Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
66 巻, 9 号
選択された号の論文の10件中1~10を表示しています
REVIEW
  • Yilun Mao, Song Wen, Mingyue Zhou, Shifei Zhu, Ligang Zhou
    原稿種別: Review
    2019 年 66 巻 9 号 p. 753-762
    発行日: 2019年
    公開日: 2019/09/28
    [早期公開] 公開日: 2019/08/10
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    Exercise is a fundamental component of diabetes management. However, choosing inappropriate type or timing of exercise is associated with mild or severe hypoglycemia either during exercise or several hours after exercise. Several studies have shown that impaired counterregulatory responses triggers hypoglycemia. Therefore, in this investigation, we explored the appropriate intensity and time of exercise in patients with diabetes. The mechanisms of counterregulatory responses and hypoglycemia associated autonomic failure (HAAF), as well as the strategies for preventing episodes of hypoglycemia after exercise were also investigated. In this study, we obtained the following results: 1) High intensity interval exercise is more suitable for diabetic patients. 2) Morning exercise reduces nocturnal hypoglycemia risks compared with midday, afternoon and evening exercise. 3) Hypoglycemia can be prevented by dietary approach, reduction or suspension of insulin dose, use of mini dose glucagon, caffeine, mitigation methods, prediction algorithm, autonomic feedback controlled close-loop insulin delivery, real time continuous glucose monitoring. Based on these results we concluded that exercise may cause severe hypoglycemia or induce blunted response in patients with diabetes. For Diabetes Mellitus (DM) patients, the intensity and time of exercise influence the occurrence of hypoglycemia. This review summarizes the clinical characteristics of different types of exercises and time of exercise that can be potentially used to educate and guide patients regarding the role of exercise in standard of care.

ORIGINAL
  • Motoki Kawasaki, Mitsuru Ito, Hirosuke Danno, Kazuyoshi Kousaka, Tomoh ...
    原稿種別: Original
    2019 年 66 巻 9 号 p. 763-768
    発行日: 2019年
    公開日: 2019/09/28
    [早期公開] 公開日: 2019/06/01
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    While patients with large goitrous thyroid diseases often have a relatively high serum free triiodothyronine (FT3)/free thyroxine (FT4) ratio, athyreotic patients have a relatively low FT3/FT4 ratio. Here we investigated the relationship between thyroid hormone status and thyroid volume (TV) among a large number of euthyroid Hashimoto thyroiditis (HT) patients. We retrospectively enrolled 2,603 untreated HT patients who visited the Kuma hospital from 2012 to 2016, and divided them into four groups as per the TV: normal TV (<20 mL), slight goiter (20 ≤ TV < 50 mL), moderate goiter (50 ≤ TV < 80 mL), and the large goiter group (≥80 mL). Baseline characteristics and laboratory data of each group were compared to those of 1,554 control subjects. The association between FT3/FT4 ratio and TV among HT patients was then analyzed. We observed a change in laboratory parameters among 13 patients in the large goiter group who were prescribed levothyroxine (LT4) for reducing TV. Compared to normal subjects, the moderate and large goiter groups exhibited significantly higher serum FT3 levels, while all HT groups exhibited lower serum FT4 levels. Serum FT3/FT4 ratios showed a positive correlation with TV (r = 0.35, p < 0.01), which was independent of age, sex, body mass index, and TgAb and TSH levels. LT4 treatment lowered serum FT3 levels and FT3/FT4 ratios significantly. Our results indicated that HT patients with increased TV tended to present with high serum FT3, low FT4, and high FT3/FT4 ratios. The elevation of deiodinase activity may be an important factor affecting thyroid hormonal balance in such patients.

  • Hengcai Yu, Wen Zhang, Chengwu Shen, Haiqing Zhang, Haochao Zhang, Yah ...
    原稿種別: Original
    2019 年 66 巻 9 号 p. 769-775
    発行日: 2019年
    公開日: 2019/09/28
    [早期公開] 公開日: 2019/06/18
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    A 49-year-old woman with hypothyroidism developed liver dysfunction after increasing dose of levothyroxine (L-T4) (Euthyrox®) from 25 μg to 50 μg. Viral hepatitis, autoimmune hepatitis and non-alcoholic steatohepatitis (NASH) were ruled out with examinations. She had no concurrent medication and had no history of infectious, chronic or any other autoimmune diseases. After cessation of Levothyroxine Sodium Tablets (Euthyrox®), liver enzymes gradually returned to normal. She was diagnosed levothyroxine-induced liver injury, based on criteria proposed in “Diagnosis and treatment guideline on drug-induced liver injury” issued by the Chinese Medical Association (2015). As an alternative 25 μg qod of Levothyroxine Sodium Tablets (Letrox®) was tried and increased gradually up to 75 μg daily. Since then liver enzymes have remained within normal range. The main difference of additive for both tablets is whether it contains lactose or not: Euthyrox® contains lactose which caused no liver injury, thus excluding the possibility that an additive of Euthyrox® contributed to liver injury. The relatively quicker and larger replacement with synthetic T4 for hypothyroidism inducing transient thyrotoxicosis was suspected, although thyroid function was normal. Immune-mediated drug-induced liver injury (DILI) was also not excluded. This is a rare case of drug-induced liver injury due to levothyroxine tablets. It reminded us that when replacement with synthetic T4 for hypothyroidism is done, smaller-dose initiation and slower-speed increase may be useful for treatment of cases similar to genetically susceptible individuals.

