Faculty Profiles - YATSUYA Hiroshi

Psychiatric and psychological adverse effects associated with dulaglutide, semaglutide, and liraglutide: A vigibase study Open Access

Nishida, K; Chrétien, B; Dolladille, C; Ebina, T; Aleksic, B; Cabé, N; Savey, V; Onoue, T; Yatsuya, H

CLINICAL NUTRITION Vol. 51 page： 252 - 265 2025.8

Language：English Publisher：Clinical Nutrition

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are crucial in managing type 2 diabetes mellitus (T2DM) and obesity. Agents like dulaglutide, semaglutide, and liraglutide mimic endogenous GLP-1, enhancing insulin secretion and promoting satiety. Beyond glycemic control, they offer cardioprotective and neuroprotective benefits. However, concerns about psychiatric adverse effects have emerged, necessitating a systematic assessment of their safety profile. Material & Methods: This multinational pharmacovigilance study utilized VigiBase® data up to December 1, 2024, focusing on adverse drug reaction (ADR) reports for GLP-1 RAs. Psychiatric ADRs were classified using MedDRA terminology. Disproportionality analyses were conducted via logistic regression to calculate reporting adjusted Reporting Odds Ratios (aRORs) within reports involving antidiabetic or anti-obesity medications. A causal forest model assessed the individual treatment effect (ITE) of semaglutide on depression and suicidality reporting. Results: Among 2,061,901 reports, 21,414 involved psychiatric ADRs for GLP-1 RAs. Significant signals were observed for anxiety (aROR: 1.26, 95%CI: 1.18–1.35), depressed mood disorders (aROR: 1.70, 95%CI: 1.57–1.84) and suicidality (aROR 1.45, 95%CI: 1.29–1.63) with semaglutide, and eating disorders with all three GLP-1 RAs (aRORs between 4.17 and 6.80). The causal forest model estimated an average treatment effect of 0.0046 for semaglutide on depression and suicidality reporting, with significant heterogeneity across regions and demographic groups. Discussion: The study found no significant increase in overall psychiatric ADR reporting for GLP-1 RAs, except for eating disorders and depression/suicidality in semaglutide-treated patients. Sensitivity analyses before June 4, 2021, found no signals, aligning with RCT data. Post-marketing reports linked semaglutide to depression and suicidal ideation, prompting regulatory investigations. The causal forest model revealed significant heterogeneity in the psychiatric safety profile of semaglutide, with regional factors influencing ADR reporting. Conclusion: While GLP-1 RAs do not show a significant increase in overall psychiatric ADR reporting, findings suggest that clinicians should remain vigilant for potential depressive symptoms and suicidality, particularly in individuals with obesity treated with semaglutide since its approval for weight management.

DOI： 10.1016/j.clnu.2025.06.011

A comparison of the diagnostic ability of 1-mm computed tomography and 3-mm magnetic resonance imaging for detecting lateral pelvic lymph node metastases from rectal cancer

Kobayashi, R; Uehara, K; Ebata, T; Yatsuya, H; Li, YY; Hida, K; Hashiguchi, Y; Ishihara, S; Ogawa, S; Shiomi, A; Kawai, K; Ajioka, Y

SURGERY TODAY Vol. 55 ( 8 ) page： 1189 - 1197 2025.8

Language：English Publisher：Surgery Today

Aim: The best modality for evaluating lateral pelvic lymph node (LPLN) metastases from rectal cancer remains unclear. This study compared the diagnostic ability of 1-mm computed tomography (CT) and 3-mm magnetic resonance imaging (MRI) in identifying LPLN metastases based on size. Methods: This observational study analyzed not individual patients but 191 sides from 100 rectal cancer patients without preoperative treatment for whom preoperative CT and MRI and corresponding pathological results for LPLNs were available. A swollen LPLN was defined as an LN with a short-axis size of ≥5 mm on 1-mm CT. Results: LPLNs were detected significantly more frequently with 1-mm CT than with 3-mm MRI (p < 0.001). Among the 117 sides without swollen LPLNs, metastasis was observed in 1.7% of patients. In contrast, LPLN metastasis was confirmed in 28.4% of 74 sides with swollen LPLNs. In the evaluation of swollen LPLNs, 3-mm MRI yielded a 34% improvement in the diagnostic performance of LPLN metastasis over 1-mm CT (categorical net reclassification improvement: 0.341, p = 0.045). Conclusions: In conclusion, 1-mm CT should be performed preoperatively to evaluate LPLNs. Further evaluations can be omitted in the absence of swollen LPLNs. In patients with swollen LPLNs, a careful assessment of LPLN metastasis should be conducted via additional MRI, even in early T-stage tumors.

