著者

Ryo Okazaki Keiichi Ozono Seiji Fukumoto Daisuke Inoue Mika Yamauchi Masanori Minagawa Toshimi Michigami Yasuhiro Takeuchi Toshio Matsumoto Toshitsugu Sugimoto

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.64, no.1, pp.1-6, 2017 (Released:2017-01-30)

参考文献数

31

被引用文献数

12 37

---

Vitamin D is indispensable for the maintenance of bone and mineral health. Inadequate vitamin D action increases the risk for various musculoskeletal/mineral events including fracture, fall, secondary hyperparathyroidism, diminished response to antiresorptives, rickets/osteomalacia, and hypocalcemia. Its most common cause in recent years is vitamin D deficiency/insufficiency, clinically defined by low serum 25-hydroxyvitamin D [25(OH)D] level. Guidelines for vitamin D insufficiency/deficiency defined by serum 25(OH)D concentrations have been published all over the world. In Japan, however, the information on the associations between serum 25(OH)D and bone and mineral disorders has not been widely shared among healthcare providers, partly because its measurement had not been reimbursed with national medical insurance policy until August 2016. We have set out to collect and analyze Japanese data on the relationship between serum 25(OH)D concentration and bone and mineral events. Integrating these domestic data and published guidelines worldwide, here we present the following assessment criteria for vitamin D sufficiency/insufficiency/deficiency using serum 25(OH)D level in Japan. 1) Serum 25(OH)D level equal to or above 30 ng/mL is considered to be vitamin D sufficient. 2) Serum 25(OH)D level less than 30 ng/mL but not less than 20 ng/mL is considered to be vitamin D insufficient. 3) Serum 25(OH)D level less than 20 ng/mL is considered to be vitamin D deficient. We believe that these criteria will be clinically helpful in the assessment of serum 25(OH)D concentrations and further expect that they will form a basis for the future development of guidelines for the management of vitamin D deficiency/insufficiency.

著者

Yasuhiro Ito Naoyoshi Onoda Takahiro Okamoto

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ20-0025, (Released:2020-04-09)

被引用文献数

3 86

---

The Japan Associations of Endocrine Surgeons has developed the revised version of the Clinical Practice Guidelines for Thyroid Tumors. This article describes the guidelines translated into English for the 35 clinical questions relevant to the therapeutic management of thyroid cancers. The objective of the guidelines is to improve health-related outcomes in patients with thyroid tumors by enabling users to make their practice evidence-based and by minimizing any variations in clinical practice due to gaps in evidential knowledge among physicians. The guidelines give representative flow-charts on the management of papillary, follicular, medullary, and anaplastic thyroid carcinoma, along with recommendations for clinical questions by presenting evidence on the relevant outcomes including benefits, risks, and health conditions from patients’ perspective. Therapeutic actions were recommended or not recommended either strongly (◎◎◎ or XXX) based on good evidence (

著者

Hidefumi Inaba Hiroyuki Ariyasu Hiroshi Iwakura Chiaki Kurimoto Ken Takeshima Shuhei Morita Hiroto Furuta Muneki Hotomi Takashi Akamizu

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ20-0371, (Released:2020-10-03)

被引用文献数

24

---

Immune-related adverse events in the thyroid glands (thyroid irAEs) during treatment with immune-checkpoint inhibitors (ICIs) are most frequent endocrine irAE. Thyroid irAE can be divided into that requiring continuous therapy for thyroid dysfunction (P-THY), and that requiring only temporal treatment (T-THY). However, predictive factors for those differential outcomes are unknown, and susceptibility of human leukocyte antigen (HLA) to thyroid irAE has never been investigated. This study aimed to elucidate clinical courses and prognosis of P-THY in comparison with T-THY in the aspect of thyroid immunity and HLA. Patients with P-THY (n = 15) that required L-T4 supplemental therapy for hypothyroidism for more than 3 months, and patients with T-THY who required no therapy or therapy within 1 month were enrolled in the study. Lower-value of TSH, higher-value of FT4, and lower value of TSH/FT4 were thought to be predictive markers to estimate P-THY. In addition, anti-thyroglobulin antibody (TgAb) levels were significantly higher in patients with P-THY than those in patients with T-THY. HLA-DPA1*01:03 and HLA-DPB1*02:01 allele, and their haplotype frequencies were significantly higher in patients with P-THY than those in controls. P-THY had better survival rate than T-THY. Pre-existing thyroid autoimmunity, the extent of thyroid dysfunction, and predisposing HLA were associated with the differential course of thyroid irAEs. It was suggested that thyroid function tests, TgAb, and HLA typing tests are useful for prediction of clinical course in thyroid irAEs.

