研究者詳細 - 大西　浩文

論文 - 大西　浩文

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Estimated Daily Intake and Seasonal Food Sources of Quercetin in Japan

Haruno Nishimuro, Hirofumi Ohnishi, Midori Sato, Mayumi Ohnishi-Kameyama, Izumi Matsunaga, Shigehiro Naito, Katsunari Ippoushi, Hideaki Oike, Tadahiro Nagata, Hiroshi Akasaka, Shigeyuki Saitoh, Kazuaki Shimamoto, Masuko Kobori

NUTRIENTS ( MDPI AG ) 7 ( 4 ) 2345 - 2358 2015年04月 [査読有り]

Quercetin is a promising food component, which can prevent lifestyle related diseases. To understand the dietary intake of quercetin in the subjects of a population-based cohort study and in the Japanese population, we first determined the quercetin content in foods available in the market during June and July in or near a town in Hokkaido, Japan. Red leaf lettuce, asparagus, and onions contained high amounts of quercetin derivatives. We then estimated the daily quercetin intake by 570 residents aged 20-92 years old in the town using a food frequency questionnaire (FFQ). The average and median quercetin intakes were 16.2 and 15.5 mg day(-1), respectively. The quercetin intakes by men were lower than those by women; the quercetin intakes showed a low correlation with age in both men and women. The estimated quercetin intake was similar during summer and winter. Quercetin was mainly ingested from onions and green tea, both in summer and in winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf lettuce, were good sources of quercetin in summer. Our results will help to elucidate the association between quercetin intake and risks of lifestyle-related diseases by further prospective cohort study and establish healthy dietary requirements with the consumption of more physiologically useful components from foods.

FABP4 is Secreted from Adipocytes by Adenyl Cyclase-PKA- and Guanylyl Cyclase-PKG-Dependent Lipolytic Mechanisms

Tomohiro Mita, Masato Furuhashi, Shinya Hiramitsu, Junnichi Ishii, Kyoko Hoshina, Shutaro Ishimura, Takahiro Fuseya, Yuki Watanabe, Marenao Tanaka, Kohei Ohno, Hiroshi Akasaka, Hirofumi Ohnishi, Hideaki Yoshida, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

OBESITY ( WILEY-BLACKWELL ) 23 ( 2 ) 359 - 367 2015年02月 [査読有り]

ObjectiveFatty acid-binding protein 4 (FABP4) is expressed in adipocytes, and elevated plasma FABP4 level is associated with obesity-mediated metabolic phenotype. Postprandial regulation and secretory signaling of FABP4 has been investigated. MethodsTime courses of FABP4 levels were examined during an oral glucose tolerance test (OGTT; n=53) or a high-fat test meal eating (n=35). Effects of activators and inhibitors of adenyl cyclase (AC)-protein kinase A (PKA) signaling and guanylyl cyclase (GC)-protein kinase G (PKG) signaling on FABP4 secretion from mouse 3T3-L1 adipocytes were investigated. ResultsFABP4 level significantly declined after the OGTT or a high-fat meal eating, while insulin level was increased. Treatment with low and high glucose concentration or palmitate for 2 h did not affect FABP4 secretion from 3T3-L1 adipocytes. FABP4 secretion was increased by stimulation of lipolysis using isoproterenol, a (3)-adrenoceptor agonist (CL316243), forskolin, dibutyryl-cAMP and atrial natriuretic peptide, and the induced FABP4 secretion was suppressed by insulin or an inhibitor of PKA (H-89), PKG (KT5823) or hormone sensitive lipase (CAY10499). ConclusionsFABP4 is secreted from adipocytes in association with lipolysis regulated by AC-PKA- and GC-PKG-mediated signal pathways. Plasma FABP4 level declines postprandially, and suppression of FABP4 secretion by insulin-induced anti-lipolytic signaling may be involved in this decline in FABP4 level.

IQ is an independent predictor of glycated haemoglobin level in young and middle-aged adults with intellectual disability

T. Yano, T. Miki, T. Itoh, H. Ohnishi, M. Asari, S. Chihiro, A. Yamamoto, K. Aotsuka, N. Kawakami, J. Ichikawa, Y. Hirota, T. Miura

Diabetic Medicine ( Blackwell Publishing Ltd ) 32 ( 1 ) 129 - 132 2015年01月 [査読有り]

