% in 2019 (an annual increase of 2.74%) in men and from 6.8 to 7.4% (an annual increase of 1.80%) in women in Fukushima. The standardized prevalence of MetS, being overweight, and diabetes is projected to continue increasing, with disparities among subareas being higher in evacuees than in non-evacuees. An annual decrease of 0.38-1.97% in hypertension was mainly observed in women. CONCLUSIONS: The prevalence of metabolic risk is higher in Fukushima as compared to the country average. The increasing metabolic risk in subareas, including the evacuation zone, highlights the need to control MetS in Fukushima residents.

Development of an application tool to support returnees in Fukushima.

To promote radiation protection and health promotion among returning residents (returnees) in coastal areas of Fukushima, eHealth principles were used to develop a new application tool (app) that can record radiation exposure and health status while providing comprehensive support to returnees. Intended users are returnees and health and welfare workers. After assessing their needs, a flowchart and prototype for operational logic were created using commercially available software tools. Professional developers will focus on improving the user interface and ensuring data security. The finished app will be compatible with mobile telephones and tablets. Utility and ease of use are paramount to serve returnees of all ages effectively.

EXTERNAL AND INTERNAL EXPOSURE TO FUKUSHIMA RESIDENTS.

The Great East Japan Earthquake of 11 March 2011, caused the Fukushima Daiichi Nuclear Power Plant Accident, which resulted in the release of a large amount of radioactive materials into the environment, and there is a serious concern about the radiation effects on the health of residents living in the affected areas. The evaluation of exposure dose is fundamental for the estimation of health effects, and whenever possible, the exposure dose should be evaluated by actual measurements as opposed to estimations. Here, the outline of the exposure doses of residents estimated from surveys or obtained by measurements is described. Fukushima Health Management Survey reported the results for 460 408 residents during the first 4 months after the accident; 66.3% received doses <1 mSv, 94.9% received <2 mSv, 99.7% received <5 mSv and the maximum dose was 25 mSv. Thus, it was demonstrated that the results from personal dosemeter measurements were comparable to the estimations. The dose assessment of internal exposure of 184 205 residents conducted by Fukushima Prefecture by using whole body counter showed that 99.986% received <1 mSv, with the maximum dose being 3 mSv. Regarding exposure of the thyroid, there is not enough data for the Fukushima accident, but it is presumed that thyroid doses are much lower than those from Chernobyl. The outline of exposure doses of residents in result of the accident is still being clarified, questions and uncertainties in dose assessment remain and further efforts for more accurate dosimetry are required continuously.

Long-term safety and efficacy of fasiglifam (TAK-875), a G-protein-coupled receptor 40 agonist, as monotherapy and combination therapy in Japanese patients with type 2 diabetes: a 52-week open-label phase III study.

This multicentre, open-label, phase III study investigated the safety and efficacy of the G-protein-coupled receptor 40 agonist fasiglifam. Japanese patients with type 2 diabetes and inadequate glycaemic control despite diet and/or exercise (n = 282), or despite diet and/or exercise plus one oral antidiabetic agent [sulphonylurea (n = 262), rapid-acting insulin secretagogue (n = 124), α-glucosidase inhibitor (n = 141), biguanide (n = 136), thiazolidinedione (n = 139) or dipeptidyl peptidase-4 inhibitor (n = 138)] were randomized to treatment with fasiglifam 25 or 50 mg once daily for 52 weeks. The primary endpoints were safety variables. The overall incidence of treatment-emergent adverse events (TEAEs) was 75.4-85.1% in the 25 mg group and 78.9-89.9% in the 50 mg group; most TEAEs were mild. Hypoglycaemia was negligible with fasiglifam monotherapy and most common with sulphonylurea combination therapy (12.4 and 9.1% for 25 and 50 mg groups, respectively). Abnormal liver-related laboratory values were uncommon. Glycated haemoglobin levels decreased from week 2 in all groups and were maintained to week 52. Although fasiglifam as monotherapy or in combination regimens was well tolerated during long-term treatment, global concerns about liver safety led to termination of its development after study completion.

Emergency Responses and Health Consequences after the Fukushima Accident; Evacuation and Relocation.