著者

Tetsuya Tagami Hironori Kimura Sumire Ohtani Tsuyoshi Tanaka Takashi Tanaka Shiro Hata Miho Saito Yasushi Miyazaki Rika Araki Masami Tanaka Kazuya Yonezawa Morio Sawamura Takuyuki Ise Atsushi Ogo Takuro Shimbo Akira Shimatsu Mitsuhide Naruse

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.58, no.6, pp.449-457, 2011 (Released:2011-06-30)

参考文献数

44

被引用文献数

13 26

---

Hypercholesterolemia is one of the most representative disorders of the common diseases. To evaluate the prevalence of hypothyroidism in the population of adult hypercholesterolemia, we prospectively examined the thyroid function in patients with untreated or treated hypercholesterolemia as a multi-center survey. Subjects were the patients who were treated with some antilipemic agents or the untreated patients whose total cholesterol (TC) was over 220 mg/dL and/or LDL-cholesterol (LDL-C) over 140 mg/dL. Among 737 cases recruited, 725 cases (300 males and 425 females) participated in the survey including the thyroid function test. The patient's backgrounds include hypertension (51%), diabetes mellitus (49%), fatty liver (17%), smoking (15%), and habitual drinking (10%). The 72% of the patients were treated with some antilipemic agents and the mean values of TC, LDL-C, triglyceride (TG), HDL-cholesterol (HDL-C), and LDL-C/HDL-C ratio (L/H) were 204.5 mg/dL, 119.6 mg/dL, 144.4 mg/dL, 60.7 mg/dL and 2.25, respectively. The primary hypothyroidism was seen in 27 cases (3.7%) (11 males, 16 females) with subclinical hypothyroidism in 17 cases (2.4%) and overt hypothyroidism in 10 cases (1.4%). The central hypothyroidism was seen in 4 cases (0.6%). The prevalence of hypothyroidism was 4.3% in patients with hypercholesterolemia. Taking account of the large number of patients with dyslipidemia and importance of avoiding unnecessary administration and associated adverse effects, evaluation of the thyroid function could be warranted in patients with dyslipidemia although cost-benefit issues waits further investigation.

著者

Sawako Takahashi Mitsuru Ito Yuzuki Masaki Mikiko Hada Mizuho Minakata Kazuyoshi Kohsaka Tomohiko Nakamura Toshihiko Kasahara Takumi Kudo Eijun Nishihara Shuji Fukata Mitsushige Nishikawa Takashi Akamizu Akira Miyauchi

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ20-0542, (Released:2020-11-25)

被引用文献数

1

---

Many previous studies including ours have reported that athyreotic patients on levothyroxine (LT4) have relatively low serum free triiodothyronine (FT3) levels, whereas patients with large goitrous diseases often have high serum FT3 levels. Here we investigated Hashimoto thyroiditis (HT) patients on LT4 to study the relationship between thyroid volume (TV) and thyroid hormone status in hypothyroid patients on LT4. We retrospectively studied 408 euthyroid HT patients treated with LT4 for hypothyroidism; divided them as per TV and compared serum levels of free thyroxine (FT4) and FT3 and the FT3/FT4 ratio in each patient group with those in euthyroid matched control group. We also evaluated the association between serum FT3 level and FT3/FT4 ratio and TV among HT patients on LT4. In patients with TV <15 mL, serum FT3 levels were significantly lower than those in controls. In patients with TV 15–80 mL, serum FT3 levels were equivalent to those in controls. In patients with TV ≥80 mL, the serum FT3 levels were significantly higher than those in controls. The serum FT3 level (r = 0.35, p < 0.01) and FT3/FT4 ratio (r = 0.42, p < 0.01) showed a positive correlation with TV. TVs in HT patients on LT4 caused differences in serum thyroid hormone balance, as increasing volume increases the serum FT3 level and FT3/FT4 ratio. Serum thyroid hormone balance in HT patients with smaller thyroids was similar to that in athyreotic patients. Mild thyrotropin suppression with LT4 is needed to achieve normal FT3 levels in such patients.

