Publications by authors named "Yasuharu Tabara"

303 Publications

Prevalence and physical characteristics of locomotive syndrome stages as classified by the new criteria 2020 in older Japanese people: results from the Nagahama study.

BMC Geriatr 2021 09 9;21(1):489. Epub 2021 Sep 9.

Human Health Sciences, Graduate School of Medicine, Kyoto University, 53, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: The Japanese Orthopaedic Association (JOA) proposed the concept of locomotive syndrome (LS) in 2007 for detecting high-risk individuals with mobility limitation. In 2020, the JOA revised the clinical decision limits and introduced LS stage 3, which carried the highest-risk for LS compared to the conventional stages, 1 and 2. The purpose of this study was to characterize the prevalence, comorbidities, and physical characteristics in each LS stage, as per the LS criteria 2020.

Methods: We analyzed 2077 participants (64.9% women; mean age, 68.3 ± 5.4 years) from the Nagahama Study aged ≥60 years. Participants were classified into 4 groups, non-LS and LS stages 1, 2, and 3, based on a 25-question Geriatric Locomotive Function Scale. The prevalence of comorbidities (sarcopenia, osteoporosis, diabetes mellitus, low back pain [LBP], and knee pain) were investigated. Physical characteristics were measured based on the physical performance tests including gait speed, five-times chair-stand, single-leg stand, and short physical performance battery; muscle strength tests including grip, knee extension, hip flexion, and abduction; and body-composition analysis including muscle quantity and quality. Differences in the prevalence of comorbidities between LS stages were tested using the chi-square test. The general linear model was performed for univariate and multivariate analyses with post-hoc test to compare the differences in physical characteristics among the LS stages.

Results: The prevalence of LS increased with age, and the mean prevalence of LS stages 1, 2, and 3 were 24.4, 5.5, and 6.5%, respectively. The prevalence of comorbidities, including sarcopenia, osteoporosis, LBP, and knee pain, increased with worsening LS stage. Physical performance tests were significantly different between LS stages 2 and 3; and muscle strength differed significantly between LS stages 1 and 2. Additionally, in terms of body composition analysis, muscle quality but not muscle quantity showed significant differences among all the LS stages.

Conclusions: Our findings suggest that muscle strengthening and dynamic training, including balance training in LS stage 1 and 2, respectively, were needed for preventing the LS progression. Individuals with LS stage 3 should perform dynamic training and muscle strengthening exercises while receiving treatment for comorbidities.
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http://dx.doi.org/10.1186/s12877-021-02440-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428127PMC
September 2021

Association between serum α1-antitrypsin levels and all-cause mortality in the general population: the Nagahama study.

Sci Rep 2021 Aug 26;11(1):17241. Epub 2021 Aug 26.

Graduate School of Public Health, Shizuoka Graduate University of Public Health, Aoi-ku, Shizuoka, 420-0881, Japan.

Circulating levels of inflammatory proteins have to be prognostic markers of all-cause mortality. α1-Antitrypsin (AAT) is a major inflammatory plasma protein, but its association with all-cause mortality is unclear. We aimed to evaluate the prognostic significance of AAT levels for all-cause mortality. Study participants comprised 9682 community residents (53.5 ± 13.3 years old). During the 9.8-year follow-up period, 313 participants died from any cause. The mortality rate increased linearly with AAT quintiles (Q1, 18.2; Q2, 24.7; Q3, 23.8; Q4, 31.9; Q5, 64.6 per 10,000 person-years). There were significant correlations between AAT and high-sensitivity C-reactive protein (hsCRP) levels (correlation coefficient, 0.331; P < 0.001). However, the Cox model analysis, when adjusted for possible covariates including hsCRP, identified the fifth AAT quintile as a risk factor for all-cause death (hazard ratio, 2.12 [95% confidence interval, 1.41-3.18]; P < 0.001). An analysis of participants older than 50 years (hazard ratio, 1.98, P < 0.001) yielded similar results. The hazard ratio increased proportionately in combination with high AAT and high hsCRP levels, and the highest hazard ratio reached 4.51 (95% confidence interval, 3.14-6.54, P < 0.001). High AAT levels were determined to be an independent risk factor for mortality in the general population.
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http://dx.doi.org/10.1038/s41598-021-96833-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390682PMC
August 2021

Estimation of Muscle Mass Using Creatinine/Cystatin C Ratio in Japanese Community-Dwelling Older People.

J Am Med Dir Assoc 2021 Aug 23. Epub 2021 Aug 23.

Division of General Medicine, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan; Department of General Medicine and Community Health Science, Sasayama Medical Center Hyogo College of Medicine, Sasayama, Hyogo, Japan.

Objectives: Sarcopenia is defined as a combination of low skeletal muscle mass index (SMI), weak muscle strength, and reduced physical function. Recently, many studies have reported that the creatinine/cystatin C ratio (Cr/CysC) is useful for evaluating muscle mass. We designed a cross-sectional study with separate model development and validation groups to develop a prediction equation to estimate bioimpedance analysis (BIA)-measured SMI with Cr/CysC.

Design: The current study was a retrospective cross-sectional study.

Setting And Participants: The model development group included 908 subjects (288 men and 620 women) from the Frail Elderly in the Sasayama-Tamba Area (FESTA) study, and the validation group included 263 subjects (112 men and 151 women) from participants in the medical checkup program at the Anti-Aging Center in Ehime Prefecture.

Measures: Multivariate regression analysis indicated that age, hemoglobin (Hb), body weight (BW), and Cr/CysC were independently associated with SMI in both men and women. The SMI prediction equation was developed as follows: Men:4.17-0.012×Age+1.24×(Cr/CysC)-0.0513×Hb+0.0598×BW Women:3.55-0.00765×Age+0.852×(Cr/CysC)-0.0627×Hb+0.0614×BW RESULTS: The SMI prediction equation was applied to the validation group and strong correlations were observed between the BIA-measured and predicted SMI (pSMI) in men and women. According to the receiver operator characteristic (ROC) analysis, the areas under the curve were 0.93 (specificity 89.0%, sensitivity 87.2%) among men and 0.88 (specificity 83.6%, sensitivity 79.6%) among women for using pSMI to identify low SMI in the model development group. The pSMI also indicated high accuracy in ROC analysis for low SMI in the validation group. The Bland-Altman plot regression showed good agreement between BIA-measured and pSMI.

