著者

Ichiro Abe Hideyuki Fujii Hanako Ohishi Kaoru Sugimoto Midori Minezaki Midori Nakagawa Saori Takahara Tadachika Kudo Makiko Abe Kenji Ohe Toshihiko Yanase Kunihisa Kobayashi

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.66, no.2, pp.187-192, 2019 (Released:2019-02-28)

参考文献数

21

被引用文献数

12

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Glucose intolerance is often observed in patients with pheochromocytoma. However, it remains controversial issue that glucose intolerance on pheochromocytoma is caused by impaired insulin secretion and/or by increased insulin resistance. We aimed to reveal the mechanism of glucose intolerance on pheochromocytoma with regard to the type and amount of catecholamines released. We evaluated 12 individuals diagnosed with pheochromocytoma and who underwent surgery to remove it. We examined glycemic parameters before and after surgery and investigated the association between the change of parameters of insulin secretion (homeostasis model assessment of β-cell function (HOMA-β)), insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) and that of urinary levels of metanephrine/normetanephrine before and after surgery. Overall, fasting plasma glucose, glycated hemoglobin (HbA1c), HOMA-β, and HOMA-IR were improved significantly after surgery. Regression analysis showed that the improvement in HOMA-β from before to after surgery was significantly positively associated with an improvement in urinary levels of metanephrine from before to after surgery and showed a significantly negative association with improvement in urinary levels of normetanephrine from before to after surgery. The improvement in HOMA-IR from before to after surgery was significantly positively associated with an improvement in urinary levels of normetanephrine from before to after surgery. Our results showed that pheochromocytoma extirpation improved glycemic parameters. Furthermore, the different effects elicited by excess amounts of adrenaline and noradrenaline on glucose intolerance were demonstrated.

著者

Toshihiko Yanase Ikumi Yanagita Kazuo Muta Hajime Nawata

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ17-0390, (Released:2017-12-14)

被引用文献数

92

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Frailty is a state of vulnerability and a consequence of cumulative decline in multiple physiological systems over a lifespan. The occurrence of frailty depends on deterioration in muscle and nerve function, declining cardiopulmonary reserve and loss of executive function. Diabetes mellitus (DM) often causes functional impairment in each of the above systems, thus leading to a loss of whole body homeostasis and deterioration in physical function. Inability of self-management in DM patients may also have considerable impact on the development of sarcopenia/frailty. Thus, there may be positive feedback between the progression of diabetic complications and frailty/sarcopenia. While various factors are involved in this process, insulin resistance or insulin depletion may be an important factor in the progression of frailty in diabetes patients since insulin is well known to be an anabolic hormone in muscle. Interestingly, in our study targeting elderly DM patients, low HbA1c was a significant and independent risk factor for frailty, as assessed using a broad sense frailty scale, the Clinical Frailty Scale (CSF), suggesting that reverse metabolism due to malnutrition in elderly type 2 DM patients might be involved. Therefore, an intervention that includes proper nutrition and exercise training may be essential for the prevention of frailty. The pathogenesis of frailty in DM patients is extensively discussed in this review.

著者

Nobuya Hamanoue Makito Tanabe Tomoko Tanaka Yuko Akehi Junji Murakami Takashi Nomiyama Toshihiko Yanase

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ16-0619, (Released:2017-03-30)

被引用文献数

5

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An age-associated androgen decrease and its pathological conditions are defined as late-onset hypogonadism (LOH). Among the various symptoms associated with LOH, a visceral fat increase is strongly associated with relatively low levels of testosterone. However, few studies have investigated the relationship between the Aging Males’ Symptoms (AMS) scores and metabolic abnormalities. Thus, we aimed to clarify this relationship by investigating the relationship between AMS scores and various markers in blood. During routine health examinations in 241 middle-aged males (52.7±7.5 years of age, mean±SD), 150 males (62.2%) displayed higher AMS values than normal. No statistical association was observed between total AMS scores and any testosterone value. All mental, physical and sexual AMS subscales were significantly positively correlated with insulin levels and HOMA-IR. Only sexual subscale scores were significantly inversely associated with free or bioavailable testosterone level. Males with insulin resistance (HOMA-IR≥2.5) demonstrated significantly higher AMS scores than those with normal insulin sensitivity (HOMA-IR<2.5). AMS values were positively correlated with fasting blood glucose, insulin and HOMA-IR values. Interestingly, univariate and multivariate analyses revealed that HOMA-IR≥2.5 was a significant predictor for detection of moderately severe AMS values (AMS≥37), whereas AMS≥37 was not a predictor of metabolic syndrome by International Diabetes Federation (IDF) criterion. In conclusion, almost 60% of healthy male subjects displayed abnormal AMS scores. AMS values were not associated with testosterone values but rather were related to insulin resistance, particularly in subjects with moderately severe AMS values. Insulin resistance-related general unwellness might be reflected by AMS values.

