研究者詳細 - 土岐　了大

土岐　了大（トキ　リョウタ）

Toki, Ryota

写真a

所属（所属キャンパス）: 医学部衛生学公衆衛生学教室（信濃町）

職名: 助教（有期）

Scopus 論文情報

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Within-Person Seasonal Variability of Aminotransferases and Long-Term Glycemic Control in Adults With Type 2 Diabetes (JDDM 85)

Toki R., Sakamoto M., Yuki M., Iida M., Yamazaki M., Ichikawa S., Horiuchi R., Maegawa H., Okamura T., Takebayashi T.

Liver International 46 （ 7 ） 2026年07月

ISSN 14783223

　概要を見る

Background & Aims: Aminotransferases are widely used for metabolic dysfunction-associated steatotic liver disease (MASLD) evaluation, especially in type 2 diabetes mellitus (T2DM). Whether within-person seasonal variation affects classification near commonly used thresholds or relates to long-term metabolic outcomes remains unclear. Methods: This registry-based cohort analysed monthly aspartate aminotransferase (AST) and alanine aminotransferase (ALT) measurements from 6039 adults with T2DM in the Japan Diabetes Clinical Data Management registry (2014–2020). Classification discordance across the 30 IU/L threshold was compared between winter-mean and summer-mean values. Individual seasonal amplitude was derived from seasonal-trend decomposition of multiply imputed monthly time series. Final glycated haemoglobin (HbA1c) and non-achievement of HbA1c < 7% were analysed using multivariable regression. Results: Both AST and ALT showed significant seasonal variation, with the highest values in late autumn to early winter and the lowest in summer (p < 0.001). Approximately one in nine patients with borderline ALT values showed discordant winter-summer classification. Each 1-SD increase in AST amplitude was associated with 0.06 percentage points higher final HbA1c (95% CI, 0.04–0.08) and higher odds of not achieving HbA1c < 7% (odds ratio, 1.14; 95% CI, 1.08–1.21; p < 0.001). ALT amplitude showed a similar but weaker, less consistent association. Conclusions: AST and ALT exhibited reproducible seasonal variation peaking in late autumn to early winter, with approximately one in nine patients near the MASLD screening threshold reclassified depending on season. Greater seasonal amplitude, especially AST, was independently associated with poorer glycemic control, supporting season-aware interpretation in routine clinical practice.
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Seasonal BMI Amplitude and Risk of Kidney Function Decline in Japanese Adults With Type 2 Diabetes (JDDM 82)

Toki R., Sakamoto M., Yuki M., Iida M., Yamazaki M., Ichikawa S., Horiuchi R., Maegawa H., Okamura T., Takebayashi T.

Diabetes Care 49 （ 6 ） 990 - 998 2026年06月

ISSN 01495992

　概要を見る

OBJECTIVE Body weight variability is linked to cardiometabolic outcomes, but its renal impact in type 2 diabetes remains uncertain. We tested whether the magnitude of seasonal BMI fluctuation is independently associated with kidney function decline. RESEARCH DESIGN AND METHODS We analyzed a nationwide, multicenter Japanese cohort (2014-2020). Monthly BMI was modeled using seasonal-trend locally estimated scatterplot smoothing to quantify each participant’s within-year peak-to-trough difference. The primary outcome was ≥40% decline in estimated glomerular filtration rate (eGFR). Secondary outcomes were ≥30% eGFR decline, creatinine doubling, incident chronic kidney disease (CKD) stage ≥3, and kidney failure. Associations were estimated using multivariable Cox models with clinic as a random effect. RESULTS Among 6,700 outpatients (median follow-up: 6.8 years), 779 reached the primary end point. Each 1-SD increase in BMI fluctuation was associated with higher risk of ≥40% eGFR decline (hazard ratio [HR] 1.23, 95% CI 1.16-1.31). The highest versus lowest tertile showed a 1.7-fold increased risk (HR 1.72, 95% CI 1.42-2.09). Patterns were consistent for ≥30% eGFR decline (HR 1.18, 95% CI 1.13-1.23), creatinine doubling (HR 1.30, 95% CI 1.17-1.45), and incident CKD stage ≥3 (HR 1.11, 95% CI 1.07-1.16). Longitudinal analyses showed steeper eGFR decline in the highest-fluctuation group. Results were robust across sensitivity analyses, including models for time-varying medication exposure. CONCLUSIONS In type 2 diabetes, larger intra-annual BMI fluctuations were independently and dose-dependently associated with kidney function decline. Seasonal BMI amplitude may identify higher-risk individuals; whether reducing seasonal BMI fluctuations improves kidney outcomes warrants prospective evaluation.
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Longitudinal Study of Plasma Metabolites During Menopause and Their Associations With Later Onset of Metabolic Syndrome

Miyake A., Iida M., Harada S., Sugiyama D., Matsumoto M., Miyagawa N., Toki R., Edagawa S., Hirata A., Kuwabara K., Okamura T., Sato A., Amano K., Hirayama A., Sugimoto M., Soga T., Tomita M., Arakawa K., Kisu I., Yamagami W., Takebayashi T.