Conclusions And Implications: Our new prediction equation to estimate SMI is easy to calculate in daily clinical practice and would be useful for diagnosing sarcopenia.
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http://dx.doi.org/10.1016/j.jamda.2021.07.029DOI Listing
August 2021

Differences in lower limb muscle strength and balance ability between sarcopenia stages depend on sex in community-dwelling older adults.

Aging Clin Exp Res 2021 Aug 20. Epub 2021 Aug 20.

Human Health Sciences, Kyoto University Graduate School of Medicine, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Aim: This study aimed to compare motor function between sarcopenia stages with respect to sex in community-dwelling older adults.

Methods: The participants, comprising 2107 community-dwelling older adults (738 men and 1369 women), were classified into 4 groups and the groups were operationally defined-normal, low muscle mass, low physical function, and sarcopenia groups. Lower limb muscle strength and balance ability were assessed for evaluating motor function. To compare motor function between sarcopenia stages, an analysis of covariance adjusted for age and body mass index was performed.

Results: Lower limb muscle strengths were significantly lower not only in the sarcopenia group but also in the low muscle mass and low physical function groups than that in the normal group in both men and women. Low hip abductor muscle strength was observed in the low physical function group compared to the low muscle mass group in women, but not in men. Timed Up and Go test results in the sarcopenia and low function groups was lower than in the normal and low muscle mass groups for men and women. One-leg standing in the low physical function group was lower than that in the normal group, only for women.

Conclusions: Reduced motor function was observed not only in older people with sarcopenia but also in older people with only low muscle mass or low physical function, and the decline in lower limb muscle strength and balance ability in the low function group were greater in older women than in older men.
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http://dx.doi.org/10.1007/s40520-021-01952-6DOI Listing
August 2021

Weak hip flexor strength predicts progression of functional capacity decline due to locomotor system dysfunction in community-dwelling older adults: A longitudinal cohort study.

Arch Gerontol Geriatr 2021 Aug 2;97:104499. Epub 2021 Aug 2.

Human Health Sciences, Graduate School of Medicine, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.

Purpose: It is critical to determine the risk factors for activities of daily living (ADL) disability caused by locomotor dysfunction. However, no longitudinal study has investigated the association between disability due to locomotive dysfunction and multidimensional factors. Therefore, we investigated the relationship between the progression of functional capacity decline due to locomotive dysfunction and multiple physical functions among older adults in a longitudinal study.

Methods: The participants comprised of 433 community-dwelling older adults. Physical function was assessed at baseline, which included handgrip strength, maximal isometric strength of hip flexion, hip extension, hip abduction, knee extension, toe flexion (index for muscle strength), the 5-time chair-stand test (index for muscle power), the one-legged stance and timed ''Up & Go'' tests (index for balance function), the 30-s stair test (index for muscle endurance), and range of motion (ROM) (an index of joint condition). Functional capacity decline due to locomotive dysfunction was assessed using the 25-question Geriatric Locomotive Function Scale (GLFS-25) before and after a 12-month period. Based on changes in the GLFS-25 score compared with baseline, the non-decline and decline groups were operationally defined. Logistic regression analyses with the groups as the dependent variable and physical function as independent variables were performed.

Results: Of the 433 participants, 189 (43.6%) were included in the decline group. Logistic regression analysis revealed hip flexor strength as a primary determinant in the progression of functional capacity decline.

Conclusion: These results suggest that among physical functions, hip flexor strength influences the progression of disability resulting from locomotive dysfunction in older adults.
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http://dx.doi.org/10.1016/j.archger.2021.104499DOI Listing
August 2021

Association of Sleep Disordered Breathing and Blood Pressure with Albuminuria: The Nagahama Study.

Ann Am Thorac Soc 2021 Aug 4. Epub 2021 Aug 4.

Graduate School of Medicine, Kyoto University, Respiratory Care and Sleep Control Medicine, Kyoto, Japan;

Rationale: Although sleep disordered breathing (SDB) may increase urinary albumin excretion (UAE) by raising nocturnal blood pressure (BP) in addition to diurnal BP, the correlation has not been investigated in a general population.

Objectives: To evaluate the relationships among UAE, SDB and BP during sleep in a large population cohort.

Methods: Among 9,850 community residents, UAE was assessed by the urinary albumin creatinine ratio (UACR) in spot urine. Sleep duration and SDB were evaluated by a wearable actigraph and pulse oximeter, respectively. We calculated the actigraphy-modified 3% oxygen desaturation index (Acti-3%ODI) by correcting the time measured by pulse oximetry according to sleep duration obtained by actigraphy. Further, participants were instructed to measure morning and sleep BP at home by a timer-equipped oscillometric device.

Results: Measurements of sleep parameters, UAE and office BP were completed in 6,568 participants. The multivariate analysis that included confounders showed a significant association of Acti-3%ODI with UACR. (β=0.06, p<0.001) Further, a positive interaction between office systolic BP (SBP) and Acti-3%ODI for UACR was found. (β=0.06, p<0.001) Among the 6,568 persons enrolled in the analysis, 5,313 completed measurements of BP at home. In this cohort, the association of Acti-3%ODI with UACR remained significant (β=0.06, p<0.001) even after morning and sleep SBP were included in the analysis. Further, mediation analysis revealed that 28.3% (95% confidence interval: 14.9-41.7%, p<0.001) of the association of Acti-3%ODI with UACR was explained by the mediation of morning and sleep SBP metrics.

