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"Shimabukuro, Michio"
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Xanthine oxidase inhibitors are associated with reduced risk of cardiovascular disease
2021
As previous studies have reported finding an association between hyperuricemia and the development of cardiovascular and chronic kidney disease, hyperuricemia is thought to be an independent risk factor for hypertension and diabetic mellitus. However, we have not been able to determine whether the use of xanthine oxidase inhibitors can reduce cardiovascular disease. The present study used the longitudinal data of the Fukushima Cohort Study to investigate the relationship between the use of xanthine oxidase inhibitors and cardiovascular events in patients with cardiovascular risks. During the 3-year period between 2012 and 2014, a total of 2724 subjects were enrolled in the study and followed. A total of 2501 subjects had hypertension, diabetic mellitus, dyslipidemia, or chronic kidney disease, and were identified as having cardiovascular risks. The effects of xanthine oxidase inhibitor use on the development of cardiovascular events was evaluated in these patients using a time to event analysis. During the observational periods (median 2.7 years), the incidence of cardiovascular events was 20.7 in subjects with xanthine oxidase inhibitor and 11.2 (/1000 person-years, respectively) in those without. Although a univariate Cox regression analysis showed that the risk of cardiovascular events was significantly higher in subjects administered xanthine oxidase inhibitors (HR = 1.87, 95% CI 1.19–2.94, p = 0.007), the risk was significantly lower in subjects administered a xanthine oxidase inhibitor after adjustment for covariates (HR = 0.48, 95% CI 0.26–0.91; p = 0.024) compared to those without. Xanthine oxidase inhibitor use was associated with reduced risk of cardiovascular disease in patients with cardiovascular risk factors.
Journal Article
Fast eating is a strong risk factor for new-onset diabetes among the Japanese general population
2019
Although many studies that have examined the relationship of type and amount of food and the frequency of eating with new onset of diabetes, there are few reports on the relationship between how meals are eaten, such as skipping breakfast, snacking or food ingestion speed, and the onset of diabetes. We investigated the relationship between eating speed, as well as other eating habits such as snacking and skip breakfast, and new onset of diabetes in a nation-wide Japanese cohort. We obtained data from the nation-wide annual health check program in Japan. In 197,825 participants without diabetes in 2008, questionnaires recorded data on the diet habits (eating speed, snack after supper or before sleep, and skipping breakfast) and unadjusted and multivariable-adjusted logistic regression models were used to measure the odds ratio of new-onset diabetes mellitus in a 3-year follow up. The proportion of fast eaters, those who snack after supper, snack before sleep, and skip breakfast was higher in the new-onset diabetes group than in the group who did not develop diabetes mellitus. As compared with the non-fast eater group, fast eaters were generally younger, had higher BMI, had more weight gain from 20 years onwards, and experienced frequent weight fluctuations of ≥3 kg within 1 year. The risk of fast eaters developing diabetes mellitus remained even after correction for multiple factors including age, body weight, rate of weight change, blood pressure, smoking, and alcohol consumption. No other eating habits were independent predictors for onset of diabetes mellitus. Results show that fast eating is a sole predisposing factor among eating habits for new-onset diabetes. Future studies were warranted to evaluate whether avoidance of fast eating is beneficial for prevention of diabetes mellitus.
Journal Article
High FIB4 index is an independent risk factor of diabetic kidney disease in type 2 diabetes
by
Masuzaki, Hiroaki
,
Tanaka, Kenichi
,
Abe, Kazumichi
in
692/163/2743/137/138
,
692/4020/4021/1607/2750
,
692/4022/1585/104
2021
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) may be linked to development of chronic kidney diseases (CKD). The FIB4 index, a noninvasive liver fibrosis score, has been reported to predict CKD in non-diabetic patients, but there are no reports yet in diabetic cases. Therefore, we evaluated the prognostic impact of FIB4 index on the risk of developing diabetic kidney disease (DKD) in Japanese patients with type 2 diabetes in a retrospective cohort study. We assessed patients with type 2 diabetes with an eGFR ≥ 60 mL/min/1.73 m
2
and without dipstick positive proteinuria (≥ 1 +) at their first visit to our department. Participants were divided into two groups based on the FIB4 index at their first visit: FIB4 index > 1.3 and FIB4 index ≤ 1.3. The primary endpoint was defined as a decrease in eGFR < 60 mL/min/1.73 m
2
or the onset of proteinuria during the course of treatment. The average age of all 584 type 2 diabetic participants (360 [61.6%] men) was 55 ± 11 years. There were 187 patients in the FIB4 index group > 1.3 (32.0%) and the median observation period was 6.0 (3.8–11.0) years. Kaplan–Meier survival analysis indicated that the risks of developing DKD, eGFR < 60 and proteinuria were all higher in FIB4 index > 1.3 patients than in FIB4 ≤ 1.3 patients. In the Cox regression analysis, an FIB4 index > 1.3 was a significant predictor for onset of DKD (HR 1.54, 95% CI 1.15–2.08) and proteinuria (HR 1.55, 95% CI 1.08–2.23), but not for an eGFR < 60 (HR 1.14, 95% CI 0.79–1.99). To the best of our knowledge, this is the first study to demonstrate that an FIB4 index > 1.3 has a prognostic impact on the development of CKD and proteinuria in type 2 diabetic patients. This warrants further investigation of the prognostic impact of the development of DKD or proteinuria.