  • Masato Furuhashi, Masayuki Koyama, Megumi Matsumoto, Takayo Murase, Ta ...
    原稿種別: Original
    2019 年 66 巻 9 号 p. 777-786
    発行日: 2019年
    公開日: 2019/09/28
    [早期公開] 公開日: 2019/05/25
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    Xanthine oxidoreductase (XOR), an enzyme of uric acid formation from hypoxanthine and xanthine, is recognized as a source of oxidative stress. Plasma activity of XOR has been reported to be a biomarker of metabolic disorders associated with obesity, liver dysfunction, insulin resistance, hyperuricemia and adipokines. We investigated longitudinal change in plasma XOR activity, which was determined by using mass spectrometry and liquid chromatography to detect [13C2, 15N2]-uric acid using [13C2, 15N2]-xanthine as a substrate, in 511 subjects (male/female: 244/267) of the Tanno-Sobetsu Study in the years 2016 and 2017. Plasma XOR activity in a basal state was significantly higher in men than in women, but no significant sex difference was observed in annual change in plasma XOR activity. Annual change in plasma activity of XOR was positively correlated with changes in each parameter, including body weight (r = 0.203, p < 0.001), body mass index, diastolic blood pressure, aspartate transaminase (AST) (r = 0.772, p < 0.001), alanine transaminase (r = 0.647, p < 0.001), γ-glutamyl transpeptidase, total cholesterol, triglycerides, uric acid, fasting glucose and HbA1c. Multivariate regression analysis demonstrated that change in AST and that in body weight were independent predictors of change in plasma XOR activity after adjustment of age, sex and changes in each variable with a significant correlation without multicollinearity. In conclusion, annual change in plasma XOR activity is independently associated with changes in liver enzymes and body weight in a general population. Improvement of liver function and reduction of body weight would decrease plasma XOR activity and its related oxidative stress as a therapeutic strategy.

  • Yohei Koizumi, Masashi Hirooka, Atsushi Hiraoka, Hironori Ochi, Takaak ...
    原稿種別: Original
    2019 年 66 巻 9 号 p. 787-792
    発行日: 2019年
    公開日: 2019/09/28
    [早期公開] 公開日: 2019/05/30
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    Lenvatinib has anti-tumor activity against advanced hepatocellular carcinoma (HCC). Hypothyroidism is also a frequent complication in patients treated with lenvatinib. However, studies on lenvatinib-induced thyroid toxicity and destructive thyroiditis are limited. Therefore, this study aimed to clarify the frequency and timing of thyroid abnormalities in lenvatinib for unresectable HCC. This retrospective study enrolled 50 patients with advanced HCC treated with lenvatinib. Patients were classified to have euthyroid, subclinical hypothyroidism, overt hypothyroidism, and thyrotoxicosis. The timing of thyroid dysfunction was assessed, and risk factors for incident hypothyroidism or thyrotoxicosis were evaluated using multivariate models. Subclinical hypothyroidism, overt hypothyroidism, and thyrotoxicosis occurred in 7 (14.0%), 26 (52.0%), and 5 (10.0%) patients, respectively. In the 33 patients with hypothyroidism, 27 (84.4%) developed the condition within 2 weeks of starting lenvatinib treatment. Of the 5 patients with thyrotoxicosis, 3 developed the condition within 8 weeks of starting lenvatinib administration. One patient developed thyrotoxicosis in only 1 week of the initiation of treatment. No correlation between the presence of antibodies and the incidence and severity of thyroid dysfunction due to the autoimmune mechanism was observed. The progression-free survival was significantly better in the hypothyroidism group. Lenvatinib treatment for unresectable HCC not only causes hypothyroidism, but also thyrotoxicosis. Moreover, these thyroid conditions develop within the early period of treatment at a higher prevalence. Patients with thyroid dysfunction had better prognosis. Based on these results, in patients administered with lenvatinib, there is need for careful assessment for the possibility of thyroid dysfunction from the onset of treatment.

