Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
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Showing 1-37 articles out of 37 articles from Advance online publication
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  • Yasuhiro Ito, Akira Miyauchi, Mitsuyoshi Hirokawa, Masatoshi Yamamoto, ...
    Type: Original
    Article ID: EJ18-0019
    [Advance publication] Released: April 20, 2018
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    The tumor-node-metastasis (TNM) staging system is most commonly adopted to evaluate the prognosis of patients with thyroid carcinoma. The 8th edition of the TNM staging system, an extensively revised version of the 7th edition, was recently released. We aimed to investigate whether and how well the 8th edition reflects the cause-specific survival (CSS) of patients with papillary thyroid carcinoma by analyzing the cases in 5,892 patients who underwent initial surgery at Kuma Hospital between 1987 and 2005. The median postoperative follow-up duration was 178 months (range: 6–357 months). One patient with T4b disease was excluded from the analysis. Overall, 116 (2.0%) patients died of thyroid carcinoma. The proportion of variance explained (PVE) for CSS in the 7th and 8th editions was 10.69 and 10.97, respectively. Using the 7th edition, CSS of patients with stage IVA and stage III disease was similar (p = 0.32). In contrast, using the 8th edition, CSS was poorer in stage II than in stage I (p < 0.001), in stage III than in stage II (p < 0.001), and in stage IVB than in stage III (p < 0.001). Similar results were observed for disease-free survival. Although we could not establish any objective evidence that the 8th edition is superior to the 7th edition, the 8th edition is simpler and more convenient, as it includes fewer stages and addresses the issue of the 7th edition where stage IVA and III patients had similar prognoses.

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  • Huanhuan Zang, Fusong Jiang, Xingbo Cheng, Hong Xu, Xingna Hu
    Type: Original
    Article ID: EJ18-0060
    [Advance publication] Released: April 17, 2018
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    Adropin has been identified as potent regulatory hormone implicated in insulin sensitivity and the maintenance of energy homeostasis. The aim of current study was to investigate serum adropin concentrations of type 2 diabetes mellitus (T2DM) patients in the fasting status, especially those overweight/obese and evaluate the relationships between adropin levels and metabolic parameters. A total of 116 T2DM patients and 60 controls with normal glucose tolerance (NGT) were recruited to the study. Adropin concentration was determined using commercial ELISA kits. Anthropometric characteristics were collected and biochemistry, glycosylated hemoglobin A1c (HbA1c) and fasting insulin (FIns) were detected by clinical laboratory. Insulin resistance was estimated by homeostasis model 2 assessment of insulin resistance (HOMA2-IR). Serum adropin levels in Chinese T2DM patients were decreased compared with the controls [3.8 (3.0–5.5) vs. 5.5 (3.7–7.9) ng/mL, p < 0.01]. Meanwhile, overweight/obese patients had more considerably reduced levels of adropin. Adropin level was negatively correlated with body mass index (BMI), high-sensitive C reactive protein (hs-CRP), triglycerides (TG), fasting plasma glucose (FPG), FIns, HOMA2-IR and HbA1c, while positively with high-density lipoprotein cholesterol (HDL-C) in study participants (p < 0.01). The correlations of adropin with glucolipid variables (TG, HDL-C, FPG, FIns, HOMA2-IR, HbA1c) still existed after adjusting the effect of BMI. Besides, HOMA2-IR and HbA1c were independent factors associated with serum adropin levels. Binary logistic regression analyses showed that adropin was significantly associated with T2DM after removing confounding factors (p < 0.01). Receiver operating characteristic (ROC) curve demonstrated adropin concentration of 5.8 ng/mL could be used as a possible optimal cut-off value to identify T2DM from non-T2DM with sensitivity of 81.9% and specificity of 46.7%. Serum adropin concentrations are decreased in Chinese T2DM patients, especially those overweight/obese. Adropin, associated with glucolipid homeostasis and insulin sensitivity, may implicate in the pathogenesis of T2DM.

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  • Boyu Chen, Zhiqiang Li, Jianhua Chen, Jue Ji, Jingyi Shen, Yufeng Xu, ...
    Type: Note
    Article ID: EJ17-0554
    [Advance publication] Released: April 14, 2018
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    Body mass index (BMI) is the most commonly used quantitative measure of adiposity. It is a kind of complex genetic diseases which are caused by multiple susceptibility genes. The first intron of fat mass and obesity-associated (FTO) has been widely discovered to be associated with BMI. Retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L) is located in the upstream region of FTO and has been proved to be linked with obesity through functional tests. We carried out a genetic association analysis to figure out the role of the FTO gene and the RPGRIP1L gene in BMI. A quantitative traits study with 6,102 Chinese female samples, adjusted for age, was performed during our project. Among the twelve SNPs, rs1421085, rs1558902, rs17817449, rs8050136, rs9939609, rs7202296, rs56137030, rs9930506 and rs12149832 in the FTO gene were significantly associated with BMI after Bonferroni correction. Meanwhile, rs9934800 in the RPGRIP1L gene showed significance with BMI before Bonferroni correction, but this association was eliminated after Bonferroni correction. Our results suggested that genetic variants in the FTO gene were strongly associated with BMI in Chinese women, which may serve as targets of pharmaceutical research and development concerning BMI. Meanwhile, we didn’t found the significant association between RPGRIP1L and BMI in Chinese women.

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  • Mariko Murakami, Yoshio Nagai, Ayumi Tenjin, Yasushi Tanaka
    Type: Original
    Article ID: EJ17-0380
    [Advance publication] Released: April 11, 2018
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    Pancreatic cancer is a highly lethal malignancy. CA19-9 is a well-known marker for diagnosis of pancreatic cancer, but the serum CA19-9 level is reported to be elevated in patients with poorly controlled diabetes. This study evaluated the sensitivity, specificity, and cut-off value of serum CA19-9 for detection of pancreatic cancer in patients with diabetes. A case-control study of 236 patients was performed. The case group was selected from diabetic patients with pancreatic cancer, while one control was selected for each case from among diabetic patients without pancreatic cancer during the same period. The case group (n = 118) and the control group (n = 118) were matched for age, sex, and pancreatic cancer risk factors. Receiver operating characteristic (ROC) curves were plotted to determine the serum CA19-9 level that predicted pancreatic cancer. Then the sensitivity and specificity of CA19-9 were calculated for the threshold value. There were no significant differences of age, sex, BMI, smoking, alcohol intake, and HbA1c between the case and control groups. According to ROC analysis, a serum CA19-9 level of 75 U/mL had the maximum sensitivity and specificity for separating diabetic patients with or without pancreatic cancer. Using this cut-off value, the sensitivity and specificity of CA19-9 for pancreatic cancer was 69.5% and 98.2%, respectively, while the area under the ROC curve was 0.875 [95%CI: 0.826–0.924]. We propose that a serum CA19-9 level of 75 U/mL should be used as the cut-off value when screening patients with diabetes for pancreatic cancer.