Aims: Here we examined whether intellectual disability is independently associated with hyperglycaemia. Methods: We recruited 233 consecutive young and middle-aged adults with intellectual disability. After exclusion of subjects on medication for metabolic diseases or with severe intellectual disability (IQ < 35), 121 subjects were divided by IQ into a group with moderate intellectual disability (35≤IQ≤50), a mild intellectual disability group (51≤IQ≤70) and a borderline group (IQ > 70). Results: HbA1c level was higher in subjects with moderate intellectual disability (42 ± 9 mmol/mol 6.0 ± 0.8%) than those in the borderline group (36 ± 4 mmol/mol 5.5 ± 0.3%) and mild intellectual disability group (37 ± 5 mmol/mol 5.5 ± 0.5%) groups. HbA1c level was correlated with age, BMI, blood pressure, serum triglycerides and IQ in simple linear regression analysis. Multiple regression analysis indicated that IQ, age, BMI and diastolic blood pressure were independent explanatory factors of HbA1c level. Conclusions: An unfavourable effect of intellectual disability on lifestyle and untoward effect of hyperglycaemia on cognitive function may underlie the association of low IQ with hyperglycaemia.

Urinary Angiotensin-Converting Enzyme 2 in Hypertensive Patients May Be Increased by Olmesartan, an Angiotensin II Receptor Blocker

Masato Furuhashi, Norihito Moniwa, Tomohiro Mita, Takahiro Fuseya, Shutaro Ishimura, Kohei Ohno, Satoru Shibata, Marenao Tanaka, Yuki Watanabe, Hiroshi Akasaka, Hirofumi Ohnishi, Hideaki Yoshida, Hideki Takizawa, Shigeyuki Saitoh, Nobuyuki Ura, Kazuaki Shimamoto, Tetsuji Miura

AMERICAN JOURNAL OF HYPERTENSION ( OXFORD UNIV PRESS ) 28 ( 1 ) 15 - 21 2015年01月 [査読有り]

BACKGROUND Angiotensin-converting enzyme 2 (ACE2) is highly expressed in the kidney and converts angiotensin (Ang) II to Ang-(1-7), a renoprotective peptide. Urinary ACE2 has been shown to be elevated in patients with chronic kidney disease. However, the effects of antihypertensive agents on urinary ACE2 remain unclear. METHODS Of participants in the Tanno-Sobetsu cohort study in 2011 (n = 617), subjects on no medication (n = 101) and hypertensive patients treated with antihypertensive agents, including the calcium channel blockers amlodipine and long-acting nifedipine; the ACE inhibitor enalapril; and the Ang II receptor blockers losartan, candesartan, valsartan, telmisartan, and olmesartan, for more than 1 year (n = 100) were enrolled, and urinary ACE2 level was measured. RESULTS Glucose and hemoglobin A1c were significantly higher in patients treated with enalapril, telmisartan or olmesartan than in the control subjects. Urinary albumin-to-creatinine ratio (UACR) was significantly higher in patients treated with enalapril than in the control subjects. Urinary ACE2 level was higher in the olmesartan-treated group, but not the other treatment groups, than in the control group. Urinary ACE2 level was positively correlated with systolic blood pressure (r = 0.211; P = 0.003), UACR (r = 0.367; P < 0.001), and estimated salt intake (r = 0.260; P < 0.001). Multivariable regression analysis after adjustment of age, sex, and the correlated indices showed that the use of olmesartan was an independent predictor of urinary ACE2 level. CONCLUSIONS In contrast with other antihypertensive drugs, olmesartan may uniquely increase urinary ACE2 level, which could potentially offer additional renoprotective effects.

Physical Activity during Winter in Old-Old Women Associated with Physical Performance after One Year: A Prospective Study.

Atsushi Mizumoto, Hikaru Ihira, Keitaro Makino, Shigeyuki Saitoh, Hirofumi Ohnishi, Taketo Furuna

Current gerontology and geriatrics research 2015 253451 - 253451 2015年 [査読有り] [国際誌]

Background. The aim of this study was to evaluate whether the decline of physical activity during winter influences physical performances (after 1 year) in old-old women. Methods. Fifty-three Japanese women (mean age: 78.4 ± 3.2 years) participated in this study. Data of physical activity was collected by using an accelerometer at baseline and 3-month follow-up, and participants who decreased step counts in this period were defined as declining groups. We measured grip strength, knee extensor strength, total length of the center of gravity, hip walking distance, and maximum walking speed to evaluate physical performances at baseline and 1-year follow-up. Repeated-measures analysis of variance determined the difference in physical performance between declining groups and maintenance group with maintained or improved step counts. Results. Daily step counts for 22 older women (41.5%) decreased during winter. A statistically significant interaction effect between group and time was found for maximum walking speed (F(1,50) = 5.23, p = 0.03). Post hoc comparisons revealed that walking speed in the maintenance group significantly increased compared with baseline (p = 0.01); the declining group showed no significant change (p = 0.44). Conclusion. Change of physical activity during winter influences the physical performance level after 1 year in community-dwelling old-old women, particularly its effect on maximum walking speed.