DOI： 10.1007/s00595-025-03018-w

Association between eveningness and low back pain among public servants in Japan: a cross-sectional analysis of the Aichi Workers' Cohort Study

Association of Adipose Tissue Insulin Resistance with Risk of Diabetes Incidents in Middle-aged Japanese Workers according to BMI states: 17 years of Follow-up of Aichi Worker's Cohort study. Open Access

Akter T, Song Z, Takada M, Hamrah MH, Wang S, Endale BT, Paththamesthrige SEP, Khine MT, Matsunaga M, Ota A, Tamakoshi K, Yatsuya H

Journal of epidemiology 2025.7

Matsunaga, M; Okegawa, R; Fujita, N; Kitajima, T; Yatsuya, H; Ota, A

EUROPEAN SPINE JOURNAL 2025.7

Language：English Publisher：European Spine Journal

Purpose: Low back pain (LBP) is a common occupational health problem. Chronotype, an individual’s preferred timing of activity and sleep, has been linked to pain perception. Previous studies have found a potential association between chronotype and LBP, although the findings were limited by small sample sizes and restricted population types. We investigated the association between evening chronotype (eveningness) and LBP in a cohort comprising public servants of various ages. Methods: We conducted a cross-sectional analysis of 4728 full-time public servants in Japan. LBP was assessed using a self-reported question. Individuals’ chronotypes were determined using the reduced Morningness–Eveningness Questionnaire. The association between chronotype and LBP was analyzed using the chi-squared test and multiple logistic regression models adjusted for age, sex, occupation, overtime work, use of the internet/email, body mass index, smoking status, exercise habits, sedentary behavior, sleep duration, sleep medication use, and depressive symptoms. Results: In total, 30% of the subjects reported LBP. The most common chronotype was intermediate type (51%), followed by morningness (38%) and eveningness (11%). A significant association between eveningness and LBP was observed. After adjusting for potential confounders, individuals with eveningness had a higher prevalence of LBP than those with morningness (36.2% vs. 28.7%; odds ratio: 1.46; 95% confidence interval: 1.16–1.83). Conclusion: Eveningness was statistically associated with LBP in a cohort of public servants. The present findings would strengthen the association’s generalizability to more varied populations.

DOI： 10.1007/s00586-025-09048-9

A comparison of modifiable risk factors for dementia among South Asian migrants and non-migrants aged 50 or older in Tasmania, Australia. Open Access

Hamrah MS, Alty J, Goldberg LR, Doherty K, Kitsos A, Bindoff A, Roccati E, Yatsuya H, Vickers JC

BMC public health Vol. 25 ( 1 ) page： 2362 2025.7

Language：English Publisher：BMC Public Health

Background: South Asian migrants are one of the fastest-growing populations in Australia, particularly in the southern island state of Tasmania. However, there is limited research evaluating their modifiable dementia risk factors. This study aimed to fill this gap by comparing risk factors in South Asian migrants to non-migrant Australians in Tasmania. Methods: A cross-sectional study was conducted with 136 South Asian migrants and 2743 non-migrant Australians aged 50 or older residing in Tasmania. Participants completed a survey questionnaire. Logistic regression models were used to assess differences in the odds of reporting modifiable dementia risk factors between the two cohorts as they responded to a survey. Results: South Asian migrants had higher odds of reporting hypertension (OR, 5.5; 95% CI, 3.5 to 8.4; p < 0.001), hypercholesterolaemia (OR, 4.4; 95% CI, 2.3 to 6.4; p < 0.001), cognitive inactivity (OR, 16.9; 95% CI, 10.4 to 28.9; p < 0.001), diabetes (OR, 5.2; 95% CI, 3.5 to 7.6; p < 0.001), smoking (OR, 3.6; 95% CI, 1.7 to 7.1; p < 0.001) and nonadherence to a Mediterranean-type diet (OR, 7.4; 95% CI, 3.5 to 18.9; p < 0.001), compared to non-migrant Australians. However, South Asian migrants had lower odds of reporting alcohol consumption (OR, 0.25; 95% CI, 0.14 to 0.43; p < 0.001). Conclusions: The risk profiles were different between South Asian migrants and non-migrant Australians, highlighting the need for targeted interventions addressing group-specific risk factors. However, the use of convenience sampling for the South Asian migrant group may limit the representativeness of the findings and affect their generalizability. However, the use of convenience sampling and the relatively small sample size of the South Asian migrant group may limit the representativeness and generalizability of the findings. Additionally, the South Asian migrant group may represent a more socioeconomically disadvantaged population compared to the non-migrant sample, which may be relatively healthier and more financially advantaged than the general Tasmanian population. The study highlights the need for targeted, culturally appropriate interventions to address these risks. Further research is needed to comprehensively assess the prevalence and determinants of modifiable dementia risk factors among South Asian migrants.