Conclusions: SDB and office SBP were independently and synergistically associated with UAE, which is considered as a risk factor for chronic kidney disease and cardiovascular events. SDB may raise UAE not only by increasing BP but involving other pathologic pathways.
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http://dx.doi.org/10.1513/AnnalsATS.202105-528OCDOI Listing
August 2021

Impacts of lipid-related metabolites, adiposity, and genetic background on blood eosinophil counts: the Nagahama study.

Sci Rep 2021 Jul 28;11(1):15373. Epub 2021 Jul 28.

Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Blood eosinophil count is a useful measure in asthma or COPD management. Recent epidemiological studies revealed that body mass index (BMI) is positively associated with eosinophil counts. However, few studies focused on the role of adiposity and fatty acid-related metabolites on eosinophil counts, including the effect of genetic polymorphism. In this community-based study involving 8265 participants (30-74 year old) from Nagahama city, we investigated the relationship between eosinophil counts and serum levels of fatty acid-related metabolites. The role of MDC1, a gene that is related to eosinophil counts in our previous study and encodes a protein that is thought to be involved in the repair of deoxyribonucleic acid damage, was also examined taking into account its interaction with adiposity. Serum levels of linoleic acid (LA) and β-hydroxybutyric acid (BHB) were negatively associated with eosinophil counts after adjustment with various confounders; however, there were positive interactions between serum LA and BMI and between serum BHB and BMI/body fat percentages in terms of eosinophil counts. In never-smokers, there was positive interaction for eosinophil counts between the CC genotype of MDC1 rs4713354 and BMI/body fat percentages. In conclusion, both serum LA and BHB have negative impacts on eosinophil counts, while adiposity shows robust positive effects on eosinophil counts, partly via genetic background in never-smokers.
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http://dx.doi.org/10.1038/s41598-021-94835-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319143PMC
July 2021

Different Associations of Skeletal Muscle Mass Index and Creatinine-To-Cystatin C Ratio With Muscle Mass and Myosteatosis: The J-SHIPP Study.

J Am Med Dir Assoc 2021 Jul 20. Epub 2021 Jul 20.

Department of Anti-aging Medicine, Ehime University Graduate School of Medicine, Toon City, Japan.

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http://dx.doi.org/10.1016/j.jamda.2021.06.033DOI Listing
July 2021

Differential Contribution of the Medial and the Lateral Side of the Joint to Symptoms in Knee Osteoarthritis: A Radiographic and Laboratory Analysis in the Nagahama Study.

Cartilage 2021 Jul 14:19476035211025817. Epub 2021 Jul 14.

Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Objective: This cross-sectional study aimed to explore the differences of the medial and lateral sides of the knee joint and precise radiographic abnormalities in contribution to the knee pain and clinical outcomes.

Design: Participants 60 years or older who underwent radiographic evaluation were included. Knee radiography was assessed using grading systems of the Osteoarthritis Research Society International (OARSI) atlas. The Japanese Knee Osteoarthritis Measure (JKOM) was evaluated as clinical outcomes. Serum high-sensitivity C-reactive protein (hsCRP) was used to evaluate systemic inflammation. We divided the participants into normal, medial-, lateral-, and medial & lateral-OA types and compared their JKOM using an analysis of covariance. Furthermore, we analyzed the relationship between the knee pain and stiffness of JKOM and the grading of each radiographic feature using a multiple regression model.

Results: Lateral- and medial & lateral-OA groups had a significantly worse symptoms in the total and the pain score, especially in movement subscales, in JKOM score. Lateral-OA groups had higher hsCRP than medial-OA group. Multivariate analysis showed that medial joint space narrowing (JSN), and lateral femoral and tibial osteophytes significantly affected knee pain (adjusted odds ratios: 1.73, 1.28, and 1.55, respectively). The radiographic changes are associated with pain more in JSN in the medial side and osteophytes in the lateral side.

Conclusion: Lateral- and medial & lateral-OA groups showed worth symptom. In addition, medial JSN and lateral osteophytes have potent effects on the knee pain.
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http://dx.doi.org/10.1177/19476035211025817DOI Listing
July 2021

Markers of cardiovascular disease risk in sleep-disordered breathing with or without comorbidities: the Nagahama Study.

J Clin Sleep Med 2021 Jun 21. Epub 2021 Jun 21.

Department of Respiratory Care and Sleep Control Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Study Objectives: Whether the association between sleep-disordered breathing (SDB) and cardiovascular disease (CVD) is independent of comorbid risk factors for CVD is controversial. The objective of this study is to elucidate whether the association between SDB severity and the surrogate markers of CVD evets differs in relation to the number of comorbidities.

Methods: This cross-sectional study included 7731 participants. Severity of SDB was determined by the oxygen desaturation index adjusted by actigraph-measured objective sleep time. Participants were stratified according to SDB severity and the number of comorbidities (hypertension, diabetes, dyslipidemia and obesity), and the associations between the maximum value of intima-media thickness of the common carotid artery (CCA-IMT-max), brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI) were evaluated.

Results: Among participants with no risk factor, CCA-IMT-max increased according to SDB severity (n = 1022, <0.0001). Even after the matching of background, the median CCA-IMT-max value was 14% higher in moderate-severe SDB cases than those without SDB (n=45 in each group, =0.020). The difference was not significant for baPWV and CAVI. On the other hand, a significant difference in CCA-IMT-max was not found in those with multiple comorbidities. Consistently, multiple regression analysis revealed an independent association between CCA-IMT-max and moderate-severe SDB for all study participants (β: 0.0222 (95% confidence interval: 0.0039-0.0405), =0.017), but the association was not significant for stratified participants with multiple comorbidities.

Conclusions: SDB severity is associated with the CCA-IMT-max level, but the independent association becomes weaker for those with multiple comorbidities.
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http://dx.doi.org/10.5664/jcsm.9460DOI Listing
June 2021

Low Carotid Flow Pulsatility Index Correlates With the Presence of Unruptured Intracranial Aneurysms.

