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1. Exercise habits in adolescence and old age are positively associated with geriatric depressive symptoms: the Bunkyo Health Study

Author: Huicong Shi, Hiroki Tabata, Hikaru Otsuka, Hideyoshi Kaga, Yuki Someya, Abulaiti Abudurezake, Saori Kakehi, Hitoshi Naito, Naoaki Ito, Tsubasa Tajima, Yasuyo Yoshizawa, Ryuzo Kawamori, Hirotaka Watada, and Yoshifumi Tamura
Subjects: physical activity, teenage, older adults, GDS-15, geriatric depression, prevalence, Public aspects of medicine, RA1-1270
Abstract: IntroductionExercise is a crucial method for preventing geriatric depression. In this cross-sectional study, we investigated the associations between exercise habits in adolescence and old age and geriatric depressive symptoms.MethodsThis study used baseline data from the Bunkyo Health Study, a prospective observational cohort study investigating the preventive effects of physical activity on causative diseases requiring long-term care. This analysis included 1,629 older adults (687 men and 942 women) aged 65–84 years who participated in the Bunkyo Health Study. Participants were divided into four groups according to their exercise habits in adolescence and old age: never exercised (none-none; NN), exercised only in old age (none-active; NA), exercised only in adolescence (active-none; AN), and exercised in adolescence and old age (active-active; AA). Geriatric depressive symptoms were defined as the short version of the Geriatric Depression Scale score ≥ 5, including depression tendency. Multivariate-adjusted logistic regression models were used to estimate the odds ratios (ORs) and associated 95% confidence intervals in each group for the prevalence of geriatric depressive symptoms compared with the NN group.ResultsThe ORs for geriatric depressive symptoms were notably lower in the AN, NA, and AA groups than in the NN group in both older men and older women.ConclusionThese results indicate that older adults with exercise habits in adolescence and/or in old age exhibit a lower prevalence of geriatric depressive symptoms.
Published: 2024
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2. Association between exercise habits in adolescence and old age and the risk of mild cognitive impairment: the Bunkyo health study

Author: Huicong Shi, Hiroki Tabata, Hikaru Otsuka, Takahito Iwashimizu, Hideyoshi Kaga, Yuki Someya, Abulaiti Abudurezake, Saori Kakehi, Hitoshi Naito, Yasuyo Yoshizawa, Ryuzo Kawamori, Hirotaka Watada, and Yoshifumi Tamura
Subjects: physical activity, cognitive function, regional brain volumes, blood markers, cross-sectional study, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: BackgroundExercise in adolescence and old age improves cognitive function in older adults, but the combined effect of exercise habits in both periods is controversial. This study aimed to clarify the relationship between exercise habits in adolescence and old age and mild cognitive impairment (MCI) and to compare regional brain volumes and blood biochemical markers associated with cognitive function in older adults.MethodsBaseline data of 1615 participants aged 65–84 years from the Bunkyo Health Study were analyzed. MCI was diagnosed using the Japanese version of the Montreal Cognitive Assessment. Participants were divided into four groups based on their exercise habits in adolescence (13–18 years) and old age: no exercise in either period (None-None), exercise in adolescence only (Active-None), exercise in old age only (None-Active), and exercise in both periods (Active-Active). Logistic regression models estimated the odds ratios (ORs) of MCI prevalence. Regional brain volumes, such as the prefrontal cortex, temporal lobe, parietal cortex, and hippocampus, and blood biochemical markers, such as BDNF, IGF-1, and homocysteine, were compared between groups.ResultsThe OR for MCI was significantly lower in the Active-Active group than in the None-None group (OR, 0.62; 95% CI, 0.41–0.94). However, there were no significant differences in regional brain volumes and blood biochemical markers between the Active-Active and None-None groups.ConclusionsOlder adults with exercise habits in both adolescence and old age have a lower risk of MCI. However, specific regional brain volumes and biochemical markers may not be associated with differences in cognitive function in older adults.
Published: 2024
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3. Dietary characteristics of urban community-dwelling older adults with low muscle mass: the bunkyo health study: a cross-sectional study

Author: Yukiko Muroga, Hideyoshi Kaga, Thu Hien Bui, Mari Sugimoto, Yuki Someya, Saori Kakehi, Hiroki Tabata, Hitoshi Naito, Abulaiti Abudurezake, Huicong Shi, Hikaru Otsuka, Yasuyo Yoshizawa, Ryuzo Kawamori, Hirotaka Watada, and Yoshifumi Tamura
Subjects: Dietary intake, Low skeletal muscle mass, Sarcopenia, Older adults, Geriatrics, RC952-954.6
Abstract: Abstract Background With the aging of the population worldwide, extending healthy life expectancy is an urgent issue. Muscle mass has been reported to be associated with physical independence and longevity. This study aimed to investigate the characteristics of food intake in urban community-dwelling older adults with low muscle mass. Methods This cross-sectional study used baseline data from the Bunkyo Health Study, which included 1618 urban community-dwelling older adults aged 65–84 years. All participants underwent measurement of body composition using bioelectrical impedance analysis and evaluation of nutrient and food intake using the brief-type self-administered diet history questionnaire. Participants were stratified by sex and divided into robust or low skeletal muscle mass index (SMI) groups according to the Asian Working Group for Sarcopenia criteria to compare differences in nutrient and food intake. Results The mean age and body mass index were 73.1 ± 5.4 years and 22.6 ± 3.1 kg/m2, respectively. The prevalence of low SMI was 31.1% in men and 43.3% in women. In men, all food intake, including total energy intake, was similar between the low SMI group and the robust group. In women, the low SMI group had less total energy intake, and consumed lower amounts of energy-producing nutrients (protein, fat, and carbohydrates), but there were only small differences in the intake of specific foods. Conclusions There were sex differences in food intake characteristics between urban community-dwelling older adults with low SMI and those who were robust. Advising women to increase their energy intake may be important in preventing muscle loss, and further research is needed in men.
Published: 2024
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4. A genome-wide association study identifies a locus associated with knee extension strength in older Japanese individuals

Author: Shuji Ito, Hiroshi Takuwa, Saori Kakehi, Yuki Someya, Hideyoshi Kaga, Nobuyuki Kumahashi, Suguru Kuwata, Takuya Wakatsuki, Masaru Kadowaki, Soichiro Yamamoto, Takafumi Abe, Miwako Takeda, Yuki Ishikawa, Xiaoxi Liu, Nao Otomo, Hiroyuki Suetsugu, Yoshinao Koike, Keiko Hikino, Kohei Tomizuka, Yukihide Momozawa, Kouichi Ozaki, Minoru Isomura, Toru Nabika, Haruka Kaneko, Muneaki Ishijima, Ryuzo Kawamori, Hirotaka Watada, Yoshifumi Tamura, Yuji Uchio, Shiro Ikegawa, and Chikashi Terao
Subjects: Biology (General), QH301-705.5
Abstract: Abstract Sarcopenia is a common skeletal muscle disease in older people. Lower limb muscle strength is a good predictive value for sarcopenia; however, little is known about its genetic components. Here, we conducted a genome-wide association study (GWAS) for knee extension strength in a total of 3452 Japanese aged 60 years or older from two independent cohorts. We identified a significant locus, rs10749438 which is an intronic variant in TACC2 (transforming acidic coiled-coil-containing 2) (P = 4.2 × 10−8). TACC2, encoding a cytoskeleton-related protein, is highly expressed in skeletal muscle, and is reported as a target of myotonic dystrophy 1-associated splicing alterations. These suggest that changes in TACC2 expression are associated with variations in muscle strength in older people. The association was consistently observed in young and middle-aged subjects. Our findings would shed light on genetic components of lower limb muscle strength and indicate TACC2 as a potential therapeutic target for sarcopenia.
Published: 2024
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5. Adipose tissue insulin resistance in young Japanese women is associated with metabolic abnormalities and dehydroepiandrosterone-sulfate

Author: Motonori Sato, Yoshifumi Tamura, Hideyoshi Kaga, Nozomu Yamasaki, Satoshi Kadowaki, Daisuke Sugimoto, Takashi Nakagata, Yuki Someya, Yuya Nishida, Ryuzo Kawamori, and Hirotaka Watada
Subjects: underweight young women, adipose tissue insulin resistance, impaired glucose tolerance, metabolic abnormality, dehydroepiandrosterone-sulfate, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: ObjectiveThe proportion of young Japanese women who are underweight is exceptionally high. We previously showed that the prevalence of impaired glucose tolerance (IGT) was high in underweight young Japanese women, and that IGT was characterized by high free fatty acid levels and adipose tissue insulin resistance (ATIR). As the next step, this study aimed to explore factors associated with elevated ATIR in this population.ParticipantsNinety-eight young, healthy, underweight women participated in this study.DesignTo investigate the relationship between ATIR and metabolic parameters, participants were divided into three groups (Low, Medium, and High) according to ATIR level. Body composition examination, oral glucose tolerance testing, and blood biochemical analysis were performed; Adipo-IR and the Matsuda index were used as indices of ATIR and systemic insulin sensitivity, respectively.ResultsParticipants in the High ATIR group had the highest prevalence of IGT (25%), and significantly higher body fat percentage, whole-body insulin resistance, and levels of insulin-like growth factor-1 and dehydroepiandrosterone sulfate (DHEA-S) than the other two groups. They were also significantly younger and had higher systolic blood pressure than the Low ATIR group. Multiple regression analysis showed that DHEA-S, which is known to enhance lipolysis in adipose tissue, was an independent correlate of ATIR.ConclusionsUnderweight Japanese women with high ATIR had impaired metabolism, a higher prevalence of IGT, higher systemic insulin resistance, and higher systolic blood pressure. DHEA-S was a determinant of high ATIR levels.
Published: 2024
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6. Sex-specific impact of rs1260326 polymorphism on metabolic traits in an older Japanese population: the Bunkyo Health Study

Author: Shota Sakamoto, Saori Kakehi, Abulaiti Abudurezake, Hideyoshi Kaga, Yuki Someya, Hiroki Tabata, Yasuyo Yoshizawa, Hitoshi Naito, Tsubasa Tajima, Naoaki Ito, Ryuzo Kawamori, Hirotaka Watada, and Yoshifumi Tamura
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Background: Metabolic syndrome involves health problems influenced by aging and genetics. The glucokinase regulatory protein ( GCKR ) rs1260326 polymorphism (Leu446) is associated with metabolic traits. This study explores the impact of the GCKR rs1260326 polymorphism on metabolic traits in older Japanese with focusing on sex-specific differences. Methods: This cross-sectional study from the Bunkyo Health Study in Tokyo, Japan, examined 883 participants aged 65–84 years. Participants were excluded with diabetes, or on drug treatment for diabetes or dyslipidemia. The GCKR P446L polymorphism was analyzed and compared their characteristics of physical activity, dietary intake, body composition, and metabolic parameters. Results: Study participants with GCKR rs1260326 genotypes (C/C 20.7%, C/T 47.6%, T/T 31.7%) had a median age of 72 years, and 60.4% were women. Men with the T/T genotype, as compared to the C/C genotype, had a lower body weight, body mass index (BMI), and skeletal mass index. This genotype also associated with lower fasting insulin, homeostasis model assessment of insulin resistance index (HOMA-IR), and higher Matsuda index, but not after adjustment for age, BMI, and physical activity. In contrast, women with the T/T genotype, compared to the C/C genotype, showed higher C-reactive protein, fibroblast growth factor 21, and Matsuda index. They also had lower fasting insulin, insulin area under the curve, and HOMA-IR; with these associations being independent of age, BMI, and physical activity. Conclusion: The GCKR rs1260326 genotype-affected metabolic traits differentially by sex in older Japanese. This highlights the need to consider sex differences in GCKR -related metabolic outcomes.
Published: 2024
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7. Assessing interstitial fluid dynamics in type 2 diabetes mellitus and prediabetes cases through diffusion tensor imaging analysis along the perivascular space

Author: Rukeye Tuerxun, Koji Kamagata, Yuya Saito, Christina Andica, Kaito Takabayashi, Wataru Uchida, Seina Yoshida, Junko Kikuta, Hiroki Tabata, Hitoshi Naito, Yuki Someya, Hideyoshi Kaga, Mari Miyata, Toshiaki Akashi, Akihiko Wada, Toshiaki Taoka, Shinji Naganawa, Yoshifumi Tamura, Hirotaka Watada, Ryuzo Kawamori, and Shigeki Aoki
Subjects: glymphatic system, insulin resistance, type 2 diabetes mellitus, prediabetes, diffusion-magnetic resonance imaging, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Background and purposeGlymphatic system in type 2 diabetes mellitus (T2DM) but not in the prodrome, prediabetes (Pre-DM) was investigated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). Association between glymphatic system and insulin resistance of prominent characteristic in T2DM and Pre-DM between is yet elucidated. Therefore, this study delves into the interstitial fluid dynamics using the DTI-ALPS in both Pre-DM and T2DM and association with insulin resistance.Materials and methodsIn our cross-sectional study, we assessed 70 elderly individuals from the Bunkyo Health Study, which included 22 with Pre-DM, 18 with T2DM, and 33 healthy controls with normal glucose metabolism (NGM). We utilized the general linear model (GLM) to evaluate the ALPS index based on DTI-ALPS across these groups, considering variables like sex, age, intracranial volume, years of education, anamnesis of hypertension and hyperlipidemia, and the total Fazekas scale. Furthermore, we have explored the relationship between the ALPS index and insulin resistance, as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) using GLM and the same set of covariates.ResultsIn the T2DM group, the ALPS index demonstrated a reduction compared with the NGM group [family-wise error (FWE)-corrected p < 0.001; Cohen's d = −1.32]. Similarly, the Pre-DM group had a lower ALPS index than the NGM group (FWE-corrected p < 0.001; Cohen's d = −1.04). However, there was no significant disparity between the T2DM and Pre-DM groups (FWE-corrected p = 1.00; Cohen's d = −0.63). A negative correlation was observed between the ALPS index and HOMA-IR in the combined T2DM and Pre-DM groups (partial correlation coefficient r = −0.35, p < 0.005).ConclusionThe ALPS index significantly decreased in both the pre-DM and T2DM groups and showed a correlated with insulin resistance. This indicated that changes in interstitial fluid dynamics are associated with insulin resistance.
Published: 2024
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8. Corrigendum: Playing basketball and volleyball during adolescence is associated with higher bone mineral density in old age: the Bunkyo Health Study

Author: Hikaru Otsuka, Hiroki Tabata, Huicong Shi, Mari Sugimoto, Hideyoshi Kaga, Yuki Someya, Hitoshi Naito, Naoaki Ito, Abulaiti Abudurezake, Futaba Umemura, Tsubasa Tajima, Saori Kakehi, Yasuyo Yoshizawa, Muneaki Ishijima, Ryuzo Kawamori, Hirotaka Watada, and Yoshifumi Tamura
Subjects: bone mass, sports type, cross-sectional study, femoral neck, lumbar spine, exercise history, Physiology, QP1-981
Published: 2024
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9. A 7 day inpatient diabetes education program improves quality of life and glycemic control 12 months after discharge

Author: Mika Kurita, Hiroaki Satoh, Hideyoshi Kaga, Satoshi Kadowaki, Yuki Someya, Yuka Tosaka, Yuya Nishida, Fuki Ikeda, Yoshifumi Tamura, and Hirotaka Watada
Subjects: Diabetes education hospitalization program, Diabetes treatment‐related quality of life, Duration of diabetes, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Aims For long‐term management of diabetes, patients with type 2 diabetes mellitus require a high level of treatment adherence, which is associated with treatment satisfaction and their quality of life (QOL). To achieve it, patient education about diabetes self‐management is essential. We routinely conduct a 7 day inpatient diabetes education program and administer the diabetes treatment‐related (DTR)‐QOL questionnaire to all participants, both before admission and at discharge. Here, we investigated whether our program improves QOL and post‐discharge glycemic control. Materials and Methods This retrospective study utilized data from patients with type 2 diabetes mellitus who participated in our program between July 2017 and March 2020 and who had been treated in our outpatient department for more than 1 year. We evaluated the relationship between at admission and at discharge diabetes treatment‐related quality of life scores and glycemic control after discharge. Results Data from 140 patients were analyzed in this study, which showed a significant improvement in the total, ‘Anxiety and dissatisfaction with treatment’, and ‘Satisfaction‐with‐treatment’ scores. A significant improvement was evident in HbA1c at 12 months after discharge. Multiple regression analysis showed that HbA1c after 12 months was independently associated with gender, duration of diabetes, and HbA1c at admission. Conclusions Our program effectively improves quality of life and post‐discharge glycemic control in patients with type 2 diabetes mellitus. It is particularly effective in patients of the male gender, with a shorter duration of diabetes mellitus and higher HbA1c at admission.
Published: 2023
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10. Effects of exercise habits in adolescence and older age on sarcopenia risk in older adults: the Bunkyo Health Study

Author: Hiroki Tabata, Hikaru Otsuka, Huicong Shi, Mari Sugimoto, Hideyoshi Kaga, Yuki Someya, Hitoshi Naito, Naoaki Ito, Abulaiti Abudurezake, Futaba Umemura, Mai Kiya, Tsubasa Tajima, Saori Kakehi, Yasuyo Yoshizawa, Ryuzo Kawamori, Hirotaka Watada, and Yoshifumi Tamura
Subjects: Adolescence, Older age, Exercise habits, Muscle function, Older adults, Sarcopenia, Diseases of the musculoskeletal system, RC925-935, Human anatomy, QM1-695
Abstract: Abstract Background Sarcopenia, defined as an age‐associated loss of skeletal muscle mass and function, is a major risk factor for requiring long‐term care. Because physical activity in adolescence and older age enhances peak muscle function in youth and prevents muscle function decline in older age, older adults with exercise habits during both periods may be at a lower risk for sarcopenia. We investigated the relationship between exercise habits in adolescence and older age and sarcopenia and its components in community‐dwelling older Japanese adults. Methods This study included 1607 community‐dwelling individuals (aged 65–84, medians 73 years, 679 men and 928 women) with complete health examinations, including measurements of skeletal muscle index, handgrip strength and gait speed, who were enrolled in the Bunkyo Health Study. We divided the participants into four groups according to exercise habits in adolescence and older age: no exercise in either period (none‐none; NN), exercise only in adolescence (active‐none; AN), exercise only in older age (none‐active; NA) and exercise in both periods (active‐active; AA). Multivariate‐adjusted logistic regression models were used to estimate the odds ratios (ORs) and associated 95% confidence intervals (CIs) in each group for the prevalence of sarcopenia, defined as low muscle mass and low muscle performance, as compared with the NN group. Low muscle performance was defined as low muscle strength and/or low gait speed. Results The total prevalence of sarcopenia was 6.6% (45/679) in men and 1.7% (16/928) in women, the total prevalence of low muscle mass was 14.3% (97/679) in men and 5.2% (48/928) in women, and the total prevalence of low muscle performance was 25.6% (174/679) in men and 19.6% (182/928) in women. In men, the ORs (95% CIs) for sarcopenia, low muscle mass and low muscle performance were significantly lower in the AA group (sarcopenia: 0.29 [0.09–0.95], P = 0.041; low muscle mass: 0.21 [0.09–0.52], P = 0.001; and low muscle performance: 0.52 [0.28–0.97], P = 0.038). In women, the OR (95% CI) for low muscle performance was significantly lower in the AA group than in the other groups (0.48 [0.27–0.84], P = 0.010), whereas none of the ORs for sarcopenia and low muscle mass were significant. Conclusions Older men with exercise habits in both adolescence and older age were at a lower risk of sarcopenia, low muscle mass and low muscle performance, whereas older women with exercise habits at both time periods were at a lower risk of low muscle performance.
Published: 2023
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11. Prediabetes is an independent risk factor for sarcopenia in older men, but not in older women: the Bunkyo Health Study