著者

Satoshi SUZUKI Hiroyoshi TSUBOCHI Andrew DARNEL Takashi SUZUKI Hironobu SASANO Zigmunt S. KROZOWSKI Takashi KONDO

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.50, no.4, pp.445-451, 2003 (Released:2003-09-11)

参考文献数

31

被引用文献数

7 13

---

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) behaves predominantly as an oxoreductase converting the receptor-inactive glucocorticoids to their active forms in vivo, while the type 2 isoform (11β-HSD2) possesses only dehydrogenase activity and inactivates cortisol in human or corticosterone in rat. We determined enzyme activity of 11β-HSD in rat lungs from fetus to adult, and examined whether 11β-HSD1 exists in alveolar type II cells, the most important site for the synthesis of pulmonary surfactant in mature lungs, by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Enzyme activity of 11β-HSD1 and 2 in lung tissue homogenate were determined as NADP+- and NAD+-dependent conversion of corticosterone to 11-dehydrocorticosterone, respectively. We found that 11β-HSD1 activity was increased progressively from 21 days gestation to 7 weeks after birth. 11 β-HSD2 activity was significantly lower than that of 11β-HSD1 throughout gestation and after birth. Immunoreactivity for 11β-HSD1 was detected in the cytoplasm of the cells in the alveolar region of adult rats. Some of these expressing 11β-HSD1 were considered to be alveolar type II cells, because of their cuboid shape and localization at the corner of the alveoli. RT-PCR demonstrated 11 β-HSD1 mRNA in isolated alveolar type II cells. Our results suggest that alveolar type II cells enhance intracellular glucocorticoid availability via 11β-HSD1. 11β-HSD1 in alveolar type II cells is thought of as an autocrine amplifier of glucocorticoid action in the lung.

著者

Ohk-Hyun Ryu Sungwha Lee Jaemyung Yu Moon-Gi Choi Hyung Joon Yoo Franco Mantero

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.61, no.2, pp.167-176, 2014 (Released:2014-02-28)

参考文献数

44

被引用文献数

32 49

---

Epidemiologic studies have shown that low vitamin D levels are associated with reduced insulin sensitivity and increased risk of developing type 2 diabetes mellitus (T2DM). However, there is little evidence that vitamin D supplementation improves glucose intolerance. We evaluated the glucose-lowering effect of vitamin D in Korean T2DM subjects. We enrolled 158 T2DM patients who had stable glycemic control [hemoglobin A1c (HbA1c) <8.5%] and vitamin D levels less than 20 ng/mL. The participants were randomized into two groups: Placebo (100 mg daily of elemental calcium administered twice a day) or Vitamin D (1000 IU daily of cholecalciferol combined with 100 mg of elemental calcium administered twice a day). We compared outdoor physical activity, glycemic control, homeostasis model of assessment - insulin resistance (HOMA-IR), and parathyroid hormone (PTH), during the 24-week intervention. We analyzed the data of 129 participants (placebo =65, vitamin D =64) who completely followed the protocol. Outdoor physical activity and oral anti-diabetic drugs did not differ between the groups. While there were significant differences in the vitamin D levels (15.6 ± 7.1 ng/mL vs 30.2 ± 10.8 ng/mL, P<0.001) and change in PTH levels (1.4 ± 15.3 pg/mL vs -5.5 ± 9.8 pg/mL, P=0.003) between the placebo and vitamin D groups, there were no differences in HbA1c (7.27 ± 0.87% vs 7.40 ± 0.90%) (P=0.415) and HOMA-IR. Serum calcium and kidney function results showed that the vitamin D supplementation was safe. While vitamin D supplementation is safe and effective in the attainment of vitamin D sufficiency, it had no effect on long-term glycemic control for T2DM in our study.

著者

Mostafa K. EL-AWADY Wael EL-GARF Lamia EL-HOUSSIENY

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.51, no.1, pp.37-46, 2004 (Released:2004-03-04)