Journal Article
Trends in Lifestyle-related Diseases and Their Risk Factors After the Fukushima Daiichi Nuclear Power Plant Accident: Results of the Comprehensive Health Check in the Fukushima Health Management Survey
2022
Residents were forced to evacuate owing to the radiation released after the Fukushima Nuclear Power Plant (NPP) accident following the Great East Japan Earthquake on 11/03/2021; thus, their lifestyles drastically changed. The Comprehensive Health Check (CHC) of the Fukushima Health Management Survey (FHMS) was performed to evaluate health statuses and prevent lifestyle-related diseases in evacuation area residents. The first part of the CHC survey is a retrospective analysis of pre- and post-disaster data on health check-ups of evacuation area residents. The second part is a cross-sectional, prospective analysis of post-disaster (fiscal year (FY) 2011–2017) data on health check-ups. Subjects were men and women living in 13 municipalities in areas surrounding the NPP in Fukushima Prefecture. Post-disaster (FY 2011–2012) overweight, hypertension, dyslipidemia, diabetes mellitus, metabolic syndrome, liver dysfunction, hyperuricemia, polycythemia and atrial fibrillation cases increased from the pre-disaster (FY 2008–2010) levels. This tendency was strongest among residents who were forced to evacuate. Proportion of overweight people remained unchanged, the prevalence of liver dysfunction decreased and the proportion of people with treated hypertension and dyslipidemia increased during FY 2011–2017. Meanwhile, the prevalence of diabetes mellitus and mean levels of HbA1c increased. Furthermore, Evacuees showed higher risks of diabetes mellitus, dyslipidemia, chronic kidney diseases and liver dysfunction than non-evacuees. Therefore, residents in the evacuation area, especially evacuees, are at high risk of developing lifestyle-related diseases, especially cardiovascular diseases; therefore, it is necessary to observe health statuses and implement measures to prevent lifestyle-related diseases.
Journal Article
Association between malnutrition and adverse renal outcomes in patients with type 2 diabetes
2025
Introduction Nutritional management is crucial in patients with chronic kidney disease. Therefore, it is important to assess nutritional status and detect malnutrition, especially in patients with diabetes. However, there is currently a lack of evidence regarding the relationship between nutritional indices and renal function in patients with type 2 diabetes. This study investigated whether the geriatric nutritional risk index (GNRI) is related to renal prognosis in type 2 diabetes patients. Materials and Methods The study included 946 type 2 diabetes patients enrolled in the Fukushima Cohort Study. The primary endpoint of this study was a renal event, defined as a combination of a 50% decline in eGFR from baseline and end‐stage kidney disease. All‐cause death and new cardiovascular events were also measured as secondary outcomes. The association between GNRI and these endpoints was assessed using Cox regression analysis. Results The median patient age was 66 years, 57% were men, the median eGFR was 67.9 mL/min/1.73 m2, and the median GNRI was 100.0. Compared to patients in the highest GNRI tertile, patients in the lowest tertile had a significantly increased risk of the renal event (HR 5.15, 95% CI 2.51–10.6) and all‐cause death (HR 2.30, 95% CI 1.20–4.42). A significant association was not observed between GNRI levels and cardiovascular events. Conclusions We observed an association between poor nutritional status, assessed by GNRI, and adverse outcomes in patients with type 2 diabetes. Nutritional status assessment has potential utility as a prognostic tool for individuals with type 2 diabetes. To prevent the progression of renal dysfunction and improve clinical prognosis in patients with diabetes, nutritional assessment, and management are of vital importance. The results of our observational cohort study indicate that a lower GNRI is associated with the risk of occurrence of a renal event, cardiovascular events, and all‐cause death in patients with type 2 diabetes. Overall, this study not only highlights the GNRI as a useful nutritional screening tool in patients with type 2 diabetes, but also underscores the importance of nutritional status assessment in these patients.