Author: Hideyoshi Kaga, Yoshifumi Tamura, Yuki Someya, Hitoshi Naito, Hiroki Tabata, Saori Kakehi, Nozomu Yamasaki, Motonori Sato, Satoshi Kadowaki, Ruriko Suzuki, Daisuke Sugimoto, Ryuzo Kawamori, and Hirotaka Watada
Subjects: sarcopenia, muscle strength, prediabetes, type 2 diabetes, Diseases of the musculoskeletal system, RC925-935, Human anatomy, QM1-695
Abstract: Abstract Background Sarcopenia is a major cause of disability in the elderly. Although type 2 diabetes is a risk factor for increased sarcopenia, the relationship between prediabetes and sarcopenia has not been elucidated. We aimed to examine the relationship between sarcopenia and prediabetes. Methods The design of this study is a cross‐sectional study. We evaluated glucose metabolism using the 75‐g oral glucose tolerance test and glycated haemoglobin, appendicular skeletal muscle mass, and hand grip strength in 1629 older adults living in an urban area of Tokyo, Japan. We investigated the frequency of sarcopenia in participants with normal glucose tolerance (NGT), prediabetes and diabetes. A multivariable logistic regression model was used to analyse the association between glucose tolerance and the prevalence of sarcopenia. Results The mean age of participants was 73.1 ± 5.4 years. In men, 44.3% had NGT, 26.6% had prediabetes, and 29.1% had diabetes. In women, the distribution was 56.1%, 28.8% and 15.2%. The prevalence of sarcopenia was 12.7% in men and 11.9% in women. Logistic regression revealed that prediabetes and diabetes are independent risk factors for sarcopenia in men (prediabetes, odds ratio [OR] = 2.081 [95% confidence interval {CI}: 1.031–4.199]; diabetes, OR = 2.614 [95% CI: 1.362–5.018]) and diabetes, but not prediabetes, is an independent risk factor for sarcopenia in women (prediabetes, OR = 1.036 [95% CI: 0.611–1.757]; diabetes, OR = 2.099 [95% CI: 1.146–3.844]). In both sexes, higher age (men, OR = 1.086 [95% CI: 1.028–1.146]; women, OR = 1.195 [95% CI: 1.142–1.251]), higher body fat percentage (men, OR = 1.346 [95% CI: 1.240–1.461]; women, OR = 1.218 [95% CI: 1.138–1.303]) and lower body mass index (men, OR = 0.371 [95% CI: 0.299–0.461]; women, OR = 0.498 [95% CI: 0.419–0.593]) were independent risk factors for sarcopenia. Conclusions Although we confirmed that diabetes mellitus is associated with sarcopenia in both sexes, prediabetes is associated with sarcopenia in men, but not in women.
Published: 2022
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12. Playing basketball and volleyball during adolescence is associated with higher bone mineral density in old age: the Bunkyo Health Study

Author: Hikaru Otsuka, Hiroki Tabata, Huicong Shi, Mari Sugimoto, Hideyoshi Kaga, Yuki Someya, Hitoshi Naito, Naoaki Ito, Abulaiti Abudurezake, Futaba Umemura, Tsubasa Tajima, Saori Kakehi, Yasuyo Yoshizawa, Muneaki Ishijima, Ryuzo Kawamori, Hirotaka Watada, and Yoshifumi Tamura
Subjects: bone mass, sports type, cross-sectional study, femoral neck, lumbar spine, exercise history, Physiology, QP1-981
Abstract: Introduction: Exercise is beneficial for increasing areal bone mineral density (aBMD) in adolescence and maintaining it in old age. Moreover, high-impact sports are more effective than low-impact sports in increasing aBMD. This study aimed to determine the types of adolescent sports played in school-based sports clubs associated with aBMD in old age.Methods: In total, 1,596 older adults (681 men and 915 women, age: 65–84 years) living in an urban area of Japan were evaluated for the femoral neck and lumbar spine aBMD using dual-energy X-ray absorptiometry. The association between adolescent sports played in sports clubs and aBMD in old age was analyzed using multiple regression analysis, with femoral neck and lumbar spine aBMD as dependent variables, and sports type and participant characteristics such as age, body weight, and serum 25-hydroxyvitamin D [25(OH)D] level, as independent variables.Results: For the femoral neck, basketball was associated with aBMD in older men (β = 0.079, p < 0.05) and women (β = 0.08, p < 0.01), whereas current body weight and 25(OH)D level were associated with aBMD in both sexes. For the lumbar spine, volleyball (β = 0.08, p < 0.01) and swimming (β = 0.06, p < 0.05) was significantly associated with lumbar spine aBMD, whereas current body weight, 25(OH)D, and diabetes mellitus were associated with aBMD in older women.Conclusion: Both men and women who played basketball in adolescence had higher femoral neck aBMD in old age. Moreover, women who played volleyball in adolescence had higher lumbar spine aBMD in old age.
Published: 2023
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13. Multidimensional background examination of young underweight Japanese women: focusing on their dieting experiences

Author: Yuka Murofushi, Shinji Yamaguchi, Haruka Kadoya, Hikaru Otsuka, Kasane Ogura, Hideyoshi Kaga, Yasuyo Yoshizawa, and Yoshifumi Tamura
Subjects: underweight, BMI, birth weight, dieting experience, exercise habit, eating habit, Public aspects of medicine, RA1-1270
Abstract: IntroductionThis study examines the background of underweight young women in Japan from multiple perspectives, focusing on whether they have ever dieted.MethodsA screening survey was administered to 5,905 underweight (BMI < 18.5 kg/m2) women aged 18–29 years, who could report their birth weight recorded in their mother-child handbook. Valid responses were obtained from 400 underweight and 189 normal-weight women. The survey collected data regarding height, weight (BMI), body image and perception of weight, dieting experience, exercise habits from elementary school age onwards, and current eating habits. Additionally, five standardized questionnaires were used (EAT-26, eHEALTH, SATAQ-3 JS, TIPI-J, and RSES). The primary analysis was a comparative analysis (t-test/χ2)—with the presence or absence of underweight and diet experience as independent variables, and each questionnaire as a dependent variable.ResultsThe screening survey revealed that approximately 24% of the total population was underweight, with a low mean BMI. Of the respondents, more than half reported their body image as skinny and a small percentage as obese. Compared with the non-diet-experienced group (NDG), the diet-experienced group (DG) had a significantly higher proportion of past to current exercise habits. There was a significantly higher percentage of disagreement responses from the DG for weight and food gain than for the NDG. The NDG weighed significantly less than the DG in terms of birth weight, and lost weight easier than the DG. Additionally, the NDG was significantly more likely to agree with increasing weight and food intake. The NDG’s exercise habits were below 40% from elementary school age to the present, predominantly owing to a dislike for exercise and a lack of opportunity to implement it. In the standardized questionnaire, the DG was significantly higher for EAT-26, eHEALTH, SATAQ-3 JS, and Conscientiousness (TIPI-J), whereas the NDG was only significantly higher for Openness (TIPI-J).DiscussionThe results suggest the need for different health education programs for underweight women who desire to lose weight and experience dieting and for those who do not. This study’s results are reflected in the development of sports opportunities optimized for each individual, and in the development of measures to ensure adequate nutritional intake.
Published: 2023
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14. Neuroimaging findings related to glymphatic system alterations in older adults with metabolic syndrome

Author: Christina Andica, Koji Kamagata, Kaito Takabayashi, Junko Kikuta, Hideyoshi Kaga, Yuki Someya, Yoshifumi Tamura, Ryuzo Kawamori, Hirotaka Watada, Toshiaki Taoka, Shinji Naganawa, and Shigeki Aoki
Subjects: Cognition, Diffusion-weighted imaging, Diffusion tensor imaging-along the perivascular space, Free water imaging, Glymphatic system, Metabolic syndrome, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Objective: The glymphatic system is a glial-based perivascular network that promotes brain metabolic waste clearance. Reduced glymphatic flow has been observed in rat models of type 2 diabetes and hypertension, indicating the role of vascular risk factors in the glymphatic system. However, little is known about how vascular risk factors affect the human glymphatic system. The present study aims to assess the relationships between metabolic syndrome (MetS), a cluster of vascular risk factors, and the glymphatic system function using diffusion magnetic resonance imaging (MRI)-based measures of water diffusivity in the glymphatic compartments, including the brain interstitial space and perivascular spaces around the deep medullary vein. We hypothesized that vascular risk factors are associated with glymphatic dysfunction, leading to cognitive impairment in older adults. Methods: This cross-sectional study assessed 61 older adults (age range, 65–82 years) who had participated in the Bunkyo Health Study, including 15 healthy controls (mean age, 70.87 ± 4.90 years) and 46 individuals with MetS (mean age, 71.76 ± 4.61 years). Fractional volume of extracellular-free water (FW) and an index of diffusion tensor imaging along the perivascular space (DTI-ALPS) were used as indirect indicators of water diffusivity in the interstitial extracellular and perivenous spaces of white matter, respectively. Results: After adjusting for age, sex, years of education, total Fazekas scale, Pittsburgh sleep quality index (PSQI) score, and intracranial volume (ICV), a significantly (P = 0.030; Cohen's d = 1.01) higher FW was observed in individuals with MetS than in the healthy controls. Furthermore, individuals with MetS had a significantly (P = 0.031; Cohen's d = 0.86) lower ALPS index than the healthy controls, with age, sex, years of education, total Fazekas scale, PSQI score, ICV, fractional anisotropy, and mean diffusivity included as confounding factors. Higher FW was significantly associated with lower ALPS index (r = −0.37; P = 0.004). Multiple linear regression (MLR) with backward elimination analyses showed that higher diastolic blood pressure (BP; standardized β = 0.33, P = 0.005) was independently associated with higher FW, whereas higher fasting plasma glucose levels (standardized β = −0.63, P = 0.002) or higher Brinkman index of cigarette consumption cumulative amount (standardized β = −0.27, P = 0.022) were associated with lower ALPS index. The lower ALPS index (standardized β, 0.28; P = 0.040) was associated with poorer global cognitive performance, which was determined using the Japanese version of the Montreal Cognitive Assessment (MOCA-J) scores. Finally, partial correlation analyses showed a significant correlation between higher FW and lower MOCA-J scores (r = −0.35; P = 0.025) and between higher FW and higher diastolic BP (r = 0.32, P = 0.044). Conclusion: The present study shows the changes in diffusion MRI-based measures reflected by the higher FW and lower ALPS index in older adults with MetS, possibly due to the adverse effect of vascular risk factors on the glymphatic system. Our findings also indicate the associations between the diffusion MRI-based measures and elevated diastolic BP, hyperglycemia, smoking habit, and poorer cognitive performance. However, owing to the limitations of this study, the results should be cautiously interpreted.
Published: 2023
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15. Glymphatic system impairment in nonathlete older male adults who played contact sports in their youth associated with cognitive decline: A diffusion tensor image analysis along the perivascular space study

Author: Yuichi Morita, Koji Kamagata, Christina Andica, Kaito Takabayashi, Junko Kikuta, Shohei Fujita, Thomas Samoyeau, Wataru Uchida, Yuya Saito, Hiroki Tabata, Hitoshi Naito, Yuki Someya, Hideyoshi Kaga, Yoshifumi Tamura, Mari Miyata, Toshiaki Akashi, Akihiko Wada, Toshiaki Taoka, Shinji Naganawa, Hirotaka Watada, Ryuzo Kawamori, Osamu Abe, and Shigeki Aoki
Subjects: repetitive head impacts, contact sports, glymphatic system, DTI-ALPS, diffusion-weighted imaging, cerebrospinal fluid, Neurology. Diseases of the nervous system, RC346-429
Abstract: Background and purposeExposure to contact sports in youth causes brain health problems later in life. For instance, the repetitive head impacts in contact sports might contribute to glymphatic clearance impairment and cognitive decline. This study aimed to assess the effect of contact sports participation in youth on glymphatic function in old age and the relationship between glymphatic function and cognitive status using the analysis along the perivascular space (ALPS) index.Materials and methodsA total of 52 Japanese older male subjects were included in the study, including 12 who played heavy-contact sports (mean age, 71.2 years), 15 who played semicontact sports (mean age, 73.1 years), and 25 who played noncontact sports (mean age, 71.3 years) in their youth. All brain diffusion-weighted images (DWIs) of the subjects were acquired using a 3T MRI scanner. The ALPS indices were calculated using a validated semiautomated pipeline. The ALPS indices from the left and right hemispheres were compared between groups using a general linear model, including age and years of education. Furthermore, partial Spearman's rank correlation tests were performed to assess the correlation between the ALPS indices and cognitive scores (Mini-Mental State Examination and the Japanese version of the Montreal Cognitive Assessment [MoCA-J]) after adjusting for age years of education and HbA1c.ResultsThe left ALPS index was significantly lower in the heavy-contact and semicontact groups than that in the noncontact group. Although no significant differences were observed in the left ALPS index between the heavy-contact and semicontact groups and in the right ALPS index among groups, a trend toward lower was found in the right ALPS index in individuals with semicontact and heavy-contact compared to the noncontact group. Both sides' ALPS indices were significantly positively correlated with the MoCA-J scores.ConclusionThe findings indicated the potential adverse effect of contact sports experience in youth on the glymphatic system function in old age associated with cognitive decline.
Published: 2023
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16. Insulin resistance and muscle weakness are synergistic risk factors for silent lacunar infarcts: the Bunkyo Health Study

Author: Yuki Someya, Yoshifumi Tamura, Hideyoshi Kaga, Daisuke Sugimoto, Satoshi Kadowaki, Ruriko Suzuki, Shigeki Aoki, Nobutaka Hattori, Yumiko Motoi, Kazunori Shimada, Hiroyuki Daida, Muneaki Ishijima, Kazuo Kaneko, Shuko Nojiri, Ryuzo Kawamori, and Hirotaka Watada
Subjects: Medicine, Science
Abstract: Abstract Insulin resistance and muscle weakness are risk factors for silent lacunar infarcts (SLI), but it is unclear whether they are still independent risk factors when adjusted for each other. In addition, the effect of their combination on SLI is completely unknown. We evaluated SLI, insulin sensitivity, and knee extensor muscle strength by magnetic resonance imaging, PREDIM, and dynamometer, respectively, in 1531 elderly people aged 65–84 years living in an urban area of Tokyo. Among the study subjects, 251 (16.4%) had SLI. Impaired insulin sensitivity (High; 1.00 [reference], Medium; 1.53 [95% confidence interval (CI) 0.94–2.48], Low; 1.86 [1.02–3.39], p for trend 0.047) and reduced muscle strength (High; 1.00 [reference], Medium; 1.40 [0.98–2.02], Low; 1.49 [1.04–2.15], p for trend 0.037) were independently associated with increased risk for SLI in the fully adjusted model. In terms of combined, subjects classified as having the lowest insulin sensitivity and lowest strength were 4.33 times (95% CI 1.64–11.45) more likely to have a SLI than those classified as having the highest insulin sensitivity and highest strength. Impaired insulin sensitivity and reduced muscle strength were independently associated with higher risk of SLI in elderly subjects, and their combination synergistically increased this risk.
Published: 2021
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17. White matter fiber-specific degeneration in older adults with metabolic syndrome

Author: Christina Andica, Koji Kamagata, Wataru Uchida, Kaito Takabayashi, Keigo Shimoji, Hideyoshi Kaga, Yuki Someya, Yoshifumi Tamura, Ryuzo Kawamori, Hirotaka Watada, Masaaki Hori, and Shigeki Aoki
Subjects: Diffusion MRI, Executive-motor dysfunction, Fixel-based analysis, Metabolic syndrome, Neurodegeneration, White matter, Internal medicine, RC31-1245
Abstract: Objective: Metabolic syndrome (MetS) is defined as a complex of interrelated risk factors for type 2 diabetes and cardiovascular disease, including glucose intolerance, abdominal obesity, hypertension, and dyslipidemia. Studies using diffusion tensor imaging (DTI) have reported white matter (WM) microstructural abnormalities in MetS. However, interpretation of DTI metrics is limited primarily due to the challenges of modeling complex WM structures. The present study used fixel-based analysis (FBA) to assess the effect of MetS on the fiber tract-specific WM microstructure in older adults and its relationship with MetS-related measurements and cognitive and locomotor functions to better understand the pathophysiology of MetS. Methods: Fixel-based metrics, including microstructural fiber density (FD), macrostructural fiber-bundle cross-section (FC), and a combination of FD and FC (FDC), were evaluated in 16 healthy controls (no components of MetS; four men; mean age, 71.31 ± 5.06 years), 57 individuals with premetabolic syndrome (preMetS; one or two components of MetS; 29 men; mean age, 72.44 ± 5.82 years), and 46 individuals with MetS (three to five components of MetS; 27 men; mean age, 72.15 ± 4.97 years) using whole-brain exploratory FBA. Tract of interest (TOI) analysis was then performed using TractSeg across 14 selected WM tracts previously associated with MetS. The associations between fixel-based metrics and MetS-related measurements, neuropsychological, and locomotor function tests were also analyzed in individuals with preMetS and MetS combined. In addition, tensor-based metrics (i.e., fractional anisotropy [FA] and mean diffusivity [MD]) were compared among the groups using tract-based spatial statistics (TBSS) analysis. Results: In whole-brain FBA, individuals with MetS showed significantly lower FD, FC, and FDC compared with healthy controls in WM areas, such as the splenium of the corpus callosum (CC), corticospinal tract (CST), middle cerebellar peduncle (MCP), and superior cerebellar peduncle (SCP). Meanwhile, in fixel-based TOI, significantly reduced FD was observed in individuals with preMetS and MetS in the anterior thalamic radiation, CST, SCP, and splenium of the CC compared with healthy controls, with relatively greater effect sizes observed in individuals with MetS. Compared with healthy controls, significantly reduced FC and FDC were only demonstrated in individuals with MetS, including regions with loss of FD, inferior cerebellar peduncle, inferior fronto-occipital fasciculus, MCP, and superior longitudinal fasciculus part I. Furthermore, negative correlations were observed between FD and Brinkman index of cigarette consumption cumulative amount and between FC or FDC and the Trail Making Test (parts B–A), which is a measure of executive function, waist circumference, or low-density lipoprotein cholesterol. Finally, TBSS analysis revealed that FA and MD were not significantly different among all groups. Conclusions: The FBA results demonstrate that substantial axonal loss and atrophy in individuals with MetS and early axonal loss without fiber-bundle morphological changes in those with preMetS within the WM tracts are crucial to cognitive and motor function. FBA also clarified the association between executive dysfunction, abdominal obesity, hyper-low-density lipoprotein cholesterolemia, smoking habit, and compromised WM neural tissue microstructure in MetS.
Published: 2022
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18. Ingestion of an exogenous ketone monoester improves the glycemic response during oral glucose tolerance test in individuals with impaired glucose tolerance: A cross‐over randomized trial