Associations of serum isoflavone, adiponectin and insulin levels with risk for epithelial ovarian cancer: Results of a case-control study

Seiko Otokozawa, Ryoichi Tanaka, Hiroshi Akasaka, Eiki Ito, Sumiyo Asakura, Hirofumi Ohnishi, Shigeyuki Saito, Tetsuji Miura, Tsuyoshi Saito, Mitsuru Mori

Asian Pacific Journal of Cancer Prevention ( Asian Pacific Organization for Cancer Prevention ) 16 ( 12 ) 4987 - 4991 2015年 [査読有り]

Background: The aim of this study was to examine the association of serum isoflavones, adiponectin, and insulin levels with ovarian cancer risk. Materials and Methods: We gathered cases with histologically confirmed epithelial ovarian cancer at Sapporo Medical University Hospital from October 2010 to September 2012. Potential controls were recruited from female inpatients without any history of cancer or diabetes mellitus in different wards of the same hospital over the same period of time. Serum isoflavones, adiponectin, and insulin levels were measured in order to estimate associations with ovarian cancer risk in a case-control study. Data from 71 cases and 80 controls were analyzed with a logistic regression model adjusting for known risk factors. Results: A significant reduction in ovarian cancer risk was observed for the high tertile of serum daidzein level versus the low (P< inf> trend< /inf> < 0.001). A significant reduction in ovarian cancer risk was also observed for the high tertile of serum glycitein level versus the low (P< inf> trend< /inf> =0.005). Furthermore, a significant reduction in ovarian cancer risk was observed for the high tertile of serum adiponectin level versus the low (P< inf> trend< /inf> =0.004). Conversely, serum insulin level showed significantly elevated risk for ovarian cancer with the high tertile versus the low P< inf> trend< /inf> < 0.001). Conclusions: Decreased serum isoflavones levels, such as those for daidzein and glycitein, decreased serum adiponectin levels, and increased serum insulin levels could be shown to be associated with elevated risk of ovarian cancer.

Pericardial Effusion and Multiple Organ Involvement Are Independent Predictors of Mortality in Patients with Systemic Light Chain Amyloidosis

Satoshi Yuda, Toshiaki Hayashi, Kenji Yasui, Atsuko Muranaka, Hirofumi Ohnishi, Akiyoshi Hashimoto, Tadao Ishida, Kazufumi Tsuchihashi, Yasuhisa Shinomura, Naoki Watanabe, Tetsuji Miura

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE ) 54 ( 15 ) 1833 - 1840 2015年 [査読有り]

Objective Left ventricular (LV) functions assessed by echocardiography and cardiac biomarkers are strong predictors of mortality in patients with systemic light chain (AL) amyloidosis. However, most previous studies have been conducted in Western countries, and the predictors of mortality in Asian patients with AL amyloidosis have not been characterized. To address this issue, we aimed to determine the predictors of mortality in Asian patients with biopsy-confirmed AL amyloidosis. Methods We retrospectively enrolled 31 patients (59 +/- 11 years, 55% men) in whom AL amyloidosis was confirmed by biopsies from cardiac or non-cardiac tissues. Of these patients, 15 (48%) met the international echocardiographic criteria for cardiac amyloidosis (mean LV wall thickness > 12 mm without other causes of LV hypertrophy). Results During a mean follow-up period of 21 +/- 20 months, 15 patients died. Non-survivors had a higher number of involved organs, lower e', and higher rates of E/e' > 15, pericardial effusion (PE), low voltage on an electrocardiogram and a New York Heart Association (NYHA) functional class >= III, compared with survivors. In multivariate analysis, a NYHA functional class >= III (p=0.024) and cardiac involvement (p=0.032) were independent predictors of PE in patients with AL amyloidosis. Multivariate Cox proportional hazard analysis indicated that PE (hazard ratio: 21.9, p=0.025) and the number of involved organs (hazard ratio: 2.8, p=0.015), but not LV diastolic parameters of tissue Doppler echocardiography, independently predict mortality in patients with AL amyloidosis. Conclusion PE and multiple organ involvement, compared with e' and E/e', are stronger predictors of mortality in patients with AL amyloidosis. The advanced disease stage of AL amyloidosis might underlie the strong association between PE and a poor outcome.