  • Aidibai Simayi, Patamu Mohemaiti
    原稿種別: Original
    2019 年 66 巻 9 号 p. 793-805
    発行日: 2019年
    公開日: 2019/09/28
    [早期公開] 公開日: 2019/06/07
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    電子付録

    The aim from this paper is to identify the main influencing factors of co-morbid depression among T2DM (Type 2 Diabetes Mellitus) patients and to provide reliable evidence for relative researches. A systematic review and meta-analysis of risk factors for co-morbid depression in T2DM was performed on all retrieved studies through an observational research of network database. Data were analyzed by Review Manager 5.3 from the extracted results, the heterogeneity index of the studies was determined using Chi-squared I2 tests and on the basis of heterogeneity, a fixed or random effect model was used to estimates the pooled effect of each influencing factor. Fourteen observational studies containing total of 82,239,298 cases that have been identified. Diabetic complications (OR = 2.91; 95%CI, 1.76–4.82, p < 0.0001), insulin use (OR = 1.71; 95%CI, 1.18–2.48, p = 0.005), education status (OR = 1.91; 95%CI, 1.30–2.81, p = 0.001) were confirmed as risk factors, while regular exercising (OR = 0.51; 95%CI, 0.27–0.96, p = 0.04), gender (OR = 0.56; 95%CI, 0.47–0.65, p < 0.0001), marital status (OR = 0.53; 95%CI, 0.34–0.83, p = 0.005), current social status (OR = 0.64; 95%CI, 0.47–0.88, p = 0.006) were confirmed as protective factors of co-morbid depression in the patients with T2DM. Subgroup analysis claimed age (≥60 years) was a risk factor and smoking was protective factor for co-morbid depression in the patients with T2DM. Being female, have diabetic complications, insulin use, education level less than secondary are risk factors. However, doing regular exercise, being married and on work are protective factors of co-morbid depression in patients with T2DM. As to the other influencing factors should be further studied.

  • Yoshihiro Takesue, Fan-Yan Wei, Hiroyuki Fukuda, Yuki Tanoue, Takahiro ...
    原稿種別: Original
    2019 年 66 巻 9 号 p. 807-816
    発行日: 2019年
    公開日: 2019/09/28
    [早期公開] 公開日: 2019/06/11
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    電子付録

    CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1) is a tRNA-modifying enzyme that catalyzes 2-methylthiolation (ms2) and has been implicated in the development of type 2 diabetes (T2D). CDKAL1-mediated ms2 is important for efficient protein translation and regulates insulin biosynthesis in pancreatic cells. Interestingly, an association between T2D and release of growth hormone (GH) has been reported in humans. However, it is unknown whether CDKAL1 is important for hormone production in the pituitary gland. The present study investigated the role of CDKAL1 in GH-producing pituitary adenomas (GHPAs). CDKAL1 activity was suppressed in GHPAs, as evidenced by a decrease in ms2, compared with non-functioning pituitary adenomas (NFPAs), which do not produce specific hormones. Downregulation of Cdkal1 using small interfering and short hairpin RNAs increased the biosynthesis and secretion of GH in rat GH3 cells. Depletion of Cdkal1 increased the cytosolic calcium level via downregulation of DnaJ heat shock protein family (Hsp40) member C10 (Dnajc10), which is an endoplasmic reticulum protein related to calcium homeostasis. This stimulated transcription of GH via upregulation of Pit-1. Moreover, CDKAL1 activity was highly sensitive to proteostatic stress and was upregulated by suppression of this stress. Taken together, these results suggest that dysregulation of CDKAL1 is involved in the pathogenesis of GHPAs, and that modulation of the proteostatic stress response might control CDKAL1 activity and facilitate treatment of GHPAs.