DOI： 10.1186/s12889-025-23426-4

Relationship between abdominal visceral adipose tissue and cardiovascular events in patients with acute coronary syndrome

Risk factors for intracerebral hemorrhage by five specific bleeding sites: Japan Public Health Center-based Prospective Study Reviewed Open Access

Kenichi Ariyada, Kazumasa Yamagishi, Tomomi Kihara, Isao Muraki, Hironori Imano, Yoshihiro Kokubo, Isao Saito, Hiroshi Yatsuya, Hiroyasu Iso, Shoichiro Tsugane, Norie Sawada

European Stroke Journal Vol. 10 ( 2 ) page： 600 - 609 2025.6

Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE Publications

Background:

Evaluating the risk factors for intracerebral hemorrhage is indispensable for primary prevention. However, the pathogenesis varies depending on the bleeding site, and few prospective studies have explored risk factors in detail for each site.

Participants and methods:

The Japan Public Health Center-based Prospective Study is a prospective study comprising a population-based sample of Japanese adults in 1990 (Cohort I) and in 1993 (Cohort II). A total of 34,137 participants (11,907 men and 22,230 women) were enrolled in this study and followed up until 2009 for Cohort I and until 2012 for Cohort II. The association between risk factors (age, sex, blood pressure, serum cholesterol, triglycerides, blood glucose, body mass index, smoking, and drinking status) and intracerebral hemorrhage by its bleeding site (lobes, putamen, thalamus, cerebellum, and brainstem) was assessed using Cox proportional hazards analysis.

Results:

During a median 20-year follow-up, 571 intracerebral hemorrhage events occurred. Hypertension was associated with an increased risk of total intracerebral hemorrhage, but not lobar hemorrhage. The multivariable hazard ratio (95% confidence intervals) was 2.09 (1.75–2.50) for total intracerebral hemorrhage. In contrast, a low serum total cholesterol level was associated only with lobar hemorrhage (1.73 (1.01–2.96)). Heavy drinking was associated with the risk of total and putamen hemorrhage, and obesity was associated with the risk of putamen hemorrhage.

Discussion and conclusion:

The present study identified different risk factors depending on the bleeding site of intracerebral hemorrhage.

DOI： 10.1177/23969873241290680

Other Link： https://journals.sagepub.com/doi/full-xml/10.1177/23969873241290680

Ueyama, C; Horibe, H; Maekawa, Y; Hiramatsu, S; Yamase, Y; Funabiki, J; Takemoto, Y; Shigeta, T; Hibino, T; Kondo, T; Yatsuya, H; Ishii, H; Murohara, T

HEART AND VESSELS 2025.5

Language：English Publisher：Heart and Vessels

Abdominal visceral adipose tissue (AVAT) is associated with the incidence of cardiovascular events (CVEs). We retrospectively evaluated the association between AVAT and the incidence of CVEs in 602 patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI). Patients were divided into four groups according to the quartiles of AVAT areas using computed tomography. The incidence of CVEs (cardiovascular death, ACS recurrence and stroke) during the follow-up period (median 49.5 months) was evaluated. Cox analysis adjusting for cardiovascular risk factors revealed that the AVAT quartile classification exhibited a significant association with the incidence of CVEs. The risk in quartile 3 (moderate AVAT areas, ≥ 106.0 to < 142.6 cm2) was significantly lower than in quartiles 1 (low AVAT areas, < 71.0cm2; P < 0.01; hazard ratio [HR], 5.06), 2 (mild AVAT areas, ≥ 71.0 to < 106.0 cm2; P < 0.01; HR, 4.25) and 4 (severe AVAT areas, ≥ 142.6 cm2; P < 0.01; HR, 4.52). Polynomial analyses revealed that quadratic model was the most appropriate to illustrate the relationship between AVAT area and the hazard ratios for CVEs (corrected Akaike's information criterion, 49.2; R2, 0.47). The AVAT area and the incidence of CVEs exhibited a U-shaped relationship in patients with ACS undergoing PCI independent of conventional cardiovascular risk factors. The risk of CVEs was the lowest in patients with moderate AVAT areas. Evaluating AVAT may provide additional information for the assessment of long-term prognosis in patients with ACS.