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  • Wenyu Jia, Dongmei Zheng, Liya Zhang, Changzhong Li, Xu Zhang, Fei Wan ...
    Type: Original
    Article ID: EJ17-0542
    [Advance publication] Released: April 10, 2018
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    Early diagnosis and optimal management for steroid 5α-reductase type 2 deficiency (5α-RD2) patients are major challenges for clinicians and mutation analysis for the 5α-reductase type 2 (SRD5A2) gene is the golden standard for the diagnosis of the disease. In silico analysis of this enzyme has not been reported due to the lack of appropriate model. Moreover, the histological and pathological changes of the gonads are largely unknown. In the present study, a 5α-RD2 patient born with abnormal external genitalia was studied and mutation analysis for SRD5A2 gene was conducted. Moreover, we constructed the homology modeling of 5α-reductase using SWISS-MODEL, followed by the molecular docking study. Furthermore, immunohistochemical staining of Ki67 for the testes tissue was conducted to investigate the potential pathological characteristics. The patient had male (46, XY) chromosomes but presented female characteristics, and the mutation analysis identified a heterozygotes mutation (p.Q6X, p.R246Q) in SRD5A2 gene. In silico analysis elucidated the potential effect of the mutation on enzyme activity. Immunohistochemical staining for the excised testes showed that 30%–50% of the germ cells were Ki67 positive, which indicated the early neoplastic potential. In conclusion, we analyzed the genotype-phenotype correlations of 5α-RD2 caused by a heterozygotes mutation (p.Q6X, p.R246Q). Importantly, we conducted the homology modeling and molecular docking for the first time, which provided a homology model for further investigations. Immunohistochemical results suggested gonadectomy or testis descent should be performed early for 5α-RD2 patient, as delayed treatment would have maintained the testes in a tumorigenic condition.

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  • Takuro Okamura, Yoshitaka Hashimoto, Masahide Hamaguchi, Akihiro Ohbor ...
    Type: Original
    Article ID: EJ18-0023
    [Advance publication] Released: April 10, 2018
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    Metabolically healthy obese (MHO) individual is known to be defended from the metabolic complications of obesity. Leukoaraiosis, which is commonly detected on brain magnetic resonance imaging (MRI), is now recognized as a risk of stroke, dementia and death. However, the association between MHO and the prevalence of leukoaraiosis is unclear. In this cross-sectional study of 796 participants who received a medical examination program, we investigated the association between MHO and the prevalence of leukoaraiosis. We used common clinical markers for definition of metabolic healthy status: blood pressure, fasting plasma glucose, triglycerides and high-density lipoprotein cholesterol concentrations. Obesity was defined by body mass index ≥25.0 kg/m2. We diagnosed leukoaraiosis by fluid-attenuated inversion recovery without hypointensity on T1-weighted images or the presence of a hyperintensity on T2-weighted images. The crude prevalence proportion of leukoaraiosis was 44.5% (case/n = 171/384) in metabolically healthy nonobese (MHNO) individual, 46.3% (44/95) in MHO individual, 62.3% (114/183) in metabolically unhealthy nonobese (MUNO) individual or 56.6% (77/136) in MUO individual. The odds ratios of prevalence of leukoaraiosis were 1.19 (95% CI 0.74–1.90, p = 0.471) for MHO, 1.79 (1.22–2.62, p = 0.003) for MUNO and 1.56 (1.03–2.37, p = 0.037) for MUO individuals after adjusting for sex, age, smoking statues, habit of exercise and alcohol, compared with MHNO individual. We revealed that MHO individuals were not related with the higher risk of leukoaraiosis, whereas MUNO and MUO individuals were.

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  • Hiromasa Goto, Tomoya Mita, Yoshio Fujitani, Shimpei Fujimoto, Kiyohit ...
    Type: Original
    Article ID: EJ18-0088
    [Advance publication] Released: April 10, 2018
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    Treatment-related quality of life (QOL) is an important aspect of diabetes management. However, no studies have compared the influence of dipeptidyl peptidase-4 inhibitors versus alpha-glucosidase inhibitors on treatment-related QOL. This prespecified sub-analysis of the Linagliptin Study of Effects on Postprandial blood glucose (L-STEP) compared the effects of linagliptin (5 mg once daily) and voglibose (0.2 mg/meal thrice daily) on treatment-related QOL in Japanese patients with type 2 diabetes (T2DM) inadequately controlled with diet and exercise therapy. Among 366 subjects in the original study, 182 in the linagliptin group and 173 in the voglibose group were included in this analysis. The outcome of this study was change in QOL as assessed by the Diabetes Therapy-Related Quality of Life 17 (DTR-QOL17) questionnaire from baseline to week 12. Compared with baseline data, total DTR-QOL17 scores were significantly higher after 12 weeks of linagliptin and voglibose treatment. The change in the total DTR-QOL17 score and the score of one domain, burden on social activities and daily activities, was significantly greater in the linagliptin group than in the voglibose group. In addition, only linagliptin treatment was identified as a factor associated with an increased total DTR-QOL17 score. Linagliptin is superior to voglibose in terms of improving treatment-related QOL in Japanese patients with T2DM.

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  • Takuya Watanabe, Atsushi Ozawa, Sumiyasu Ishii, Takuya Tomaru, Nobuyuk ...
    Type: Original
    Article ID: EJ16-0387
    [Advance publication] Released: April 04, 2018
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    Patients with adrenal insufficiency require appropriate glucocorticoid replacement therapy; however, reliable biological parameters for optimizing glucocorticoid supplementation are limited. The physician has to rely primarily on clinical judgment, carefully taking into account signs and symptoms potentially suggestive of over- or under-replacement. We have found that some patients who are viewed as receiving sufficient doses of glucocorticoids occasionally exhibit morning headache or morning discomfort, which may be caused by unrecognized nocturnal hypoglycemia. Our aim in this study was to evaluate the usefulness of continuous glucose monitoring (CGM) for detecting unrecognized hypoglycemia and optimizing glucocorticoid replacement therapy in adult patients with central hypoadrenalism. Six patients with central hypoadrenalism of various etiologies were included in this study. All patients exhibited occasional morning headache or discomfort. We performed CGM to measure plasma glucose levels in all patients, and CGM identified unrecognized hypoglycemia episodes at midnight and early in the morning in five patients (83%). The CGM findings were used to fine-tune the dosing and regimens of glucocorticoid replacement and to re-evaluate glucose levels to avoid further unrecognized hypoglycemic events. This optimization of hydrocortisone supplementation prevented additional nocturnal hypoglycemia incidences in all cases. The addition of L-thyroxine with hydrocortisone continued to provide favorable glycemic control. Occasional symptoms also improved after maintenance in all patients. These findings demonstrated that CGM may represent a powerful tool for identifying unrecognized hypoglycemia and for optimizing supplementary hormones in patients with central hypoadrenalism, thereby improving their quality of life.