Journal Article
Metabolically and immunologically beneficial impact of extra virgin olive and flaxseed oils on composition of gut microbiota in mice
by
Ikematsu, Shinya
,
Masuzaki, Hiroaki
,
Namba, Toyotaka
in
Antimicrobial agents
,
Antimicrobial peptides
,
Chemistry
2020
Purpose
Extra virgin olive oil (EVOO) and flaxseed oil (FO) contain a variety of constituents beneficial for chronic inflammation and cardio-metabolic derangement. However, little is known about the impact of EVOO and FO on dysbiosis of gut microbiota, intestinal immunity, and barrier. We, therefore, aimed to assess the impact of EVOO and FO on gut microbiota, mucosal immunity, barrier integrity, and metabolic health in mice.
Methods
C57BL/6 J mice were exposed to a low-fat (LF), lard (HF), high fat-extra virgin olive oil (HF-EVOO), or high fat-flaxseed oil (HF-FO) diet for 10 weeks. Gut microbiota assessment was undertaken using 16S rRNA sequencing. Levels of mRNA for genes involved in intestinal inflammation and barrier maintenance in the intestine and bacterial infiltration in the liver were measured by qPCR.
Results
HF-EVOO or HF-FO mice showed greater diversity in gut microbiota as well as a lower abundance of the Firmicutes phylum in comparison with HF mice (
P
< 0.05). The qPCR analyses revealed that mRNA level of FoxP3, a transcription factor, and IL-10, an inducer of regulatory T cells, was significantly elevated in the intestines of mice-fed HF-EVOO in comparison with mice-fed HF (
P
< 0.05). The mRNA level of the antimicrobial peptide, RegӀӀӀγ, was markedly elevated in the intestines of HF-EVOO and HF-FO compared with HF group (
P
< 0.05).
Conclusions
Our data suggest that the consumption of EVOO or FO can beneficially impact gut microbiota, enhance gut immunity, and assist in the preservation of metabolic health in mice.
Journal Article
Hematological parameters of anemia and prognosis of non-dialysis-dependent chronic kidney disease: the Fukushima CKD cohort study
by
Kazama, Sakumi
,
Tanaka, Kenichi
,
Watanabe, Tsuyoshi
in
Anemia
,
Cardiovascular diseases
,
Cohort analysis
2023
BackgroundMean corpuscular volume (MCV) and red cell distribution width (RDW), as well hemoglobin, are reported to be associated with mortality in various populations. However, associations between such hematological parameters and adverse outcomes in patients with CKD have not been sufficiently elucidated.MethodsA total of 1,320 participants enrolled in the Fukushima CKD Cohort Study were examined to investigate associations between hematological parameters of anemia (MCV and RDW) and adverse outcomes, such as ESKD, all-cause death, and cardiovascular events, in patients with non-dialysis-dependent CKD. Baseline hematological parameters were grouped as follows: hemoglobin into 3 categories (< 11.0 g/dL, 11.0 ≤ − < 13.0 g/dL [reference], and ≥ 13.0 g/dL); MCV into 5 categories (< 90 fL, ≥ 90 – < 94 fL [reference], ≥ 94 − < 98 fL, ≥ 98 − < 102 fL, and ≥ 102 fL); and RDW into 2 categories (< 13.6% [reference] vs ≥ 13.6%).ResultsDuring the median observational period of 4.7 years, 120 patients developed ESKD, 160 developed cardiovascular events, and 122 died. Hemoglobin < 11 g/dL (hazard ratio [HR] 1.56, 95% confidence interval [CI], 1.00–2.42), MCV < 90 fL (HR 2.01, 95% CI 1.14–3.54), and RDW ≥ 13.6% (HR 1.57, 95% CI 1.01–2.42) were significantly associated with higher risks of ESKD. Hemoglobin < 11 g/dL, MCV ≥ 98 fL, and RDW ≥ 13.6% were significantly associated with higher risks of all-cause death. No significant associations between hematological parameters and risk of cardiovascular events were confirmed.ConclusionIn patients with non-dialysis-dependent CKD, MCV, RDW, and hemoglobin were associated with increased risks of ESKD and all-cause mortality.