Urinary Excretion of Fatty Acid-Binding Protein 4 is Associated with Albuminuria and Renal Dysfunction

Yusuke Okazaki, Masato Furuhashi, Marenao Tanaka, Tomohiro Mita, Takahiro Fuseya, Shutaro Ishimura, Yuki Watanabe, Kyoko Hoshina, Hiroshi Akasaka, Hirofumi Ohnishi, Hideaki Yoshida, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

PLOS ONE ( PUBLIC LIBRARY SCIENCE ) 9 ( 12 ) e115429 2014年12月 [査読有り]

Background: Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is expressed in not only adipocytes and macrophages but also peritubular capillaries in the normal kidney. We recently demonstrated that ectopic expression of FABP4, but not FABP1 known as liver FABP (L-FABP), in the glomerulus is associated with progression of proteinuria and renal dysfunction. However, urinary excretion of FABP4 has not been investigated. Methods: Subjects who participated in the Tanno-Sobetsu Study, a study with a population-based cohort design, in 2011 (n=392, male/female: 166/226) were enrolled. Urinary FABP4 (U-FABP4) and urinary albumin-to-creatinine ratio (UACR) were measured. Change in estimated glomerular filtration rate (eGFR) was followed up one year later. Results: In 93 (23.7%) of the 392 subjects, U-FABP4 level was below the sensitivity of the assay. Subjects with undetectable U-FABP4 were younger and had lower UACR and higher eGFR levels than subjects with measurable U-FABP4. U-FABP4 level was positively correlated with age, systolic blood pressure and levels of serum FABP4 (S-FABP4), triglycerides, hemoglobin A1c (HbA1c), urinary FABP1 (U-FABP1) and UACR (r=0.360, p<0.001). Age, S-FABP4, U-FABP1 and UACR were independent predictors of U-FABP4. On the other hand, systolic blood pressure, HbA1c and U-FABP4 were independently correlated with UACR. Reduction in eGFR after one year was significantly larger in a group with the highest tertile of baseline U-FABP4 than a group with the lowest tertile. Conclusions: Urinary FABP4 level is independently correlated with level of albuminuria and possibly predicts yearly decline of eGFR. U-FABP4 would be a novel biomarker of glomerular damage.

Elevation of circulating fatty acid-binding protein 4 is independently associated with left ventricular diastolic dysfunction in a general population

Takahiro Fuseya, Masato Furuhashi, Satoshi Yuda, Atsuko Muranaka, Mina Kawamukai, Tomohiro Mita, Shutaro Ishimura, Yuki Watanabe, Kyoko Hoshina, Marenao Tanaka, Kohei Ohno, Hiroshi Akasaka, Hirofumi Ohnishi, Hideaki Yoshida, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

CARDIOVASCULAR DIABETOLOGY ( BIOMED CENTRAL LTD ) 13 126 2014年08月 [査読有り]

Background: Fatty acid-binding protein 4 (FABP4) is expressed in both adipocytes and macrophages. Recent studies have shown secretion of FABP4 from adipocytes and association of elevated serum FABP4 level with obesity, insulin resistance, hypertension, and atherosclerosis. However, little is known about role of FABP4 in cardiac function. Methods: From the database of the Tanno-Sobetsu Study, data for 190 subjects (male/female: 82/108) who were not treated with any medication and underwent echocardiography in 2011 or 2012 were retrieved for analyses of relationships between serum FABP4 concentration, metabolic markers and parameters of echocardiography. Results: Serum FABP4 level was positively correlated with age, body mass index (BMI), blood pressure (BP), LDL cholesterol, HOMA-R and mean left ventricular (LV) wall thickness (LVWT, males: r = 0.315, females: r = 0.401, p < 0.01) and was negatively correlated with HDL cholesterol, estimated glomerular filtration rate (eGFR) and peak myocardial velocity during early diastole (e'; males: r = -0.434, females: r = -0.353, p < 0.01), an index of LV diastolic function. However, no significant correlation was found between FABP4 level and LV end-diastolic dimension, LV ejection fraction or LV mass index. There were significant correlations of e' with age, BMI, BP, eGFR, brain natriuretic peptide (BNP), FABP4, metabolic markers and LVWT. Multivariate regression analysis adjusted by HOMA-R, BMI, eGFR, BNP or LVWT in addition to age, gender and BP revealed that serum FABP4 concentration was independently correlated with e'. Conclusions: Elevation of circulating FABP4 may contribute to LV diastolic dysfunction in a general population.