Author: Takashi Nakagata, Yoshifumi Tamura, Hideyoshi Kaga, Motonori Sato, Nozomu Yamasaki, Yuki Someya, Satoshi Kadowaki, Daisuke Sugimoto, Hiroaki Satoh, Ryuzo Kawamori, and Hirotaka Watada
Subjects: Impaired glucose tolerance, Insulin secretion, Ketone, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Aims/Introduction As a low‐carbohydrate diet and the use of sodium–glucose transporter‐2 inhibitors are both known to increase D‐beta‐hydroxybutyrate levels, the effect of these levels on glucose metabolism has attracted attention. We investigated the acute effects of ketone monoester (KM) ingestion on blood glucose levels during the 75‐g oral glucose tolerance test (OGTT) in participants with impaired glucose tolerance. Materials and Methods Nine Japanese adults aged 48–62 years (4 men, 5 women) with impaired glucose tolerance participated in this study. After participants fasted overnight, we carried out OGTT for 180 min with and without KM ingestion on two separate days in a randomized cross‐over design. We compared the area under the curve (AUC) of D‐beta‐hydroxybutyrate, glucose, insulin, C‐peptide, glucagon and free fatty acids during OGTT. Results The AUC of D‐beta‐hydroxybutyrate during OGTT was significantly higher with KM than without KM (KM 5995.3 ± 1257.1 mmol/L·h; without KM 116.1 ± 33.9 mmol/L·h, P
Published: 2021
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19. Characteristics associated with elevated 1‐h plasma glucose levels during a 75‐g oral glucose tolerance test in non‐obese Japanese men

Author: Motonori Sato, Yoshifumi Tamura, Yuki Someya, Kageumi Takeno, Hideyoshi Kaga, Satoshi Kadowaki, Daisuke Sugimoto, Saori Kakehi, Takashi Funayama, Yasuhiko Furukawa, Ruriko Suzuki, Takashi Nakagata, Miho Nishitani‐Yokoyama, Kazunori Shimada, Hiroyuki Daida, Shigeki Aoki, Hiroaki Sato, Ryuzo Kawamori, and Hirotaka Watada
Subjects: 1‐h plasma glucose levels, Insulinogenic index, Non‐obese, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Elevated 1‐h plasma glucose (1h‐PG; ≥155 mg/dL) during an oral glucose tolerance test is a risk factor for type 2 diabetes. However, the metabolic characteristics of non‐obese Asians with elevated 1h‐PG are unknown. Thus, we studied 59 non‐obese Japanese men with normal glucose tolerance. We divided study participants into the Low 1h‐PG group (
Published: 2020
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20. Shape of the glucose response curve during an oral glucose tolerance test is associated with insulin clearance and muscle insulin sensitivity in healthy non‐obese men

Author: Hideyoshi Kaga, Yoshifumi Tamura, Kageumi Takeno, Saori Kakehi, Yuki Someya, Takashi Funayama, Yasuhiko Furukawa, Ruriko Suzuki, Daisuke Sugimoto, Satoshi Kadowaki, Miho Nishitani‐Yokoyama, Kazunori Shimada, Hiroyuki Daida, Shigeki Aoki, Adria Giacca, Hiroaki Sato, Ryuzo Kawamori, and Hirotaka Watada
Subjects: Insulin clearance, Insulin resistance, Shape of glucose response curve, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Individuals with a monophasic glucose response curve (GRC) during a 75‐g oral glucose tolerance test have a higher risk for type 2 diabetes than those with a biphasic GRC. However, no studies have addressed the association between GRC type and insulin clearance. Thus, we studied 49 healthy non‐obese Japanese men. We divided study participants into the monophasic or biphasic group based on the shape of their GRC. We evaluated tissue‐specific insulin sensitivity and insulin clearance using a two‐step hyperinsulinemic‐euglycemic clamp. The monophasic group had more visceral fat, lower insulin clearance and lower muscle insulin sensitivity than the biphasic group, whereas liver and adipose tissue insulin sensitivity, and insulin secretion were comparable. In conclusion, healthy non‐obese men with a monophasic GRC have lower insulin clearance and muscle insulin sensitivity.
Published: 2020
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21. Short-Term SGLT2 Inhibitor Administration Does Not Alter Systemic Insulin Clearance in Type 2 Diabetes

Author: Motonori Sato, Yoshifumi Tamura, Hideyoshi Kaga, Nozomu Yamasaki, Mai Kiya, Satoshi Kadowaki, Daisuke Sugimoto, Takashi Funayama, Yuki Someya, Saori Kakehi, Shuko Nojiri, Hiroaki Satoh, Ryuzo Kawamori, and Hirotaka Watada
Subjects: SGLT2 inhibitor, insulin clearance, insulin resistance, ectopic fat, hyperinsulinemic euglycemic clamp, Biology (General), QH301-705.5
Abstract: Background: Decreased insulin clearance could be a relatively upstream abnormality in obesity, metabolic syndrome, and nonalcoholic fatty liver disease. Previous studies have shown that sodium-glucose cotransporter 2 inhibitor (SGLT2i) increases insulin–C-peptide ratio, a marker of insulin clearance, and improves metabolic parameters. We evaluated the effects of the SGLT2i tofogliflozin on metabolic clearance rate of insulin (MCRI) with a hyperinsulinemic euglycemic clamp study, the gold standard for measuring systemic insulin clearance. Methods: Study participants were 12 Japanese men with type 2 diabetes. We evaluated MCRI and tissue-specific insulin sensitivity with a hyperinsulinemic euglycemic clamp (insulin infusion rate, 40 mU/m2·min) before and immediately after a single dose (n = 12) and 8 weeks (n = 9) of tofogliflozin. We also measured ectopic fat in muscle and liver and the abdominal fat area using 1H-magnetic resonance spectroscopy and magnetic resonance imaging, respectively, before and after 8 weeks of tofogliflozin. Results: MCRI did not change after a single dose of tofogliflozin (594.7 ± 67.7 mL/min·m2 and 608.3 ± 90.9 mL/min·m2, p = 0.61) or after 8 weeks (582.5 ± 67.3 mL/min·m2 and 602.3 ± 67.0 mL/min·m2, p = 0.41). The 8-week treatment significantly improved glycated hemoglobin and decreased body weight (1.7%) and the subcutaneous fat area (6.4%), whereas insulin sensitivity and ectopic fat in muscle and liver did not change significantly. Conclusions: MCRI did not change after a single dose or 8 weeks of tofogliflozin. Increased MCRI does not precede a decrease in body fat or improved glycemic control.
Published: 2021
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22. Correlates of insulin clearance in apparently healthy non-obese Japanese men

Author: Hideyoshi Kaga, Yoshifumi Tamura, Kageumi Takeno, Saori Kakehi, Takashi Funayama, Yasuhiko Furukawa, Miho Nishitani-Yokoyama, Kazunori Shimada, Hiroyuki Daida, Shigeki Aoki, Adria Giacca, Akio Kanazawa, Ryuzo Kawamori, and Hirotaka Watada
Subjects: Medicine, Science
Abstract: Abstract Hyperinsulinemia observed in obese subject is caused at least in part by low metabolic clearance rate of insulin (MCRI). However, the determinants of MCRI in non-obese subjects are not fully understood. To investigate the correlates of MCRI in healthy non-obese men (BMI
Published: 2017
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23. Skeletal muscle function and need for long-term care of urban elderly people in Japan (the Bunkyo Health Study): a prospective cohort study

Author: Kazuo Kaneko, Yuki Someya, Yoshifumi Tamura, Hideyoshi Kaga, Shuko Nojiri, Kazunori Shimada, Hiroyuki Daida, Muneaki Ishijima, Shigeki Aoki, Takashi Miida, Satoshi Hirayama, Seiki Konishi, Nobutaka Hattori, Yumiko Motoi, Hisashi Naito, Ryuzo Kawamori, and Hirotaka Watada
Subjects: Medicine
Abstract: Purpose The proportion of elderly individuals (age ≥65 years) in Japan reached 27.7% in 2017, the highest in the world. A serious social problem in a super-aged society is the rise in the number of elderly people who need long-term care (LTC), which is mainly due to cerebrovascular disease, dementia, age-related frailty, falls and fractures, and joint disease. We hypothesised that decreased muscle mass, muscle strength and insulin sensitivity are the common risk factors for these diseases related to needing LTC. We developed a prospective cohort study of elderly subjects in an urban community to test this hypothesis. The primary objective is to prospectively investigate associations between muscle mass, muscle strength, and insulin sensitivity and incidence of main disease and risk factors of needing LTC. The primary outcomes are the incidence of cerebrovascular disease and cognitive decline.Participants Participants were 1629 people aged 65–84 years living in 13 communities in an urban area (Bunkyo-ku, Tokyo, Japan). Average age was 73.1±5.4 years.Findings to date We obtained baseline data on cognitive function, cerebral small vessel disease (SVD) determined by brain MRI, body composition, bone mineral density, arteriosclerosis, physical function, muscle mass, muscle strength and insulin sensitivity. Mild cognitive impairment and dementia were observed in 18.1% and 3.3% of participants, respectively. The prevalence of cerebral SVD was 24.8%. These characteristics are similar to those previously reported in elderly Japanese subjects.Future plans We will ask participants about their health status, including incidence of cerebrovascular disease, falls, fractures and other diseases every year by mail. We plan to re-evaluate cognitive function, brain MRI parameters and other parameters at 5 and 10 years after the baseline evaluation. We will evaluate whether low muscle function (muscle mass, muscle strength or insulin sensitivity) is a risk factor for cognitive decline or cerebrovascular disease.
Published: 2019
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24. Author Correction: Both higher fitness level and higher current physical activity level may be required for intramyocellular lipid accumulation in non-athlete men

Author: Nozomu Yamasaki, Yoshifumi Tamura, Kageumi Takeno, Saori Kakehi, Yuki Someya, Takashi Funayama, Yasuhiko Furukawa, Hideyoshi Kaga, Ruriko Suzuki, Daisuke Sugimoto, Satoshi Kadowaki, Motonori Sato, Takashi Nakagata, Miho Nishitani-Yokoyama, Kazunori Shimada, Hiroyuki Daida, Shigeki Aoki, Hiroaki Satoh, Ryuzo Kawamori, and Hirotaka Watada
Subjects: Medicine, Science
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2021
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25. Playing basketball and volleyball during adolescence is associated with higher bone mineral density in old age: the Bunkyo Health Study.

Author: Hikaru Otsuka, Hiroki Tabata, Huicong Shi, Mari Sugimoto, Hideyoshi Kaga, Yuki Someya, Hitoshi Naito, Naoaki Ito, Abudurezake, Abulaiti, Umemura, Futaba, Tsubasa Tajima, Saori Kakehi, Yasuyo Yoshizawa, Muneaki Ishijima, Ryuzo Kawamori, Hirotaka Watada, and Yoshifumi Tamura
Abstract: Introduction: Exercise is beneficial for increasing areal bone mineral density (aBMD) in adolescence and maintaining it in old age. Moreover, high-impact sports are more effective than low-impact sports in increasing aBMD. This study aimed to determine the types of adolescent sports played in school-based sports clubs associated with aBMD in old age. Methods: In total, 1,596 older adults (681 men and 915 women, age: 65-84 years) living in an urban area of Japan were evaluated for the femoral neck and lumbar spine aBMD using dual-energy X-ray absorptiometry. The association between adolescent sports played in sports clubs and aBMD in old age was analyzed using multiple regression analysis, with femoral neck and lumbar spine aBMD as dependent variables, and sports type and participant characteristics such as age, body weight, and serum 25-hydroxyvitamin D [25(OH)D] level, as independent variables. Results: For the femoral neck, basketball was associated with aBMD in older men (ß = 0.079, p < 0.05) and women (ß = 0.08, p < 0.01), whereas current body weight and 25(OH)D level were associated with aBMD in both sexes. For the lumbar spine, volleyball (ß = 0.08, p < 0.01) and swimming (ß = 0.06, p < 0.05) was significantly associated with lumbar spine aBMD, whereas current body weight, 25(OH)D, and diabetes mellitus were associated with aBMD in older women. Conclusion: Both men and women who played basketball in adolescence had higher femoral neck aBMD in old age. Moreover, women who played volleyball in adolescence had higher lumbar spine aBMD in old age. [ABSTRACT FROM AUTHOR]
Published: 2024
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26. Efficacy and Safety of 5-Aminolevulinic Acid Combined with Iron on Skeletal Muscle Mass Index and Physical Performance of Patients with Sarcopenia: A Multicenter, Double-Blinded, Randomized-Controlled Trial (ALADDIN Study)

Author: Watada, Yoshifumi Tamura, Hideyoshi Kaga, Yasuko Abe, Hidenori Yoshii, Hiroaki Seino, Toru Hiyoshi, Nobuichi Kuribayashi, Ikuo Inoue, and Hirotaka
Subjects: 5-aminolevulinic acid, hand grip, iron, sarcopenia, skeletal muscle mass index, sodium ferrous citrate
Abstract: Sarcopenia is a geriatric syndrome characterized by decreased physical performance, muscle mass, and strength. Since the intake of 5-aminolevulinic acid (ALA) with iron can increase muscle mass and mitochondria in mice and elevate physical exercise performance in humans, the beneficial effects of ALA in patients with sarcopenia are expected, but this remains unexplored in the literature. This study aimed to assess the efficacy and dose dependency of ALA combined with iron in sarcopenia by measuring skeletal muscle mass index (SMI). Subjects with sarcopenia were enrolled and randomized into the ALA and sodium ferrous citrate (SFC) intake groups (ALA50/SFC29, ALA100/SFC29, ALA150/SFC29, ALA 100/SFC57, and ALA0/SFC29 placebo) and ingested the assigned study food for 12 weeks. The primary endpoint, the change in SMI from baseline to week 12, did not differ significantly between the groups. Hand grip significantly increased or tended to increase from baseline after 12 weeks with all doses of ALA or SFC compared with the placebo group. No consistent changes were observed in the other endpoints, including calf circumference, physical function, or quality of life (QOL). Although this study suggests safe administration and the possibility of ALA improving hand grip strength in patients with sarcopenia, further investigation is required.
Published: 2023
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27. A Short-Term High-Fat Diet Worsens Insulin Sensitivity with Changes in Metabolic Parameters in Non-Obese Japanese Men

Author: Watada, Satoshi Kadowaki, Yoshifumi Tamura, Daisuke Sugimoto, Hideyoshi Kaga, Ruriko Suzuki, Yuki Someya, Nozomu Yamasaki, Motonori Sato, Saori Kakehi, Akio Kanazawa, Ryuzo Kawamori, and Hirotaka
Subjects: insulin resistance, insulin clearance, non-obese, East Asian, gut microbiota, ectopic fat
Abstract: A short-term high-calorie high-fat diet (HCHFD) impairs insulin sensitivity in non-obese South Asian but not Caucasian men; however, the effect of short-term HCHFD on insulin sensitivity in East Asians is unknown. We recruited 21 healthy non-obese Japanese men to evaluate metabolic parameters and gut microbiota before and after 6-day HCHFD consisting of a regular diet plus a 45% energy excess with dairy fat supplementation. We evaluated tissue-specific insulin sensitivity and metabolic clearance rate of insulin (MCRI) using a two-step hyperinsulinemic euglycemic clamp, glucose tolerance using the glucose tolerance test, and measured ectopic fat in muscle and the liver using ¹H-magnetic resonance spectroscopy. The primary outcome of this study was insulin sensitivity measured by the clamp study. The secondary/exploratory outcomes were other metabolic changes. After HCHFD, levels of circulating lipopolysaccharide binding protein (LBP), a marker of endotoxemia, increased by 14%. In addition, intramyocellular lipid levels in the tibialis anterior and soleus and intrahepatic lipid levels increased by 47%, 31%, and 200%, respectively. Insulin sensitivity decreased by 4% in muscle and 8% in liver. However, even with reduced insulin sensitivity, glucose metabolism was maintained by increased serum insulin concentrations due to lower MCRI and higher endogenous insulin secretion during the clamp. Glucose levels during the meal tolerance test were comparable before and after HCHFD. In conclusion, short-term HCHFD impaired insulin sensitivity in the muscle and livers of non-obese Japanese men with increased LBP and ectopic fat accumulation. Elevated insulin levels from modulated insulin secretion and clearance might contribute to the maintenance of normal glucose metabolism during the clamp and meal tolerance test.
Published: 2023
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28. Comparison of Brain Volume Measurements Made with 0.3- and 3-T MR Imaging

Author: Koji Kamagata, Keigo Shimoji, Akifumi Hagiwara, Christina Andica, Yuki Someya, Yujiro Otsuka, Ryuzo Kawamori, Hirotaka Watada, Masami Goto, Hideyoshi Kaga, Kanako K. Kumamaru, Ryusuke Irie, Kiyotaka Nemoto, Akihiko Wada, Syo Murata, Masaaki Hori, Haruyoshi Hoshito, Shigeki Aoki, and Yoshifumi Tamura
Subjects: medicine.diagnostic_test, Intraclass correlation, business.industry, Brain, Reproducibility of Results, Magnetic resonance imaging, Magnetic Resonance Imaging, Mr imaging, Correlation, Imaging, Three-Dimensional, Nuclear magnetic resonance, Neuroimaging, Brain size, Healthy volunteers, medicine, Humans, Radiology, Nuclear Medicine and imaging, business
Abstract: The volumes of intracranial tissues of 40 healthy volunteers acquired from 0.3- and 3-T scanners were compared using intraclass correlation coefficients, correlation analyses, and Bland-Altman analyses. We found high intraclass correlation coefficients, high Pearson's correlation coefficients, and low percentage biases in all tissues and most of the brain regions, although small differences were observed in some areas. These findings may support the validity of brain volumetry with low-field magnetic resonance imaging.
Published: 2022
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29. Empagliflozin in Patients with Chronic Kidney Disease