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  • Yasuhiro Ito, Akira Miyauchi, Mitsuyoshi Hirokawa, Masatoshi Yamamoto, ...
    Type: Original
    Article ID: EJ17-0524
    [Advance publication] Released: April 04, 2018
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    Follicular thyroid carcinoma (FTC), a form of differentiated thyroid carcinoma, is the second most common malignancy arising from thyroid follicular cells. Recently, the tumor-node-metastasis (TNM) classification for differentiated thyroid carcinoma was revised from the 7th to the 8th edition. The diagnostic criteria for poorly differentiated carcinoma (PDC) were also updated in the latest World Health Organization (WHO) classification. In this study, we investigated whether these changes are appropriate for accurately predicting prognosis. Three hundred and twenty-nine patients diagnosed with postoperative pathologically confirmed FTC, who underwent initial surgery at our hospital between 1984 and 2004, were enrolled. For this study, patients were re-evaluated and diagnosed with FTC (N = 285) or PDC (N = 44) without typical nuclear findings of papillary thyroid carcinoma. For FTC, the 8th TNM classification was a more accurate predictor of prognosis than the 7th TNM classification. In the 8th TNM classification, cause-specific survival became significantly poorer from Stage I to IVB. The cause-specific survival of PDC based on the latest WHO classification was worse than, but did not significantly differ from, that of PDC based only on the former WHO classification. For PDC, neither of the TNM classifications could accurately predict prognosis. Taken together, we conclude that (1) the 8th TNM classification more accurately reflects the prognosis of FTC than the 7th TNM classification; (2) PDC based on the former WHO classification should be retained, at least in Japan; and (3) the TNM classification may not be suitable for predicting the prognosis of PDC.

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  • Taku Tsuburai, Tomomi Nakamura, Hiromi Yoshikata, Etsuko Miyagi, Hidey ...
    Type: Original
    Article ID: EJ17-0498
    [Advance publication] Released: March 31, 2018
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    Most patients with Turner syndrome (TS) exhibit amenorrhea due to premature ovarian failure. Therefore, estrogen replacement therapy (ERT) is required; however, even after undergoing ERT, it is not rare for bone mass acquisition to be insufficient. This study was conducted in two stages, involving a cross-sectional and a prospective interventional study. We recruited 52 TS patients undergoing ERT due to amenorrhea (categorized into low (LB group; n = 23), and normal (NB group; n = 29) bone mass groups) and 7 TS patients who maintained ovarian function (spontaneous menstrual cycle group (MC group)) as controls. We compared bone associated markers between the three groups (LB, NB, and MC). Furthermore, the LB group had concomitant treatment with eldecalcitol (ELD) and ERT for 12 months. The bone mineral density (BMD) of the lumber spine (L2-4) and the bone metabolism markers were then compared before and after the treatment. The bone metabolism markers were significantly higher in the LB group than the NB and MC groups. Furthermore, with the concomitant use of ELD and ERT in the LB group, BMD increased significantly (pre-treatment 0.710 ± 0.056 g/cm2 vs. 0.736 ± 0.062 g/cm2 after 12 months; p < 0.001). TS patients with insufficient bone mass acquisition even after ERT were characterized by a higher turnover in bone metabolism. Therefore, the concomitant use of ELD was considered an effective adjuvant therapy for increasing bone mass.

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  • Masataka Suwa, Takayuki Imoto, Akira Kida, Takashi Yokochi, Mitsunori ...
    Type: Original
    Article ID: EJ17-0517
    [Advance publication] Released: March 28, 2018
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    Previous studies suggested that reduced muscular strength was one of the potential predictor of prevalence of diabetes mellitus. The purpose of this study was to investigate the association between toe flexor strength (TFS) and handgrip strength (HGS) and the prevalence of diabetes mellitus. Cross-sectional analysis was conducted using data from 1,390 Japanese males (35–59 years). TFS and HGS were measured and medical examinations undertaken. The prevalence of diabetes mellitus was defined as fasting blood glucose ≥126 mg/dL, glycated hemoglobin ≥6.5% (48 mmol/mol), and/or current use of anti-diabetes mellitus drugs. A total of 114 participants had diabetes mellitus. TFS in participants with diabetes mellitus was significantly lower than that in persons not suffering from diabetes mellitus but HGS was not. Odds ratio (OR) and 95% confidence interval (CI) per 1-standard deviation–increase in muscular strength measurements for the prevalence of diabetes mellitus were obtained using a multiple logistic regression model. Prevalence of diabetes mellitus was inversely related to TFS (OR 0.769, 95% CI 0.614–0.963), TFS/body mass (BM) (0.696, 0.545–0.889) and TFS/body mass index (BMI) (0.690, 0.539–0.882) after adjustment of covariates. Such associations were not observed in HGS (OR 0.976, 95% CI 0.773–1.232), HGS/BM (0.868, 0.666–1.133) or HGS/BMI (0.826, 0.642–1.062). These results suggested that poor TFS was associated with an increased prevalence of diabetes mellitus independent of visceral fat accumulation, but HGS was not, in middle-aged males. TFS may be a better marker for the prevalence of diabetes mellitus than HGS.

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  • Toshihiko Yanase, Yutaka Oki, Takuyuki Katabami, Michio Otsuki, Kazuno ...
    Type: Opinion
    Article ID: EJ17-0456
    [Advance publication] Released: March 23, 2018
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    New diagnostic criteria and the treatment policy for adrenal subclinical Cushing’s syndrome (SCS) are proposed on behalf of the Japan Endocrine Society. The Japanese version has been published, and the essential contents are presented in this English-language version. The current diagnostic criteria for SCS have elicited two main problems: (i) the relatively low reliability of a low range of serum cortisol essential for the diagnosis by an overnight 1-mg dexamethasone suppression test (DST); (ii) different cutoff values for serum cortisol after a 1-mg DST compared with those of other countries. Thus, new criteria are needed. In the new criteria, three hierarchical cortisol cutoff values, 5.0, 3.0 and 1.8 μg/dL, after a 1-mg DST are presented. Serum cortisol ≥5 μg/dL after a 1-mg DST alone is considered sufficient to judge autonomous cortisol secretion for the diagnosis of SCS, and the current criterion based on serum cortisol ≥3 μg/dL after a 1-mg DST can continue to be used. Clinical evidence suggests that serum cortisol ≥1.8–2.9 μg/dL after a 1-mg DST is not always normal, so cases who meet the cutoff value as well as a basal adrenocorticotropic hormone (ACTH) level <10 pg/mL (or poor ACTH response to corticotropin-releasing hormone (CRH)) and nocturnal serum cortisol ≥5 μg/dL are proposed to have SCS. We suggest surgery if cases show serum cortisol ≥5 μg/dL after a 1-mg DST (or are disheartened by treatment-resistant problems) or suspicious cases of adrenal cancer according to tumor imaging.