Effectiveness of influenza vaccine in children in day-care centers of Sapporo

Mitsuru Mori, Junko Hasegawa, Satoko Showa, Aiko Matsushima, Hirofumi Ohnishi, Yuko Yoto, Hiroyuki Tsutsumi

PEDIATRICS INTERNATIONAL ( WILEY-BLACKWELL ) 56 ( 1 ) 53 - 56 2014年02月 [査読有り]

Counts of Slackia sp strain NATTS in Intestinal Flora are Correlated to Serum Concentrations of Equol both in Prostate Cancer Cases and Controls in Japanese Men

Yukiko Sugiyama, Yoshie Nagata, Fumimasa Fukuta, Akio Takayanagi, Naoya Masumori, Taiji Tsukamoto, Hiroshi Akasaka, Hirofumi Ohnishi, Shigeyuki Saito, Tetsuji Miura, Kaoru Moriyama, Hirokazu Tsuji, Hideyuki Akaza, Mitsuru Mori

ASIAN PACIFIC JOURNAL OF CANCER PREVENTION ( ASIAN PACIFIC ORGANIZATION CANCER PREVENTION ) 15 ( 6 ) 2693 - 2697 2014年 [査読有り]

Background: Isoflavones, which are included in soybeans, have been suggested to protect against prostate cancer. Equol, one of isoflavones, is an intestinally derived bacterial metabolite of daidzein. A newly identified equol-producing bacterium, Slackia sp. strain NATTS, with a high equol-producing activity was isolated from human feces in Japanese adults. Counts of Slackia sp. strain NATTS in intestinal flora have not been assessed with regard to prostate cancer risk. In this study, we investigated the association of serum isoflavones and counts of Slackia sp. strain NATTS with prostate cancer risk in a case-control study. Materials and Methods: Concentrations of isoflavones and counts of Slackia sp. strain NATTS in feces were measured from 44 patients with prostate cancer and 28 hospital controls. The risk of prostate cancer was evaluated in terms of odds ratios (ORs) and 95% confidence intervals (CIs) by the logistic regression analysis. Results: The detection proportions of Slackia sp. strain NATTS in cases and controls were 34.1% and 25.0%, respectively. Counts of Slackia sp. strain NATTS were significantly correlated with serum concentrations of equol both in cases and controls (Spearman correlation coefficients, r(s)=0.639 and r(s)=0.572, p<0.01, respectively). Serum concentrations of genistein, daidzein, glycitein, and equol were not significantly associated with risk of prostate cancer. Conclusions: This study found that counts of Slackia sp. strain NATTS correlated with serum concentrations of equol both in prostate cancer cases and controls, but serum isoflavone concentrations were not associated with risk of prostate cancer in our patients.

Relation of Serum Adiponectin Levels and Obesity with Breast Cancer: A Japanese Case-Control Study

Machiko Minatoya, Goro Kutomi, Hiroaki Shima, Sumiyo Asakura, Seiko Otokozawa, Hirofumi Ohnishi, Hiroshi Akasaka, Tetsuji Miura, Mitsuru Mori, Koichi Hirata

ASIAN PACIFIC JOURNAL OF CANCER PREVENTION ( ASIAN PACIFIC ORGANIZATION CANCER PREVENTION ) 15 ( 19 ) 8325 - 8330 2014年 [査読有り]

Background: It is known that obesity is one of the risk factors for breast cancer although the association may differ between ethnic groups and with the menopausal status. Recently obesity-related risk factors including serum adiponectin and insulin levels have been analyzed together with BMI in association with breast cancer risk. Materials and Methods: We measured serum high molecular weight (HMW) adiponectin and insulin levels in a hospital based case-control study, including 66 sets of Japanese female breast cancer cases and age and menopausal status matched controls. Serum levels of HMW adiponectin, insulin levels and body mass index (BMI) were examined in association with breast cancer risk with adjustment for the various known risk factors by menopausal status. Results: Women in the highest HMW adiponectin levels showed significant reduced risk of breast cancer in both pre and postmenopausal women (odds ratio (OR), 0.01; 95% confidence interval (CI), 0.00-0.26 and 0.13; 0.03-0.57, respectively). Lower BMI showed decreased breast cancer risk in both pre and postmenopausal women (OR, 0.04; 95% CI, 0.00-0.69, OR, 0.28; 95% CI, 0.07-1.11, respectively). Conclusions: These results indicated that higher serum HMW adiponectin levels and lower BMI are associated with a decreased breast cancer risk in both pre and postmenopausal women in Japan, adding evidence for the obesity link.