Author: Herrington, William G, Staplin, Natalie, Wanner, Christoph, Green, Jennifer B, Hauske, Sibylle J, Emberson, Jonathan R, Preiss, David, Judge, Parminder, Mayne, Kaitlin J, Ng, Sarah Y A, Sammons, Emily, Zhu, Doreen, Hill, Michael, Stevens, Will, Wallendszus, Karl, Brenner, Susanne, Cheung, Alfred K, Liu, Zhi-Hong, Li, Jing, Hooi, Lai Seong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Maggioni, Aldo P, Pontremoli, Roberto, Deo, Rajat, Goto, Shinya, Rossello, Xavier, Tuttle, Katherine R, Steubl, Dominik, Petrini, Michaela, Massey, Dan, Eilbracht, Jens, Brueckmann, Martina, Landray, Martin J, Baigent, Colin, Haynes, Richard, The EMPA-KIDNEY Collaborative Group: Colin Baigent, Martin J Landray, Christoph Wanner, William G Herrington, Richard Haynes, Jennifer B Green, Sibylle J Hauske, Martina Brueckmann, Mark Hopley, Maximillian von-Eynatten, Jyothis George, Susanne Brenner, Alfred K Cheung, David Preiss, Zhi-Hong Liu, Jing Li, Laiseong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Roberto Pontremoli, Aldo P Maggioni, Natalie Staplin, Jonathan Emberson, Stefan Hantel, Shinya Goto, Rajat Deo, Katherine R Tuttle, Michael Hill, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Xavier Rossello, Emily Sammons, Doreen Zhu, Peter Sandercock, Rudolf Bilous, Charles Herzog, Paul Whelton, Janet Wittes, Derrick Bennett, Patricia Achiri, Chrissie Ambrose, Cristina Badin, Jill Barton, Richard Brown, Andy Burke, Sebastian Butler, Rejive Dayanandan, Pia Donaldson, Robert Dykas, Lucy Fletcher, Kate Frederick, Hannah Kingston, Mo Gray, Emily Harding, Akiko Hashimoto, Lyn Howie, Susan Hurley, Ryonfa Lee, Nik Luker, Kevin Murphy, Mariko Nakahara, John Nolan, Michelle Nunn, Sorcha Mulligan, Akiko Omata, Sandra Pickworth, YanRu Qiao, Shraddha Shah, Karen Taylor, Alison Timadjer, Monique Willett, Liz Wincott, Qin Yan, Hui Yu, Louise Bowman, Fang Chen, Robert Clarke, Michelle Goonasekera, Waseem Karsan, Marion Mafham, Christina Reith, Mohammed Zayed, Ritva Ellison, Rowan Moys, Will Stevens, Kevin Verdel, Karl Wallendszus, Chris Bowler, Anna Brewer, Andy Measor, Guanguo Cui, Charles Daniels, Angela Field, Bob Goodenough, Ashley Lawson, Youcef Mostefai, Dheeptha Radhakrishnan, Samee Syed, Shuang Xia, Ruth Adewuyi-Dalton, Thomas Arnold, Anne-Marie Beneat, Anoushka Bhatt, Chloe Bird, Andrew Breach, Laura Brown, Mark Caple, Tatyana Chavagnon, Karen Chung, Sarah Clark, Luminita Condurache, Katarzyna Eichstadt, Marta Espino Obrero, Scarlett Forest, Helen French, Nick Goodwin, Andrew Gordon, Joanne Gordon, Cat Guest, Tina Harding, Michal Hozak, Matthew Lacey, David MacLean, Louise Messinger, Stewart Moffat, Martin Radley, Claire Shenton, Sarah Tipper, Jon Tyler, Lesley Weaving, James Wheeler, Elissa Williams, Tim Williams, Hamish Woodhouse, Angela Chamberlain, Jo Chambers, Joanne Davies, Denise Donaldson, Pati Faria-Shayler, Denise Fleming-Brown, Jennifer Ingell, Carol Knott, Anna Liew, Helen Lochhead, Juliette Meek, Isabel Rodriguez-Bachiller, Andrea Wilson, Patrick Zettergren, Rach AitSadi, Ian Barton, Alex Baxter, Yonghong Bu, Lukasz Danel, Sonja Grotjahn, Rijo Kurien, Michael Lay, Archie Maskill, Aleksandra Murawska, Rachel Raff, Allen Young, Rebecca Sardell, Vladimir Cejka, Marcela Fajardo-Moser, Christian Hartner, Doris Poehler, Janina Renner, Franziska Scheidemantel, Miya Bryant, Anita Hepditch, Cassandra Johnson, Erin Latore, Yolanda Miller, Lauren Price, Merilee Whalen, Ashleigh Wheeler, Jenny Ingell, Yu An, Yinghua Chen, Peiling Chen, Hao Dai, Hong Du, Fang Feng, Qing Guo, Libo Hou, Wuhanbilige Hundei, Binbin Jin, Yan Li, Jiamin Liu, Xia Song, Yanping Wang, Yanwu Yu, Ning Zhang, Lingshan Zhao, Hui Zhong, Cheng Beng Goh, Ye Mun Low, Soon Yi Sor, Farah Hanis Zulkipli, Sarojini Sivanandam, Natsuki Arai, Ai Fukasawa, Mizue Furukawa, Keisuke Habuki, Shoko Hayashi, Wakako Isari, Saki Kanegae, Maria Kawai, Reiki Kobayashi, Takako Kuramae, Chika Kuribayashi, Sawako Maeno, Satoshi Masumoto, Tomoko Morisaki, Minoru Oda, Kazue Sawada, Kenta Sugamori, Ayana Tatsuzawa, Aiko Tomita, Kazuyuki Yuasa, Hiroko Inazawa, Amanda Axler, Kerri Gallo, Ester Baldini, Barbara Bartolomei Mecatti, Francesca Bianchini, Martina Ceseri, Laura Cipressa, Gianna Fabbri, Andrea Lorimer, Donata Lucci, Sharang Ghavampour, Anja Knoppe, Hans Schmidt-Gurtler, Hubert Dumann, Sybille Merscher, Margret Patecki, Georg Rainer Schlieper, Anke Torp, Bianca Weber, Maja Zietz, Bernd Hohenstein, Urs Benck, Diliana Draganova, Thomas Weinreich, Lothar Wolf, Jasmine Gaidu, Hanna Reiner, Mandy Visnjic, Daniel Steffl, Marie Breitenfeldt, Annette Kraemer-Guth, Christine Braun, Simone Hagge, Michael Schomig, Stephan Matthias, Dominik Stoffler, Beate Schumacher, Thomas Sitter, Louise Fuessl, Julia Krappe, Jerome Loutan, Volker Vielhauer, Luciano Andriaccio, Magdalena Maurer, Bernhard Winkelmann, Martin Dursch, Linda Seifert, Linda Tenbusch, Julia Weinmann-Menke, Simone Boedecker, Wiebke Kaluza-Schilling, Daniel 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Bolduc, Marie-Christine Talbot, Leslie Cham, Vesta Lai, Josephine Tse, Shivinder Jolly, Tabbatha Duck, Scott Lyle, Rachel Epp, Camille Galloway, Susan Haskett, Elizabeta Matvienko, Liam Paulsen, Louise Moist, Zabrina Lozon, Tina Ramsey, Brittany Whitmore, Bader Al-Zeer, Paula Macleod, Aoife O'Sullivan, Zainab Sheriff, Sam Tholl, Amritanshu Pandey, Samantha Armstrong, Bethelihem Gebeyehu, Patrick Toth, Ronald Goldenberg, Mahsa Jahangiriesmaili, Shariff Sanguila, Neethi Suresh, Tanvi Talsania, Nadia Zalunardo, Mohsen Agharazii, Marie-Pier Roussel, Annie Saillant, France Samson, Harpreet Bajaj, Miken Bhavsar, Parul Dhall, Gagandeep Dhillon, Bhupinder Grewal, Taniya Nimbkar, Francois Madore, Guylaine Marcotte, Oren Steen, Mathura Bullen, Shayani Raguwaran, Andre Valleteau, Marie-France Langlois, Christine Brown, Andrew Steele, Melissa Garrity, Taneera Ghate, Holly Robinson, Michael Tolibas, Chetna Tailor, Lauren Elliott, Christine McClary-Wright, Fadia Boreky, Sameh Fikry, Ayesha Ali, Chintankumar Barot, Wagdy Basily, Thisun Saram, Vinay Varad, Hasnain Khandwala, Alex Aguilera, Patricia Alvarez, Balwinder Gill, Nazihah Huda, Aamir Navivala, Daniel Pinto, Micheli Bevilacqua, Elaine Fung, Geraldine Hernandez, Puneet Mann, Jaskiran Saini, Remi Rabasa-Lhoret, Danijela Bovan, Marie Devaux, Cecilia Barnini, Giovanna Leoncini, Luca Manco, Giulia Nobili, Matteo Piemontese, Filippo Aucella, Rachele Grifa, Francesco Totaro, Gaetano La Manna, Irene Capelli, Giuseppe Cianciolo, Sarah Lerario, Fulvia Zappulo, Alberto Rosati, Filippo Fani, Giuseppe Spatoliatore, Loreto Gesualdo, Francesco Pesce, Maria Russo, Maria Zippo, Cesira Cafiero, Daria Motta, Simona Bianco, Donatella Bilucaglia, Piergiorgio Messa, Laura Pavone, Federica Tripodi, Simone Vettoretti, Paola Fioretto, Gianni Carraro, Filippo Farnia, Anna Postal, Alessandro D'Amelio, Antonio Cardone, Giovanni Piccinni, Annalisa Aloisi, Francesco Scolari, Federico Alberici, Alice Guerini, Chiara Saccà, Chiara Salviani, Roberta Zani, Luca De Nicola, Carlo Garofalo, Maria Elena Liberti, Roberto Minutolo, Luigi Pennino, Lucio Polese, Paolo Mené, Simona Barberi, Clorinda Falcone, Francesco Russo, Maurizio Caroppo, Gennaro Santorelli, Rodolfo Rivera, Domenico Santoro, Alfio Giuffrida, Fortunata Zirino, Cristina Calvi, Luca Estienne, Giovanni Gambaro, Concetta Gangemi, Vittorio Ortalda, Giuseppina Pessolano, Giuseppe Grandaliano, Rocco Baccaro, Pietro Ferraro, Roberto Mangiacapra, Marco Melandri, Nadia Foligno, Rita Quartagno, Giuseppe Vezzoli, Elena Brioni, William G, Herrington, Natalie, Staplin, Christoph, Wanner, Jennifer B, Green, Sibylle J, Hauske, Jonathan R, Emberson, David, Prei, Parminder, Judge, Kaitlin J, Mayne, Sarah Y A, Ng, Emily, Sammon, Doreen, Zhu, Michael, Hill, Will, Steven, Karl, Wallendszu, Susanne, Brenner, Alfred K, Cheung, Zhi-Hong, Liu, Jing, Li, Lai Seong, Hooi, Wen, Liu, Takashi, Kadowaki, Masaomi, Nangaku, Adeera, Levin, David, Cherney, Aldo P, Maggioni, Roberto, Pontremoli, Rajat, Deo, Shinya, Goto, Xavier, Rossello, Katherine R, Tuttle, Dominik, Steubl, Michaela, Petrini, Dan, Massey, Jens, Eilbracht, Martina, Brueckmann, Martin J, Landray, Colin, Baigent, Richard, Hayne, EMPA-KIDNEY Collaborative Group: Colin Baigent, The, J Landray, Martin, Wanner, Christoph, G Herrington, William, Haynes, Richard, B Green, Jennifer, J Hauske, Sibylle, Brueckmann, Martina, Hopley, Mark, von-Eynatten, Maximillian, George, Jyothi, Brenner, Susanne, K Cheung, Alfred, Preiss, David, Liu, Zhi-Hong, Li, Jing, Hooi, Laiseong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Pontremoli, Roberto, P Maggioni, Aldo, Staplin, Natalie, Emberson, Jonathan, Hantel, Stefan, Goto, Shinya, Deo, Rajat, R Tuttle, Katherine, Hill, Michael, Judge, Parminder, J Mayne, Kaitlin, A Ng, Sarah Y, Rossello, Xavier, Sammons, Emily, Zhu, Doreen, Sandercock, Peter, Bilous, Rudolf, Herzog, Charle, Whelton, Paul, Wittes, Janet, Bennett, Derrick, Achiri, Patricia, Ambrose, Chrissie, Badin, Cristina, Barton, Jill, Brown, Richard, Burke, Andy, Butler, Sebastian, Dayanandan, Rejive, Donaldson, Pia, Dykas, Robert, Fletcher, Lucy, Frederick, Kate, Kingston, Hannah, Gray, Mo, Harding, Emily, Hashimoto, Akiko, Howie, Lyn, Hurley, Susan, Lee, Ryonfa, Luker, Nik, Murphy, Kevin, Nakahara, Mariko, Nolan, John, Nunn, Michelle, Mulligan, Sorcha, Omata, Akiko, Pickworth, Sandra, Qiao, Yanru, Shah, Shraddha, Taylor, Karen, Timadjer, Alison, Willett, Monique, Wincott, Liz, Yan, Qin, Yu, Hui, Bowman, Louise, Chen, Fang, Clarke, Robert, Goonasekera, Michelle, Karsan, Waseem, Mafham, Marion, Reith, Christina, Zayed, Mohammed, Ellison, Ritva, Moys, Rowan, Stevens, Will, Verdel, Kevin, Wallendszus, Karl, Bowler, Chri, Brewer, Anna, Measor, Andy, Cui, Guanguo, Daniels, Charle, Field, Angela, Goodenough, Bob, Lawson, Ashley, Mostefai, Youcef, Radhakrishnan, Dheeptha, Syed, Samee, Xia, Shuang, Adewuyi-Dalton, Ruth, Arnold, Thoma, Beneat, Anne-Marie, Bhatt, Anoushka, Bird, Chloe, Breach, Andrew, Brown, Laura, Caple, Mark, Chavagnon, Tatyana, Chung, Karen, Clark, Sarah, Condurache, Luminita, Eichstadt, Katarzyna, Espino Obrero, Marta, Forest, Scarlett, French, Helen, Goodwin, Nick, Gordon, Andrew, Gordon, Joanne, Guest, Cat, Harding, Tina, Hozak, Michal, Lacey, Matthew, Maclean, David, Messinger, Louise, Moffat, Stewart, Radley, Martin, Shenton, Claire, Tipper, Sarah, Tyler, Jon, Weaving, Lesley, Wheeler, Jame, Williams, Elissa, Williams, Tim, Woodhouse, Hamish, Chamberlain, Angela, Chambers, Jo, Davies, Joanne, Donaldson, Denise, Faria-Shayler, Pati, Fleming-Brown, Denise, Ingell, Jennifer, Knott, Carol, Liew, Anna, Lochhead, Helen, Meek, Juliette, Rodriguez-Bachiller, Isabel, Wilson, Andrea, Zettergren, Patrick, Aitsadi, Rach, Barton, Ian, Baxter, Alex, Bu, Yonghong, Danel, Lukasz, Grotjahn, Sonja, Kurien, Rijo, Lay, Michael, Maskill, Archie, Murawska, Aleksandra, Raff, Rachel, Young, Allen, Sardell, Rebecca, Cejka, Vladimir, Fajardo-Moser, Marcela, Hartner, Christian, Poehler, Dori, Renner, Janina, Scheidemantel, Franziska, Bryant, Miya, Hepditch, Anita, Johnson, Cassandra, Latore, Erin, Miller, Yolanda, Price, Lauren, Whalen, Merilee, Wheeler, Ashleigh, Ingell, Jenny, An, Yu, Chen, Yinghua, Chen, Peiling, Dai, Hao, Du, Hong, Feng, Fang, Guo, Qing, Hou, Libo, Hundei, Wuhanbilige, Jin, Binbin, Li, Yan, Liu, Jiamin, Song, Xia, Wang, Yanping, Yu, Yanwu, Zhang, Ning, Zhao, Lingshan, Zhong, Hui, Beng Goh, Cheng, Mun Low, Ye, Yi Sor, Soon, Hanis Zulkipli, Farah, Sivanandam, Sarojini, Arai, Natsuki, Fukasawa, Ai, Furukawa, Mizue, Habuki, Keisuke, Hayashi, Shoko, Isari, Wakako, Kanegae, Saki, Kawai, Maria, Kobayashi, Reiki, Kuramae, Takako, Kuribayashi, Chika, Maeno, Sawako, Masumoto, Satoshi, Morisaki, Tomoko, Oda, Minoru, Sawada, Kazue, Sugamori, Kenta, Tatsuzawa, Ayana, Tomita, Aiko, Yuasa, Kazuyuki, Inazawa, Hiroko, Axler, Amanda, Gallo, Kerri, Baldini, Ester, Bartolomei Mecatti, Barbara, Bianchini, Francesca, Ceseri, Martina, Cipressa, Laura, Fabbri, Gianna, Lorimer, Andrea, Lucci, Donata, Ghavampour, Sharang, Knoppe, Anja, Schmidt-Gurtler, Han, Dumann, Hubert, Merscher, Sybille, Patecki, Margret, Rainer Schlieper, Georg, Torp, Anke, Weber, Bianca, Zietz, Maja, Hohenstein, Bernd, Benck, Ur, Draganova, Diliana, Weinreich, Thoma, Wolf, Lothar, Gaidu, Jasmine, Reiner, Hanna, Visnjic, Mandy, Steffl, Daniel, Breitenfeldt, Marie, Kraemer-Guth, Annette, Braun, Christine, Hagge, Simone, Schomig, Michael, Matthias, Stephan, Stoffler, Dominik, Schumacher, Beate, Sitter, Thoma, Fuessl, Louise, Krappe, Julia, Loutan, Jerome, Vielhauer, Volker, Andriaccio, Luciano, Maurer, Magdalena, Winkelmann, Bernhard, Dursch, Martin, Seifert, Linda, Tenbusch, Linda, Weinmann-Menke, Julia, Boedecker, Simone, Kaluza-Schilling, Wiebke, Kraus, Daniel, Krieger, Carina, Schmude, Margit, Schreiber, Anne, Eckrich, Ewelina, Tschope, Diethelm, Arbi, Abdulwahab, Lee-Barkey, Young, Stratmann, Bernd, Prib, Natalie, Rolfsmeier, Sina, Schneider, Irina, Rump, Lar, Stegbauer, Johanne, Pötz, Christine, Schemmelmann, Mara, Schmidt, Claudia, Koch, Michael, Aker, Sendogan, Küpper, Annika, Martin, Manuela, Pfab, Thiemo, Albert, Christian, Haase, Michael, Zander, Barbara, Schneider-Danwitz, Claudia, Seeger, Wolfgang, Seeger, Wolf-Adam, Zemann, Britta, Stellbrink, Christoph, Marx, Kristin, Stellbrink, Ekaterina, Brettschneider, Britta, Watson, Stephanie, Iselt, Marion, Klausmann, Gerhard, Kummer, Inga-Nadine, Kutschat, Auguste, Streitenberger, Simone, Girndt, Matthia, Markau, Silke, Girakossyan, Ina, Hanf, Claudia, Beige, Joachim, Wendt, Ralph, Schmidt, Ulrike, Schneider, Andrea, Veelken, Roland, Donhauser, Claudia, Becker, Lui, Miftari, Nexhat, Wolfling, Ricarda, Morlok, Sarah, Hugo, Christian, Paliege, Alexander, Passauer, Jen, Stumpf, Julian, Fleischer, Annegret, Haaser, Kerstin, Kraemer, Bernhard, Jochims, Jan, Kruger, Bernd, Foellinger, Claudia, Reisler, Anastassiya, Strutz, Frank, Haack, Stefan, Hohenstatt, Ursula, Busch, Martin, Herfurth, Konstantin, Wolf, Gunter, Paul, Rainer, Haller, Hermann, Kaufeld, Jessica, Menne, Jan, Bahlmann-Kroll, Elisabeth, Bergner, Angela, Weihprecht, Horst, Er, Aydin, Sonntag, Florian, Turan, Elif, Wittmann, Michael, Klauser, Franziska, Voigt, Eva, Schettler, Volker, Schulz, Egbert, Rohnstock, Madlen, Schettler, Elke, Schroppel, Bernd, van Erp, Rene, Kachele, Martin, Ludwig, Ulla, Schulte-Kemna, Lena, Kmietschak, Waltraud, Preiss, Elke, Ruocco, Martina, Heine, Gunnar, Brzoska, Martin, Gabel, Sebastian, Büttner, Christina, Sabarai, Asma, Banas, Bernhard, Bergler, Tobia, Ehrl, Yvonne, Putz, Franz, Schuster, Antonia, Kuhn, Stefanie, Schramm, Torsten, Degenhardt, Stefan, Schmidt, Gerhard, Weiland, Lea, Giebeln-Hudnell, Ulrike, Kielstein, Jan, Eden, Gabriele, Fuchs, Brigitte, Morig, Gina, Winkler, Manuela, Darius, Harald, Kriatselis, Charalampo, Roesch, Carl-Philipp, Maselli, Astrid, Alscher, Dominik, Ketteler, Marku, Schanz, Moritz, Schricker, Severin, Rettenmaier, Bianka, Schwab, Andrea, Pergola, Pablo, Leal, Irene, Cagle, Melissa, Romo, Anna, Torres, Anthony, Joshi, Sucharit, Barrett, Kulli, Africano, Alexi, Dodds, Vicki, Gowen, Dorleena, Morris, Ashlee, Fernandez, Juan, Jimenez, Guillermo, Viera, Ricardo, Bruce, Kendaling, Barrios, Ryan, Garcia, Maylin, Garcia, Kerelyn, Leal, Iradi, Tietjen, David, Bains, David, Castillo, Carlo, Brewer, Genielle, Davis, Justin, Freking, Natalie, Golson, Brittany, Ham, Sally, Roesch, Jesslyn, Suchinda, Pusadee, Beigh, Shameem, Lilavivat, Usah, Bilton, Joyce, Bocchicchia, Kim, Turner, Jeffrey, Dahl, Neera, Peixoto, Aldo, Kavak, Yasemin, Liberti, Lauren, Nair, Hari, Page, Nicola, Rosenberg, Stephanie, Simmons, Kathryn, Isakova, Tamara, Frazier, Rebecca, Mehta, Rupal, Srivastava, Anand, Fox, Patrick, Hecktman, Jonathan, Hodakowski, Alexander, Martinez, Carlo, Phillips, Rachel, Stevenson, Alexi, Mustafa, Reem, Jansson, Kyle, Kimber, Cassandra, Stubbs, Jason, Tuffaha, Ahmad, Yarlagadda, Sri, Griffin, Debbie, Laundy, Elisabeth, Tang, Zhuo, Alicic, Radica, Cooper, Ann, Davis, Lisa, Gore, Ashwini, Goldfaden, Rebecca, Harvill, Leslie, Hichkad, Lisa, Johns, Barry, Jones, Thoma, Merritt, Kayla, Sheldon, Jennifer, Stanfield, Jennifer, Alexander, Lindsay, Preston, Kaitlyn, Wood, Lindsey, Pradhan, Rajesh, Deraad, Roger, Mcintosh, Kelli, Raymond, Loui, Shepperd, Michael, Mclaughlin, Susan, Seifert, Mary, Shepherd, Andrew, Aiello, Joseph, Durham, William, Loudermilk, Laurie, Manley, John, Burnette, Sabrina, Evans, Stephanie, Johnson, Tara, Sloan, Lance, Ann Acosta, Judy, Gillham, Stacy, Sloan, Katia, Squyres, Sueann, Rocco, Michael, Hawfield, Amret, Bagwell, Ben, Richmond, Lauren, Soufer, Joseph, Clarke, Subha, Aliu, Amanda, Calabrese, Kristine, Davis, Amanda, Poma, Veronica, Spinola, Tracy, Magee, Jame, Silva, Ricardo, Choksi, Rushab, Dajani, Lorraine, Evans, John, George, Anil, Krish, Prasanth, Martins, Gerard, Sheikh-Ali, Mae, Sutton, David, Driver, Freda, Hanburry, Abraham, Hume, Laura, Hurst, Amber, Taddeo, Matthew, Turner, Marla, Yousif, Veronica, Beddhu, Srinivasan, Al-Rabadi, Laith, Abraham, Nikita, Caamano, Amalia, Carle, Judy, Gonce, Victoria, Staylor, Kaitlyn, Zhou, Na, Bansal, Shweta, Bhattarai, Manoj, Sharma, Kumar, Debnath, Subrata, Garza, Aliseiya, Velagapudi, Chakradhar, Rovner, Sergio, Almeida, Javier, Casares, Pablo, Stewart-Ray, Verlaine, Almaraz, Rene, Dayrell, Renata, Moncada, Ana, Pulido, Ricardo, Rodriquez, Roxana, Deeb, Wasim, Degoursey, Kathryn, Gloria, Rodel, Greene, Trevor, Miller, Robert, Pereira, Edward, Roura, Miguel, Domingo, Debbie, Dorestin, Sasha, Hodge, William, Jackson, Cathy, Lund, Deborah, Taylor, Katrina, Boren, Kenneth, Cleveland, Brittany, Gaiser, Sandra, Sahani, Mandeep, Aldrich, Logan, Edmerson, Exodu, Limon, Edmond, Valletta, Cole, Vasquez, Patricia, Provenzano, Christopher, Brar, Navkiranjot, Henderson, Heather, Keith, Bellovich, Khai, Qur, Khairullah, Quresh, Makos, Gail, Topf, Joel, Gasko, Sherry, Henschel, Rosemarie, Knapp, Kaitlin, Kozlowski, Teresa, Lafleur, Paula, Varughese, Ashwathy, Xue, Hui, Wu, Patricia, Arechiga, Olga, Darbeau, Shan, Fechter, Michael, Martinez, Stephanie, Hanson, Lenita, Cooper, Nyla, Madera, Areli, Cadorna, Jay, Sheridan, Rita, Sparks, Helen, Eilerman, Bradley, Bodine, Susanne, Eid, Wael, Flora, Rebecca, Avery, Amber, Hardy, Cashmere, Biscoveanu, Mihaela, Nagelberg, Steven, Cummins, Tracey, Rahbari-Oskoui, Frederic, Oommen, Anju, Forghani, Zohreh, Hitchcock, Stacie, Hosein, Darya, Watkins, Diane, Patel, Minesh, Lambert, Anthony, Newman, Elizabeth, Wood, Autumn, Ross, Tammy, Topping, Stephany, Mulhern, Jeffrey, Murphy, Lorna, Vasseur, Ann, Greenwood, Gregory, Hadley, Alexander, Laurienti, Denise, Marshall, Christopher, Mclean, Nichola, Satko, Scott, Caudill, Brandy, Maris, Jacob, Rogers, Janice, Vanhoy, Cindy, Thomas, George, Nakhoul, George, O'Toole, John, Taliercio, Jonathan, Cooperman, Leslie, Markovic, Marina, Tucky, Barbara, Dev, Devasmita, Hasan, Alia, Yalamanchili, Hima, Jain, Namita, Mcneil, Lesley, Wines, Eric, Park, Jean, Ghazi, Adline, Hamm, Mia, Patel, Teja, Mottl, Amy, Chang, Emily, Derebail, Vimal, Cole, Emmie, Froment, Anne, Kelley, Sara, Osmond