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  • Shanshan Wu, Kai Dong, Jiajia Wang, Yaxin Bi
    Type: Original
    Article ID: EJ17-0539
    [Advance publication] Released: March 23, 2018
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    Type 2 diabetes is a serious threat to human health all over the world. It is particularly important to look for the pathogenesis of type 2 diabetes. Researchers have found that obesity was associated with a broad chronic inflammatory response and type 2 diabetes. And tumor necrosis factor alpha (TNF-α) is one of the most important cytokines related with obesity. To explore the functional role of TNF-α in the regulation of glucose homeostasis, TNF-α receptor 1 and TNF-α receptor 2 double knockout (TNFR1/R2 DKO) mouse model were used in our study. After high fat diet (HFD) feeding, we detected that the insulin resistance was dramatically improved and circulated TNF-α was upregulated in TNFR1/R2 DKO mice. Surprisingly, glucose homeostasis was worsened, when we down regulate the levels of plasma TNF-α in TNFR1/R2 DKO mice by administering Adeno associated virus-shRNA-TNF-α (AAV-shTNF-α). Subsequently, in ob/ob mice, we confirmed that the glucose homeostasis could be improved when we up regulate the levels of plasma TNF-α by administering Adeno associated virus-TNF-α (AAV-TNF-α). Our findings suggested that TNFR1 and TNFR2 may not be the only receptors for TNF-α and TNF-α probably plays a positive role in reducing insulin resistance via a TNFRs-independent way in diabetic mice.

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  • Junko Hirooka-Nakama, Kimiko Enomoto, Kentaro Sakamaki, Kentaro Kurasa ...
    Type: Original
    Article ID: EJ18-0027
    [Advance publication] Released: March 20, 2018
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    We aimed to determine the optimal gestational weight gain (GWG) in Japanese women with a Body Mass Index (BMI) ≥25 kg/m2. The present retrospective study investigated singleton pregnancies in 6,781 Japanese women registered in the Japan Society of Obstetrics and Gynecology system in 2013. We divided overweight and obese women into four GWG categories based on the Institute of Medicine (IOM) recommended: weight loss, small weight gain, within IOM criteria, and above IOM criteria. The adjusted odds ratios and predicted probabilities of maternal and neonatal outcomes of interest with weight change were calculated. In overweight women, GWG was associated with neonatal birth weight. In the loss and small gain subgroups, there was a significant increase in small for gestational age (SGA) and low birth weight neonates (LBW). Predicted probabilities showed the lowest risk was observed in a weight gain of 0 kg; the risk sharply increased at a gain of 11.5 kg. In obese women, weight gain increased the prevalence of large for gestational age (LGA) neonates; however; SGA was not associated with GWG. Predicted probabilities showed an increase in the risk with weight gain. The observed optimal GWG was 0 to 11.5 kg in overweight, and weight loss in obese, pregnant Japanese women.

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  • Ayana Suzuki, Mitsuyoshi Hirokawa, Aki Ito, Nami Takada, Miyoko Higuch ...
    Type: Original
    Article ID: EJ17-0402
    [Advance publication] Released: March 14, 2018
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    The pathogenesis of thyroid lymphoepithelial cysts is controversial, and two hypotheses have been proposed, namely derivation from branchial-derived remnants or from squamous metaplasia of the follicular cells. The aim of this study was to clarify the pathogenesis of thyroid lymphoepithelial cysts. We performed pathological and immunohistochemical examination of 21 thyroid lymphoepithelial cysts, 13 non-neoplastic squamous metaplasia samples without thyroid carcinoma, 13 solid cell nests, and 14 lateral cervical cysts. On ultrasound, half of thyroid lymphoepithelial cysts were interpreted as calcified nodules regardless of no calcification. Thyroid lymphoepithelial cysts and squamous metaplasia tended to be located in the central and lower portions of the thyroid, while solid cell nests were located in the upper and central portions (p < 0.05). In 95.2% of patients with thyroid lymphoepithelial cysts and all patients with squamous metaplasia, lesions were histologically associated with chronic thyroiditis forming lymph follicles. Hashimoto’s disease was serologically confirmed in 18 patients with lymphoepithelial cysts (85.7%) and 10 patients with squamous metaplasia (76.9%). Immunohistochemically, lymphoepithelial cysts showed nuclear positivity for PAX8, thyroid transcription factor 1, and p63. One lateral cervical cyst (7.1%) showed positive staining for PAX8, while solid cell nests were PAX8-negative. In three (14.3%) cases of thyroid lymphoepithelial cysts, squamous cells located on the superficial layer were focally and weakly positive for CEA. We concluded that thyroid lymphoepithelial cysts originate from follicular cells and are unrelated to solid cell nests and lateral cervical cysts arising from branchial-derived remnants.

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  • Itsuko Miyazawa, Aya Kadota, Katsuyuki Miura, Motozumi Okamoto, Takash ...
    Type: Original
    Article ID: EJ17-0415
    [Advance publication] Released: March 10, 2018
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    The prevalence of obesity is increasing globally in patients with diabetes. This study aimed to examine 12-year trends of increasing obesity in Japanese patients with diabetes, and their clinical features. The study used results of the Shiga Diabetes Clinical Survey, which recorded medical performance in diabetic patients in 2000, 2006 and 2012. Data were analyzed from 14,205, 14,407 and 21,449 adult patients in these three years, respectively. Overweight and obesity prevalence and the clinical features of diabetes patients were examined, stratified by body mass index (BMI) and age. The prevalence of overweight (BMI 25–30 kg/m2) and obesity (BMI ≥30 kg/m2) were 27.0% and 5.1% in 2000, 28.9% and 7.3% in 2006 and 30.9% and 10.0% in 2012. Glycemic control, blood pressure and serum lipid profile improved over 12 years in all BMI categories. However, glycemic and triglyceride control were insufficient in obese patients aged <65 years (hemoglobin A1c 7.5 ± 1.4%, triglyceride 197.7 ± 178.4 mg/dL in 2012). The percentage of patients who used antihypertensive and lipid-lowering drugs increased and patients with higher BMI had increased frequency of using these drugs, both in young and old age groups. Higher BMI was significantly and positively associated with albuminuria. In summary, overweight and obesity have increased in Japanese diabetic patients, particularly for younger generations. Findings suggest that obesity may lead to poorer glycemic control, blood pressure and lipid profiles. Overweight and obesity are important modifiable risk factors for diabetes, suggesting that more active weight-control interventions are warranted.