Physical Functions, Health-Related Outcomes, Nutritional Status, and Blood Markers in Community-Dwelling Cancer Survivors Aged 75 Years and Older

Hikaru Ihira, Atsushi Mizumoto, Keitarou Makino, Keisuke Yasuda, Yoko Miyabe, Shigeyuki Saitoh, Hirofumi Ohnishi, Taketo Furuna

ASIAN PACIFIC JOURNAL OF CANCER PREVENTION ( ASIAN PACIFIC ORGANIZATION CANCER PREVENTION ) 15 ( 7 ) 3305 - 3310 2014年 [査読有り]

Background: A cancer survivor is defined as anyone who has been diagnosed with cancer, from the time of diagnosis through the rest of their life. The purpose of this study was to examine whether physical functions, health-related outcomes, nutritional status and blood markers in community-dwelling cancer survivors aged 75 years and older are different from those who do not have cancer Materials and Methods: Two hundred seventy-five participants were asked by physicians, nurses, and physical therapists, questions regarding cancer history in a face-to-face interview. Data were collected for demographic information, physical functions, such as handgrip strength, knee extension power, abdominal muscle strength, static standing balance, walking speed and the timed-up-and-go test, health-related outcomes, nutritional status, and blood markers. The measured parameters of survivor diagnosed with cancer were compared with those without a history of cancer. Results: Thirty-seven older adults were previously diagnosed with cancer. Female cancer survivors had lower knee extension power (p<0.05), abdominal muscle strength (p<0.05), walking speed (p<0.05), timed-up-and-go test score (p<0.05), and time to spend on walking per day (p<0.05) than older women without a history of cancer. In men, none of the measured parameters were significantly different between cancer survivors and older men with no history of cancer. Conclusions: The present study shows that partial physical function of women cancer survivors aged 75 years and older differs from that in women with no history of cancer.

Circulating Levels of Fatty Acid-Binding Protein Family and Metabolic Phenotype in the General Population

Shutaro Ishimura, Masato Furuhashi, Yuki Watanabe, Kyoko Hoshina, Takahiro Fuseya, Tomohiro Mita, Yusuke Okazaki, Masayuki Koyama, Marenao Tanaka, Hiroshi Akasaka, Hirofumi Ohnishi, Hideaki Yoshida, Shigeyuki Saitoh, Tetsuji Miura

PLOS ONE ( PUBLIC LIBRARY SCIENCE ) 8 ( 11 ) e81318 2013年11月 [査読有り]

Objective: Fatty acid-binding proteins (FABPs) are a family of 14-15-kDa proteins, and some FABPs have been to be used as biomarkers of tissue injury by leak from cells. However, recent studies have shown that FABPs can be secreted from cells into circulation. Here we examined determinants and roles of circulating FABPs in a general population. Methods: From the database of the Tanno-Sobetsu Study, a study with a population-based cohort design, data in 2011 for 296 subjects on no medication were retrieved, and FABP1 similar to 5 in their serum samples were assayed. Results: Level of FABP4, but not the other isoforms, showed a gender difference, being higher in females than in males. Levels of all FABPs were negatively correlated with estimated glomerular filtration rate (eGFR), but a distinct pattern of correlation with other clinical parameters was observed for each FABP isoform; significant correlates were alanine aminotransferase (ALT), blood pressure (BP), and brain natriuretic peptide (BNP) for FABP1, none besides eGFR for FABP2, age, BP, and BNP for FABP3, age, waist circumference (WC), BP, BNP, lipid variables, high-sensitivity C-reactive protein (hsCRP), and HOMA-R for FABP4, and age, WC, BP, ALT, BNP, and HOMA-R for FABP5. FABP4 is the most strongly related to metabolic markers among FABPs. In a multivariate regression analysis, FABP4 level was an independent predictor of HOMAR after adjustment of age, gender, WC, BP, HDL cholesterol, and hsCRP. Conclusions: Each FABP isoform level showed a distinct pattern of correlation with clinical parameters, although levels of all FABPs were negatively determined by renal function. Circulating FABP4 appears to be a useful biomarker for detecting preclinical stage of metabolic syndrome, especially insulin resistance, in the general population.