Foster, Jordan, Mahabadi, Vahid, Jafari, Golriz, Kamarzarian, Anita, Arriaga, Wendy, Arteaga, Daisy, Machicado, Rosario, Naverrete, Genesi, Kumar, Prashant, Nazeer, Imran, Urquia, Karina, Glider, Tammi, Jones, Vickie, Rucker, Savannah, Wiley, Jennifer, Pandey, Rahul, Arroyo, Jesu, Pariani, Harish, Ahmad, Mohammad, Mozaffari, Shahin, Perez, Erika, Budoff, Matthew, Roy, Sion, Birudaraju, Divya, Ghanem, Ahmed, Hamal, Sajad, Aronoff, Stephen, Joye Petr, Elisa, Sachson, Richard, Wiebel, Jaime, Akram, Sana, Jones, Laurie, Knight, Curti, Tarlac, Maurie, Ahmed, Shahbaz, Szerlip, Harold, Akinfolarin, Akinwande, Mehta, Ankit, Camp, Shana, Castro, Cindy, Cooper, Zanaida, Terry, Jessica, Awad, Ahmed, Kothapalli, Bhavya, Lustig, Ryan, Alfaress, Serine, Jasim, Hyder, Parrigon, Mary, Karounos, Denni, Ahmed, Sadiq, Berry, Maggie, Oremus, Ruth, Hernandez-Cassis, Carlo, Ugwu, Elia, Junejo, Nazia, Suazo, Nancy, Segal, Mark, Kazory, Amir, Brown, Sherry, Daniels, Tristan, Dayi, Sofia, Hogan, Renee, Mccray, Kathy, Stickley, Jennifer, Rahman, Mahboob, Dobre, Mirela, Negrea, Lavinia, Padiyar, Aparna, Pradhan, Nishigandha, Rashidi, Arash, Sarabu, Nagaraju, Donley, Vicki, Young, Tricia, Oguchi, Godson, Onyema, Judepatrick, Damianik, Kahla, Dienes, Jack, Plummer-Morgan, Judith, Roman, Marilyn, Skipper, Mauver, Villaruel, Stacey-Ann, Williams, Krystle, Sugimoto, Danny, Dugas, Jeffrey, Ahmed, Ismeal, Bhairoo, Jamie, Rijos, Dolore, Salim, Huzaifa, Gavrila, Madita, Lafferty, Kathryn, Rabara, Ria, Ruse, Sally, Weetman, Maria, Bushnell, Jame, Power, Albert, Jenkins, Alison, Jones, Stefanie, Scott, Amanda, Byrne, Cath, Jesky, Mark, Cowley, Alison, Mchaffie, Emma, Waterfall, Holly, Taylor, Jo, Bough, Laura, Phillips, Thoma, Winter-Goodwin, Barbara, Phin Kon, Sui, Macdougall, Iain, Lioudaki, Eirini, Shah, Sapna, Sharpe, Claire, Aguilar, Francisco, Hernandez Pena, Abegail, Pugay, Conception, Te, Amelia, Finn, Hugh, Hanif, Wasim, Mostafa, Samiul, Aitken, Alice, Draxlbauer, Katharine, Grobovaite, Evelina, Kearney, Jennifer, Mccarthy, Theresa, Gentile, Giorgio, Browne, Duncan, Chellamuthu, Palanichamy, Dugal, Tabinda, Chant, Terri, Jones, Laura, Laity, Emily, Miners, Megan, Muir, Jame, Swanson, Elizabeth, Frankel, Andrew, Tomlinson, Jame, Alegata, Marlon, Almasarwah, Rashid, Apostolidi, Anthoula, Vourvou, Maria, Walters, Thoma, Taal, Maarten, Dukka, Hari, Kolhe, Nitin, Mcdonald, Carly, White, Kelly, Ugni, Shiva, Gunda, Smita, Oluyombo, Rotimi, Brindle, Vicki, Coutts, Ping, Fuller, Tracy, Nadar, Evelyn, Ramadoss, Suresh, Motherwell, Nichola, Pajak, Susannah, Tonks, Louise, Bhandari, Sunil, Bodington, Richard, Hazara, Adil, Fellowes, Dominic, Wong, Christopher, Goldsmith, Christopher, Barnes, Sherald, Bennett, Ann, Burston, Claire, Hope, Samantha, Hunt, Nicola, Kurian, Lini, Fish, Richard, Farrugia, Daniela, Lee, Judy, Sadler, Emma, Turner, Hannah, Hill, Christopher, Brown, Henry, Masengu, Agne, Maxwell, Peter, Bleakley, Nina, Murtagh, Hugh, Petchey, William, Yiu, Vivian, Kellett, Joanne, Williams, Angharad, Clarke, Helen, Carnall, Victoria, Benyon, Sarah, Blake, Caroline, Estcourt, Stephanie, Piper, Jane, Morgan, Neal, Hutchinson, Carolyn, Mckinley, Teresa, Woodman, Alastair, Graham, Judi, Leonard, Niall, Smyth, John, Adell, Vicki, Hagan, Samantha, Caplin, Ben, Oomatia, Amin, Damian, Eleanor, Sobande, Toluleyi, Doulton, Tim, Delaney, Michael, Montasser, Mahmoud, Hansen, Jenny, Loader, David, Moon, Angela, Morris, France, Sinha, Smeeta, Chukwu, Chukwuma, Hudson, Amy, Campbell, Diane, Kershaw, Melanie, Whittaker, Stephanie, Irtiza-Ali, Ayesha, Ghalli, Farid, Nosseir, Heba, Leslie, Allison, Trivedi, Kate, Fraser, Donald, Alhadj Ali, Mohammad, Griffin, Sian, Latif, Farah, Witczak, Justyna, Wonnacott, Alexa, Jeffers, Lynda, Webley, Yvette, Phelan, Paul, Miller-Hodges, Eve, Geddes, Ailsa, Glenwright, Margaret, Hunter, Amy, Pickett, Thoma, Moriarty, Jim, Hill, Linda, Tyler, Amanda, Ayub, Waqar, Evans, Gail, Hewins, Sue, Hewitt, Davina, Read, Kerry, Bell, Samira, Cosgrove, Leanne, Craik, Rachel, Murray, Shona, Bhandary, Nitin, Coles, Holly, Easow, Rashmi, Joseph, Maya, Khwaja, Arif, Jackson, Yvonne, Mbuyisa, Angeline, Sellars, Rachel, Chitalia, Nihil, Mohandas, Cynthia, Gherman, Anca, Kamundi, Charlotte, Olufuwa, Olumide, Mccafferty, Kieran, Adeleke, Adedolapo, Healy, Cara, Jeyarajah, Damini, Kinsella-Perks, Edward, Smith, Richard, Camilleri, Brian, Buckman, Carol, Finch, Jenny, Rivers, Vanessa, Connor, Andrew, Carr, Sheila, Shainberg, Lisa, Lewington, Andrew, Baker, Richard, Dorey, Suzannah, Tobin, Kay, Wheatley, Rosalyn, Banerjee, Debasish, Hull, Richard, Abat, Sharirose, Paul, Riny, Karim, Mahzuz, Htet, Zay, Tufail, Saad, Varma, Ravi, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Tropman, Emily, Abdul-Samad, Thahir, Grace, Anne, Phipps, Marie, Suckling, Rebecca, Somalanka, Subash, Sood, Bhrigu, Swift, Pauline, Acheampong, Sarah, Ansu, Kwame, Augustin, Martia, Sampson, Anna, Vinall, Lynn, Wren, Kim, Wanninayake, Shamila, Wooding, Nichola, Edwards, Heather, Owen, Lydia, Bolton, Stephanie, Carson, Marion, Matthews, Michael, Brunskill, Nigel, Jesus-Silva, Jorge, Howson, Alex, Quashie-Akponeware, Mary, Tindall, Hilary, Nethaji, Chidambaram, Eldon, Helen, Patel, Rajan, Mark, Patrick, Rankin, Alastair, Sullivan, Michael, Forsyth, Kirsty, Mcdougall, Rowan, Dasgupta, Tanaji, Davies, Louisa, Ryder, Maggie, Grimmer, Philip, Macdonald, Clare, Webster, Mary, Newcastle, Newcastle, Ellam, Timothy, Wong, Edwin, Meshykhi, Christine, Webster, Andrea, Wilson, Peter, Vilar, Enric, Berdeprado, Jocelyn, Doctolero, Eunice, Wilkinson, Lily, Mccarroll, Frank, Ammar, Hesham, Kuan, Ying, Moran, Conor, Shivashankar, Girish, Campbell, Ryan, Glowski, Deborah, Mcdermott, Paula, Ali, Amar, Patel, Zuber, Bond, Christine, Whalley, Gillian, Zhang, Haitao, Yang, Liu, Zhang, Lihua, Kan, Tingting, Zhu, Ling, Zhao, Jinghong, Hou, Weiping, Wu, Jing, Cheng, Hong, Bian, Weijing, Zhao, Zhirui, Shao, Fengmin, Cao, Huixia, Jiao, Xiaojing, Niu, Peiyuan, Niu, Jianying, Chen, Yu, Zhang, Lihong, Zhu, Shenglang, Lin, Haiyan, Yao, Shaopeng, Chen, Jiehui, Jiang, Ying, Hu, Ying, Xiao, Huaying, Yang, Fuye, Zhang, Xinzhou, Guo, Baochun, Jin, Qiu, Liu, Lixia, Xiao, Xiangcheng, Xie, Yanyun, Meng, Ting, Xu, Chuanwen, Huang, Jie, Xu, Yanmei, Kong, Weixin, Wang, Xiaoliang, Liu, Qianpan, Wang, Xueying, Gao, Ming, Hu, Xiumei, Lu, Ying, Wang, Li, Peng, Kun, Wang, Wei, Gong, Qiuhong, Cai, Jianfang, Li, Xiaojue, Liu, Xuejiao, Zhou, Shuhan, Liu, Hong, Weng, Yao, Tang, Shuai, Yao, Yao, Zhao, Shi, Cheng, Chen, Wei, Wei, Li, Na, Aqashiah Mazlan, Sadanah, Zubaidah Bahtar, Alia, Katiman, Elliyyin, Othman, Noraini, Mushahar, Lily, Mazlan, Nurdiana, Sharafina Safiee, Nur, Ramasamy, Sarasa, Seng Wong, Hin, Ahmad Rosdi, Hajar, Zhao Zhi Tan, Esther, Fan Tay, Ju, Seng Teng, Kok, Yahaya, Hasnah, Jiun Liu, Wen, Wee Ee, Lik, Kay Leong Khoo, Kenneth, Mohd Yusoff, Yuana, Safhan Mohamad Nor, Fariz, Kamil Ahmad, Mohd, Ramli Seman, Mohd, Hui Hong Tan, Clare, Lui Sian Ngu, Laura, Yoke May Chan, Jaime, Peji, Javelin, Loong Loh, Chek, Yan Lee, Yee, Ramanaidu, Sridhar, Mean Thong, Kah, Hong Wong, Yik, Junus, Suria, Hua Ching, Chen, Faisal Asmee, Mohammad, Ruziana Ku Md Razi, Ku, Leong Low, Chun, Sze Bing Sim, Christopher, Duan Tham, Zhang, Kamila Abdullah, Noor, Meng Chen, Tai, Chieh Chan, Yong, Chang, Eason, Yean Kang, Huan, Quan Lee, Kai, Ann Lee, Sue, Kheng Lee, Aik, Vinathan, Jeevika, Abdul Cader, Rizna, Mustafar, Ruslinda, Kamaruzaman, Lydia, Mohd, Rozita, Ismail, Rahimah, Men Leong, Chong, Koon Low, Chee, Wei Wong, Liang, Adnan, Norlezah, Ibrahim, Sabariah, Zaimi Abdul Wahab, Mohamad, Bavanandan, Sunita, Shen Lim, Yik, Hazlina Wan Mohamad, Wan, Munirah Jaafar, Siti, Ashykeen Mohd Fauzi, Nur, Sudin, Aziee, Kun Lim, Soo, Chung Gan, Chye, Hing, Albert, Ahmad Faizal Alaidin Razali, Wan, Fong Liew, Yew, Bao Tyng Chan, Chelsia, Chih Cheng, Mei, Chen Ong, Yu, Meng Ong, Loke, Amalina Mohamed Affandi, Farah, Rahmat, Korina, Chai Peng, Ban, Amat, Masayu, Hadafi Ahmad, Nuzaimin, Yee Mah, Doo, Loon Tye, Yi, Azhari, Zaid, Nabilah Mohamad Zaini, Siti, Aidil Musa, Mohd, Ahmad Miswan, Norazinizah, Ramli, Rafizanur, Aziah Ahmad, Nor, Leong Goh, Bak, Izah Ahmad, Nurul, Huda Ibrahim, Fairol, Jian Ng, Tze, Shanmuganathan, Malini, Lian Tay, Li, Harun, Zaiha, Ramli, Salmi, 'Ain Yusof, Nurul, Abd Rahman, Rossenizal, Iqbal Abdul Hafidz, Muhammad, Hidayati Mohd Sharif, Nur, Yasmoon Awang, Irda, Nakashima, Eitaro, Imamine, Rui, Minatoguchi, Makiko, Miura, Yukari, Nakaoka, Miduki, Suzuki, Yoshiki, Yoshikawa, Hitomi, Shin, Koki, Fujita, Kanae, Iwasa, Misuzu, Sasajima, Haruka, Sato, Airi, Hamamoto, Yoshiyuki, Fujita, Yuki, Haraguchi, Takuya, Hyo, Takanori, Izumi, Kiyohiro, Komiya, Toshiyuki, Kubota, Sodai, Kurose, Takeshi, Kuwata, Hitoshi, Nakatani, Susumu, Oishi, Kaori, Okamoto, Saki, Okamura, Kaori, Takeoka, Jun, Tanaka, Nagaaki, Tanigaki, Katsuya, Toda, Naohiro, Watanabe, Koin, Komori, Hiromi, Kumuji, Rika, Takesada, Asako, Tanaka, Aya, Maruyama, Shoichi, Hasegawa, Tomonori, Ishiguro, Akiko, Ishimoto, Takuji, Ito, Kazuhiro, Kamimura, Yutaka, Kato, Noritoshi, Kato, Sawako, Kojima, Hiroshi, Kosugi, Tomoki, Maeda, Kayaho, Mizuno, Masasi, Saito, Shoji, Sato, Hitomi, Sato, Yuka, Suzuki, Yasuhiro, Tanaka, Akihito, Yasuda, Yoshinari, Hasegawa, Fujiko, Hayashi, Maiko, Higashi, Shizuka, Shimamura, Kaho, Sumi, Momoko, Tajima, Kazuki, Unekawa, Chimaki, Wakayama, Kana, Wakita, Yukiko, Otani, Takatoshi, Imai, Ayako, Kawashima, Sayaka, Kogure, Eri, Sato, Tomoe, Takezawa, Misato, Yoshida, Shinya, Araki, Hideo, Katsuda, Yuko, Konishi, Masahiro, Matsunaga, Takahiro, Oe, Masashi, Ogane, Kunihiro, Sakai, Masato, Takahashi, Tomoko, Yamano, Takahiro, Yokoyama, Takuya, Ito, Hitomi, Katayama, Masayo, Kuroda, Emi, Ikeda, Toru, Kojo, Takuma, Yoshidome, Etsuo, Mizumachi, Rieko, Yamamoto, Akane, Yamasaki, Narihisa, Yamasaki, Yoshihiko, Wada, Jun, Eguchi, Jun, Higuchi, Chigusa, Katayama, Akihiro, Kinomura, Masaru, Kitagawa, Masashi, Kitamura, Shinji, Miyamoto, Satoshi, Morinaga, Hiroshi, Nakatsuka, Atsuko, Nojima, Ichiro, Shikata, Kenichi, Sugiyama, Hitoshi, Tanabe, Katsuyuki, Tsuji, Kenji, Uchida, Haruhito, Watanabe, Mayu, Hashimoto, Chie, Kato, Takahiro, Yamamoto, Sayaka, Wada, Takehiko, Fukagawa, Masafumi, Hamano, Naoto, Koizumi, Masahiro, Komaba, Hirotaka, Nakagawa, Yosuke, Iwamoto, Michiyo, Masutani, Kosuke, Katanosaka, Akane, Kiyota, Mayu, Uchi, Hikari, Ueda, Yuka, Yamamoto, Sonoka, Nagasu, Hajime, Itano, Seiji, Iwakura, Tsukasa, Kadoya, Hiroyuki, Kanda, Eiichiro, Kashihara, Naoki, Kidokoro, Kengo, Kondo, Megumi, Sasaki, Tamaki, Satoh, Minoru, Tokuyama, Atsuyuki, Umeno, Reina, Wada, Yoshihisa, Yamamoto, Toshiya, Yamanouchi, Yu, Abe, Masumi, Inukai, Yoko, Ogawa, Wataru, Asahara, Shunichiro, Fujii, Hideki, Goto, Shunsuke, Hirota, Yushi, Hosooka, Tetsuya, Kono, Keiji, Nishi, Shinichi, Okada, Yuko, Sakaguchi, Kazuhiko, Sugawara, Kenji, Takahashi, Michiko, Takai, Tomoko, Tamori, Yoshikazu, Watanabe, Kentaro, Kitajima, Miyu, Nishi, Misaki, Wada, Junko, Ito, Yasuhiko, Kamiya, Hideki, Asai, Akimasa, Asai, Nao, Asano, Saeko, Banno, Shogo, Ejima, Yohei, Hase, Hanako, Hayami, Tomohide, Himeno, Tatsuhito, Ishikawa, Takahiro, Ito, Mayumi, Iwagaitsu, Shiho, Kasagi, Rina, Kato, Yoshiro, Kato, Makoto, Kato, Koichi, Katsuno, Takayuki, Kawai, Miyuka, Kinashi, Hiroshi, Kondo, Masaki, Koshino, Masako, Matsuoka, Naoya, Morishita, Yoshiaki, Motegi, Mikio, Nakamura, Jiro, Shimoda, Hiromi, Sugiyama, Hirokazu, Tsunekawa, Shin, Yamaguchi, Makoto, Takahashi, Kazuyo, Watada, Hirotaka, Funayama, Takashi, Furukawa, Yasuhiko, Gohda, Tomohito, Goto, Hiromasa, Kaga, Hideyoshi, Kanaguchi, Yasuhiko, Kanazawa, Akio, Kaneko, Kayo, Kano, Toshiki, Kihara, Masao, Kimura, Shogo, Kobayashi, Takashi, Maiguma, Masayuki, Makita, Yuko, Mano, Satoshi, Mita, Tomoya, Miyatsuka, Takeshi, Murakoshi, Maki, Muto, Masahiro, Nakata, Masami, Nakata, Junichiro, Nishida, Yuya, Nohara, Nao, Ogihara, Takeshi, Sato, Daisuke, Sato, Junko, Sato, Hiroaki, Suzuki, Yusuke, Suzuki, Ruka, Suzuki, Hitoshi, Takagi, Miyuki, Tamura, Yoshifumi, Uchida, Toyoyoshi, Ueda, Seiji, Asawa, Miki, Miyaji, Minako, Nagashima, Eri, Shibata, Yoshie, Yanagisawa, Eri, Yamauchi, Toshimasa, Hirakawa, Yosuke, Nishi, Hiroshi, Shojima, Nobuhiro, Horikawa, Satoko, Nakayama, Yukiko, Yamada, Naoko, Omori, Yuki, Yano, Shintaro, Ioka, Miyabi, Kuwabara, Nahoko, Nagano, Remi, Nozawa, Megumi, Osawa, Yumi, Maegawa, Hiroshi, Kume, Shinji, Araki, Shinichi, Miyazawa, Itsuko, Morino, Katsutaro, Kawai, Ikuko, Sobata, Masumi, Takaoka, Motoko, Iwaita, Yasushi, Udagawa, Takashi, Inamori, Ami, Kawase, Aya, Yamanaka, Aya, Shimano, Hitoshi, Fujita, Akiko, Iwasaki, Hitoshi, Kai, Hirayasu, Osaki, Yoshinori, Saito, Chie, Sekiya, Motohiro, Tsunoda, Ryoya, Yamagata, Kunihiro, Nakamura, Rikako, Yamada, Aiko, Ohsugi, Mitsuru, Awazawa, Motoharu, Bouchi, Ryotaro, Hashimoto, Shota, Hashimoto, Makiko, Hisatake, Tomoko, Ihana, Noriko, Ishizuka, Koko, Izumi, Kazuo, Kajio, Hiroshi, Kobayashi, Michi, Kodani, Noriko, Maruyama, Koji, Matsumoto, Michihiro, Matsushita, Maya, Nakamura, Tomoka, Sugiyama, Takehiro, Tanabe, Akiyo, Terakawa, Aiko, Ueki, Kojiro, Orimo, Yuko, Ozawa, Takako, Takahira, Eriko, Yamasaki, Yoshimitsu, Haneda, Masakazu, Tomita, Tadahiro, Akimoto, Saori, Fujimoto, Akihiro, Ishihara, Kenji, Murakami, Chiho, Nishiyama, Akiyo, Toyonaga, Yukiko, Uozumi, Kana, Yamaji, Yukihiro, Shigehara, Tetsuya, Okajyo, Jun, Shimizu, Yukihiro, Iwasaki, Shingo, Fukao, Yuki, Furusho, Megumi, Nunokawa, Shintaro, Katagiri, Hideki, Izumi, Tomohito, Kaneko, Keizo, Kodama, Shinjiro, Miyazaki, Mariko, Munakata, Yuichiro, Nagasawa, Tasuku, Oe, Yuji, Sugawara, Hiroto, Takahashi, Kei, Hirata, Kazushige, Inomata, Keiko, Otomo, Shoko, Uchida, Taeko, Yamashita, Chigusa, Kiyosue, Arihiro, Tamura, Ryota, Dube, Francoi, Bolduc, Marilene, Talbot, Marie-Christine, Cham, Leslie, Lai, Vesta, Tse, Josephine, Jolly, Shivinder, Duck, Tabbatha, Lyle, Scott, Epp, Rachel, Galloway, Camille, Haskett, Susan, Matvienko, Elizabeta, Paulsen, Liam, Moist, Louise, Lozon, Zabrina, Ramsey, Tina, Whitmore, Brittany, Al-Zeer, Bader, Macleod, Paula, O'Sullivan, Aoife, Sheriff, Zainab, Tholl, Sam, Pandey, Amritanshu, Armstrong, Samantha, Gebeyehu, Bethelihem, Toth, Patrick, Goldenberg, Ronald, Jahangiriesmaili, Mahsa, Sanguila, Shariff, Suresh, Neethi, Talsania, Tanvi, Zalunardo, Nadia, Agharazii, Mohsen, Roussel, Marie-Pier, Saillant, Annie, Samson, France, Bajaj, Harpreet, Bhavsar, Miken, Dhall, Parul, Dhillon, Gagandeep, Grewal, Bhupinder, Nimbkar, Taniya, Madore, Francoi, Marcotte, Guylaine, Steen, Oren, Bullen, Mathura, Raguwaran, Shayani, Valleteau, Andre, Langlois, Marie-France, Brown, Christine, Steele, Andrew, Garrity, Melissa, Ghate, Taneera, Robinson, Holly, Tolibas, Michael, Tailor, Chetna, Elliott, Lauren, McClary-Wright, Christine, Boreky, Fadia, Fikry, Sameh, Ali, Ayesha, Barot, Chintankumar, Basily, Wagdy, Saram, Thisun, Varad, Vinay, Khandwala, Hasnain, Aguilera, Alex, Alvarez, Patricia, Gill, Balwinder, Huda, Nazihah, Navivala, Aamir, Pinto, Daniel, Bevilacqua, Micheli, Fung, Elaine, Hernandez, Geraldine, Mann, Puneet, Saini, Jaskiran, Rabasa-Lhoret, Remi, Bovan, Danijela, Devaux, Marie, Barnini, Cecilia, Leoncini, Giovanna, Manco, Luca, Nobili, Giulia, Piemontese, Matteo, Aucella, Filippo, Grifa, Rachele, Totaro, Francesco, La Manna, Gaetano, Capelli, Irene, Cianciolo, Giuseppe, Lerario, Sarah, Zappulo, Fulvia, Rosati, Alberto, Fani, Filippo, Spatoliatore, Giuseppe, Gesualdo, Loreto, Pesce, Francesco, Russo, Maria, Zippo, Maria, Cafiero, Cesira, Motta, Daria, Bianco, Simona, Bilucaglia, Donatella, Messa, Piergiorgio, Pavone, Laura, Tripodi, Federica, Vettoretti, Simone, Fioretto, Paola, Carraro, Gianni, Farnia, Filippo, Postal, Anna, D'Amelio, Alessandro, Cardone, Antonio, Piccinni, Giovanni, Aloisi, Annalisa, Scolari, Francesco, Alberici, Federico, Guerini, Alice, Saccà, Chiara, Salviani, Chiara, Zani, Roberta, DE NICOLA, Luca, Garofalo, Carlo, Elena Liberti, Maria, Minutolo, Roberto, Pennino, Luigi, Polese, Lucio, Mené, Paolo, Barberi, Simona, Falcone, Clorinda, Russo, Francesco, Caroppo, Maurizio, Santorelli, Gennaro, Rivera, Rodolfo, Santoro, Domenico, Giuffrida, Alfio, Zirino, Fortunata, Calvi, Cristina, Estienne, Luca, Gambaro, Giovanni, Gangemi, Concetta, Ortalda, Vittorio, Pessolano, Giuseppina, Grandaliano, Giuseppe, Baccaro, Rocco, Ferraro, Pietro, Mangiacapra, Roberto, Melandri, Marco, Foligno, Nadia, Quartagno, Rita, Vezzoli, Giuseppe, Brioni, Elena, and Group, EMPA-KIDNEY Collaborative
Subjects: chronic renal disease, empagliflozin, empa-kidney, General Medicine
Abstract: Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; PConclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110. opens in new tab; EudraCT number, 2017-002971-24. opens in new tab.)
Published: 2023