参考文献数

44

被引用文献数

11 17

---

Testosterone and 5α-dihydrotestosterone (DHT) are the principal male hormones (androgens) in mammals. The enzyme, steroid 5α reductase catalyzes the conversion of testosterone (T) to its biologically potent steroid (DHT) in androgen dependent tissues. Two 5α reductase isoenzymes have been identified in rat tissues. The type I isoenzyme has been shown to be predominately expressed in the rat liver, whereas androgen target tissues of the genital tract express mainly isoenzyme II. The effects of androgens and glucocorticoids on the abundance of steroid 5α reductase type I (5αR1) messenger RNA in the rat liver were examined. Steady state levels of 5αR1 mRNA decreased dramatically to 1.5% of control levels 14 days following adrenalectomy (ADX), whereas dexamethasone (Dex) administered (0.5 mg/100 g) to ADX animals enhanced the expression of 5αR1 to twice its' normal values within 40 hours. Bilateral orchiectomy induced, within eight days, the expression of 5αR1 mRNA in the rat liver to 1.75 fold the normal value while testosterone injection failed to reduce this enhanced expression in castrated animals. Addition of Dex (1 μM) to primary cultures of rat hepatocyte resulted in a five- and three-fold reduction in the mRNA expression of 5αR1 after 24 and 48 hours, respectively. DHT (0.5 μM) however, induced the expression of 5αR1 mRNA by two- and seven-fold 24 and 48 hours post-treatment, respectively. In vitro nuclear run-on analysis of the 5αR1 gene showed no correlation between the rate of synthesis and steady state levels of this mRNA either in the intact liver or in cultured hepatocytes. These results appear to suggest that glucocorticoids and androgens differentially regulate 5αR1 mRNA in the rat liver. Moreover, our findings appear to indicate that regulation of 5αR1 gene is primarily at the post-transcriptional level.

著者

Kyuzi Kamoi You Shinozaki Kazuo Furukawa Hideo Sasaki

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.59, no.4, pp.353-363, 2012 (Released:2012-04-28)

参考文献数

33

被引用文献数

4 4

---

Glucose-dependent insulinotropic polypeptide (GIP) secretion in diabetic Europeans with type 1 (T1DM) and type 2 (T2DM) following test meal (TM) has been shown to be normal. In Japanese patients with T2DM, GIP secretion was also normal. We determined whether GIP secretin is influenced by various factors. Plasma glucose (PG), serum insulin (s-IRI), serum C-peptide (s-CPR), and plasma total GIP (p-total GIP) levels were measured at 0, 30, and 60 minutes after TM (560 kcal) in patients with T1DM (n = 15, group 1) and T2DM (n = 29, group 2) treated with various medications. HbA1c was also measured. At baseline, means of age, BMI, HbA1c, PG, s-CPR, SUIT (secretory unit in transplantation) and p-total GIP were significantly lower in group 1 than in group 2. Each mean of postprandial p-total GIP levels after TM in all patients was more dramatically increased than other factors. The area under the curve (AUC) of p-total GIP levels in early-phase (0 to 30 min) was significantly positively correlated with BMI in group 2 but not in group 1, and not with other factors. These results indicate that the GIP secretion after TM in diabetic Japanese patients was dramatically increased, and the AUC of GIP secretion in early-phase was positively correlated with BMI in non-obese and obese patients with T2DM, but not with T1DM. The increase was not influenced by gender, age, glycemic control, duration of disease, micro- or macro-vascular disturbances, or oral drugs.

著者

Ritsuko Yamamoto-Honda Yoshihiko Takahashi Yasumichi Mori Shigeo Yamashita Yoko Yoshida Shoji Kawazu Yasuhiko Iwamoto Hiroshi Kajio Hidekatsu Yanai Shuichi Mishima Nobuhiro Handa Kotaro Shimokawa Akiko Yoshida Hiroki Watanabe Kazuhiko Ohe Takuro Shimbo Mitsuhiko Noda

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ16-0521, (Released:2017-03-18)

被引用文献数

6

---

Type 2 diabetes, which is characterized by a combination of decreased insulin secretion and decreased insulin sensitivity, can be delayed or prevented by healthy lifestyle behaviors. Therefore, it is important that the population in general understands their personal risk at an early age to reduce their chances of ever developing the disease. A family history of hypertension is known to be associated with insulin resistance, but the effect of a family history of hypertension on the onset of type 2 diabetes has not well been examined. We performed a retrospective study examining patient age at the time of the diagnosis of type 2 diabetes by analyzing a dataset of 1,299 patients (1,021 men and 278 women) who had been diagnosed as having type 2 diabetes during a health checkup. The mean ± standard deviation of the patient age at the time of the diagnosis of diabetes was 49.1 ± 10.4 years for patients with a family history of hypertension and 51.8 ± 11.4 years for patients without a family history of hypertension (p < 0.001). A multivariate linear regression analysis showed a significant association between a family history of hypertension and a younger age at the time of the diagnosis of type 2 diabetes, independent of a family history of diabetes mellitus and a male sex, suggesting that a positive family history of hypertension might be associated with the accelerated onset of type 2 diabetes.