HbA(1c) and the Risks for All-Cause and Cardiovascular Mortality in the General Japanese Population NIPPON DATA90

Masaru Sakurai, Shigeyuki Saitoh, Katsuyuki Miura, Hideaki Nakagawa, Hirofumi Ohnishi, Hiroshi Akasaka, Aya Kadota, Yoshikuni Kita, Takehito Hayakawa, Takayoshi Ohkubo, Akira Okayama, Tomonori Okamura, Hirotsugu Ueshima

DIABETES CARE ( AMER DIABETES ASSOC ) 36 ( 11 ) 3759 - 3765 2013年11月 [査読有り]

OBJECTIVEAssociations between HbA(1c) and cardiovascular diseases (CVD) have been reported mainly in Western countries. It is not clear whether HbA(1c) measurements are useful for assessing CVD mortality risk in East Asian populations.RESEARCH DESIGN AND METHODSThe risk for cardiovascular death was evaluated in a large cohort of participants selected randomly from the overall Japanese population. A total of 7,120 participants (2,962 men and 4,158 women; mean age 52.3 years) free of previous CVD were followed for 15 years. Adjusted hazard ratios (HRs) and 95% CIs among categories of HbA(1c) (<5.0%, 5.0-5.4%, 5.5-5.9%, 6.0-6.4%, and 6.5%) for participants without treatment for diabetes and HRs for participants with diabetes were calculated using a Cox proportional hazards model.RESULTSDuring the study, there were 1,104 deaths, including 304 from CVD, 61 from coronary heart disease, and 127 from stroke (78 from cerebral infarction, 25 from cerebral hemorrhage, and 24 from unclassified stroke). Relations to HbA(1c) with all-cause mortality and CVD death were graded and continuous, and multivariate-adjusted HRs for CVD death in participants with HbA(1c) 6.0-6.4% and 6.5% were 2.18 (95% CI 1.22-3.87) and 2.75 (1.43-5.28), respectively, compared with participants with HbA(1c) <5.0%. Similar associations were observed between HbA(1c) and death from coronary heart disease and death from cerebral infarction.CONCLUSIONSHigh HbA(1c) levels were associated with increased risk for all-cause mortality and death from CVD, coronary heart disease, and cerebral infarction in general East Asian populations, as in Western populations.

Glucagon-Like Peptide-1 Secretory Function as an Independent Determinant of Blood Pressure: Analysis in the Tanno-Sobetsu Study

Mayumi Yoshihara, Hiroshi Akasaka, Hirofumi Ohnishi, Takayuki Miki, Tetsuaki Furukawa, Satoshi Yuda, Shigeyuki Saitoh, Tetsuji Miura

PLOS ONE ( PUBLIC LIBRARY SCIENCE ) 8 ( 7 ) e67578 2013年07月 [査読有り]

Aims: Roles of glucagon-like peptide-1 (GLP-1) in extra-pancreatic tissues remain unclear. The aim of this study was to examine determinants of GLP-1 secretory function and possible contribution of GLP-1 to blood pressure (BP) regulation. Methods and Results: We recruited 128 subjects who received annual examinations and 75g-oral glucose tolerance tests (OGTT) in the Tanno-Sobetsu cohort. Subjects on regular medications for cardiovascular and/or metabolic diseases were excluded, and data for the remaining 103 subjects were used for the univariate and multivariate analyses. Age, plasma glucose (PG), hemoglobin A1c (HbA1c), plasma insulin, and serum lipids were not selected as independent determinants of fasting GLP-1 level by multiple linear regression analysis. However, age and female sex were selected as independent positive determinants of the area under the curve of GLP-1 level during OGTT (AUC(GLP-1)), an index of GLP-1 secretory function. Multiple linear regression analysis indicated that AUC(GLP-1) was an independent negative predictor of systolic BP (SBP), while AUC(GLP-1) was not correlated with fasting PG or HbA1c level. In subgroup analyses using the median of AUC(GLP-1) to divide the study subjects into high and low GLP-1 response groups, AUC(GLP-1) was significantly correlated with both SBP and diastolic BP (r = 0.40 and 0.28, respectively) in the low GLP-1 response group but not in the high GLP-1 response group. Conclusions: The results of the present study suggest that GLP-1 secretory function is involved in prevention of BP elevation and that the GLP-1 response to oral glucose rather increases with aging perhaps as an adaptive phenomenon.

無症状の日本人被験者において改変JASリスク層化は頸動脈プラークを予測するか(Does Revised JAS Risk Stratification Predict Carotid Plaque in Asymptomatic Japanese?)