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  • Michiko Wada, Makoto Kita, Kaoru Kawasaki, Toru Kusakabe, Tetsuya Taga ...
    Type: Note
    Article ID: EJ17-0426
    [Advance publication] Released: March 10, 2018
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    Maternal Graves’ disease (GD) during pregnancy may influence thyroid function in fetuses. Neonates born to mothers with high serum TSH receptor antibody (TRAb) levels have been reported to develop ‘neonatal GD’. Therefore, evaluations of serum thyroid hormone and TRAb levels in neonates upon birth are crucial for a prompt diagnosis. At delivery, we measured TRAb with third-generation TRAb test using an M22 human monoclonal antibody in neonates by collecting umbilical cord blood in a blood collection tube with lithium-heparin, which provides a whole blood/plasma sample. In recent years, we have encountered positive TRAb levels (more than 2.0 IU/L) in nineteen neonates born to mothers with GD whose thyroid hormone levels were almost within the reference range and serum TRAb levels were less than 10 IU/L. All the neonates with positive TRAb levels did not exhibit thyrotoxicosis. However, when we measured TRAb levels with serum sample in six out of the nineteen cases, their serum TRAb levels were all negative, suggesting a discrepancy of TRAb levels between in lithium-heparin plasma from umbilical cord blood and serum. Moreover, this discrepancy was observed in neonates born to euthyroid mothers, adult active GD patients and healthy volunteers. Since lithium-heparin plasma from umbilical cord blood is widely used in laboratory tests at delivery, we may encounter ‘false-positive’ TRAb, which may, in turn, lead to a misdiagnosis of neonatal GD. This is a pitfall of third-generation TRAb measurements in neonates, particularly at delivery, and needs to be considered by obstetricians and neonatologists.

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  • Yinhua Ni, Tao Wu, Luna Yang, Yang Xu, Tsuguhito Ota, Zhengwei Fu
    Type: Original
    Article ID: EJ17-0500
    [Advance publication] Released: March 10, 2018
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    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.

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  • Takuo Kubota, Hirofumi Nakayama, Taichi Kitaoka, Yosikazu Nakamura, Se ...
    Type: Original
    Article ID: EJ18-0008
    [Advance publication] Released: March 10, 2018
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    There is concern that vitamin D deficiency is prevalent among children in Japan as well as worldwide. We conducted a nationwide epidemiologic survey of symptomatic vitamin D deficiency to observe its incidence rate among Japanese children. A questionnaire inquiring the number of new patients with vitamin D deficiency rickets and/or hypocalcemia for 3 years was sent to 855 randomly selected hospitals with a pediatrics department in Japan. In this survey, we found that 250 children were diagnosed with symptomatic vitamin D deficiency. The estimated number of patients with symptomatic vitamin D deficiency per year was 183 (95% confidence interval (CI): 145–222). The overall annual incidence rate among children under 15 years of age was 1.1 per 100,000 population (95% CI: 0.9–1.4). The second survey has provided detailed information on 89 patients with symptomatic vitamin D deficiency under 5 years of age in hospitals in the current research group. The nationwide and second surveys estimated the overall annual incidence rate of symptomatic vitamin D deficiency in children under 5 years of age to be 3.5 (2.7–4.2) per 100,000 population. The second survey revealed 83% had bowed legs, 88% had exclusive breastfeeding, 49% had a restricted and/or unbalanced diet and 31% had insufficient sun exposure among the 89 patients. This is the first nationwide survey on definitive clinical vitamin D deficiency in children in Japan. Elucidating the frequency and characteristics of symptomatic vitamin D deficiency among children is useful to develop preventative public health strategies.

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  • Kunihiko Hanew, Toshiaki Tanaka, Reiko Horikawa, Tomonobu Hasegawa, Su ...
    Type: Original
    Article ID: EJ17-0401
    [Advance publication] Released: March 07, 2018
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    The reported prevalence of complications in Turner Syndrome (TS) was highly variable because of the rarity and the limited numbers analyzed. Again, possible presence of other complications that are not described as specific for TS, is also speculated. To resolve these issues, a questionnaire survey was conducted in hGH treated 492 patients with adult TS (17–42 years). The possible association with these complications and karyotypes were also analyzed. The complications and their prevalence were as follows: chronic thyroiditis (25.2%), inflammatory bowel disease (1.8%), congenital cardiovascular anomaly (11.8%), urinary tract malformation (11.8%), low bone mineral density (BMD) (42.9%), scoliosis (8.4%), hearing loss (6.2%), epilepsy (2.8%) and schizophrenia (0.9%). The majority of prevalence of these diseases in TS was higher than in the general population. In distribution, the most frequent karyotype was 45,X monosomy (28.9%), followed by 45,X/46,X,Xi (16.9%), 46,X,Xi (9.1%), and 45,X/46,XX (6.3%), while other mosaic 45,X was noted in 29.9%. Regarding the karyotype, cardiovascular anomaly was more frequent in the 45,X group and less in the 46,X,Xi group. Urinary tract malformation and epilepsy were frequently associated with the chromosome 45,X. The prevalence of low BMD was noticed more in the chromosome 46,X,Xi and 45,X/46,X,Xi, and less in other mosaic 45,X. In conclusion, the more exact prevalence of diverse complications was clarified and it exceeded the prevalence of the majority of complications in general population. As novel findings, it was observed that the prevalence of epilepsy was significantly high, and epilepsy and low BMD were frequently associated with the specific karyotypes.

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  • Ayumi Imbe, Keiji Tanimoto, Yuiko Inaba, Satoshi Sakai, Kanako Shishik ...
    Type: Original
    Article ID: EJ17-0431
    [Advance publication] Released: March 06, 2018
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    Diabetic patients often suffer from muscle cramps. This study aimed to compare the quality of life (QOL) of diabetic patients with and without muscle cramps and to investigate the effect of L-carnitine supplementation in diabetic patients with muscle cramps. A total of 91 patients with diabetes were enrolled in this study: 69 patients with muscle cramps and 22 patients without muscle cramps. Muscle cramps and QOL were evaluated using the muscle cramp questionnaire and the Short Form 36 health survey version 2 (SF-36), respectively. Clinical characteristics were compared between diabetic patients with and without muscle cramps. In the prospective portion of the study, 25 diabetic patients with muscle cramps received L-carnitine supplementation (600 mg/day orally) for 4 months. The questionnaires were administered before and after supplementation. The SF-36 scores in diabetic patients with muscle cramps were lower than those in patients without muscle cramps on the subscales of physical function, role physical, bodily pain, vitality, general health, and social function. In the 25 patients with muscle cramps who received L-carnitine supplementation, the monthly frequency of muscle cramps and Wong-Baker FACES® Pain Rating Scale scores were significantly decreased. Scores on the following SF-36 subscales improved after L-carnitine supplementation: body pain, vitality, social function, and role emotional. This study demonstrated that muscle cramps decrease the QOL in patients with diabetes, and L-carnitine supplementation may improve the QOL by reducing the frequency and severity of muscle cramps in these patients.