著者

Satoshi Yoshino Eijiro Yamada Shuichi Okada Yasuyo Nakajima Ryo Shibusawa Ryota Uehara Shunichi Matsumoto Kazuhiko Horiguchi Emi Ishida Tsugumichi Saito Masanobu Yamada

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ19-0488, (Released:2020-02-06)

被引用文献数

4

---

The Abbott FreeStyle Libre flash glucose monitoring system (FGM) is a recently introduced, but widespread continuous glucose monitoring system. While its mean absolute relative difference (MARD) value indicating its accuracy is acceptable with reference to the self-monitoring of blood glucose (SMBG) levels, few reports have examined the MARD in sensor glucose values of FGM (FGM-SG) with reference to plasma glucose (PG) levels and the factors determining it. We performed oral glucose tolerance tests (OGTTs) in 25 Japanese subjects without diabetes. Parkes error grid analyses showed that FGM-SG with either SMBG or PG levels as a reference met International Organization for Standardization criteria. The MARD in FGM-SG with reference to SMBG levels was 10.9 ± 4.1% during OGTTs. Surprisingly, the MARD in FGM-SG with reference to PG levels was 20.3 ± 10.3% during OGTTs, revealing a discrepancy in the accuracy of FGM-SG compared with that of PG levels; moreover, the MARD showed negative correlations with fasting blood sugar level, homeostasis model assessment insulin resistance index, and body mass index (BMI). Multiple regression analyses revealed that BMI contributed the most to the MARD when FGM-SG and PG level were compared, as lean individuals have a greater MARD regardless of glucose levels. Inaccurate FGM data could potentially increase the risk of inappropriate treatment; consideration of such factors is critical to ensure reliable FGM values.

著者

Yoshifumi Saisho Kinsei Kou Kumiko Tanaka Takayuki Abe Hideaki Kurosawa Akira Shimada Shu Meguro Toshihide Kawai Hiroshi Itoh

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.58, no.4, pp.315-322, 2011 (Released:2011-04-29)

参考文献数

17

被引用文献数

46 72

---

Type 2 diabetes is a progressive disease and most patients with type 2 diabetes eventually need insulin therapy. The objective of this study was to clarify C-peptide immunoreactivity (CPR), a marker of beta cell function, as a predictor of requirement for insulin therapy. We conducted a retrospective study of 579 consecutive subjects with type 2 diabetes who were admitted to our hospital from 2000 to 2007 and were able to be followed up for at least 6 months after discharge. Fasting and postprandial serum CPR and urinary CPR levels had been measured during admission. Information about insulin therapy at the last visit was obtained from medical records. At the last visit, 364 subjects (62.9%) were treated with insulin. Mean interval between discharge and the last visit was 4.5 ± 2.3 years. Serum and urine CPR levels at baseline were significantly associated with insulin treatment at the last visit (P

著者

TETSUO NISHIKAWA TAKASHI IIZUKA MASAO OMURA NOBUHIKO KURAMOTO TAKASHI MIKI HIROKO ITO SHYOZO CHIBA

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.43, no.6, pp.671-677, 1996 (Released:2006-11-25)