The Fukushima accident was a compounding disaster following the strong earthquake and huge tsunami. The direct health effects of radiation were relatively well controlled considering the severity of the accident, not only among emergency workers but also residents. Other serious health issues include deaths during evacuation, collapse of the radiation emergency medical system, increased mortality among displaced elderly people and public healthcare issues in Fukushima residents. The Fukushima mental health and lifestyle survey disclosed that the Fukushima accident caused severe psychological distress in the residents from evacuation zones. In addition to psychiatric and mental health problems, there are lifestyle-related problems such as an increase proportion of those overweight, an increased prevalence of hypertension, diabetes mellitus and dyslipidaemia and changes in health-related behaviours among evacuees; all of which may lead to an increased cardiovascular disease risk in the future. The effects of a major nuclear accident on societies are diverse and enduring. The countermeasures should include disaster management, long-term general public health services, mental and psychological care, behavioural and societal support, in addition to efforts to mitigate the health effects attributable to radiation.

Efficacy and safety of pioglitazone added to alogliptin in Japanese patients with type 2 diabetes mellitus: a multicentre, randomized, double-blind, parallel-group, comparative study.

A phase IV, multicentre, randomized, double-blind, parallel-group, comparative study was conducted in Japanese subjects with type 2 diabetes mellitus (T2DM) who had inadequate glycaemic control, despite treatment with alogliptin in addition to diet and/or exercise therapy. Subjects with glycated haemoglobin (HbA1c) concentrations of 6.9-10.5% were randomized to receive 16 weeks' double-blind treatment with pioglitazone 15 mg, 30 mg once daily or placebo added to alogliptin 25 mg once daily. The primary endpoint was the change in HbA1c from baseline at the end of treatment period (week 16). Both pioglitazone 15 and 30 mg combination therapy resulted in a significantly greater reduction in HbA1c than alogliptin monotherapy [-0.80 and -0.90% vs 0.00% (the least squares mean using analysis of covariance model); p < 0.0001, respectively]. The overall incidence rates of treatment-emergent adverse events were similar among the treatment groups. Pioglitazone/alogliptin combination therapy was effective and generally well tolerated in Japanese subjects with T2DM and is considered to be useful in clinical settings.

Efficacy and safety of fasiglifam (TAK-875), a G protein-coupled receptor 40 agonist, in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise: a randomized, double-blind, placebo-controlled, phase III trial.

AIM: To assess the efficacy and safety of fasiglifam 25 and 50 mg in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise. METHODS: This phase III, double-blind, placebo-controlled, multicentre study included 192 patients randomized to once-daily treatment with fasiglifam 25 mg (n = 63) or 50 mg (n = 62) or placebo (n = 67) for 24 weeks. The primary efficacy endpoint was the change from baseline in glycated haemoglobin (HbA1c) at week 24. RESULTS: At week 24, both fasiglifam groups had significantly reduced HbA1c levels compared with the placebo group (p < 0.0001). The least squares mean change from baseline in HbA1c was 0.16% with placebo, -0.57% with fasiglifam 25 mg and -0.83% with fasiglifam 50 mg. The percentage of patients who achieved an HbA1c target of <6.9% at week 24 was also significantly higher (p < 0.05) for fasiglifam 25 mg (30.2%) and 50 mg (54.8%) compared with placebo (13.8%). Fasiglifam significantly reduced fasting plasma glucose levels at all assessment points, starting from week 2. The incidence and types of treatment-emergent adverse events in each fasiglifam group were similar to those in the placebo group, and hypoglycaemia was reported in 1 patient receiving fasiglifam 50 mg. There were no clinically meaningful changes in body weight in any treatment group. CONCLUSIONS: Fasiglifam significantly improved glycaemic control and was well tolerated, with a low risk of hypoglycaemia in Japanese patients with type 2 diabetes inadequately controlled by diet and exercise; however, in a recent review of data from overall fasiglifam global clinical trials, concerns about liver safety arose and the clinical development of fasiglifam was terminated after this trial was completed.

Macrophage deficiency in osteopetrotic (op/op) mice inhibits activation of satellite cells and prevents hypertrophy in single soleus fibers.