著者

Yuko Akehi Makito Tanabe Hiromi Yano Yuichi Takashi Daiji Kawanami Takashi Nomiyama Toshihiko Yanase

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.69, no.11, pp.1303-1312, 2022 (Released:2022-11-28)

参考文献数

22

被引用文献数

1

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The Aging Males’ Symptoms (AMS) score, developed to screen for late-onset hypogonadism (LOH), contains 17 questions regarding mental, physical, and sexual parameters. In the Japanese guidelines, a free testosterone (FT) <8.5 pg/mL is recommended for testosterone treatment. However, previous studies have shown no correlation between total AMS scores and testosterone concentration. We aimed to develop a better questionnaire for the detection of testosterone deficiency in men, for the diagnosis of LOH. In 234 Japanese men, aged 40–64 years, we analyzed the relationships of AMS with serum total testosterone (TT), FT, calculated FT (cFT), and calculated bioavailable testosterone (cBT), and identified useful questions for the detection of testosterone deficiency. Four scores, a decrease in muscular strength, a decrease in ability to perform sexually or the frequency, a decrease in the number of morning erections, and a decrease in sexual desire/libido, were negatively associated with two or more of the above four testosterone parameters, and the sum of these four scores (named the selective score) correlated with TT and cFT, independent of age. Statistical analysis revealed an association between insulin resistance and testosterone deficiency, and a higher selective score in smokers than non-smokers. Cubic function model analysis and logistic regression analysis revealed that selective scores ≥10 corresponded with the testosterone concentrations recommended for the diagnosis of LOH, including FT <8.5 pg/mL, independent of age, insulin resistance, and smoking. Thus, the selective score represents a simple and useful means for screening of testosterone deficiency in Japanese men, as an indicator of LOH.

著者

Yuya Fujihara Nobuya Hamanoue Hiromi Yano Makito Tanabe Yuko Akehi Takashi Nomiyama Toshihiko Yanase

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.66, no.7, pp.637-645, 2019 (Released:2019-07-28)

参考文献数

41

被引用文献数

8 13

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Low endogenous testosterone and sex hormone-binding globulin (SHBG) concentrations have been reported to be associated with metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD). However, little is known about the relationships between testosterone or SHBG and liver fibrosis in NAFLD. Thus, we aimed to clarify the relationships between serum testosterone or SHBG concentration and fibrosis-4 (FIB-4) index, a marker of liver fibrosis. Serum testosterone was assayed in various forms (total testosterone [TT], calculated free testosterone [cFT], calculated bioavailable testosterone [cbT], and SHBG) and metabolic markers were also measured in 363 Japanese men (mean age 51.1 ± 8.7 years) at routine health examinations. We then attempted to identify the factors contributing to liver fibrosis by investigating the associations between the metabolic markers, including testosterone, and FIB-4 index. People with a relatively high FIB-4 index (≥1.3) demonstrated lower cFT, cbT, homeostasis model assessment (HOMA)-β, low-density lipoprotein-cholesterol, and blood urea nitrogen, but higher SHBG, than those with a lower FIB-4 index (<1.3). There were no significant differences in HbA1c, fasting glucose concentration, HOMA-R, or metabolic syndrome prevalence between the two groups. Binary regression analysis revealed that SHBG ≥52 nmol/L and cFT <8.0 ng/dL were statistically significant risk factors for FIB-4 index ≥1.3. Receiver operating characteristic analysis revealed that cFT <7.62 ng/dL (area under the curve [AUC] = 0.639) and SHBG ≥49.8 nmol/L (AUC = 0.649) were the strongest risk factors for FIB-4 index ≥1.3. In contrast to previous findings showing low SHBG concentrations in NAFLD, we provide evidence that high SHBG and low bioactive testosterone are associated with liver fibrosis.