参考文献数

19

被引用文献数

5 4

---

The present investigations were performed in order to clarify the effects of mazindol on body weight and insulin sensitivity in patients with morbid obesity who had already been treated with a verylow- calorie diet containing 480kcal food (VLCD) with various amino acids. We attempted to study whether a further decrease in body weight would be achieved by the administration of mazindol, because it is difficult to obtain sufficient and continuous reduction of body weight after VLCD therapy. Thirteen female severely obese subjects were 51.0±13.9 years old (25-73 years old), with a mean height of 154.7±5.6cm (146.0-160.5cm), mean weight of 84.5±9.4kg (69-98kg) and a mean body mass index (BMI) of 35.3±3.6kg/m2 (29.2-41.0kg/m2). Their mean body weight decreased to 76.7±2.2kg (net decrease: 6.3±0.9kg) after VLCD therapy for 2-4 weeks. Then they were treated by the administration of mazindol with diet restriction (1000-1200kal/day). Mazindol administration resulted in a further weight reduction of 2.9±0.5kg after 4 weeks, 4.9±0.5kg after 8 weeks and 6.9±0.9kg after 12 weeks. Their blood pressure was not changed after mazindol treatment. The responses of blood glucose and insulin levels in a 75g oral glucose tolerance test (OGTT) were not significantly different before and after mazindol administration. The blood glucose area calculated from the data obtained during OGTT for 120min did not significantly differ before and after mazindol administration, while the insulin area significantly decreased after mazindol treatment (from 98.0±12.1 before administration to 70.1±7.8). The mean M value reflecting insulin sensitivity in the whole body determined by euglycemic glucose clamping was increased significantly after mazindol treatment (from 4.92±0.30mg/kg/min to 6.36± 0.43mg/kg/min). The results demonstrated that mazindol administration with diet restriction further reduced body weight in the morbidly obese subjects after treatment with VLCD, with an increase in the M value and a decrease in insulin release. The results suggest that mazindol is useful for reducing body weight as well as improving insulin sensitivity.

著者

Taisuke Uchida Hideki Yamaguchi Chinami Kushima Tadato Yonekawa Masamitsu Nakazato

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ19-0198, (Released:2019-09-13)

被引用文献数

7

---

We report a case of a 47-year-old woman with hypercalcemia 6 months after discontinuation of denosumab. She underwent right mastectomy for breast cancer and had received aromatase inhibitor and denosumab therapy for 5 years. Thirst, appetite loss, and bilateral ankle pain began few months after cessation of denosumab. She was admitted to the hospital for hypercalcemia and hyperthyroidism 6 months after the last dose of denosumab. Laboratory investigations revealed hypercalcemia, normophosphatemia, normal renal function, and elevated levels of fibroblast growth factor 23 (FGF-23). Serum tartrate-resistant acid phosphatase 5b and urine N-terminal cross-linked telopeptide of type I collagen were both elevated, and bone scintigraphy revealed increase of whole bone uptake. Radiological examinations showed no recurrence of breast cancer or tumors that secrete intact PTH or FGF-23. Hypercalcemia, which lasted for 1 month, was refractory to discontinuation of the aromatase inhibitor, normalization of thyroid hormone levels, saline hydration, and calcitonin administration, but was effectively treated with zoledronic acid. Abnormal uptake on bone scintigraphy and ankle pain both resolved a few months after treatment, and hypercalcemia has not recurred in the ensuing 2 years. In conclusion, we found elevated levels of circulating FGF-23 with hypercalcemia following the discontinuation of denosumab. FGF-23 might be a surrogate marker for massive bone resorption triggered by discontinuation of long-term denosumab treatment.

著者

Yinhua Ni Tao Wu Luna Yang Yang Xu Tsuguhito Ota Zhengwei Fu

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.65, no.5, pp.569-578, 2018 (Released:2018-05-28)

参考文献数

59

被引用文献数

19

---

Oxidative stress caused free radical and mitochondrial damage plays a critical role in the progression of aging and age-related damage at the cellular and tissue levels. Antioxidant supplementation has received growing attention and the effects of antioxidant on aging are increasingly assessed in both animal and human studies. However, additional and more promising treatments that contribute to the expansion of anti-aging therapies are needed. Astaxanthin, a super antioxidant carotenoid and free radical scavenger, inhibits lipid peroxidation more potently than vitamin E. In the present study, we investigated the preventative effects of astaxanthin on aging using an accelerated aging model: mice chronically treated with a combination of D-galactose and jet lag. After 6 weeks of treatment, astaxanthin administration tended to protect the liver weight loss in aged mice. It is probably by upregulating the mRNA expression of galactose-1-phosphate uridyltransferase, which contribute to the enhancement of D-galactose metabolism. Astaxanthin supplementation also improved muscle endurance of aged mice in a swimming test. These results were associated with reduced oxidative stress in serum and increased anti-oxidative enzymes activities and mRNA expression in vivo. Moreover, astaxanthin reversed the dysregulation of aging-related gene expression caused by the combination of D-galactose and jet lag in the liver and kidney of mice. In conclusion, astaxanthin prevents liver weight loss, ameliorates locomotive muscular function, exerts significant anti-aging effects by reducing oxidative stress and improving the expression of age-related genes in D-galactose and jet lag-induced aging model.