Effects of macrophage on the responses of soleus fiber size to hind limb unloading and reloading were studied in osteopetrotic homozygous (op/op) mice with inactivated mutation of macrophage colony-stimulating factor (M-CSF) gene and in wild-type (+/+) and heterozygous (+/op) mice. The basal levels of mitotically active and quiescent satellite cell (-46 and -39% vs. +/+, and -40 and -30% vs. +/op) and myonuclear number (-29% vs. +/+ and -28% vs. +/op) in fibers of op/op mice were significantly less than controls. Fiber length and sarcomere number in op/op were also less than +/+ (-22%) and +/op (-21%) mice. Similar trend was noted in fiber cross-sectional area (CSA, -15% vs. +/+, P = 0.06, and -14% vs. +/op, P = 0.07). The sizes of myonuclear domain, cytoplasmic volume per myonucleus, were identical in all types of mice. The CSA, length, and the whole number of sarcomeres, myonuclei, and mitotically active and quiescent satellite cells, as well as myonuclear domain, in single muscle fibers were decreased after 10 days of unloading in all types of mice, although all of these parameters in +/+ and +/op mice were increased toward the control values after 10 days of reloading. However, none of these levels in op/op mice were recovered. Data suggest that M-CSF and/or macrophages are important to activate satellite cells, which cause increase of myonuclear number during fiber hypertrophy. However, it is unclear why their responses to general growth and reloading after unloading are different.

Responses of knee extensor muscles to leg press training of various types in human.

Responses of m. vastus lateralis to 8-week resistive training of various types at leg press mashine were investigated in 30 male subjects. Training loads were 25, 65 and 85% of one repetition maximum for low (LI), medium (MI), and high intensity (HI) training groups respectively, while angular velocities of contraction differed considerably between groups. The total work done during training session was identical. The maximum strengths during isokinetic knee extension in LI and HI groups were increased at most angular velocities. In group MI increments were obtained only during concentric contractions. Significant improvement of fatigue resistance and maximum oxygen consumption (V(O2max)) was seen only in group MI and LI, respectively. The training-related increase of cross-sectional area in type II fibers in m. vastus lateralis was in the order of HI > MI > LI group, and that of type I fibers was opposite. The increased myonuclear number was found for HI group. The data suggest that fiber hypertrophy, fatigue resistance and V(O2max) changes were related to the type of training.

A prospective, randomized, double-blind, controlled trial on the efficacy of carbon dioxide insufflation in gastric endoscopic submucosal dissection.

BACKGROUND AND STUDY AIMS: Carbon dioxide (CO2) insufflation is expected to be safe and effective in endoscopic submucosal dissection (ESD) as well as in other endoscopic procedures. The present study aimed to clarify the usefulness and safety of CO2 insufflation in gastric ESD. PATIENTS AND METHODS: A total of 102 consecutive patients were randomly assigned to CO2 insufflation (CO2 group, n = 54) or air insufflation (Air group, n = 48). Abdominal pain and distension were chronologically recorded on a 100-mm visual analog scale (VAS). The volume of residual gas in the digestive tract was measured by computed tomography performed immediately after ESD. RESULTS: Abdominal pain on a 100-mm VAS in the CO2 vs. Air group was 4 vs. 3 immediately after ESD, 4 vs. 4 one hour after the procedure, 3 vs. 3 three hours after the procedure, and 1 vs. 4 the next morning, showing no difference between the groups. In addition, there was no difference in abdominal distension on the 100-mm VAS over the time course of the study. The volume of residual gas in the digestive tract in the CO2 group was significantly smaller than that in the Air group (643 mL vs. 1037 mL, P < 0.001). The dose of sedative drugs did not differ between the groups. Neither the incidences of complications nor clinical courses differed between the groups. CONCLUSIONS: Compared with air insufflation, CO2 insufflation during gastric ESD significantly reduced the volume of residual gas in the digestive tract but not the VAS score of abdominal pain and distension.

Chemerin-ChemR23 signaling in tooth development.

Our long-term goal is to identify and characterize molecular mechanisms regulating tooth development, including those mediating the critical dental epithelial-dental mesenchymal (DE-DM) cell interactions required for normal tooth development. The goal of this study was to investigate Chemerin (Rarres2)/ChemR23(Cmklr1) signaling in DE-DM cell interactions in normal tooth development. Here we present, for the first time, tissue-specific expression patterns of Chemerin and ChemR23 in mouse tooth development. We show that Chemerin is expressed in cultured DE progenitor cells, while ChemR23 is expressed in cultured DM cells. Moreover, we demonstrate that ribosomal protein S6 (rS6) and Akt, downstream targets of Chemerin/ChemR23 signaling, are phosphorylated in response to Chemerin/ChemR23 signaling in vitro and are expressed in mouse tooth development. Together, these results suggest roles for Chemerin/ChemR23-mediated DE-DM cell signaling during tooth morphogenesis.