30. Association between Lifespan Exercise Habits and Cognitive Function in Older Age: the Bunkyo Health Study

Author: Huicong Shi, Hiroki Tabata, Hikaru Otsuka, Yuki Someya, Hideyoshi Kaga, Hitoshi Naito, Abudurezake Abulaiti, Futaba Umemura, Mai Kiya, Naoaki Ito, Tsubasa Tajima, Yasuyo Yoshizawa, Saori Kakehi, Ryuzo Kawamori, and Yoshifumi Tamura
Subjects: Psychiatry and Mental health, Cellular and Molecular Neuroscience, Developmental Neuroscience, Epidemiology, Health Policy, Neurology (clinical), Geriatrics and Gerontology
Published: 2022
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31. Association of

Author: Mari, Sugimoto, Hiroki, Tabata, Hideyoshi, Kaga, Yuki, Someya, Saori, Kakehi, Abulaiti, Abudurezake, Hitoshi, Naito, Naoaki, Ito, Huicong, Shi, Hikaru, Otsuka, Futaba, Umemura, Yasuyo, Yoshizawa, Ryuzo, Kawamori, Hirotaka, Watada, and Yoshifumi, Tamura
Subjects: Male, Cross-Sectional Studies, Alcohol Drinking, Genotype, Aldehyde Dehydrogenase, Mitochondrial, Humans, Female, Polymorphism, Single Nucleotide, Aged
Abstract: Dietary habits are associated with various diseases and assessed by dietary patterns (DPs). Since the
Published: 2022

32. A 7 day inpatient diabetes education program improves quality of life and glycemic control 12 months after discharge.

Author: Kurita, Mika, Hiroaki Satoh, Hideyoshi Kaga, Satoshi Kadowaki, Yuki Someya, Yuka Tosaka, Yuya Nishida, Fuki Ikeda, Yoshifumi Tamura, and Hirotaka Watada
Subjects: GLYCEMIC control, TYPE 2 diabetes, DIABETES, PATIENT satisfaction, QUALITY of life
Abstract: Aims: For long-term management of diabetes, patients with type 2 diabetes mellitus require a high level of treatment adherence, which is associated with treatment satisfaction and their quality of life (QOL). To achieve it, patient education about diabetes self-management is essential. We routinely conduct a 7 day inpatient diabetes education program and administer the diabetes treatment-related (DTR)-QOL questionnaire to all participants, both before admission and at discharge. Here, we investigated whether our program improves QOL and post-discharge glycemic control. Materials and Methods: This retrospective study utilized data from patients with type 2 diabetes mellitus who participated in our program between July 2017 and March 2020 and who had been treated in our outpatient department for more than 1 year. We evaluated the relationship between at admission and at discharge diabetes treatmentrelated quality of life scores and glycemic control after discharge. Results: Data from 140 patients were analyzed in this study, which showed a significant improvement in the total, 'Anxiety and dissatisfaction with treatment', and 'Satisfactionwith-treatment' scores. A significant improvement was evident in HbA1c at 12 months after discharge. Multiple regression analysis showed that HbA1c after 12 months was independently associated with gender, duration of diabetes, and HbA1c at admission. Conclusions: Our program effectively improves quality of life and post-discharge glycemic control in patients with type 2 diabetes mellitus. It is particularly effective in patients of the male gender, with a shorter duration of diabetes mellitus and higher HbA1c at admission. [ABSTRACT FROM AUTHOR]
Published: 2023
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33. Adipose Insulin Resistance and Decreased Adiponectin Are Correlated With Metabolic Abnormalities in Nonobese Men