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  • Yao Xu, Weilin Shi, Ruhui Song, Wenlin Long, Hui Guo, Shiliang Yuan, T ...
    Type: Original
    Article ID: EJ17-0496
    [Advance publication] Released: February 27, 2018
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    Copy number variation (CNV) has emerged as another important genetic marker in addition to SNP for understanding etiology of complex disease. Kv channel interacting protein 1 (KCNIP1) is a Ca2+-dependent transcriptional modulator that contributes to the regulation of insulin secretion. Previous genome-wide CNV assay identified the KCNIP1 gene encompassing a CNV region, however, its further effect and risk rate on type 2 diabetes (T2D) have rarely been addressed, especially in Chinese population. The current study aims to detect and excavate genetic distribution profile of KCNIP1 CNV in Chinese T2D and control populations, and further to investigate the associations with clinical characteristics. Divergent patterns of the KCNIP1 CNV were identified (p < 0.01), in which the copy number gain was predominant in T2D, while the copy number normal accounted for the most in control group. Consistently, the individuals with copy number gain showed significant risk on T2D (OR = 4.550, p < 0.01). The KCNIP1 copy numbers presented significantly positive correlations with fasting plasma glucose and glycated hemoglobin in T2D. For OGTT test, the T2D patients with copy number gain had remarkably elevated glucose contents (60, 120, 180-min, p < 0.05 or p < 0.01) and diminished insulin levels (60, 120-min, p < 0.05) than those with copy number loss and normal, which suggested that the KCNIP1 CNV was correlated with the glucose and insulin action. This is the first CNV association study of the KCNIP1 gene in Chinese population, and these data indicated that KCNIP1 might function as a T2D-susceptibility gene whose dysregulation alters insulin production.

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  • Xiao-song Yuan, Ming Zhang, Hui-yan Wang, Jian Jiang, Bin Yu
    Type: Note
    Article ID: EJ17-0508
    [Advance publication] Released: February 27, 2018
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    By biochemical and epidemiological similarity with type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM) has some overlap between prediction markers and risk factors of T2DM. The present study aimed to establish that secreted frizzled-related protein 4 (SFRP4) and ficolin-3 levels, which have been linked to insulin resistance and the development of T2DM, are elevated in GDM women. A longitudinal prospective cohort study of 86 GDM and 273 normal glucose tolerant (NGT) pregnant women was performed. The clinical parameters, lipid profiles, and serum SFRP4 and ficolin-3 levels were tested during the early and late second-trimester and third-trimester of pregnancy. Both SFRP4 and ficolin-3 levels were significantly higher in GDM women as compared to the NGT participants at three test points (p < 0.01). Spearman’s correlation analysis showed that serum SFRP4 levels were significantly positively correlated with ficolin-3 during the early and late second-trimester and third-trimester of pregnancy. The elevated SFRP4 and ficolin-3 concentrations at 16–18 weeks gestation significantly associated with GDM were conformed using binary logistic regression analysis after controlling for other variables [odds ratios (OR) with 95% confidence intervals (CI) for SFRP4: 2.84 (1.78–4.53), p < 0.01; for ficolin-3: 2.45 (1.55–3.88), p < 0.01]. In Conclusions, increased SFRP4 and ficolin-3 levels are significantly associated with GDM development and might be important risk factors for this pregnancy complication.

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  • Toshiya Matsuzaki, Altankhuu Tungalagsuvd, Munkhsaikhan Munkhzaya, Tak ...
    Type: Original
    Article ID: EJ17-0136
    [Advance publication] Released: February 23, 2018
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    Kisspeptin/neurokinin B (NKB)/dynorphin (Dyn) (KNDy) neuron in hypothalamic arcuate nucleus plays a key role in GnRH/LH pulsatile secretion. We aimed to determine whether stimulation of NKB/neurokinin 3 receptor (NK3R) signaling and inhibition of Dyn/kappa-opioid receptor (KOR) signaling recover LH secretion that is suppressed by acute fasting in male rats. Furthermore, we determined dose dependent effect of NKB/NK3R signaling on serum LH level under acute fasting condition in male mice. Mature male rats were injected saline (0.1 mL) and senktide (20 μg/kg), a NK3R agonist, or nor-BNI (800 μg/kg), a KOR antagonist intraperitoneally (ip) after 72 h fasting. And mature male mice were injected multiple doses of senktide, ip after 48 h fasting. Blood and brain sample were collected 90 min after injections for LH measurement and hypothalamic mRNA expressions. All three studies showed significantly lower LH concentration in fasted groups than non-fasted groups. Senktide did not recover LH suppressed by acute fasting in male rats, whereas nor-BNI injected male rats showed significantly higher LH than 72 h fasted male rats (p < 0.05). Mice study showed significantly higher LH concentration in higher doses senktide groups than 48 h fasted group and one of lower doses senktide group. These results suggest that stimulation of NKB/NK3R signaling and attenuation of Dyn/KOR signaling could recover suppressed LH secretion under acute fasting condition in male rodents.

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  • Mengyao Bai, Yun Liu, Feiye Zhou, Yuqing Zhang, Qin Zhu, Linlin Zhang, ...
    Type: Original
    Article ID: EJ17-0543
    [Advance publication] Released: February 22, 2018
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    Glucose promotes insulin secretion primarily via its metabolism and the production of metabolic coupling factors in beta-cells. The activation of AMP-activated protein kinase (AMPK), an energy sensor, results in a decrease in insulin secretion from beta-cells, but its mechanism remains largely unknown. Berberine, an oral anti-diabetic drug, has been shown to activate AMPK in multiple peripheral tissues. Here, we examined the effects of berberine and AMPK activation on insulin secretion and glucose oxidation in rat islets. Our results showed that berberine inhibited glucose-stimulated insulin secretion from rat islets with AMPK activation. When glucose concentration was elevated to 25 mmol/L, the inhibitory action of berberine on insulin secretion disappeared. Furthermore, berberine significantly decreased oxygen consumption rate (OCR) and ATP production induced by high glucose in rat islets. Although adenovirus-mediated overexpression of constituent-activated AMPK markedly decreased GSIS and OCR in rat islets, the inhibition of AMPK by compound C did not reverse berberine-suppressed OCR. In addition, berberine attenuated glucose-stimulated expression of fatty acid synthase. These results indicate that berberine-mediated deceleration of glucose oxidation is tightly link to the decreased insulin secretion in islets independent of AMPK activation and inhibition of fatty acid synthesis may also contribute to the effect of berberine on insulin secretion.