Journal Article
Association of red blood cell distribution width/albumin ratio with renal prognosis among patients with type 2 diabetes mellitus: A retrospective cohort study
2025
Introduction The red blood cell distribution width/albumin ratio (RAR) has been reported to be a prognostic marker for adverse clinical outcomes. However, there is limited data on the relationship between RAR and renal function in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the effect of RAR on renal prognosis in patients with T2DM. Research Design and Methods This retrospective cohort study included 907 patients with T2DM enrolled in the Fukushima Cohort Study, divided into two groups (high and low RAR) according to their baseline RAR. The association between RAR and renal events was assessed using Kaplan–Meier curves and multivariate Cox regression analyses. Receiver operating characteristic (ROC) curve analyses, as well as the net reclassification index (NRI) and integrated discrimination improvement (IDI), examined the differences between RAR and red blood cell distribution width (RDW) alone. Results The high RAR group showed an increased risk of renal events in the Kaplan–Meier curve analysis. Compared with the low RAR group, the high RAR group showed an increased risk of renal events (adjusted hazard ratio [HR]: 3.40, 95% confidence interval: 1.76–6.57). RAR exhibited a significantly higher area under the curve (AUC), NRI, and IDI for renal events than RDW. Conclusion We observed an association between high RAR and worse renal outcomes in patients with T2DM. RAR assessment may have potential utility as a predictive tool for renal prognosis. Red cell distribution width (RDW)/serum albumin ratio (RAR) is a novel and simple inflammatory marker and has emerged as a reliable prognostic marker in various diseases. Our study reveals that a high RAR is a practical and easily obtainable predictive tool for assessing renal risk in patients with T2DM, thereby offering a tangible benefit to healthcare professionals and patients. Given the increasing global prevalence of T2DM and its association with chronic kidney disease, identifying simple and accessible biomarkers for predicting renal outcomes is crucial for improving patient management. Our study significantly contributes to diabetes care in clinical practice for early risk stratification of patients with T2DM.
Journal Article
Fast walking is a preventive factor against new-onset diabetes mellitus in a large cohort from a Japanese general population
by
Fujimoto, Shouichi
,
Narita, Ichiei
,
Asahi, Koichi
in
692/163/2743/137/773
,
692/700/459/1748
,
Body mass index
2021
Based on questionnaires from 197,825 non-diabetic participants in a large Japanese cohort, we determined impact of (1) habit of exercise, (2) habit of active physical activity (PA) and (3) walking pace on new-onset of type 2 diabetes mellitus. Unadjusted and multivariable-adjusted logistic regression models were used to determine the odds ratio of new-onset diabetes mellitus incidence in a 3-year follow-up. There were two major findings. First, habits of exercise and active PA were positively associated with incidence of diabetes mellitus. Second, fast walking, even after adjusting for multiple covariates, was associated with low incidence of diabetes mellitus. In the subgroup analysis, the association was also observed in participants aged ≥ 65 years, in men, and in those with a body mass index ≥ 25. Results suggest that fast walking is a simple and independent preventive factor for new-onset of diabetes mellitus in the health check-up and guidance system in Japan. Future studies may be warranted to verify whether interventions involving walking pace can reduce the onset of diabetes in a nation-wide scale.
Journal Article
Relationship Between Risk of Hyper-Low-density Lipoprotein Cholesterolemia and Evacuation After the Great East Japan Earthquake
by
Ohira, Tetsuya
,
Kawasaki, Yukihiko
,
Okazaki, Kanako
in
Body mass index
,
Body size
,
Cardiovascular diseases
2022
Background: The Great East Japan Earthquake and the Fukushima Daiichi nuclear disaster forced the evacuation of residents and led to many changes in lifestyle for the evacuees. The Comprehensive Health Check was implemented to support the prevention of lifestyle-related disease and we analyzed the effect of prolonged evacuation (average of 3.0 years) on the new onset of hyper-LDL cholesterolemia.Methods: The study participants were Japanese adults living near the Fukushima Daiichi nuclear power plant in Fukushima Prefecture. Annual health checkups focusing on metabolic syndromes were conducted for persons ≥40 years by the Specific Health Checkup. Based on data from annual checkups from 2011 or 2012, we followed 18,670 participants without hyper-LDL cholesterolemia who underwent at least one other annual checkup during 2013–2015.Results: We found that the new onset of hyper-LDL cholesterolemia was 31% higher in evacuees than in non-evacuees. Evacuees had a significantly higher prevalence of obesity, hypertension, and diabetes, and higher frequency of weight change. Furthermore, logistic regression model analysis showed that the evacuation was significantly associated with the new onset of hyper-LDL cholesterolemia after adjusting age, gender, body mass index, smoking habit, alcohol consumption, diabetes, weight change, sleep deprivation, and exercise.Conclusion: The findings of the present study suggest that prolonged evacuation after a disaster is a risk factor for the new onset of hyper-LDL cholesterolemia, and lead to an increase in cardiovascular disease. It is therefore important to follow-up evacuees and recommend lifestyle changes where necessary.
Journal Article