Author: Kazunori Shimada, Kageumi Takeno, Saori Kakehi, Takashi Funayama, Yoshifumi Tamura, Daisuke Sugimoto, Nozomu Yamasaki, Ruriko Suzuki, Yasuhiko Furukawa, Hiroaki Satoh, Motonori Sato, Shigeki Aoki, Ryuzo Kawamori, Miho Nishitani-Yokoyama, Hiroyuki Daida, Hideyoshi Kaga, Satoshi Kadowaki, Yuki Someya, Hirotaka Watada, and Mai Kiya
Subjects: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Ideal Body Weight, Adipose tissue, Context (language use), Biochemistry, Body Mass Index, Cohort Studies, Endocrinology, Insulin resistance, Japan, Metabolic Diseases, Internal medicine, Body Fat Distribution, Humans, Medicine, Dyslipidemias, Adiponectin, business.industry, Biochemistry (medical), Fatty liver, Middle Aged, medicine.disease, Obesity, Adipose Tissue, Insulin Resistance, business, Body mass index, Dyslipidemia
Abstract: Context Adipose tissue dysfunction is characterized by decreased adiponectin (AN) levels and impaired adipose tissue insulin sensitivity (ATIS) and is associated with metabolic disorders. While Asians readily develop metabolic disease without obesity, it remains unclear how decreased AN level and impaired ATIS affect metabolic abnormalities in nonobese Asians. Design and Setting To investigate the relationships between decreased AN level, impaired ATIS, and metabolic abnormalities, we studied 94 Japanese men whose body mass index was less than 25 kg/m2. We divided the subjects into 4 groups based on their median AN level and ATIS, the latter calculated as the degree of insulin-mediated suppression of free fatty acids during hyperinsulinemic euglycemic clamp, and compared the metabolic parameters in the 4 groups. Results The High-ATIS/High-AN group (n = 29) showed similar anthropometric data to the High-ATIS/Low-AN group (n = 18). In contrast, both the Low-ATIS/High-AN (n = 18) and Low-ATIS/Low-AN (n = 29) groups showed significantly lower muscle insulin sensitivity than the High-ATIS groups. The intrahepatic lipid level in the Low-ATIS/Low-AN group was significantly higher than that in the High-ATIS groups. In addition, the Low-ATIS/Low-AN group had a significantly higher fasting serum triglyceride level and significantly lower high-density lipoprotein cholesterol level than the other 3 groups. Conclusions In nonobese Japanese men with high ATIS, the AN level was not associated with metabolic characteristics. On the other hand, subjects with low ATIS showed reduced muscle insulin sensitivity, and those with a decreased AN level demonstrated multiple metabolic abnormalities, represented by fatty liver and dyslipidemia.
Published: 2021
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34. A decrease in plasma glucose levels is required for increased endogenous glucose production with a single administration of a sodium‐glucose co‐transporter‐2 inhibitor tofogliflozin

Author: Takashi Funayama, Yoshifumi Tamura, Shuko Nojiri, Hiroaki Satoh, Yasuhiko Furukawa, Mai Kiya, Motonori Sato, Satoshi Kadowaki, Yuki Someya, Hirotaka Watada, Nozomu Yamasaki, Hideyoshi Kaga, Ryuzo Kawamori, Ruriko Suzuki, Saori Kakehi, and Daisuke Sugimoto
Subjects: Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Sodium, medicine.medical_treatment, chemistry.chemical_element, 030209 endocrinology & metabolism, Endogeny, Type 2 diabetes, 030204 cardiovascular system & hematology, Glucagon, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Glucosides, Sodium-Glucose Transporter 2, Internal medicine, Internal Medicine, Humans, Insulin, Medicine, Benzhydryl Compounds, Sodium-Glucose Transporter 2 Inhibitors, business.industry, Transporter, medicine.disease, Glucose, Diabetes Mellitus, Type 2, Pharmaceutical Preparations, chemistry, SGLT2 Inhibitor, business, Tofogliflozin
Abstract: Aim To investigate whether changes in endogenous glucose production (EGP) and insulin and glucagon levels are elicited by the decrease in plasma glucose (PG) levels induced by the sodium-glucose co-transporter-2 (SGLT2) inhibitor tofogliflozin. Materials and methods We evaluated EGP in 12 Japanese patients with type 2 diabetes under the conditions of no drugs administered (CON), single administration of the SGLT2 inhibitor tofogliflozin (TOF), and single administration of TOF with adjustment of PG levels with exogenous glucose infusion to mimic changes in PG levels observed with CON (TOF + G). We evaluated changes in EGP and levels of C-peptide and glucagon from baseline to 180 minutes after drug administration. Results Endogenous glucose production decreased in the CON (-0.22 ± 0.11 mg/kg·min) and TOF + G experiments (-0.31 ± 0.24 mg/kg·min), but not in the TOF experiment (+0.08 ± 0.19 mg/kg·min). The decrease in C-peptide was significantly greater in the TOF experiment (-0.11 ± 0.06 nmol/L) than in the CON (-0.03 ± 0.06 nmol/L) and the TOF + G experiments (-0.01 ± 0.11 nmol/L), while the increase in glucagon was significantly greater in the TOF experiment (+11.1 ± 6.3 pmol/L), but not in the TOF + G experiment (+8.6 ± 7.6 pmol/L) compared to the CON experiment (+5.1 ± 4.3 pmol/L). Conclusions These results indicate that the decrease in PG levels induced by SGLT2 inhibitor administration is required for the increase in EGP and decrease in insulin secretion.
Published: 2021
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35. Ingestion of an exogenous ketone monoester improves the glycemic response during oral glucose tolerance test in individuals with impaired glucose tolerance: A cross‐over randomized trial

Author: Motonori Sato, Hiroaki Satoh, Nozomu Yamasaki, Takashi Nakagata, Satoshi Kadowaki, Yuki Someya, Hirotaka Watada, Yoshifumi Tamura, Hideyoshi Kaga, Daisuke Sugimoto, and Ryuzo Kawamori
Subjects: Blood Glucose, Male, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Fatty Acids, Nonesterified, Impaired glucose tolerance, Eating, 0302 clinical medicine, Insulin, Ingestion, Cross-Over Studies, 3-Hydroxybutyric Acid, C-Peptide, Insulin secretion, Area under the curve, Articles, General Medicine, Ketones, Middle Aged, Clinical Trial, Ketone, Clinical Science and Care, Area Under Curve, Female, medicine.medical_specialty, 030209 endocrinology & metabolism, Glycemic Control, Carbohydrate metabolism, Glucagon, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Glucose Intolerance, Internal Medicine, medicine, Humans, Glycemic, business.industry, Glucose Tolerance Test, RC648-665, medicine.disease, Glucose, 030104 developmental biology, Endocrinology, business
Abstract: Aims/Introduction As a low‐carbohydrate diet and the use of sodium–glucose transporter‐2 inhibitors are both known to increase D‐beta‐hydroxybutyrate levels, the effect of these levels on glucose metabolism has attracted attention. We investigated the acute effects of ketone monoester (KM) ingestion on blood glucose levels during the 75‐g oral glucose tolerance test (OGTT) in participants with impaired glucose tolerance. Materials and Methods Nine Japanese adults aged 48–62 years (4 men, 5 women) with impaired glucose tolerance participated in this study. After participants fasted overnight, we carried out OGTT for 180 min with and without KM ingestion on two separate days in a randomized cross‐over design. We compared the area under the curve (AUC) of D‐beta‐hydroxybutyrate, glucose, insulin, C‐peptide, glucagon and free fatty acids during OGTT. Results The AUC of D‐beta‐hydroxybutyrate during OGTT was significantly higher with KM than without KM (KM 5995.3 ± 1257.1 mmol/L·h; without KM 116.1 ± 33.9 mmol/L·h, P, Ketone monoester lowers glucose level during the oral glucose tolerance test in individuals with impaired glucose tolerance. This improvement was associated with decreased insulin clearance and elevated early phase insulin level.
Published: 2020
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36. Age-Related Changes in Relaxation Times, Proton Density, Myelin, and Tissue Volumes in Adult Brain Analyzed by 2-Dimensional Quantitative Synthetic Magnetic Resonance Imaging

Author: Shimpei Kato, Kotaro Fujimoto, Ryuzo Kawamori, Yuki Someya, Hirotaka Watada, Shigeki Aoki, Koji Kamagata, Masaaki Hori, Christina Andica, Yoshifumi Tamura, Akihiko Wada, Syo Murata, Hideyoshi Kaga, Ryusuke Irie, Akifumi Hagiwara, Issei Fukunaga, and Shohei Fujita
Subjects: Adult, Male, Relaxometry, relaxometry, MDME, 030218 nuclear medicine & medical imaging, White matter, 03 medical and health sciences, Myelin, 0302 clinical medicine, Nuclear magnetic resonance, Parenchyma, medicine, Humans, Brain segmentation, Radiology, Nuclear Medicine and imaging, Prospective Studies, Myelin Sheath, quantitative synthetic MRI, Aged, volumetry, medicine.diagnostic_test, Chemistry, aging, Relaxation (NMR), Brain, Magnetic resonance imaging, Original Articles, General Medicine, Magnetic Resonance Imaging, myelin, medicine.anatomical_structure, Volume fraction, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, Protons, 030217 neurology & neurosurgery
Abstract: Supplemental digital content is available in the text., Objectives Quantitative synthetic magnetic resonance imaging (MRI) enables the determination of fundamental tissue properties, namely, T1 and T2 relaxation times and proton density (PD), in a single scan. Myelin estimation and brain segmentation based on these quantitative values can also be performed automatically. This study aimed to reveal the changes in tissue characteristics and volumes of the brain according to age and provide age-specific reference values obtained by quantitative synthetic MRI. Materials and Methods This was a prospective study of healthy subjects with no history of brain diseases scanned with a multidynamic multiecho sequence for simultaneous measurement of relaxometry of T1, T2, and PD. We performed myelin estimation and brain volumetry based on these values. We performed volume-of-interest analysis on both gray matter (GM) and white matter (WM) regions for T1, T2, PD, and myelin volume fraction maps. Tissue volumes were calculated in the whole brain, producing brain parenchymal volume, GM volume, WM volume, and myelin volume. These volumes were normalized by intracranial volume to a brain parenchymal fraction, GM fraction, WM fraction, and myelin fraction (MyF). We examined the changes in the mean regional quantitative values and segmented tissue volumes according to age. Results We analyzed data of 114 adults (53 men and 61 women; median age, 66.5 years; range, 21–86 years). T1, T2, and PD values showed quadratic changes according to age and stayed stable or decreased until around 60 years of age and increased thereafter. Myelin volume fraction showed a reversed trend. Brain parenchymal fraction and GM fraction decreased throughout all ages. The approximation curves showed that WM fraction and MyF gradually increased until around the 40s to 50s and decreased thereafter. A significant decline in MyF was first noted in the 60s age group (Tukey test, P < 0.001). Conclusions Our study showed changes according to age in tissue characteristic values and brain volumes using quantitative synthetic MRI. The reference values for age demonstrated in this study may be useful to discriminate brain disorders from healthy brains.
Published: 2020
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37. Decreased Muscle Strength of Knee Flexors is Associated with Impaired Muscle Insulin Sensitivity in Non-Diabetic Middle-Aged Japanese Male Subjects

Author: Yoshifumi Tamura, Toshio Yanagiya, Ruriko Suzuki, Daisuke Sugimoto, Satoshi Kadowaki, Ryuzo Kawamori, Yasuhiko Furukawa, Keisuke Watanabe, Yuki Someya, Hirotaka Watada, Hideyoshi Kaga, Takashi Funayama, Kageumi Takeno, Saori Kakehi, Toshiyuki Kurihara, and Hiroaki Eshima
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Non-obese, Isometric exercise, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Risk factor, Muscle strength, business.industry, Brief Report, Insulin sensitivity, Type 2 Diabetes Mellitus, musculoskeletal system, medicine.disease, Clamp, Endocrinology, business
Abstract: Introduction Reduced muscle strength is a high risk factor for type 2 diabetes mellitus, and this association is especially strong in non-obese male individuals. However, it remains unclear how reduced muscle strength affects susceptibility to diabetes. We have examined whether lower limb muscle strength is associated with insulin resistance in non-obese Japanese male subjects. Methods Measurements from 64 non-diabetic, non-obese, middle-aged Japanese men were analyzed. Insulin sensitivity in muscle was measured using the hyperinsulinemic-euglycemic clamp. Isometric muscle strength of the knee extensor and flexor muscles was evaluated using a dynameter. Results Lower muscle strength of knee flexors, but not knee extensors, was associated with impaired muscle insulin sensitivity (knee flexor muscles: low, medium, and high strength was 6.6 ± 2.2, 7.3 ± 2.0, and 8.8 ± 2.2 mg/kg per minute, respectively, p for trend
Published: 2020
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38. Fasting serum free glycerol concentration is a potential surrogate marker of visceral obesity and insulin sensitivity in middle-aged Japanese men

Author: Takashi Miida, Miwa Isshiki, Atsushi Hori, Satoshi Hirayama, Akiko Hirayama, Yoshifumi Tamura, Tsuyoshi Ueno, Ryuzo Kawamori, Hirotaka Watada, and Hideyoshi Kaga
Subjects: Adult, Blood Glucose, Glycerol, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Adipose tissue, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Japan, Internal medicine, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Triglycerides, Aged, Lipoprotein lipase, Nutrition and Dietetics, Triglyceride, business.industry, Insulin, Fasting, Middle Aged, Postprandial Period, medicine.disease, Postprandial, Endocrinology, Adipose Tissue, chemistry, Obesity, Abdominal, Insulin Resistance, Metabolic syndrome, Cardiology and Cardiovascular Medicine, business, Biomarkers, Homeostasis
Abstract: Triglyceride (TG) is a tri-ester composed of a glycerol and 3 fatty acids. Degradation of TG in adipose tissue is increased in the fasting state but inhibited in the postprandial state. Although insulin suppresses adipose TG degradation, patients with insulin resistance have high concentrations of insulin and free glycerol (FG) in the fasting state.We examined whether the fasting FG concentration reflects visceral obesity and insulin sensitivity in middle-aged Japanese men.We measured the fasting serum FG concentration in 72 males aged 30 to 50 years using a simple enzymatic method. The subjects were divided into tertiles according to their homeostasis model assessment of insulin resistance (HOMA-IR). Besides routine glucose- and lipid-related parameters, we determined insulin sensitivity as the rate of glucose disappearance in a 2-step hyperinsulinemic-euglycemic clamp and the abdominal visceral fat area (VFA) by magnetic resonance imaging.The highest HOMA-IR tertile group had a higher fasting FG concentration than the middle- and lowest-tertile groups (0.077 ± 0.024 vs 0.063 ± 0.017 and 0.061 ± 0.016 mmol/L, P .05 and P .01). The FG concentration was positively correlated with VFA (rs = 0.36; P .01) and the HOMA-IR score (rs = 0.26, P .05) but negatively correlated with insulin sensitivity (rs = -0.26, P .05). Multivariate regression analysis revealed that the FG concentration is independently associated with VFA and insulin sensitivity.The fasting FG concentration reflects VFA and insulin sensitivity in middle-aged Japanese men. The fasting FG concentration may be a potential surrogate marker of visceral obesity and insulin resistance in outpatients.
Published: 2020
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39. Reduced muscle strength of knee extensors is a risk factor for silent lacunar infarcts among Japanese elderly people: the Bunkyo Health Study

Author: Shuko Nojiri, Shigeki Aoki, Yuki Someya, Yoshifumi Tamura, Hirotaka Watada, Muneaki Ishijima, Kazuo Kaneko, Yumiko Motoi, Hideyoshi Kaga, Hiroyuki Daida, Nobutaka Hattori, Daisuke Sugimoto, Satoshi Kadowaki, Ryuzo Kawamori, Ruriko Suzuki, and Kazunori Shimada
Subjects: Lacunar Infarcts, medicine.medical_specialty, Physical medicine and rehabilitation, Knee extensors, Cross-sectional study, business.industry, Muscle strength, Medicine, Elderly people, Risk factor, business, Community based study
Published: 2020
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40. Shape of the glucose response curve during an oral glucose tolerance test is associated with insulin clearance and muscle insulin sensitivity in healthy non‐obese men

Author: Takashi Funayama, Hiroyuki Daida, Yoshifumi Tamura, Hiroaki Sato, Yasuhiko Furukawa, Satoshi Kadowaki, Kageumi Takeno, Miho Nishitani-Yokoyama, Yuki Someya, Adria Giacca, Hirotaka Watada, Shigeki Aoki, Daisuke Sugimoto, Ruriko Suzuki, Saori Kakehi, Hideyoshi Kaga, Kazunori Shimada, and Ryuzo Kawamori
Subjects: 0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Short Report, Adipose tissue, 030209 endocrinology & metabolism, Type 2 diabetes, Insulin clearance, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Oral glucose tolerance, Shape of glucose response curve, business.industry, Insulin, Insulin sensitivity, General Medicine, Articles, RC648-665, medicine.disease, 030104 developmental biology, Clamp, Endocrinology, Clinical Science and Care, business
Abstract: Individuals with a monophasic glucose response curve (GRC) during a 75‐g oral glucose tolerance test have a higher risk for type 2 diabetes than those with a biphasic GRC. However, no studies have addressed the association between GRC type and insulin clearance. Thus, we studied 49 healthy non‐obese Japanese men. We divided study participants into the monophasic or biphasic group based on the shape of their GRC. We evaluated tissue‐specific insulin sensitivity and insulin clearance using a two‐step hyperinsulinemic‐euglycemic clamp. The monophasic group had more visceral fat, lower insulin clearance and lower muscle insulin sensitivity than the biphasic group, whereas liver and adipose tissue insulin sensitivity, and insulin secretion were comparable. In conclusion, healthy non‐obese men with a monophasic GRC have lower insulin clearance and muscle insulin sensitivity., A monophasic glucose response curve during 75‐g oral glucose tolerance test in apparently healthy non‐obese men is associated with reduced insulin clearance, lower muscle insulin sensitivity and more visceral fat accumulation compared with a biphasic curve.
Published: 2020

41. Characteristics associated with elevated 1‐h plasma glucose levels during a 75‐g oral glucose tolerance test in non‐obese Japanese men

Author: Hiroyuki Daida, Takashi Funayama, Kazunori Shimada, Takashi Nakagata, Shigeki Aoki, Satoshi Kadowaki, Miho Nishitani-Yokoyama, Kageumi Takeno, Hiroaki Sato, Motonori Sato, Daisuke Sugimoto, Yasuhiko Furukawa, Yuki Someya, Hirotaka Watada, Yoshifumi Tamura, Ryuzo Kawamori, Ruriko Suzuki, Saori Kakehi, and Hideyoshi Kaga
Subjects: 0301 basic medicine, Adult, Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Population, Short Report, 030209 endocrinology & metabolism, Type 2 diabetes, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Japan, Internal medicine, Diabetes mellitus, Glucose Intolerance, Internal Medicine, medicine, Humans, Prospective Studies, Oral glucose tolerance, Risk factor, education, Glycated Hemoglobin, Plasma glucose, education.field_of_study, Adiponectin, business.industry, General Medicine, Articles, Glucose Tolerance Test, Middle Aged, RC648-665, medicine.disease, Prognosis, Non‐obese, 030104 developmental biology, Endocrinology, Clinical Science and Care, 1‐h plasma glucose levels, Insulinogenic index, Insulin Resistance, business, Corrigendum, Biomarkers, Follow-Up Studies
Abstract: Elevated 1‐h plasma glucose (1h‐PG; ≥155 mg/dL) during an oral glucose tolerance test is a risk factor for type 2 diabetes. However, the metabolic characteristics of non‐obese Asians with elevated 1h‐PG are unknown. Thus, we studied 59 non‐obese Japanese men with normal glucose tolerance. We divided study participants into the Low 1h‐PG group (, Characteristics of non‐obese Asians with elevated 1‐h plasma glucose are unknown. Individuals with elevated 1‐h plasma glucose have lower insulinogenic index and adiponectin. Insulin sensitivity was similar between the low and high 1‐h plasma glucose groups.
Published: 2020

42. Associations of Exercise Habits in Adolescence and Old Age with Risk of Osteoporosis in Older Adults: The Bunkyo Health Study