Kawamukai Mina, Yuda Satoshi, Fujito Takefumi, Nishida Junichi, Mochizuki Atsushi, Kouzu Hidemichi, Muranaka Atsuko, Akasaka Hiroshi, Kokubu Nobuaki, Shimoshige Shinya, Ohnishi Hirofumi, Hashimoto Akiyoshi, Saitoh Shigeyuki, Tsuchihashi Kazufumi, Watanabe Naoki, Miura Tetsuji

Circulation Journal ( (一社)日本循環器学会 ) 77 ( Suppl.I ) 97 - 98 2013年03月

Associations between serum 25-hydroxyvitamin D concentration and physical performance in old-old people living in a northern area of Japan

Mizumoto A, Ihira H, Yasuda K, Makino K, Miyabe Y, Saitoh S, Ohnishi H, Suzuki T, Furuna T

Journal of Gerontology & Geriatric Research 2 ( 4 ) 135 2013年 [査読有り]

Consumption of dairy products and death from cardiovascular disease in the Japanese general population: the NIPPON DATA80.

Imako Kondo, Toshiyuki Ojima, Mieko Nakamura, Shinya Hayasaka, Atsushi Hozawa, Shigeyuki Saitoh, Hirofumi Ohnishi, Hiroshi Akasaka, Takehito Hayakawa, Yoshitaka Murakami, Nagako Okuda, Katsuyuki Miura, Akira Okayama, Hirotsugu Ueshima

Journal of epidemiology ( 1 ) 23 ( 1 ) 47 - 54 2013年 [査読有り] [国内誌]

BACKGROUND: Recent Western studies show an inverse association between milk and dairy product intake and cardiovascular disease (CVD). We studied the association between consumption of milk and dairy products and CVD death in Japan. METHODS: Men and women aged 30 years or older were followed for 24 years. All had participated in a national nutrition survey in 300 health districts throughout Japan in 1980. The Cox proportional hazards model was used to assess mortality risk according to tertiles of milk and dairy product intake, with the high consumption group as reference. Hazard ratios (HRs) per 100-g/day increase in consumption were also estimated. RESULTS: During the 24-year follow-up period, there were 893 CVD deaths, 174 deaths from coronary heart disease (CHD), and 417 stroke deaths among 9243 participants. For women, the HRs for death from CVD, CHD, and stroke in the low consumption group were 1.27 (95% CI: 0.99-1.58; P for trend = 0.045), 1.67 (0.99-2.80; P = 0.02), and 1.34 (0.94-1.90; P = 0.08), respectively, after adjustment for age, body mass index, smoking status, alcohol drinking habits, history of diabetes, use of antihypertensives, work category, and total energy intake. With each 100-g/day increase in consumption of milk and dairy products, HRs tended to decrease for deaths from CVD (HR, 0.86; 95% CI, 0.74-0.99), CHD (0.73; 0.52-1.03), and stroke (0.81; 0.65-1.01) in women. No significant association was observed in men. CONCLUSIONS: Consumption of milk and dairy products was inversely associated with CVD death among women in Japan.

Prospective Study on Waist Circumference and Risk of All-Cause and Cardiovascular Mortality - Pooled Analysis of Japanese Community-Based Studies

Isao Saito, Yoshihiro Kokubo, Yutaka Kiyohara, Yasufumi Doi, Shigeyuki Saitoh, Hirofumi Ohnishi, Yoshihiro Miyamoto

CIRCULATION JOURNAL ( JAPANESE CIRCULATION SOC ) 76 ( 12 ) 2867 - 2874 2012年12月 [査読有り]

Background: The aim of the present study was to clarify the association between waist circumference and all-cause and cardiovascular disease (CVD) mortality risk in relatively lean Japanese subjects. Methods and Results: A total of 3,554 men and 4,472 women who had no history of CVD were examined and their waist circumference measured at baseline. The subjects were aged >= 10 years and were obtained from 3 prospective cohort studies during 1988-1996. Hazard ratios for all-cause and CVD mortality were analyzed over a follow-up period Of 14.7 years using a Cox proportional hazards model and penalized spline method, after adjustment for study cohort, age, smoking, alcohol drinking, hypertension, dyslipidemia, and diabetes. Compared with the lowest quintile, the highest quintile of waist circumference in men was associated with a linear reduction in all-cause mortality risk (multivariate-adjusted hazard ratio, 0.73; 95% confidence interval: 0.60-0.89; P for trend=0.001). CVD mortality risk was increased in men aged 65 years with a higher waist circumference. This relationship was U-shaped. Waist circumference was not associated with all-cause or CVD mortality risk in women. Conclusions: Waist circumference was associated inversely with increased risk of all-cause death in men, but not in women. Middle-aged men with a greater waist circumference potentially have an increased risk of CVD mortality. (Circ J 2012; 76: 2867-2874)

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