J Am Heart Assoc 2021 Jul 22;10(13):e018626. Epub 2021 Jun 22.

Department of Geriatric Medicine and Neurology Ehime University Graduate School of Medicine Toon, Ehime Japan.

Background We assessed cases of incidental unruptured intracranial aneurysm (UIA) discovered on screening magnetic resonance angiography to identify hemodynamic and atherosclerotic risk factors. Methods and Results The data of 1376 healthy older subjects (age range, 31-91 years) without cerebro- or cardiovascular diseases who underwent brain magnetic resonance angiography as part of a medical checkup program at a health screening center were examined retrospectively. We looked for an increase in classical risk factors for UIAs (age, sex, hypertension, and smoking) and laboratory data related to lifestyle diseases among subjects with UIAs. Brachial-ankle pulse wave velocity, central systolic blood pressure, radial augmentation index, and carotid flow pulsatility index were also compared between those with and without UIAs. We found UIAs in 79 (5.7%) of the subjects. Mean age was 67.1±9.0 years, and 55 (70%) were women. Of the 79 aneurysms, 75 (95%) were in the anterior circulation, with a mean diameter of 3.1 mm (range, 2.0-8.0 mm). Subjects with UIAs were significantly older and had more severe hypertension. The carotid flow pulsatility index was significantly lower in subjects with UIAs and negatively and independently correlated with UIAs. Tertile analysis stratified by carotid flow pulsatility index revealed that subjects with lower indices had higher levels of low-density lipoprotein cholesterol. Conclusions The presence of UIAs correlated with lower carotid flow pulsatility index and elevated low-density lipoprotein cholesterol in the data from a population of healthy older volunteers. A reduced carotid flow pulsatility index may affect low-density lipoprotein cholesterol elevation by some molecular pathways and influence the development of cerebral aneurysms. This may guide aneurysm screening indications for institutions where magnetic resonance angiography is not routine.
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http://dx.doi.org/10.1161/JAHA.120.018626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403298PMC
July 2021

Sodium Excretion, Salt Sensitivity, and Obstructive Sleep Apnea.

Ann Am Thorac Soc 2021 Jun 7. Epub 2021 Jun 7.

Nihon University School of Medicine Graduate School of Medicine, 38113, Department of Sleep Medicine and Respiratory Care, Itabashi-ku, Tokyo, Japan.

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http://dx.doi.org/10.1513/AnnalsATS.202105-541LEDOI Listing
June 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Brachial-ankle pulse wave velocity and cardio-ankle vascular index are associated with future cardiovascular events in a general population: The Nagahama Study.

J Clin Hypertens (Greenwich) 2021 07 26;23(7):1390-1398. Epub 2021 May 26.

Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Faster pulse wave velocity (PWV) is known to be associated with the incidence of cardiovascular diseases (CVD). The aim of this study was to clarify the hypothesis that PWV may be associated with future CVD events even when its time-dependent changes were adjusted. We also investigated a prognostic significance of cardio-ankle vascular index, another index of arterial stiffness. Study participants included 8850 community residents. The repeated measures of the clinical parameters at 5.0 years after the baseline were available for 7249 of the participants. PWV was calculated using the arterial waveforms measured at the brachia and ankles (baPWV). The cardio-ankle vascular index was calculated by estimated pulse transit time from aortic valve to tibial artery. During the 8.53 years follow-up period, we observed 215 cases of CVD. The incidence rate increased linearly with baPWV quartiles (per 10 000 person-years: Q1, 2.7; Q2, 12.6; Q3, 22.5; Q4, 76.2), and the highest quartile was identified as an independent determinant of incident CVD by conventional Cox proportional hazard analysis adjusted for known risk factors [hazard ratio (HR), 4.00; p = .007]. Per unit HR of baPWV (HR, 1.15; p < .001) remained significant in the time-dependent Cox regression analysis including baPWV and other clinical values measured at 5-year after the baseline as time-varying variables (HR, 1.14; p < .001). The cardio-ankle vascular index was also associated with CVD with similar manner though the associations were less clear than that of baPWV. baPWV is a good risk marker for the incidence of CVD.
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http://dx.doi.org/10.1111/jch.14294DOI Listing
July 2021

Protocol for development and validation of a prediction model for 5-year risk of incident overactive bladder in the general population: the Nagahama study.

BMC Urol 2021 May 13;21(1):78. Epub 2021 May 13.

Department of Urology, Faculty of Medicine, Kyoto University Graduate School of Medicine, 54 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: An accurate prediction model could identify high-risk subjects of incident Overactive bladder (OAB) among the general population and enable early prevention which may save on the related medical costs. However, no efficient model has been developed for predicting incident OAB. In this study, we will develop a model for predicting the onset of OAB at 5-year in the general population setting.

Methods: Data will be obtained from the Nagahama Cohort Project, a longitudinal, general population cohort study. The baseline characteristics were measured between Nov 28, 2008 and Nov 28, 2010, and follow-up was performed every 5 years. From the total of 9,764 participants (male: 3,208, female: 6,556) at baseline, we will exclude participants who could not attend the follow-up assessment and those who were defined as having OAB at baseline. The outcome will be incident OAB defined using the Overactive Bladder Symptom Score (OABSS) at follow-up assessment. Baseline questionnaires (demographic, health behavior, comorbidities and OABSS) and blood test data will be included as predictors. We will develop a logistic regression model utilizing shrinkage methods (LASSO penalization method). Model performance will be evaluated by discrimination and calibration. Net benefit will be evaluated by decision curve analysis. We will perform an internal validation and a temporal validation of the model. We will develop a web-based application to visualize the prediction model and facilitate its use in clinical practice.