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  • Kei Sawada, Shigehiro Karashima, Mitsuhiro Kometani, Rie Oka, Yoshimic ...
    Type: Original
    Article ID: EJ17-0440
    [Advance publication] Released: February 20, 2018
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    Obstructive sleep apnea syndrome (OSAS) is often associated with metabolic disorders such as obesity and type 2 diabetes and may contribute to cardiovascular events. A novel class of antidiabetic drugs, the sodium glucose cotransporter 2 inhibitors (SGLT2i) reduce body weight (BW), although there is limited data on their impact on OSAS. We therefore evaluated the effect of SGLT2i on OSAS in patients with type 2 diabetes. The presented study was a retrospective design in 18 patients with type 2 diabetes with OSAS (4 males, age range 39–81 yr) administrated a SGLT2i. HbA1c, BW, body mass index (BMI), blood pressure (BP) and apnea hypopnea index (AHI) were evaluated before and after SGLT2i administration. The relationships between the reduction in AHI and the other variables were examined using Pearson correlation analysis. We have got result that SGLT2i reduced AHI from 31.9 ± 18.0 to 18.8 ± 11.5 events per hr (p = 0.003). HbA1c, BW and BMI decreased significantly, whereas BP did not. The Pearson correlation analysis showed a significant relationship between the reduction in AHI and pre-administration of AHI. In conclusion, SGLT2i reduced not only HbA1c, BW and BMI but also AHI significantly and therefore has potential as an effective treatment of OSAS.

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  • Kanako Kojima-Ishii, Naoko Toda, Kazuhiro Okubo, Vlad Tocan, Noriko Oh ...
    Type: Original
    Article ID: EJ17-0485
    [Advance publication] Released: February 20, 2018
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    Children born small for gestational age (SGA) are at a higher risk for metabolic disorders later in life. In this study, we aimed to characterize young SGA children without catch-up growth and evaluate the effects of GH treatment on endocrinological, metabolic, and immunological parameters. Study design is a one-year single hospital-based study included prospective observation of SGA patients during 12 months of GH treatment. Clinical and laboratory profiles of SGA children at baseline were compared with controls born appropriate size for age. Twenty-six SGA children (median age, 3.4 years) and 26 control children (median age, 3.8 years) were enrolled. Anthropometric, hematologic, biochemical, immunological, and endocrinological parameters were assessed at baseline and 1, 3, 6, 9, and 12 months after the start of GH treatment. As a result, median height SD score (SDS) of SGA children increased by +0.42 with 12-month GH treatment. Body mass index SDS was lower in SGA children than in controls. Serum apolipoprotein A1 increased, whereas apolipoprotein B decreased during GH treatment. Serum leptin and resistin levels, which were lower in SGA children than in controls at baseline, did not change remarkably with GH treatment. Monocyte counts, which were lower in SGA patients at baseline, increased after GH treatment. Neutrophil counts significantly increased after GH treatment. Natural killer cell ratios, which were higher in SGA patients, decreased after GH treatment. In conclusion, there was no evidence suggesting metabolic abnormalities in SGA children. Serum apolipoprotein changes might predict the beneficial role of GH treatment in lowering cardiometabolic risk.

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  • Toshie Iijima, Takafumi Niitani, Seiichi Tanaka, Kazunori Yanagi, Teru ...
    Type: Note
    Article ID: EJ17-0465
    [Advance publication] Released: February 16, 2018
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    We describe a very rare case of concurrent variant type 3 autoimmune polyglandular syndrome (APS) and pulmonary arterial hypertension (PAH). A previously healthy 65-year-old Japanese woman was referred to our university hospital with a 2-month history of general fatigue and hyperglycemia. Laboratory tests revealed severe hyperglycemia (plasma glucose 543 mg/dL and HbA1c 10.7%) with ketonuria (3+). Glutamic acid decarboxylase (GAD) and IA-2 antibodies were positive, and the serum C peptide level was markedly decreased to 0.2 ng/mL. Accordingly, type 1 diabetes was diagnosed. Hashimoto’s thyroiditis was also diagnosed because she had a diffuse goiter and a mild hypothyroidism (TSH 8.20 μU/mL, and FT4 0.80 ng/mL) with positive autoantibodies for thyroid peroxidase and thyroglobulin. There was neither adrenal insufficiency nor hypocalcemia. In addition, chest X ray showed a suspicious PAH by a dilation of both pulmonary arteries, especially right descending artery, and right heart catheterization confirmed the presence of PAH. HLA Class II genotyping revealed DRB1-DQB1*0901-*0303, a common susceptibility haplotype in Japanese patients with type 3 APS or acute-onset type 1 diabetes. The combination of variant type 3 APS and PAH is extremely rare and to the best of knowledge, this is the first case reported in a Japanese patient.

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  • Masao Takenobu, Sueyoshi Moritani, Kana Yoshioka, Tsuyoshi Morisaki, H ...
    Type: Original
    Article ID: EJ17-0553
    [Advance publication] Released: February 15, 2018
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    Thyroid metastasis from head and neck squamous cell carcinoma (SCC) is a very rare form of rarely observed metastatic thyroid tumor. We herein report a case of thyroid metastasis from oropharyngeal SCC (OSCC). The patient was a 68-year-old male diagnosed with p16-positive tonsillar OSCC on the right side with multiple lymph node metastases and a thyroid mass, which was determined as metastatic p16-positive OSCC by immunohistochemistry of specimens collected by fine-needle aspiration cytology (FNAC). He received one cycle of induction chemotherapy followed by concurrent chemoradiotherapy. No visible primary lesions were observed after treatment. The disappearance of the tonsillar lesion was considered to be a complete response by the magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT). The thyroid lesion was also decreased, but a solid lesion with unclear boundaries in the right thyroid lobe remained. Therefore, the patient underwent total thyroidectomy to remove any residual tumor. Postoperative pathological evaluation revealed no residual viable carcinoma cells in the resected specimen. As illustrated in this case, immunohistochemistry of the FNAC specimen for p16 was successful in determining the thyroid tumor as a metastatic lesion from the oropharynx. Although radical radiotherapy might be sufficient to control thyroid gland metastasis of OSCC, in this case, early-stage remedial surgery was thought to be necessary for a secure radical cure.