著者

Yutaka Seino Kohei Kaku Nobuya Inagaki Masakazu Haneda Takashi Sasaki Atsushi Fukatsu Michito Ubukata Soichi Sakai Yoshishige Samukawa

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.62, no.7, pp.593-603, 2015 (Released:2015-07-31)

参考文献数

20

被引用文献数

13 23

---

Luseogliflozin, a selective sodium glucose cotransporter 2 inhibitor, was demonstrated in a previous 24-week study of type 2 diabetic patients to be efficacious and well tolerated. This study mainly aimed to evaluate the long-term safety of luseogliflozin monotherapy in Japanese type 2 diabetic patients based on the Japanese guidelines. Additionally, long-term efficacy was also evaluated. Patients on diet and exercise therapy alone with an HbA1c of 6.9-10.5% received luseogliflozin 2.5 mg once daily for 52 weeks. For patients with insufficient glycemic control, this dose was able to be increased to 5 mg at Week 24. Adverse events (AEs), clinical laboratory tests, vital signs and 12-lead electrocardiograms were used to assess safety. Efficacy endpoints consisted of changes in HbA1c, fasting plasma glucose (FPG), and body weight from baseline. Of 299 patients who received luseogliflozin, 279 completed the study. Most AEs were mild in severity with incidences of AEs and adverse drug reactions at 75.3% and 16.7%, respectively. Although hypoglycemia was observed in 7 patients (2.3%), no major hypoglycemic episodes occurred. The incidences of AEs of special interest, including pollakiuria, volume depletion and urinary tract/genital infections, were at acceptable levels. Luseogliflozin significantly lowered HbA1c (-0.50%, P< 0.001), FPG (-16.3 mg/dL, P< 0.001) and body weight (-2.68 kg, P< 0.001) at Week 52 compared to baseline. Up-titration to 5 mg further improved glycemic control. In this long-term study of Japanese type 2 diabetic patients, luseogliflozin monotherapy was well tolerated for 52 weeks and provided a sustained glycemic lowering effect and reduced body weight.

著者

Jing Xue Xiaorong Li Ping Liu Ke Li Liping Sha Xiaoli Yang Lili Zhu Zhen Wang Youping Dong Li Zhang Hong Lei Xiaoxia Zhang Xiaoying Dong Hao Wang

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ18-0567, (Released:2019-07-03)

被引用文献数

71

---

Polycystic ovary syndrome (PCOS) represents an endocrine disorder, which is closely related with gut microbiota. Inulin, a kind of probiotics, has been proven to alleviate gut microbiota dysbiosis. Metformin, a biguanide agent, shows beneficial effects on chronic metabolic diseases. Our objective was to assess the effects and associated mechanisms of inulin and metforin on attenuation of PCOS in mice. Mice were divided into 4 groups: control group (CON), model group (MOD), inulin group (INU), metformin group (MET). The last three groups were fed 6 mg of dehydroepiandrosterone (DHEA) per 100 g body weight and 60% high-fat diet to generate mice model. After 21 days of intervention, mice were euthanized and associated indications were investigated. Body weight (BW) and testosterone (T) levels were significantly decreased, but estradiol (E2) levels were increased in INU or MET group, respectively. Ovary HE staining demonstrated that inulin or metformin ameliorated PCOS morphology. Inflammatory indicators from plasma and ovary including TNF-α, IL-6, and IL-17A were decreased in INU or MET group. Moreover, IL-10 in ovary of INU or MET group was increased. Sequencing and analysis of gut microbiota showed that compared to MOD group, Bifidobacterium was increased, but Proteobacteria, Helicobacter and Parasutterella were decreased in INU group. Helicobacter was decreased in MET group. Correlation analysis showed that gut microbiota was correlated with inflammatory factors. Our results revealed that inulin and metformin alleviated PCOS via anti-inflammation and modulating gut microbiota, which may contribute to potential clinical therapy for the disease.