DOI： 10.1007/s00380-025-02557-z

Utility of long-term systolic blood pressure variability for predicting the development of type 2 diabetes mellitus Open Access

Song, Z; Li, YY; Hong, YJ; Chiang, CF; Matsunaga, M; He, YP; Ota, A; Tamakoshi, K; Yatsuya, H

NAGOYA JOURNAL OF MEDICAL SCIENCE Vol. 87 ( 2 ) page： 220 - 236 2025.5

Publisher：Nagoya Journal of Medical Science

Better identification of individuals at high risk for type 2 diabetes mellitus (T2DM) requires risk-prediction models incorporating novel predictors. Accordingly, this study aimed to evaluate the merits of including long-term systolic blood pressure variability (SBPV) in predicting T2DM incidence in a Japanese cohort of 3017 participants (2446 men, 571 women; age, 36–65 years) in 2007, who were followed up until March 2019. Consecutive SBP values, recorded between 2003 and 2007, were regressed annually for each participant. The slope and root-mean-square error of the regression line were calculated for each individual to represent SBPV. The significance of SBPV was examined by adding it to a multivariate Cox model incorporating age, sex, smoking status, regular exercise, family history of diabetes, body mass index, blood levels of triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. The c-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to compare the performance of the prediction models without (Model 1) and with (Model 2) SBPV. During the 9.8-year follow-up period, 135 participants developed T2DM. Although a statistically significant difference in c-index between Model 1 (0.785) and Model 2 (0.786) was not found, the NRI (8.312% [p < 0.001]) and IDI (0.700% [p = 0.012]) demonstrated that the performance of Model 2 improved compared with Model 1. In conclusion, results suggested that long-term SBPV slightly improved predictive utility for T2DM when added to a conventional prediction model. The study was registered at University Hospital Medical Information Network Clinical Trial registry (UMIN000052544, https://www.umin.ac.jp/).

DOI： 10.18999/nagjms.87.2.220

Analysis of the changes in health-related quality of life and employment status after surgery in patients with lung cancer: a single-center longitudinal study Open Access

Association between eveningness and depressive symptoms in daytime workers: A cross-sectional analysis of the Aichi Workers’ Cohort Study Reviewed Open Access

Kazuhito Ishihara, Tsuyoshi Kitajima, Atsuhiko Ota, Hiroshi Yatsuya, Nakao Iwata

Fujita Medical Journal Vol. 11 ( 2 ) page： 64 - 69 2025.5

Language：English Publisher：Fujita Medical Society

Objectives: Eveningness (evening preference in chronotype) has been reported to be associated with a number of psychiatric problems. We examined a cross-sectional association between eveningness and depressive symptoms in daytime workers.Methods: The subjects were 4410 civil servants (71.7% male, aged 18–69 years [mean, 43.5 years]) with no history of depressive disorder who did not perform shift work, and for whom there were no missing data. The association between eveningness, determined using the reduced Morningness–Eveningness Questionnaire, and depressive symptoms, determined using the shorter form of the Central Epidemiological Studies Depression scale, was assessed with logistic regression analysis adjusted for potential confounding factors (gender, income, living alone, breakfast intake, coffee consumption, drinking habits, exercise, smoking, working hours, sleep duration, and difficulty falling asleep).Results: Of the subjects, 529 (12.0%) had eveningness, and 1408 (31.9%) reported depressive symptoms. Depressive symptoms were reported more frequently by those with eveningness than by those with other chronotypes (57.3% vs 28.5%). The association between eveningness and depression (gender- and age-adjusted odds ratio, 3.27; 95% confidence interval, 2.71–3.95) was significant after adjustment for the other confounding factors (odds ratio, 2.40; 95% confidence interval, 1.96–2.95).Conclusions: Our results suggest that eveningness is associated with depressive symptoms among day workers and that this association is independent of potential confounding factors. Further longitudinal studies are needed to examine the causal relationship.