  • Satoshi Ugi, Katsutaro Morino, Tsuyoshi Yamaguchi, Hiroshi Yamamoto, S ...
    原稿種別: Original
    2019 年 66 巻 9 号 p. 817-826
    発行日: 2019年
    公開日: 2019/09/28
    [早期公開] 公開日: 2019/06/01
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    Laparoscopic sleeve gastrectomy has been proven effective in treating obesity-associated type 2 diabetes mellitus (T2DM). However, reports of the effect of laparoscopic sleeve gastrectomy on glucose metabolism in Japanese obese patients with T2DM are rare. The aim of this study was to evaluate the effects of laparoscopic sleeve gastrectomy on glucose tolerance in Japanese obese patients with T2DM, and to analyze factors influencing diabetes remission after surgery. This was a retrospective analysis of data for 24 consecutive patients with T2DM who underwent laparoscopic sleeve gastrectomy. We investigated weight loss and its impact on T2DM 1 year postoperatively. We also compared baseline characteristics and postoperative factors between patients who achieved diabetes remission and patients without remission. Mean body weight loss and percent total weight loss were 23.9 kg and 23.3%, respectively. Mean hemoglobin A1c levels dropped from 7.3 ± 0.3% to 6.1 ± 0.2%, and 18 patients (75%) achieved diabetes remission 1 year postoperatively. Patients achieving remission had significantly lower hemoglobin A1c levels (p = 0.026), higher fasting C-peptide values (p < 0.001), shorter diabetes duration (p < 0.001), lower insulin requirement (p = 0.002), and higher area under the insulin response curve (p < 0.001) and insulinogenic index (p < 0.001) during oral glucose tolerance testing. In conclusion, laparoscopic sleeve gastrectomy is an effective treatment for Japanese obese patients with T2DM. Preserving insulin secretion is the major determinant of diabetes remission.

  • Yang Tang, Xiaoyun Zhu, Hui Feng, Lili Zhu, Shouqiang Fu, Bingtan Kong ...
    原稿種別: Original
    2019 年 66 巻 9 号 p. 827-835
    発行日: 2019年
    公開日: 2019/09/28
    [早期公開] 公開日: 2019/06/18
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    The novel Graves disease (GD) model was established in BALB/c mice with recombinant adenovirus expressing the full-length human TSHR (Ad-TSHR289) by three times immunizations for nearly three months. Reducing the frequency of immunizations may shorten the modeling time to improve the efficiency of the study. In this study, female BALB/c mice were immunized one time with an adenovirus expressing the autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). At the 3, 6, 12, 17 weeks after the immunization, mice were sacrificed. The blood was collected and thyroids were removed. T3, T4, TRAB and thyroid weight/body weight (TW/BW) were tested. Compared with the Normal control (NC) group, the incidence of hyperthyroidism at 3, 6, 12 and 17 weeks after immunization were about 66.67%, 100%, 100%, and 100%. Meanwhile, the incidences of goiter were nearly 50%, 83.33%, 100% and 100% at the same stages. Therefore, modeling rates of GD were about 50%, 83.33%, 100%, 100% at 3, 6, 12 and 17 weeks after immunization. T3 in serum continues to increase from 3 weeks to 17 weeks after immunization. Serum TRAb reached to peak at 6 weeks and remained from 12 weeks after immunization, while T4 and TW/BW had kept steady from 6 weeks. There are positive correlations between T3, T4 and TRAb, TRAb and TW/BW, as well as T3, T4 and TW/BW. GD model can be constructed by primary immunization with Ad-TSHR289, which could be detected at 3 weeks and at least until the 17 weeks after primary immunization. It would improve the efficiency of GD research.

  • Goro Sasaki, Tomohiro Ishii, Naoaki Hori, Naoko Amano, Keiko Homma, Se ...
    原稿種別: Original
    2019 年 66 巻 9 号 p. 837-842
    発行日: 2019年
    公開日: 2019/09/28
    [早期公開] 公開日: 2019/06/08
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    Steroid 5α-reductase type 2 deficiency (5αRD2) is a congenital disorder of sex development caused by impairment of conversion from testosterone (T) to 5α-dihydrotestosterone (DHT). DHT deficiency leads to various degrees of undervirilized external genitalia including micropenis, primarily correlated with mutations of the SRD5A2 gene that encodes 5α-reductase type 2. Four Japanese boys with isolated micropenis were diagnosed as 5αRD2 by elevated ratios of serum T/DHT, and decreased ratios of urinary 5α/5β-reduced steroid metabolites. Genetic analyses for SRD5A2 identified that the four patients shared a hypomorphic mutation R227Q that has a residual activity related to the mild-form of 5αRD2. For prepubertal micropenis, DHT was transdermally applied to the four patients at the ages of 4–11 year, increasing a median of stretched penile lengths (SPLs) from 2.6 cm (–2.5 SD) to 4.4 cm (–0.2 SD). Nevertheless, the post-pubertal penile growth was apparently retarded, despite normal levels of T secreted from well-developed testes. The second course of DHT treatment underwent at ages of 12–18 year, but unable to normalize SPLs at a range of 6.0 to 7.0 cm (–3.4 to –2.4 SD). The prostate volumes of two patients were variable at 8.1 and 21 cm3, and a sperm cell count of one patient was normal as young adult. DHT treatment contributes to development of the penis and prostate, which are favorable for the potential fertility of 5αRD2 adults. Meanwhile, the retarded penile growth and a risk of prostate overgrowth may complicate the post-pubertal management with DHT for 5αRD2 males.

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