Discussion: This will be the first study to develop a model to predict the incidence of OAB.
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http://dx.doi.org/10.1186/s12894-021-00848-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120704PMC
May 2021

Association of Creatinine-to-Cystatin C Ratio with Myosteatosis and Physical Performance in Older Adults: The Japan Shimanami Health Promoting Program.

J Am Med Dir Assoc 2021 Apr 27. Epub 2021 Apr 27.

Department of Anti-aging Medicine, Ehime University Graduate School of Medicine, Toon City, Japan.

Objective: Sarcopenia is a risk factor for poor outcomes in older adults. Identification of plasma markers may facilitate screening of sarcopenia. We previously reported that creatinine-to-cystatin C ratio is a simple marker of muscle mass. To further assess the clinical relevance of the creatinine-to-cystatin C ratio, we investigated its association with myosteatosis and physical performance.

Design: Observational study.

Setting And Participants: Cross-sectional analysis of the dataset obtained from a Japanese population consisting of 1468 older (≥60 years of age) community residents.

Methods: The mean attenuation values of the skeletal muscle calculated from computed tomography images of the midthigh were used as an index of myosteatosis, while the cross-sectional area of the muscle was used as a proxy for muscle mass. Physical performance was assessed by 1-leg standing time.

Results: Creatinine-to-cystatin C ratio was positively associated with the cross-sectional area of muscle fiber-rich muscles, while it showed an inverse association with fat-rich muscle areas, resulting in the positive association between creatinine-to-cystatin C ratio and the mean attenuation value of the skeletal muscle [creatinine-to-cystatin C ratio quartiles (Q), Q1: 47.4 ± 4.8, Q2: 48.9 ± 4.4, Q3: 49.8 ± 4.1, Q4: 50.9 ± 3.7, P < .001]. The results of the linear regression analysis adjusted for major covariates (including muscle cross-sectional area) identified creatinine-to-cystatin C ratio as an independent determinant of the mean attenuation value (Q1: reference, Q2: β = 0.07, P = .019, Q3: β = 0.11, P < .001, Q4: β = 0.16, P < .001). Low creatinine-to-cystatin C ratio was independently associated with 1-leg standing time, although the association was attenuated substantially by adjusting for skeletal muscle cross-sectional area and mean attenuation value.

Conclusion And Implications: Creatinine-to-cystatin C ratio was associated with myosteatosis in older adults, independent of the muscle mass. Creatinine-to-cystatin C ratio may serve as a convenient marker of sarcopenia.
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http://dx.doi.org/10.1016/j.jamda.2021.03.021DOI Listing
April 2021

Age-related changes in gait speeds and asymmetry during circular gait and straight-line gait in older individuals aged 60-79 years.

Geriatr Gerontol Int 2021 May 29;21(5):404-410. Epub 2021 Mar 29.

Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Aim: The present study aimed to investigate the age-related changes in gait speeds and asymmetry during circular and straight-line gaits among older adults aged 60-79 years.

Methods: The study included 391 community-dwelling older adults aged >60 years, who participated in the Nagahama cohort study. They were assigned to four age groups: 60-64 years (early 60s), 65-69 years (late 60s), 70-74 years (early 70s) and 75-79 years (late 70s). For the circular gait test, the time required to walk twice around a 1-m diameter circle for right and left rotations were measured. The average time of the two trials was measured as the circular gait time, and the side-to-side difference in the circular gait times was calculated as an asymmetry index. Walking speed, asymmetry of step length, and asymmetry of stance duration time during straight-line gait at comfortable and maximal walking pace were measured.

Results: Circular gait time in older women in the late 70s group was significantly slower than that in other age groups; however, no age-related change was observed in older men. Maximal gait speeds in the early and late 70s groups were significantly slower than those in the early 60s group.

Conclusions: Age-related decline in circular gait speed was observed in older women aged ≥75 years, but not in older men. Maximal straight-line gait speed decreased significantly in both genders after the age of 70 years. Geriatr Gerontol Int 2021; 21: 404-410.
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http://dx.doi.org/10.1111/ggi.14150DOI Listing
May 2021

Genome wide association study of HTLV-1-associated myelopathy/tropical spastic paraparesis in the Japanese population.

Proc Natl Acad Sci U S A 2021 03;118(11)

Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, 606-8507 Kyoto, Japan;

HTLV-1-associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genome-wide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers. We also performed comprehensive genotyping of , , , , , and genes using next-generation sequencing technology for 651 HAM/TSP patients and 804 carriers. A strong association was observed in class I ( = 1.54 × 10) and class II ( = 1.21 × 10) loci with HAM/TSP. Association analysis using genotyping results showed that * ( = 2.61 × 10), * ( = 4.97 × 10), * ( = 1.15 × 10) and * ( = 2.30 × 10) were associated with disease risk, while * ( = 3.03 × 10), * ( = 1.06 × 10) and * ( = 1.78 × 10) worked protectively. Logistic regression analysis identified amino acid position 7 in the G-BETA domain of HLA-DRB1 as strongly associated with HAM/TSP ( = 9.52 × 10); individuals homozygous for leucine had an associated increased risk of HAM/TSP (odds ratio, 9.57), and proline was protective (odds ratio, 0.65). Both associations were independent of the known risk associated with proviral load. DRB1-GB-7-Leu was not significantly associated with proviral load. We have identified DRB1-GB-7-Leu as a genetic risk factor for HAM/TSP development independent of proviral load. This suggests that the amino acid residue may serve as a specific marker to identify the risk of HAM/TSP even without knowledge of proviral load. In light of its allele frequency worldwide, this biomarker will likely prove useful in HTLV-1 endemic areas across the globe.
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http://dx.doi.org/10.1073/pnas.2004199118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980450PMC
March 2021

Coexistence of low back pain and lumbar kyphosis is associated with increased functional disability in knee osteoarthritis: the Nagahama Study.

Arthritis Care Res (Hoboken) 2021 Feb 19. Epub 2021 Feb 19.

Kyoto University, Department of Physical Therapy, Human Health Sciences, Graduate School of Medicine, Kyoto, Japan.