Author: Hikaru Otsuka, Hiroki Tabata, Huicong Shi, Hideyoshi Kaga, Yuki Someya, Abudurezake Abulaiti, Hitoshi Naito, Futaba Umemura, Saori Kakehi, Muneaki Ishijima, Ryuzo Kawamori, Hirotaka Watada, and Yoshifumi Tamura
Subjects: bone mineral density, osteoporosis, exercise habit, adolescence, older adults, musculoskeletal diseases, Medicine, General Medicine, Article
Abstract: We investigated effects of exercise habits (EHs) in adolescence and old age on osteoporosis prevalence and hip joint and lumbar spine bone mineral density (BMD). Body composition and BMD in 1596 people aged 65–84 years living in Bunkyo-ku, Tokyo, were measured using dual-energy X-ray absorptiometry. We divided participants into four groups by a combination of EHs in adolescence and old age: none in either period (None-None), only in adolescence (Active-None), only in old age (None-Active), and in both periods (Active-Active). Logistic regression models were employed to estimate multivariable-adjusted odds ratios (ORs) for osteoporosis determined by T-score (less than −2.5 SD) using the None-None reference group. In men, the combination of EHs in adolescence and old age was not associated with osteoporosis prevalence. However, the lumbar spine’s BMD was significantly higher in the Active-Active than the None-Active group (p = 0.043). In women, the Active-Active group had lower lumbar spine osteoporosis prevalence than the None-None group (OR 0.65; 95% CI, 0.42–1.00, p = 0.049). Furthermore, hip BMD was significantly higher in the Active-Active group than in the other three groups (p = 0.001). Older women with EHs in adolescence and old age had higher lumbar BMD and lower risk of osteoporosis.
Published: 2021

43. Association of ALDH2 Genotypes and Alcohol Intake with Dietary Patterns: The Bunkyo Health Study

Author: Mari Sugimoto, Hiroki Tabata, Hideyoshi Kaga, Yuki Someya, Saori Kakehi, Abulaiti Abudurezake, Hitoshi Naito, Naoaki Ito, Huicong Shi, Hikaru Otsuka, Futaba Umemura, Yasuyo Yoshizawa, Ryuzo Kawamori, Hirotaka Watada, and Yoshifumi Tamura
Subjects: Nutrition and Dietetics, dietary patterns, ALDH2 genotype, alcohol intake, Food Science
Abstract: Dietary habits are associated with various diseases and assessed by dietary patterns (DPs). Since the ALDH2 genotype is correlated with alcohol and several food preferences, this genotype is probably associated with DPs. In this cross-sectional study of 1612 elderly adults, we investigated the effects of the ALDH2 genotype on DPs and the mediating role of alcohol intake. We identified the ALDH2 genotype and conducted a dietary history survey, then used principal component analysis to determine DPs for each gender. We performed multiple regression analysis to determine the independent contribution of the ALDH2 genotype and alcohol intake to DP scores. We identified three DPs: the “Japanese side dish type” (DP1), the “Japanese dish with alcohol type” (DP2), and the “Western dish with alcohol type” (DP3). In men, the single nucleotide polymorphism ALDH2 rs671 was significantly associated with all DP scores. When alcohol intake was added as a covariate, ALDH2 rs671 was still significantly correlated with the DP2 score but not with the DP1 or DP3 score, and alcohol intake was significantly correlated with all DP scores. In women, ALDH2 rs671 was significantly associated with the DP2 and DP3 scores; however, after adding alcohol intake as a covariate, these associations disappeared, and alcohol intake significantly correlated with all DP scores. In conclusion, the ALDH2 genotype was associated with several DPs in elderly adults, but most associations were mediated by alcohol intake.
Published: 2022
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44. Insulin resistance and muscle weakness are synergistic risk factors for silent lacunar infarcts: the Bunkyo Health Study

Author: Muneaki Ishijima, Satoshi Kadowaki, Yuki Someya, Hirotaka Watada, Kazuo Kaneko, Yumiko Motoi, Shuko Nojiri, Shigeki Aoki, Yoshifumi Tamura, Kazunori Shimada, Nobutaka Hattori, Hiroyuki Daida, Daisuke Sugimoto, Ryuzo Kawamori, Ruriko Suzuki, and Hideyoshi Kaga
Subjects: Male, medicine.medical_specialty, Urban Population, Science, behavioral disciplines and activities, Article, Insulin resistance, Japan, Internal medicine, Medicine, Elderly people, Humans, Prospective Studies, Aged, Aged, 80 and over, Multidisciplinary, Muscle Weakness, Knee extensors, medicine.diagnostic_test, business.industry, Diabetes, Models, Cardiovascular, Insulin sensitivity, Muscle weakness, Magnetic resonance imaging, Middle Aged, medicine.disease, Confidence interval, Lacunar Infarcts, Stroke, Risk factors, Stroke, Lacunar, Cardiology, Female, medicine.symptom, Pre-diabetes, Insulin Resistance, business
Abstract: Insulin resistance and muscle weakness are risk factors for silent lacunar infarcts (SLI), but it is unclear whether they are still independent risk factors when adjusted for each other. In addition, the effect of their combination on SLI is completely unknown. We evaluated SLI, insulin sensitivity, and knee extensor muscle strength by magnetic resonance imaging, PREDIM, and dynamometer, respectively, in 1531 elderly people aged 65–84 years living in an urban area of Tokyo. Among the study subjects, 251 (16.4%) had SLI. Impaired insulin sensitivity (High; 1.00 [reference], Medium; 1.53 [95% confidence interval (CI) 0.94–2.48], Low; 1.86 [1.02–3.39], p for trend 0.047) and reduced muscle strength (High; 1.00 [reference], Medium; 1.40 [0.98–2.02], Low; 1.49 [1.04–2.15], p for trend 0.037) were independently associated with increased risk for SLI in the fully adjusted model. In terms of combined, subjects classified as having the lowest insulin sensitivity and lowest strength were 4.33 times (95% CI 1.64–11.45) more likely to have a SLI than those classified as having the highest insulin sensitivity and highest strength. Impaired insulin sensitivity and reduced muscle strength were independently associated with higher risk of SLI in elderly subjects, and their combination synergistically increased this risk.
Published: 2021

45. Higher C-Peptide Level During Glucose Clamp Is Associated With Muscle Insulin Resistance in Nonobese Japanese Men

Author: Hideyoshi Kaga, Yuki Someya, Yoshifumi Tamura, Hirotaka Watada, Miho Nishitani-Yokoyama, Takashi Funayama, Yasuhiko Furukawa, Akio Kanazawa, Kazunori Shimada, Daisuke Sugimoto, Ruriko Suzuki, Satoshi Kadowaki, Ryuzo Kawamori, Adria Giacca, Hiroyuki Daida, Shigeki Aoki, Kageumi Takeno, and Saori Kakehi
Subjects: 0301 basic medicine, medicine.medical_specialty, Diabetes, Pancreatic and Gastrointestinal Hormones, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Context (language use), 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, insulin resistance, Internal medicine, medicine, Hyperinsulinemia, Clinical Research Articles, C-peptide, business.industry, nonobese, Insulin, Healthy subjects, Insulin sensitivity, medicine.disease, 030104 developmental biology, Endocrinology, Clamp, chemistry, hyperinsulinemia, business, feedback inhibition of insulin secretion
Abstract: Context Circulating C-peptide is generally suppressed by exogenous insulin infusion. However, steady-state serum C-peptide (SSSC) levels during hyperinsulinemic-euglycemic clamp in obese subjects are higher than in healthy subjects, which may contribute to hyperinsulinemia to compensate for insulin resistance. Even in healthy subjects, interindividual variations in SSSC levels are present; however, the characteristics of subjects with high SSSC levels in those populations have not been fully elucidated. Objective To investigate the clinical parameters associated with interindividual variations in SSSC levels in apparently healthy, nonobese Japanese men. Design and Participants We studied 49 nonobese (BMI < 25 kg/m2), healthy Japanese men. We evaluated SSSC and insulin sensitivity using hyperinsulinemic-euglycemic clamp with tracer. Intrahepatic lipid (IHL) was measured using proton magnetic resonance spectroscopy. Results We divided subjects into high and low SSSC groups based on the median SSSC value and compared their clinical parameters. Compared with the low SSSC group, the high SSSC group had IHL accumulation, impaired muscle insulin sensitivity, reduced insulin clearance, and hyperinsulinemia during a 75-g oral glucose tolerance test (OGTT). All of these factors were significantly correlated with SSSC. Conclusions In healthy, nonobese men, higher SSSC was associated with impaired muscle insulin sensitivity, IHL accumulation, and hyperinsulinemia during OGTT. These findings suggest that higher endogenous insulin secretion during hyperinsulinemia, along with reduced insulin clearance, may be an early change to maintain metabolic status in the face of moderate muscle insulin resistance, even in healthy, nonobese men.
Published: 2019
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46. Sarcopenic obesity is associated with cognitive impairment in community-dwelling older adults: The Bunkyo Health Study

Author: Yuki Someya, Yoshifumi Tamura, Hideyoshi Kaga, Daisuke Sugimoto, Satoshi Kadowaki, Ruriko Suzuki, Shigeki Aoki, Nobutaka Hattori, Yumiko Motoi, Kazunori Shimada, Hiroyuki Daida, Muneaki Ishijima, Kazuo Kaneko, Shuko Nojiri, Ryuzo Kawamori, and Hirotaka Watada
Subjects: Male, Sarcopenia, Nutrition and Dietetics, Cross-Sectional Studies, Hand Strength, Humans, Cognitive Dysfunction, Dementia, Female, Independent Living, Obesity, Critical Care and Intensive Care Medicine, Aged
Abstract: Coexistence of obesity and decreased muscle strength, defined as sarcopenic obesity, is often observed in the older adults. The present study investigated whether sarcopenic obesity, defined as reduced handgrip strength and increased body mass index (BMI), is associated with cognitive impairment.Study participants include 1615 older adults aged 65-84 years who lived in an urban area of Tokyo, Japan and participated in the Bunkyo Health Study. Mild cognitive impairment (MCI) and dementia were defined based on ≤22 points of Montreal Cognitive Assessment and ≤23 points of the Mine-Mental State Examination, respectively. Handgrip strength was measured using a dynamometer in a standing position. We divided participants into four groups according to their sarcopenia (probable) (handgrip strength28 kg in men and18 kg in women) and obesity status (BMI ≥25 kg/mMean age was 73.1 ± 5.4 years, and 57.6% of study participants were female. The prevalence of control, obesity, sarcopenia, and sarcopenic obesity was 59.4%, 21.2%, 14.6%, and 4.7%, respectively. The prevalence of MCI and dementia, respectively, was highest in participants with sarcopenic obesity, followed by those with sarcopenia, obesity, and control. After multivariate adjustment, sarcopenic obesity was independently associated with increased odds of MCI and dementia compared with the control (MCI: 2.11 [95% confidence interval, 1.12-3.62]; dementia: 6.17 [2.50-15.27]).Sarcopenic obesity was independently associated with MCI and dementia among Japanese older adults. Future studies are necessary to clarify the causal relationship.
Published: 2021

47. Cover Image, Volume 23, Issue 5

Author: Nozomu Yamasaki, Yoshifumi Tamura, Hideyoshi Kaga, Motonori Sato, Mai Kiya, Satoshi Kadowaki, Ruriko Suzuki, Yasuhiko Furukawa, Daisuke Sugimoto, Takashi Funayama, Yuki Someya, Saori Kakehi, Shuko Nojiri, Hiroaki Satoh, Ryuzo Kawamori, and Hirotaka Watada
Subjects: Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine
Published: 2021
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48. Insulin Resistance and Muscle Weakness Are Synergistic Risk Factors for Silent Lacunar Infarcts: the Bunkyo Health Study: a Cross Sectional Study

Author: Kazunori Shimada, Daisuke Sugimoto, Nobutaka Hattori, Kazuo Kaneko, Yumiko Motoi, Satoshi Kadowaki, Ryuzo Kawamori, Muneaki Ishijima, Hideyoshi Kaga, Hiroyuki Daida, Shigeki Aoki, Yuki Someya, Hirotaka Watada, Ruriko Suzuki, Yoshifumi Tamura, and Shuko Nojiri
Subjects: Lacunar Infarcts, medicine.medical_specialty, Insulin resistance, business.industry, Cross-sectional study, Internal medicine, Cardiology, Medicine, Muscle weakness, cardiovascular diseases, medicine.symptom, business, medicine.disease
Abstract: Background: Previous studies showed that insulin resistance and reduced muscle strength are risk factors for silent lacunar infarcts, but it is unclear whether they are still independent risk factors when adjusted for each other. In addition, the effect of their combination on silent lacunar infarcts is completely unknown.Methods: We evaluated silent lacunar infarcts, insulin sensitivity, and knee extensor muscle strength by magnetic resonance imaging, PREDIM (an index for insulin sensitivity), and dynamometer, respectively, in 1531 elderly people aged 65–84 years living in an urban area of Tokyo. Results: Among the study subjects, 251 (16.4%) had silent lacunar infarcts. Impaired insulin sensitivity (High; 1.00 [reference], Medium; 1.53 [95% confidence interval (CI): 0.94-2.48], Low; 1.86 [95%CI: 1.02-3.39], p for trend 0.047) and reduced muscle strength (High; 1.00 [reference], Medium; 1.40 [95%CI: 0.98-2.02], Low; 1.49 [95%CI: 1.04-2.15], p for trend 0.037) were independently associated with increased risk for silent lacunar infarcts in the fully adjusted model. In terms of combined, subjects classified as having the lowest insulin sensitivity and lowest strength were 4.33 times (95%CI: 1.64-11.45) more likely to have a silent lacunar infarct than those classified as having the highest insulin sensitivity and highest strength.Conclusions: Impaired insulin sensitivity and reduced muscle strength were independently associated with higher risk of silent lacunar infarcts in elderly subjects, and their combination synergistically increased this risk.
Published: 2021
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49. Effects of Synbiotic Supplementation on Chronic Inflammation and the Gut Microbiota in Obese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study

Author: Junko Sato, Yuichiro Yamashiro, Takehiro Katahira, Shoko Tamaki, Hideyoshi Kaga, Hirotaka Watada, Tomoaki Shimizu, Hiromasa Goto, Masanori Aida, Akio Kanazawa, Yasuto Yoshida, Takuya Takahashi, Kosuke Azuma, and Luka Suzuki
Subjects: Male, 0301 basic medicine, chronic inflammation, ved/biology.organism_classification_rank.species, Bifidobacterium pseudocatenulatum, Synbiotics, Type 2 diabetes, Bifidobacterium breve, Gut flora, Gastroenterology, law.invention, Feces, Probiotic, 0302 clinical medicine, fluids and secretions, law, Bifidobacterium, Nutrition and Dietetics, biology, synbiotic, food and beverages, Middle Aged, Lacticaseibacillus casei, C-Reactive Protein, Treatment Outcome, Female, type 2 diabetes, Inflammation Mediators, lcsh:Nutrition. Foods and food supply, probiotic, medicine.medical_specialty, Lactobacillus casei, galacto-oligosccharides (GOSs), 030209 endocrinology & metabolism, lcsh:TX341-641, digestive system, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, Obesity, Aged, Inflammation, gut microbiota, ved/biology, business.industry, medicine.disease, biology.organism_classification, Gastrointestinal Microbiome, 030104 developmental biology, Diabetes Mellitus, Type 2, Chronic Disease, business, Food Science
Abstract: The aim of this study was to investigate the effects of 24-week synbiotic supplementation on chronic inflammation and the gut microbiota in obese patients with type 2 diabetes. We randomized 88 obese patients with type 2 diabetes to one of two groups for 24 weeks: control or synbiotic (Lacticaseibacillus paracasei strain Shirota (previously Lactobacillus casei strain Shirota) and Bifidobacterium breve strain Yakult, and galactooligosaccharides). The primary endpoint was the change in interleukin-6 from baseline to 24 weeks. Secondary endpoints were evaluation of the gut microbiota in feces and blood, fecal organic acids, high-sensitivity C-reactive protein, lipopolysaccharide-binding protein, and glycemic control. Synbiotic administration for 24 weeks did not significantly affect changes in interleukin-6 from baseline to 24 weeks (0.35 ± 1.99 vs. −0.24 ± 1.75 pg/mL, respectively). Relative to baseline, however, at 24 weeks after synbiotic administration there were positive changes in the counts of Bifidobacterium and total lactobacilli, the relative abundances of Bifidobacterium species such as Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum, and the concentrations of acetic and butyric acids in feces. No significant changes in inflammatory markers were found in the synbiotic group compared to the control group. However, synbiotic administration at least partially improved the gut environment in obese patients with type 2 diabetes.
Published: 2021

50. Prevalence and Features of Impaired Glucose Tolerance in Young Underweight Japanese Women

Author: Motonori Sato, Mai Kiya, Hideyoshi Kaga, Yuki Someya, Hirotaka Watada, Takashi Nakagata, Yoshifumi Tamura, Nozomu Yamasaki, Satoshi Kadowaki, Hiroaki Satoh, Daisuke Sugimoto, and Ryuzo Kawamori
Subjects: Adult, Blood Glucose, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Adipose tissue, 030209 endocrinology & metabolism, Type 2 diabetes, Biochemistry, Impaired glucose tolerance, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Endocrinology, Insulin resistance, Japan, Thinness, Internal medicine, Glucose Intolerance, Prevalence, Medicine, Humans, 030212 general & internal medicine, Oral glucose tolerance, Insulin secretion, business.industry, Biochemistry (medical), nutritional and metabolic diseases, Insulin sensitivity, Glucose Tolerance Test, medicine.disease, Prognosis, Cross-Sectional Studies, Case-Control Studies, Female, Underweight, medicine.symptom, business, Biomarkers, Follow-Up Studies
Abstract: Objective In Japan, while it is known that underweight women over the age of 40 years have a high risk for type 2 diabetes, there is a lack of clarity on the association between glucose tolerance and underweight in younger women. Accordingly, we investigate the prevalence and features of impaired glucose tolerance (IGT) in young underweight Japanese women. Designs and Methods In this cross-sectional study, we recruited 56 normal weight and 98 underweight young Japanese women and evaluated their glucose tolerance levels using an oral glucose tolerance test. Then, we compared the clinical characteristics associated with normal glucose tolerance (NGT) and IGT in the underweight women. Insulin secretion, whole-body insulin sensitivity, and adipose tissue insulin resistance values were measured using the insulinogenic index, whole-body insulin sensitivity index (Matsuda index), and adipose insulin resistance index (Adipo-IR), respectively. Fitness level (peak VO2) was measured using an ergometer. Results The prevalence of IGT was higher in the underweight women than the normal weight women (13.3% vs 1.8%). The underweight women with IGT showed a lower insulinogenic index, lower peak VO2, and Matsuda index and a higher fasting free fatty acid level and Adipo-IR than those with NGT. The whole-body composition was comparable between the NGT and IGT groups. Conclusions The prevalence of IGT was higher in young Japanese women with underweight than those with a normal weight. The underweight women with IGT showed impaired early-phase insulin secretion, low fitness levels, and reduced whole-body and adipose tissue insulin sensitivity levels.
Published: 2020

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