A pilot study to assess mediastinal emphysema after esophageal endoscopic submucosal dissection with carbon dioxide insufflation.

BACKGROUND AND AIMS: Mediastinal emphysema sometimes develops following esophageal endoscopic submucosal dissection (ESD) without perforation because the esophagus has no serosa. Carbon dioxide (CO2) insufflation during esophageal ESD may reduce the incidence of mediastinal emphysema. The aim of the present study was to compare the incidence and severity of post-ESD mediastinal emphysema in patients receiving CO2 insufflation vs. standard air insufflation during esophageal ESD. PATIENTS AND METHODS: A total of 27 patients who had undergone esophageal ESD with insufflation of CO2 between July 2009 and March 2010 were enrolled in this study (CO2 group). Another 105 patients who had undergone esophageal ESD with air insufflation between March 2004 and May 2009 were included as historical controls (air group). Multi-detector row computed tomography (MDCT) was carried out immediately after ESD. A conventional chest radiograph was taken the next day. Mediastinal emphysema findings on MDCT and radiography were compared between the groups. RESULTS: Mediastinal emphysema detected by chest radiography was 0 % in the CO2 group vs. 6.6 % in the air group (n.s.). Mediastinal emphysema on MDCT was significantly less frequent in the CO2 group compared with the air group (30 % vs. 63 %; P = 0.002). The severity of mediastinal emphysema also tended to be lower in the CO2 group. CONCLUSIONS: Whereas mediastinal emphysema detected by radiography is not so common, MDCT immediately after ESD revealed a certain prevalence of post-ESD mediastinal emphysema. Insufflation of CO2 rather than air during esophageal ESD significantly reduced postprocedural mediastinal emphysema. CO2 can be considered as insufflating gas for esophageal ESD.

Effect of forest bathing on physiological and psychological responses in young Japanese male subjects.

OBJECTIVE: To provide scientific evidence supporting the efficacy of forest bathing as a natural therapy by investigating its physiological benefits using biological indicators in outdoor settings. STUDY DESIGN: Within-group comparisons were used to examine psychological and physiological responses to exposure to real forest and urban environments. METHODS: Young Japanese male adults participated in a 3-day, 2-night field experiment. Physiological responses as well as self-reported psychological responses to forest and urban environmental stimuli were measured in real settings. The results of each indicator were compared against each environmental stimulus. RESULTS: Heart rate variability analysis indicated that the forest environment significantly increased parasympathetic nervous activity and significantly suppressed sympathetic activity of participants compared with the urban environment. Salivary cortisol level and pulse rate decreased markedly in the forest setting compared with the urban setting. In psychological tests, forest bathing significantly increased scores of positive feelings and significantly decreased scores of negative feelings after stimuli compared with the urban stimuli. CONCLUSION: Physiological data from this field experiment provide important scientific evidence on the health benefits of forest bathing. The results support the concept that forest bathing has positive effects on physical and mental health, indicating that it can be effective for health promotion. Despite the small sample size in this study, a very clear tendency towards positive physiological and psychological outcomes in forests was observed.

A day trip to a forest park increases human natural killer activity and the expression of anti-cancer proteins in male subjects.