Objective: To examine the association of low back pain (LBP) and lumbar kyphosis with functional disabilities and knee symptoms in patients with knee osteoarthritis (OA).

Methods: We analyzed 586 participants (80.1% female; age, 68.8 ± 5.2 years) from the Nagahama Study who were aged ≥60 years and had radiographically confirmed knee OA. The Knee Scoring System (KSS) was used to assess functional disabilities and knee symptoms. LBP was defined as the presence of any persistent back pain for more than 3 months. Lumbar kyphosis was determined by skin-surface methods using a computer-aided electronic device called the Spinal Mouse. Multiple linear regression analysis was used for assessing the association of LBP and lumbar kyphosis with the KSS scores. Subgroup analyses based on sex were also performed.

Results: LBP and lumbar kyphosis were independently associated with a lower KSS function score after adjustment for covariates (mean difference [95%CI, confidence interval] = -4.96 [-7.56 to -2.36] points for LBP alone, -4.47 [-8.51 to -0.43] points for lumbar kyphosis alone, and -13.86 [-18.86 to -8.86] points for the coexistence of LBP and lumbar kyphosis, respectively). The coexistence of LBP and lumbar kyphosis in women was associated with a lower KSS symptom score (mean difference [95%CI] = -4.49 [-6.42 to -2.55] points).

Conclusion: These findings suggest that both LBP and lumbar kyphosis are useful clinical signals indicating functional disability and knee symptoms in patients with knee OA.
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http://dx.doi.org/10.1002/acr.24580DOI Listing
February 2021

Data resource profile of Shizuoka Kokuho Database (SKDB) using integrated health- and care-insurance claims and health checkups: the Shizuoka Study.

J Epidemiol 2021 Jan 30. Epub 2021 Jan 30.

Research Support Center, Shizuoka General Hospital.

BackgroundAnalyzing real-world data, including health insurance claims, may help provide insights into preventing and treating various diseases. We developed a database covering Shizuoka Prefecture (Shizuoka Kokuho Database [SKDB]) in Japan, which included individual-level linked data on health- and care-insurance claims and health checkup results.MethodsAnonymized claims data on health insurance (National Health Insurance [age <75 years] and Latter-Stage Elderly Medical Care System [age ≥75 years]), care insurance, subscriber lists, annual health checkups, and all dates of death were collected from 35 municipalities in Shizuoka Prefecture. To efficiently link claims and health checkups, unique individual IDs were assigned using a novel procedure.ResultsFrom April 2012 to September 2018, the SKDB included 2,230,848 individuals (men, 1,019,687; 45.7%). The median age (min-max) of men and women was 60 (0-106) and 62 (0-111) years, respectively. During the study period, the median subscription time was 4.4 years; 40.8% of individuals continuously subscribed for the 6.5 years; 213,566 individuals died. Health checkup data were available for 654,035 individuals, amounting to 2,469,648 records. Care-service recipient data were available for 283,537 individuals; they used care insurance to pay for care costs.ConclusionsSKDB, a population-based longitudinal cohort, provides a comprehensive dataset covering health checkups, disorders, medication, and care service. This database may provide a robust platform to identify epidemiological problems and generate hypotheses for preventing and treating disorders in the elderly.
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http://dx.doi.org/10.2188/jea.JE20200480DOI Listing
January 2021

Relationship between Intraocular Pressure and Coffee Consumption in a Japanese Population without Glaucoma: The Nagahama Study.

Ophthalmol Glaucoma 2021 May-Jun;4(3):268-276. Epub 2020 Nov 5.

Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Purpose: To evaluate the association between daily coffee consumption and intraocular pressure (IOP) in healthy persons without glaucoma and the association between daily coffee consumption and history of glaucoma.

Design: Cross-sectional study.

Participants: A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016.

Methods: All participants underwent a standardized ophthalmic examination. Self-reporting questionnaires were completed by all participants. First, the association between habitual coffee consumption and IOP among nonglaucoma individuals was evaluated by a multivariate linear regression analysis, adjusting for possible confounders. Second, the association between habitual coffee consumption and history of glaucoma also was evaluated using a multivariate logistic regression analysis.

Main Outcome Measures: The association between habitual coffee consumption and IOP among nonglaucoma individuals.

Results: Of 9850 participants, 9418 did not have history of glaucoma. Among these participants, the mean ± standard deviation IOP of both eyes was 14.7 ± 2.9 mmHg. The multivariate regression analysis revealed that habitual coffee consumption was associated significantly with IOP (P < 0.001): the higher the consumption of coffee, the lower the IOP of an individual. The IOP of the group who consumed coffee most frequently (3 times daily or more) was 0.4 mmHg lower (95% confidence interval, 0.2-0.5 mmHg lower) than that of the group that consumed coffee least frequently (less than once daily). However, the logistic regression analysis showed that habitual coffee consumption was not associated significantly with history of glaucoma (P = 0.53).

Conclusions: Frequent coffee consumption was associated with a slightly lower IOP in people without glaucoma but was not associated with a decreased risk of glaucoma developing. Additional experimental studies are needed to examine the effects of coffee on IOP and glaucoma risk.
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http://dx.doi.org/10.1016/j.ogla.2020.09.019DOI Listing
November 2020

Extracellular-to-intracellular water ratios are associated with functional disability levels in patients with knee osteoarthritis: results from the Nagahama Study.

Clin Rheumatol 2021 Jul 23;40(7):2889-2896. Epub 2021 Jan 23.

Department of Physical Therapy, Human Health Sciences, Graduate School of Medicine, Kyoto University, 53-Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Introduction/objectives: To test the hypothesis that greater extracellular-to-intracellular water (ECW/ICW) ratios in lower-limb muscles are associated with worsened functional abilities in patients with knee osteoarthritis (OA).