Journal of Clinical Endocrinology and Metabolism 111 （ 6 ） e1672 - e1680 2026年06月

ISSN 0021972X

　概要を見る

Context: Previous metabolomics studies suggest potential associations between menopausal changes in lipids and an increased risk of metabolic syndrome (MetS). However, longitudinal data on other key metabolites, such as branched-chain amino acids (BCAAs) and homocysteine, remain limited, and most studies lack long-term follow-up across the menopause transition. Objective: This study aimed to investigate longitudinal changes in circulating metabolites during menopause over a mean follow-up of 5 years and assess their associations with subsequent MetS development. Methods: Premenopausal women from the Tsuruoka Metabolomics Cohort Study who participated in at least one follow-up survey were included. Menopausal status, data on MetS, and plasma metabolites profiled using capillary electrophoresis mass spectrometry were assessed at each visit. Thirty-one metabolites were examined for associations with menopausal status using mixed-effects models. The association of these menopause-related metabolites with MetS development was examined via logistic regression analysis adjusted for follow-up duration. Results: Among 953 women (aged 43.8 ± 5.4 years), 316 (33.2%) reached menopause during follow-up (5.0 ± 1.1 years). Eighteen metabolites changed significantly with menopause, particularly those related to BCAA metabolism, urea cycle, and homocysteine metabolism. Of 695 women without MetS at baseline, 65 (9.4%) developed MetS. Glutamate (odds ratio [95% CI]: 1.95 [1.49-2.57]) was associated with higher MetS risk. Higher levels of glutamate, valine, leucine, and cystine were significantly associated with the development of hyperglycemia. Conclusion: Longitudinal changes in charged metabolites occur across the menopausal transition, with specific metabolites such as glutamate possibly contributing to the metabolic alterations underlying increased MetS risk.
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Serum total apoptosis inhibitor of macrophage, metabolomic signatures, and incident dyslipidemia: A population-based prospective study

Toki R., Harada S., Arai S., Hirata A., Iida M., Miyagawa N., Edagawa S., Ishikawa T., Hirayama A., Sugimoto M., Okamura T., Miyazaki T., Takebayashi T.

Journal of Clinical Lipidology 20 （ 4 ） 806 - 816 2026年04月

ISSN 19332874

　概要を見る

BACKGROUND The role of the apoptosis inhibitor of macrophages (AIM) in human lipid metabolism remains unclear. OBJECTIVE This study aimed to investigate the cross-sectional associations between serum AIM and plasma metabolites and to determine if baseline AIM concentrations predict incident dyslipidemia. METHODS This study used a community-based cohort of 3139 participants for cross-sectional metabolomic analysis. Among them, 1292 participants without dyslipidemia at baseline were followed prospectively for up to 8.5 years. Cox proportional hazards models were used to estimate hazard ratios for incident high low-density lipoprotein cholesterol (LDL-C) and metabolic dyslipidemia (high triglycerides and/or low high-density lipoprotein cholesterol [HDL-C]) across AIM tertiles. RESULTS Cross-sectionally, higher AIM concentrations were associated with elevated acylcarnitines and tricarboxylic acid cycle intermediates. Longitudinally, higher baseline AIM was associated with an increased risk of developing metabolic dyslipidemia in women (highest vs lowest tertile hazard ratio, 1.84) and showed a similar but smaller nonsignificant trend in men. The risk for high LDL-C was significantly increased in women but not in men. These associations remained robust after multivariable adjustment. CONCLUSION Elevated baseline AIM concentrations were prospectively associated with the development of metabolic dyslipidemia in women, with a similar but nonsignificant trend in men, and with high LDL-C in women. The related metabolomic profile suggests enhanced lipolysis and altered lipid metabolism. Therefore, AIM may serve as a biomarker for future dyslipidemia, particularly for triglyceride and HDL-C dysregulation.
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Cardiovascular Risk of Alcohol Consumption due to Renal Impairment: A 10-Year Prospective Study in a Community-Dwelling Japanese Population

Hirata A., Harada S., Iida M., Matsumoto M., Miyagawa N., Toki R., Edagawa S., Shibuki T., Kuwabara K., Kohsaka S., Izawa Y., Sawano M., Takizawa T., Shoji S., Katsumata M., Sugiyama D., Okamura T., Takebayashi T.

Journal of Atherosclerosis and Thrombosis 33 （ 6 ） 775 - 797 2026年

ISSN 13403478

　概要を見る

Aims: The association between alcohol consumption and the risk of cardiovascular disease (CVD) varies according to the presence of underlying cardiovascular risk factors. Incorporating such risk factors may be important to effectively reduce harmful alcohol use through health guidance. However, whether the risk of alcohol consumption is affected due to renal impairment remains unclear. Methods: A total of 10,583 community-dwelling Japanese adults (mean age 59.4 (SD 10.1) years; 46% men) were followed for 10 years. Alcohol consumption was categorized into five groups for men: never drinkers, former drinkers, light drinkers (＜20 g/day), moderate drinkers (20-39 g/day), and heavy drinkers (≥ 40 g/day), and four groups for women with moderate and heavy combined. Cox proportional hazards models estimated hazard ratios for incident CVD stratified by the presence or absence of reduced estimated glomerular filtration rate (eGFR) (＜60 mL/min/1.73m<sup>2)</sup> and proteinuria, with adjustment for confounders. Results: Among men with proteinuria, alcohol consumption was associated with a higher risk of atherosclerotic CVD, whereas an inverse association was observed in men without proteinuria [hazard ratio (95% confidence interval): moderate drinkers without proteinuria, 0.58 (0.34-0.97); moderate drinkers with proteinuria, 3.49 (1.15-10.56)]. Moderate to heavy drinking increased the risk of intracerebral hemorrhage irrespective of the renal status. In women, moderate to heavy drinking was associated with an increased CVD risk only when proteinuria was present. In contrast, a reduced eGFR did not clearly affect the association in either sex. Conclusions: The CVD risk associated with alcohol consumption may differ according to the renal status, particularly depending on the presence or absence of proteinuria.
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