We previously reported that 2-night/3-day trips to forest parks enhanced human NK activity, the number of NK cells, and intracellular anti-cancer proteins in lymphocytes, and that this increased NK activity lasted for more than 7 days after the trip in both male and female subjects. In the present study, we investigated the effect of a day trip to a forest park on human NK activity in male subjects. Twelve healthy male subjects, aged 35-53 years, were selected after giving informed consent. The subjects experienced a day trip to a forest park in the suburbs of Tokyo. They walked for two hours in the morning and afternoon, respectively, in the forest park on Sunday. Blood and urine were sampled in the morning of the following day and 7 days after the trip, and the NK activity, numbers of NK and T cells, and granulysin, perforin, and granzyme A/B-expressing lymphocytes, the concentration of cortisol in blood samples, and the concentration of adrenaline in urine were measured. Similar measurements were made before the trip on a weekend day as the control. Phytoncide concentrations in the forest were measured. The day trip to the forest park significantly increased NK activity and the numbers of CD16(+) and CD56(+) NK cells, perforin, granulysin, and granzyme A/B-expressing NK cells and significantly decreased CD4(+) T cells, the concentrations of cortisol in the blood and adrenaline in urine. The increased NK activity lasted for 7 days after the trip. Phytoncides, such as isoprene, alpha-pinene, and beta-pinene, were detected in the forest air. These findings indicate that the day trip to the forest park also increased the NK activity, number of NK cells, and levels of intracellular anti-cancer proteins, and that this effect lasted for at least 7 days after the trip. Phytoncides released from trees and decreased stress hormone levels may partially contribute to the increased NK activity.

Cross-cultural comparison of the sleep-disordered breathing prevalence among Americans and Japanese.

The aim of the present study was to compare the prevalence of sleep-disordered breathing among Hispanic and white Americans and Japanese. A 1-night sleep study using a single-channel airflow monitor was performed on 211 Hispanics and 246 Whites from the Minnesota field centre (St Paul, MN, USA) of the Multi-Ethnic Study of Atherosclerosis (MESA), and 978 Japanese from three community-based cohorts of the Circulatory Risk in Communities Study (CIRCS) in Japan. The respiratory disturbance index and sleep-disordered breathing, defined as a respiratory disturbance index of > or =15 events x h(-1), were estimated. The prevalence of sleep-disordered breathing was higher in males (34.2%) than females (14.7%), and among Hispanics (36.5%) and Whites (33.3%) than among Japanese (18.4%), corresponding to differences in body mass index. Within body mass index strata, the race difference in sleep-disordered breathing was attenuated. This was also true when body mass index was adjusted for instead of stratification. The strong association between body mass index and sleep-disordered breathing was similar in Japanese and Americans. The prevalence of sleep-disordered breathing was lower among Japanese than among Americans. However, the association of body mass index with sleep-disordered breathing was strong, and similar among the race/ethnic groups studied. The majority of the race/ethnic difference in sleep-disordered breathing prevalence was explained by a difference in body mass index distribution.

Nocturnal intermittent hypoxia and the development of type 2 diabetes: the Circulatory Risk in Communities Study (CIRCS).

AIMS/HYPOTHESIS: Although the associations between obstructive sleep apnoea and type 2 diabetes mellitus have been reported in cross-sectional design studies, findings on the prospective association between the two conditions are limited. We examined prospectively the association between nocturnal intermittent hypoxia as a surrogate marker of obstructive sleep apnoea and risk of type 2 diabetes. METHODS: A total of 4,398 community residents aged 40 to 69 years who had participated in sleep investigation studies between 2001 and 2005 were enrolled. Nocturnal intermittent hypoxia was assessed by pulse-oximetry and defined by the number of oxygen desaturation measurements < or =3% per h, with five to <15 per h corresponding to mild and 15 events or more per h corresponding to moderate-to-severe nocturnal intermittent hypoxia, respectively. The development of type 2 diabetes was defined by: (1) fasting serum glucose > or =7.00 mmol/l (126 mg/dl); (2) non-fasting serum glucose > or =11.1 mmol/l (200 mg/dl); and/or (3) initiation of glucose-lowering medication or insulin therapy. Multivariable model accounted for age, sex, BMI, smoking status, current alcohol intake, community, borderline type 2 diabetes, habitual snoring, excessive daytime sleepiness, sleep duration and (for women) menopausal status. RESULTS: By the end of 2007, 92.2% of participants had been followed up (median follow-up duration [interquartile range] 3.0 [2.9-4.0] years) and 210 persons identified as having developed diabetes. The multivariable-adjusted hazard ratio (95% CI) for developing type 2 diabetes was 1.26 (0.91-1.76) among those with mild nocturnal intermittent hypoxia and 1.69 (1.04-2.76) among those with moderate-to-severe nocturnal intermittent hypoxia (p = 0.03 for trend). CONCLUSIONS/INTERPRETATION: Nocturnal intermittent hypoxia was associated with increased risk of developing type 2 diabetes among middle-aged Japanese.