Methods: We analyzed data from 787 participants (82.2% female; mean age, 69.6 ± 5.3 years) from the Nagahama Prospective Cohort who were ≥60 years old and had radiographically confirmed bilateral knee OA. The Knee Scoring System (KSS) was used to assess functional abilities. Lower-limb ECW/ICW ratios and skeletal mass index values were determined with multi-frequency bioelectrical impedance analysis (BIA). Multiple linear regression analysis was used to test for associations between ECW/ICW ratios and functional abilities. Subgroup analyses based on OA severities and symptomaticity were also conducted.

Results: Increased ECW/ICW ratios were associated with a 4.38-point decrease in the KSS function scores (95% confidence interval [CI], 3.15-5.62 points) after adjusting for covariates. This association varied according to the degree of knee symptoms, especially in individuals with radiologically mild OA. ECW/ICW ratios in individuals with asymptomatic mild OA were associated with a 2.14-point decrease in the KSS function score (95% CI, 0.32-3.96 points), whereas those in individuals with severe symptomatic mild OA were associated with a 6.16-point decrease (95% CI, 2.13-10.19 points).

Conclusions: Our findings indicate that higher ECW/ICW ratios are associated with greater functional disability in patients with knee OA. Therefore, ECW/ICW ratio measurements with multi-frequency BIA can serve as valuable indicators for functional disability in patients with knee OA. Key Points • Higher extracellular-to-intracellular water (ECW/ICW) ratios are associated with greater functional disability levels in patients with knee osteoarthritis (OA). • ECW/ICW ratios are useful clinical signs as a biomarker for poor functional abilities in patients with knee OA.
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http://dx.doi.org/10.1007/s10067-021-05591-0DOI Listing
July 2021

Gastroesophageal reflux disease is a risk factor for sputum production in the general population: the Nagahama study.

Respir Res 2021 Jan 6;22(1). Epub 2021 Jan 6.

Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54, Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

Background: Chronic sputum production in the general population is historically associated with clinical indices including male sex and smoking history. However, its relationship with gastroesophageal reflux disease (GERD), which may prove an underlying factor in sputum production, is unclear. We aimed to clarify factors associated with sputum production in the general population in cross-sectional and longitudinal manners.

Methods: In the Nagahama study, a community-based cohort study, 9804 subjects were recruited between 2008 and 2010 (baseline assessment), 8293 of whom were followed from 2013 to 2015 (follow-up assessment). This study contained a self-completed questionnaire which included medical history, assessment of sputum production, and a frequency scale for symptoms of GERD. A Frequency Scale for Symptoms of Gastroesophageal Reflux Disease score of ≥ 8 was defined as GERD. In addition to the frequency of sputum production at each assessment, frequency of persistent sputum production defined as sputum production at both assessments was examined.

Results: Frequency of sputum production was 32.0% at baseline and 34.5% at follow-up. Multivariable analysis demonstrated that sputum production at baseline was significantly associated with GERD [odds ratio (OR), 1.92; 95% confidence interval (CI) 1.73-2.13] and post-nasal drip (PND) (OR, 2.40; 95% CI 2.15-2.68), independent of other known factors such as older age, male sex and smoking history. These associations between sputum production and GERD or PND were also observed at follow-up. In longitudinal analysis, 19.4% had persistent sputum production and 12.3% had transient sputum production, i.e., at baseline only. Multivariable analysis for risk of persistence of sputum production revealed that persistent sputum production was associated with GERD and PND, in addition to the known risk factors listed above. The proportion of subjects with GERD at both assessments was highest among subjects with persistent sputum production.

Conclusions: Cross-sectional and longitudinal analysis demonstrated an association in the general population between sputum production and GERD, as well as PND, independent of known risk factors. The presence of GERD should be assessed in patients complaining of sputum production.
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http://dx.doi.org/10.1186/s12931-020-01601-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788913PMC
January 2021

Clinical and Genetic Characteristics of Pachydrusen in Eyes with Central Serous Chorioretinopathy and General Japanese Individuals.

Ophthalmol Retina 2021 Sep 10;5(9):910-917. Epub 2020 Dec 10.

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Purpose: To survey the prevalence and clinical and genetic characteristics of pachydrusen in eyes with central serous chorioretinopathy (CSC) and those of Japanese individuals in the general population.

Design: Prospective, observational cohort study.

Participants: One thousand thirty-seven Japanese patients were included in this study. Three hundred seven patients (614 eyes) had treatment-naïve CSC without choroidal neovascularization in either eye, whereas 730 individuals (1640 eyes) were Japanese individuals from the general population without explicit ocular diseases.

Methods: Pachydrusen were detected using color fundus photography, and subfoveal choroidal thickness was measured using OCT. Genotypic distributions of 3 single nucleotide polymorphisms, ARMS2 A69S, CFH I62V, and CFH Y402H, were evaluated.

Main Outcome Measures: Prevalence of pachydrusen and association with choroidal thickness.

Results: The prevalence of pachydrusen was significantly higher among CSC patients than among the general population group (40.1% vs. 15.6%; P < 0.001). Individuals with pachydrusen in either group were significantly older than those without pachydrusen (CSC patients: 62.1 years vs. 48.8 years [P < 0.001]; general individuals: 70.3 years vs. 51.9 years [P < 0.001]). No significant difference was found in subfoveal choroidal thickness between those with and without pachydrusen (CSC patients: 370 μm vs. 375 μm; [P = 0.574]; general population: 297 μm vs. 303 μm [P = 0.521]). However, after adjusting for age, gender, and refractive error, subfoveal choroidal thickness was notably thicker in individuals with pachydrusen than that in individuals without pachydrusen in both groups (P = 0.003 and P = 0.013, respectively). No significant difference was found in genotype distributions between CSC patients with pachydrusen and those without it; whereas, the T allele frequency of ARMS2 A69S was higher in general population individuals with pachydrusen than that in general population individuals without pachydrusen (42.2% vs. 33.9%; P < 0.001; OR, 1.86, adjusted for age, gender, and choroidal thickness).