著者

Takashi Nomiyama Dai Shimono Tsuyoshi Horikawa Yuki Fujimura Tomohiro Ohsako Yuichi Terawaki Takashi Fukuda Ryoko Motonaga Makito Tanabe Toshihiko Yanase Collaborators of Fukuoka Study of Ipragliflozin (FUSION) trial

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.65, no.8, pp.859-867, 2018 (Released:2018-08-27)

参考文献数

23

被引用文献数

20 21

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Sodium–glucose co-transporter-2 inhibitors are newly established anti-diabetic agents with a unique glucose-lowering mechanism. In the present study, we investigated the efficacy and safety of the sodium–glucose co-transporter-2 inhibitor ipragliflozin (Ipra) for metabolic markers and cardiovascular parameters in Japanese patients with type 2 diabetes mellitus (T2DM). This study was an investigator-initiated, open-label, single-arm, multicenter prospective study. Patients with T2DM were treated with 50 mg Ipra for 24 and 52 weeks. The primary outcome investigated was the reduction of glycated hemoglobin (HbA1c) level. The secondary outcome was the change in other metabolic and cardiovascular parameters by 24 weeks. Before and after 52 weeks of treatment, carotid intima-media thickening (IMT) was measured by echography. A total of 134 patients were recruited in the study. A 24-week treatment with 50 mg Ipra daily significantly reduced HbA1c level (–0.6%, p < 0.01). Body mass index (BMI), blood pressure and serum C-peptide were reduced significantly (p < 0.05), while serum glucagon level was unchanged. Interestingly, the serum adiponectin and high-density lipoprotein (HDL) cholesterol levels were significantly increased by Ipra. However, 52 weeks of Ipra treatment did not change carotid IMT. Multiple regression analysis revealed that the only significant contributing factor for HbA1c reduction by Ipra was baseline HbA1c level. These data suggest that Ipra decreased not only glucose level but also BMI, blood pressure and serum C-peptide, and the contributing factor for HbA1c reduction by Ipra was baseline HbA1c level. Further, Ipra improved serum adiponectin and HDL cholesterol levels.

著者

Tetsuo Nishikawa Fumitoshi Satoh Yuichi Takashi Toshihiko Yanase Hiroshi Itoh Isao Kurihara Hirotaka Shibata Yutaka Oki Mitsuhide Naruse Hidehiko Sasamoto Katsuhiko Kuwa

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ21-0278, (Released:2021-07-22)

被引用文献数

17

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A commutability confirmation test for the blood aldosterone measurement was performed on liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) as a designated comparison method (DCM) and four chemiluminescent enzyme immunoassay (CLEIA) measurement procedures based on metrological traceability. A conventional radioimmunoassay (RIA) and two measurement procedures of CLEIA which obtains RIA equivalent values were also compared. The relationship between the DCM value and the CLEIA value with respect to 120 pg/mL of the RIA value, which is the screening criterion of primary aldosteronism (PA) was clarified. For the correlation test, 75 samples of patient serum and plasma were used. Regression analysis revealed that the standardized LC-MS/MS and four CLEIA measurement procedures were in good agreement. This is the effect of measurement specificity and calibration using by certified reference material (CRM). The median of the LC-MS/MS corresponding to 120 pg/mL of RIA was 48.5 pg/mL. In the mean of standardized four CLEIA values corresponding to the 48.5 pg/mL of LC-MS/MS value was 47.51 pg/mL and the standard deviation (SD) was 2.93 pg/mL. However, the correlation between the RIA value and the RIA equivalent of the two measurement procedures by CLEIA differed depending on the measurement procedure. This is due to the influence of RIA measurement performance. Standardized CLEIA measurements are suitable for routine measurement procedure. When converting the LC-MS/MS equivalent value by the standardized CLEIA to the conventional RIA value, it is necessary to use the conversion formula.

著者

Makito Tanabe Yuko Akehi Takashi Nomiyama Junji Murakami Toshihiko Yanase

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ14-0313, (Released:2014-10-23)

被引用文献数

2 21

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Endogenous testosterone is known to be protective against metabolic syndrome (MetS) in men. While various markers of testosterone status including serum total testosterone (TT), free testosterone (measured using analogue ligand RIA [aFT]), calculated FT (cFT), calculated bioavailable T (cbT), and sex-hormone binding globulin (SHBG) are recognized, it is unclear which of these markers are the most appropriate ones for the detection of MetS. We measured various testosterone values and metabolic markers in 249 healthy Japanese males (mean age 52.7 ± 7.4 yr) and analyzed which testosterone value is most associated with various metabolic parameters, including MetS as diagnosed according to the International Diabetes Federation (IDF, 2009 version) or with the Japanese criteria. Age had no effect on the TT level but significantly decreased aFT, cFT, and cbT levels and significantly increased the SHBG level. All testosterone values and SHBG showed weak inverse relationships with the metabolic markers BMI, waist circumference, insulin, HOMA-R, and HOMA-β, with the strongest relationship being to TT. TT and SHBG were significantly lower in men with MetS than in men without MetS. All testosterone values gradually decreased as the number of MetS components increased. Multivariate analysis revealed that the TT median value of <4.0 ng/mL was the only significant marker for the detection of MetS. These results were essentially the same regardless of whether the diagnosis of MetS was based on the IDF or the Japanese criteria. In conclusion, among various testosterone values, TT is the most reliable indicator of MetS in middle-aged Japanese men.