著者

Ippei Kanazawa

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.64, no.11, pp.1043-1053, 2017 (Released:2017-11-29)

参考文献数

80

被引用文献数

2 65

---

Accumulating evidence has shown that bone and glucose metabolism are closely associated with each other. Since the risk of osteoporotic fractures is increased in patients with diabetes mellitus (DM), osteoporosis is recently recognized as one of diabetic complications, called DM-induced bone fragility. Previous studies showed that collagen cross-links of advanced glycation end products (AGEs) and dysfunctions of osteoblast and osteocyte are involved in DM-induced bone fragility. Circulating levels of AGEs and homocysteine are increased in patients with DM, and they directly impair the functions of osteoblast and osteocyte, resulting in decreased bone formation and bone remodeling. On the other hand, bone is recently recognized as an endocrine organ. Previous studies based on in vitro and animal studies showed that osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, may regulate glucose homeostasis. Although several clinical studies reported the relationship between osteocalcin and glucose metabolism, further large-scale and intervention studies are necessary to confirm the beneficial effects of osteocalcin on glucose metabolism in human. It has been shown that adenosine monophosphate-activated protein kinase (AMPK), an intracellular energy sensor, is involved in bone metabolism. Adiponectin and metformin stimulate osteocalcin expression and the differentiation of osteoblasts via AMPK activation. Also, AMPK activation protects against oxidative stress-induced apoptosis of osteocytes. These findings suggest that AMPK in osteoblasts and osteocytes may be a therapeutic target for DM-induced bone fragility.

著者

Kazutaka Aoki Haruhiro Sato Yasuo Terauchi

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ19-0041, (Released:2019-04-23)

被引用文献数

14

---

Elevation of postprandial plasma glucose is correlated with an increase in cardiovascular events, and alpha-glucosidase inhibitors (αGIs) are effective at reducing postprandial glucose levels. In Japan, the αGIs acarbose, voglibose, and miglitol have been available since 1993, 1994, and 2006, respectively. Dipeptidyl peptidase-4 (DPP-4) inhibitors are also effective at reducing postprandial glucose levels, and they have been available in Japan since 2009. A combination therapy of αGI, miglitol, and the DPP-4 inhibitor, sitagliptin, is more effective at decreasing postprandial glucose levels than monotherapy with either miglitol or sitagliptin. Moreover, the combination therapy of miglitol and sitagliptin is more effective at increasing postprandial active glucagon-like peptide-1 (GLP-1) levels than monotherapy. Peptide YY (PYY) has appetite-suppressing and gastric-emptying effects similar to GLP-1. In healthy individuals, miglitol increases the postprandial total PYY; however, combination therapy of miglitol and vildagliptin does not change postprandial total PYY levels. αGIs are typically prescribed to be taken just before a meal, which can result in decreased drug adherence. Different patterns of αGI intake were examined, and the results showed that miglitol or acarbose administration after a meal is effective. The effects of taking miglitol dissolved in water during a meal appeared to be similar to that of taking miglitol as a tablet just before a meal. The long-term effects of taking miglitol dissolved in water should be evaluated in future studies. αGIs may be effective even when they are not taken before a meal, and a more flexible administration may improve drug adherence.

著者

Yoshinori Ozeki Takayuki Masaki Yuichi Yoshida Mitsuhiro Okamoto Manabu Anai Koro Gotoh Yuichi Endo Masayuki Ohta Masafumi Inomata Hirotaka Shibata

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ18-0543, (Released:2019-04-23)

被引用文献数

7

---

In this study, we investigated the relationships between body weight (BW), computed tomography (CT)-assessed abdominal adipose tissue, and the glycemic metabolic profile in obese Japanese patients following laparoscopic sleeve gastrectomy (LSG). This study analyzed adipose tissue compartments using CT methods before and 1 year after LSG. Thirty obese patients were studied, and variables measured included visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), density of VAT (VAT-D), and density of SAT (SAT-D). We also examined the parameters in patients according to whether they had type-2 diabetes (T2DM). LSG induced significant losses in BW, SAT, and VAT after LSG. Additionally, SAT-D and VAT-D both increased and fasting plasma glucose (FPG) and HbA1c, but not C-peptide, decreased after surgery. ΔSAT and ΔVAT were positively related, and ΔSAT-D and ΔVAT-D were negatively related to ΔBW and/or FPG. Furthermore, a multivariate regression model showed that total BW loss (TBWL) was closely related to ΔSAT (β = 0.84; p < 0.001) and ΔVAT-D (β = –0.45; p < 0.05) and improvement of FPG was related to ΔVAT (β = 0.61; p < 0.05) after LSG. Finally, ΔFPG was correlated with ΔVAT in 16 T2DM patients (r = 0.58; p < 0.05) but not in non-T2DM patients. TBWL was related to ΔSAT and ΔVAT-D, and improvement of FPG was related to ΔVAT in obese Japanese patients after LSG.