Conclusions: Pachydrusen was observed more frequently in CSC patients compared with individuals from the general population. In both groups, pachydrusen was associated with a thicker choroid, suggesting that pachydrusen should be considered as a significant sign of pachychoroid.
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http://dx.doi.org/10.1016/j.oret.2020.12.004DOI Listing
September 2021

Cerebral small vessel disease genomics and its implications across the lifespan.

Nat Commun 2020 12 8;11(1):6285. Epub 2020 Dec 8.

University of Alabama at Birmingham School of Medicine, Birmingham, AL, 35233, USA.

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
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http://dx.doi.org/10.1038/s41467-020-19111-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722866PMC
December 2020

Glycemic Control and Insulin Improve Muscle Mass and Gait Speed in Type 2 Diabetes: The MUSCLES-DM Study.

J Am Med Dir Assoc 2021 04 2;22(4):834-838.e1. Epub 2020 Dec 2.

Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Japan. Electronic address:

Objectives: Type 2 diabetes is a risk factor for sarcopenia. Evidence on the prevention of sarcopenia using blood glucose-lowering therapy is limited. We aimed to examine the relationship between changes in glycemic control and sarcopenia and the effect of antidiabetic agents against sarcopenia in patients with type 2 diabetes.

Design: We conducted an observational longitudinal study.

Setting And Participants: In total, 588 Japanese patients with diabetes of an ongoing multicenter study completed 1-year follow-up measurements for sarcopenia and clinical data.

Methods: The data set of the Multicenter Study for Clarifying Evidence for Sarcopenia in patients with Diabetes Mellitus (the MUSCLES-DM study) was analyzed.

Results: During the follow-up period, the frequency of sarcopenia marginally increased, and the means of skeletal muscle mass index (SMI), handgrip strength, and gait speed did not show any changes. However, on dividing into 5 groups depending on the degree of changes in glycated hemoglobin (HbA) value, the patients with a decrease of ≥1% in HbA exhibited a significant increase in SMI. Our analysis revealed similar results for gait speed but not handgrip strength. Using the multiple linear regression model, we identified that a ≥1% decrease in HbA value was an independent determinant of the changes in SMI and gait speed. We also determined that insulin use at baseline was an independent factor for the changes in SMI.

Conclusions And Implications: Correction of poor glycemic control and use of insulin were significantly associated with the increase in skeletal muscle mass or gait speed in Japanese patients with type 2 diabetes. The current finding increases our understanding of the importance of glycemic control for the prevention of cardiovascular diseases and sarcopenia.
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http://dx.doi.org/10.1016/j.jamda.2020.11.003DOI Listing
April 2021

Obesity with radiological changes or depression was associated with worse knee outcome in general population: a cluster analysis in the Nagahama study.

Arthritis Res Ther 2020 11 27;22(1):280. Epub 2020 Nov 27.

Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Background: In knee osteoarthritis (OA), pain is the most frequent and dominant symptom. However, which factors other than radiological changes contribute to the symptoms is unresolved. The aims of this study were to identify factors affecting knee pain from various variables with radiological changes taken into count and exploratively examine what subgroups or phenotype could be identified by cluster analysis using the identified knee pain factors.

Methods: Patients 60 years or older who underwent radiographic evaluation were included in this cross-sectional study, and those subjects who completed a questionnaire about knee symptoms without missing data were eligible for analysis. Multiple regression analysis was used to examine the associations between selected variables and The Japanese Knee Osteoarthritis Measure (JKOM) pain score. We grouped the subjects by cluster analysis using identified variables.

Results: Two thousand five hundred forty-two subjects were included in the full set of analyses. Age, body mass index (BMI), radiological grade, bone mineral density (BMD), and high-sensitivity C-reactive protein (hs-CRP) showed a statistically significant correlation with radiological showing the strongest value. For dichotomous variable, presence of depression showed a statistically significant result. We used BMI, radiological grade, BMD, hs-CRP, and presence of depression as a variable for cluster analysis and identified six subgroups: (1) minimal joint disease subgroup, (2) male and high BMD subgroup, (3) high CRP subgroup, (4) severe radiological OA subgroup, (5) depressive subgroup, and (6) moderate radiological OA with high BMI subgroup, showing the worst knee outcome.

Conclusion: This study identified the factors affecting knee pain other than radiological changes and identified six subgroups of knee outcome in the general population. The results showed that obesity with radiological changes or depression was associated with worse knee outcome.
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http://dx.doi.org/10.1186/s13075-020-02375-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694310PMC
November 2020

Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data.

J Hum Genet 2021 Jun 23;66(6):557-567. Epub 2020 Nov 23.

Department of Statistical Genetics, Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Human immune systems are very complex, and the basis for individual differences in immune phenotypes is largely unclear. One reason is that the phenotype of the immune system is so complex that it is very difficult to describe its features and quantify differences between samples. To identify the genetic factors that cause individual differences in whole lymphocyte profiles and their changes after vaccination without having to rely on biological assumptions, we performed a genome-wide association study (GWAS), using cytometry data. Here, we applied computational analysis to the cytometry data of 301 people before receiving an influenza vaccine, and 1, 7, and 90 days after the vaccination to extract the feature statistics of the lymphocyte profiles in a nonparametric and data-driven manner. We analyzed two types of cytometry data: measurements of six markers for B cell classification and seven markers for T cell classification. The coordinate values calculated by this method can be treated as feature statistics of the lymphocyte profile. Next, we examined the genetic basis of individual differences in human immune phenotypes with a GWAS for the feature statistics, and we newly identified seven significant and 36 suggestive single-nucleotide polymorphisms associated with the individual differences in lymphocyte profiles and their change after vaccination. This study provides a new workflow for performing combined analyses of cytometry data and other types of genomics data.
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http://dx.doi.org/10.1038/s10038-020-00874-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144016PMC
June 2021
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