著者

Yoshihiro Miyake Keiko Tanaka Tetsuo Nishikawa Mitsuhide Naruse Ryoichi Takayanagi Hironobu Sasano Yoshiyu Takeda Hirotaka Shibata Masakatsu Sone Fumitoshi Satoh Masanobu Yamada Hajime Ueshiba Takuyuki Katabami Yasumasa Iwasaki Hirotoshi Tanaka Yusuke Tanahashi Shigeru Suzuki Tomonobu Hasegawa Noriyuki Katsumata Toshihiro Tajima Toshihiko Yanase

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ13-0353, (Released:2013-09-28)

被引用文献数

7 36

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The Research Committee of Disorders of Adrenal Hormones, Japan, undertook a nationwide epidemiological study of primary aldosteronism (PA). The present study was undertaken as a part of this study to reveal the relationship between type of treatment and the prognosis of PA. In the primary survey, 4161 patients with PA during the period January 1, 2003-December 31, 2007 were reported from 3252 departments of internal medicine, pediatrics and urology. In the secondary survey, a questionnaire that requested detailed clinical information on individual patients was sent to those departments reporting patients in the primary survey. In total, data on 1706 patients with PA were available in the present study. Among patients with bilateral or unilateral aldosterone-producing adenoma, after adjustment for age at which prognosis was examined, sex, surgical treatment and medical treatment, surgical treatment was significantly associated with amelioration of hypertension (adjusted odds ratio [OR]: 0.47 [95% confidence interval (CI): 0.29–0.77]) and hypokalemia (adjusted OR: 0.17 [95% CI: 0.11–0.29]). No significant relationship was observed between medical treatment and such prognosis in this group of patients. Among patients with bilateral or unilateral adrenal hyperplasia, surgical, but not medical, treatment was significantly associated with amelioration of hypokalemia (adjusted OR: 0.23 [95% CI: 0.06–0.74]), while there was no relationship between surgical or medical treatment and the prognosis of hypertension. In conclusion, surgery offered a better prognosis of PA than medication with regards to hypertension and hypokalemia, with the limitation that a new anti-aldosterone drug, eplerenone, was not available during the study period.

著者

Keita Noda Bo Zhang Atsushi Iwata Hiroaki Nishikawa Masahiro Ogawa Takashi Nomiyama Shin-ichiro Miura Hideto Sako Kunihiro Matsuo Eiji Yahiro Toshihiko Yanase Keijiro Saku on behalf of the STYLIST Study Investigators

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.76, no.6, pp.1335-1344, 2012 (Released:2012-05-25)

参考文献数

30

被引用文献数

10 15 4

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Background: Dietary habits are associated with obesity, and both are important contributing factors to lifestyle-related diseases. The STYLIST study examined the effects of dietary counseling by registered dietitians and the delivery of proper calorie-controlled meals (UMIN Registration No: 000006582). Methods and Results: Two-hundred adult patients with hypertension and/or diabetes mellitus were randomly divided into 2 groups with/without dietary counseling and consumed an ordinary diet for 4 weeks. Each group was then subdivided into 2 groups with/without dietary counseling and received calorie-controlled lunch and dinner boxes for the next 4 weeks. The calories in the delivered meals were based on the subject's ideal body weight (BW) and physical activity level. BW, waist circumference, blood pressure, and laboratory data, including glycoalbumin, were measured at 0, 4, and 8 weeks. BW and the other parameters were significantly reduced during the study period in patients who received diet counseling in the ordinary diet period and/or delivered meal period but not in patients without dietary counseling, as assessed by linear mixed models for longitudinal data. Conclusions: The combination of dietary counseling by dietitians and delivery of calorie-controlled meals was effective in reducing BW, as well as blood pressure and glycoalbumin, in patients with hypertension and/or diabetes mellitus. (Circ J 2012; 76: 1335-1344)