DOI： 10.20407/fmj.2024-021

Yuka Kadomatsu, Toru Oga, Atsuhiko Ota, Hiroshi Yatsuya, Yuta Kawasumi, Harushi Ueno, Taketo Kato, Shota Nakamura, Tetsuya Mizuno, Toyofumi Fengshi Chen-Yoshikawa

General Thoracic and Cardiovascular Surgery 2025.4

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Abstract

Objective

This study analyzed the changes in health-related quality of life (HRQOL) and employment status of patients undergoing lung cancer surgery in Japan.

Methods

This was a single-center, prospective study on patients who underwent lung anatomical resection. The eligible patients completed self-reported HRQOL and employment surveys at baseline and 6 and 12 months postoperatively. HRQOL was assessed using questionnaires including the European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30) and EORTC QLQ and Lung Cancer module and additional social engagement and work-related stress evaluation tools.

Results

In total, 93 patients completed the baseline survey, and 80 provided survey data at 6 months postoperatively. The HRQOL scores of several factors significantly declined immediately after the surgery and then gradually improved. The EORTC global health score, which represents overall health status, returned to baseline levels at 12 months postoperatively. However, symptoms such as fatigue, dyspnea, and coughing did not return to baseline levels at 12 months postoperatively. Approximately 68% of the patients who were employed preoperatively continued to work at 12 months postoperatively.

Conclusions

Lung cancer surgery significantly affected the HRQOL and employment status of the patients within the first 6 months after surgery. For patients who decide to return to work before full recovery of QOL, we consider the need for enhanced support to assist them as they can reintegrate into work and activities of daily living.

DOI： 10.1007/s11748-025-02144-z

Other Link： https://link.springer.com/article/10.1007/s11748-025-02144-z/fulltext.html

日比野瑞歩, 李媛英, 宋澤安, 髙田碧, 洪英在, 福田知里, 王爽, 桶川龍世, 西尾七海, 服部優奈, 太田充彦, 玉腰浩司, 八谷寛

東海公衆衛生雑誌 Vol. 12 ( 2 ) page： 135 - 142 2025.3

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：東海公衆衛生学会

目的　中部地方の自治体職員を対象に，朝食欠食と5年後の抑うつ状態発症との関連を，愛知職域コホート研究のデータを用いて検討することを目的とした。方法　愛知職域コホート研究の2013年のベースライン調査に参加した20-54歳の対象者のうちベースライン時に抑うつがない,あるいはうつ病の治療中ではない者のうち2018年調査にも参加した2004人 (男性1452人,女性552人)を研究対象とした。抑うつ状態の評価はCenter for Epidemiologic Studies Depression Scale日本語短縮 (11項目)を使用し，8点以上を抑うつとみなした。朝食欠食は朝食摂取頻度が週6回以下と定義した。さらに，5年間の朝食欠食の変化を「非欠食 (2013年)→非欠食 (2018年)」，「欠食→非欠食」，「非欠食→欠食」，「欠食→欠食」の4パターンに分けた分析も実施した。多変量ロジスティック回帰分析を用いて，性 (男性，女性[閉経前]，女性[閉経後])，年齢，学歴，配偶者・14歳未満の子供の同居の有無，肥満 (BMI≧25 kg/m2），喫煙状況，運動頻度，アルコール摂取量，睡眠時間，ストレス，ファミリー・ワーク・コンフリクト，ワーク・ファミリー・コンフリクトを調整し，2018年の抑うつ発症のオッズ比 (OR)と95%信頼区間 (CI)を推定した。結果　2018年に新たに抑うつ状態となったのは261人 (13%)であった。朝食欠食と抑うつ発症には調整要因に独立した統計学的に有意な正の関連が認められた (OR: 1.39，95%CI: 1.01-1.90)。朝食欠食の変化パターン別の分析でも「非欠食→非欠食」群に比べて「欠食→欠食」群は抑うつ発症と有意な正の関連を示した (OR: 1.53，95%CI: 1.06-2.21)。結論　朝食欠食と抑うつ発症には調整要因に独立した正の関連が認められた。

DOI： 10.24802/tpha.2024-07