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  • Mincheol Kang, Jain Jeong, Jinhee Lee, Song Park, Yonghun Sung, Minjee ...
    Type: Original
    Article ID: EJ17-0363
    [Advance publication] Released: February 09, 2018
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    Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) sub-family, plays a major role in angiogenesis and vasculogenesis. Previous study demonstrated that PlGF-overexpressing transgenic (Tg) mice had gestational loss. In addition, PlGF secretion was up-regulated in isolated T lymphocytes (T-cell) upon CD3/CD28 stimulation, suggesting that PlGF could be a regulator of T-cell differentiation and development. T-cells are well known to play a critical role in obesity-induced inflammation. Therefore, to verify the possible link of diet-induced obesity (DIO) with inflammation and related metabolic disorders, such as insulin resistance, we fed high-fat diet (HFD) to Tg mice for 16 weeks. Adiposity and glucose intolerance significantly increase in Tg mice fed a HFD (Tg HFD) compared to wild-type (WT) mice fed HFD (WT HFD). In addition, macrophage infiltrations were significantly higher in the epididymal white adipose tissue (EWAT), liver, and pancreatic islets of Tg HFD mice compared to WT HFD mice. In the in vitro study, we showed that isolated CD4+ T-cells from Tg mice further differentiate into type 1 (Th1) and type 17 (Th17) helper T-cells via CD3/CD28 stimulation. Furthermore, we observed that the pro-inflammatory cytokines IL-6, IL-17, and TNFα, are remarkably increased in Tg mice compared to WT mice. These findings demonstrate that PlGF overexpression in T-cells might lead to inflammatory T-cell differentiation and accumulation in adipose tissue (AT) or metabolism-related tissues, contributing to the development of systemic metabolic disorders. Thus, PlGF may provide an effective therapeutic target in the management of obesity-induced inflammation and related metabolic disorders.

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  • Mitsuyoshi Hirokawa, Nami Takada, Hideyuki Abe, Ayana Suzuki, Miyoko H ...
    Type: Original
    Article ID: EJ17-0462
    [Advance publication] Released: February 08, 2018
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    We report three cases of thyroid sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE), which is an extremely rare variant of mucoepidermoid carcinoma (MEC). The aims of this report were to describe the clinicopathological findings, including results from immunohistochemical and fluorescence in situ hybridization analysis of thyroid SMECE, as well as to discuss the distinction between thyroid SMECE and its salivary counterpart. The cases included a 63-year-old female, a 44-year-old male, and a 66-year-old female, with all patients presenting with Hashimoto’s thyroiditis. Nodal metastasis was not found in any of the three cases. Neither regional recurrences nor distant metastases were found in any patient during the follow-up, which was 20 years, 3 years, and 18 months, respectively. Histologically, tumors were composed of epidermoid carcinoma cells, intermediate type carcinoma cells, and goblet cell-type mucus-secreting carcinoma cells, with all tumors displaying a sclerotic stroma with eosinophilic and lymphocytic infiltration. The formation of eosinophilic abscess in the tumor nests that might be a novel characteristic finding of SMECE was observed. Immunohistochemically, the carcinoma cells were positive for cytokeratin 34βE12, TTF-1, and PAX8, but negative for thyroglobulin. In two cases, increased IgG4-positive plasma cells were observed. Mastermind-like transcriptional coactivator 2 (MAML2), according to fluorescence in situ hybridization, was intact in all cases. In conclusion, thyroid SMECE has favorable outcomes and seems to be genetically different from salivary MEC. This is the first report to describe the presence of increased IgG4-positive plasma cells in the stroma of SMECE.

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  • Ryosuke Sakai, Yoshitaka Hashimoto, Emi Ushigome, Akane Miki, Takuro O ...
    Type: Original
    Article ID: EJ17-0414
    [Advance publication] Released: January 27, 2018
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    Skipping breakfast or irregular breakfast is associated with poor glycemic control. However, a relationship between the timing of dinner and glycemic control in people with type 2 diabetes remains indefinite. Therefore, we investigated the relationship between late-night-dinner and glycemic control in people with type 2 diabetes. We performed questionnaire survey for lifestyle factors in this cross-sectional study. We defined having dinner later than eight pm as late-night-dinner. We examined the differences in clinical and metabolic parameters between those who have late-night-dinner and those who do not have. We also examined the relationship between late-night-dinner and HbA1c, using multiple regression analysis. Ninety-five people (23.2%) had a late-night-dinner, among 409 people with type 2 diabetes. Metabolic parameters (mean (SD) or median (interquartile range)) of people with late-night-dinner were worse than those of without, including body mass index (BMI) (24.4 (4.0) vs. 23.2 (3.4) kg/m2, p = 0.006), triglycerides (1.5 (1.1–2.1) vs. 1.2 (0.8–1.7) mmol/L, p < 0.001), HDL-cholesterol (1.4 (0.4) vs. 1.6 (0.4) mmol/L, p = 0.004) and hemoglobin A1c (58.1 (13.3) vs. 55.2 (10.2) mmol/mol, (7.5 (1.2) vs. 7.2 (0.9) %), p = 0.023)). Late-night-dinner (standardized regression coefficient = 0.13, p = 0.028) was associated with hemoglobin A1c after adjusting for age, BMI, sex, duration of diabetes, smoking, exercise, alcohol, snacking after dinner, nighttime sleep duration, time from dinner to bedtime, skipping breakfast, and medication for diabetes. Late-night-dinner is independently associated with poor glycemic control in people with type 2 diabetes.

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  • Akira Kurozumi, Yosuke Okada, Hiroaki Satoh, Ikuo Inoue, Hiroko Chimor ...
    Type: Original
    Article ID: EJ17-0386
    [Advance publication] Released: January 25, 2018
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    Recently, we reported that linagliptin had equivalent efficacy to voglibose in reducing postprandial blood glucose levels in drug-naïve patients with type 2 diabetes (L-STEP Study). As a sub-study of the L-STEP Study we examined the effect of linagliptin on postprandial lipids profile. Between October 2012 and April 2014, the study enrolled patients with type 2 diabetes mellitus who had inadequate glycemic control. Patients were randomly assigned to either the linagliptin group (5 mg once daily, n = 85) or the voglibose group (0.2 mg/meal thrice daily, n = 71). Meal tolerance tests were performed at baseline (week 0) and endpoint (week 12). The increments in 4-h postprandial triglyceride, remnant lipoprotein cholesterol (RLP-C), and apolipoprotein B48 (ApoB48) from baseline to endpoint in the linagliptin group were lower (p < 0.001, p = 0.025 and p < 0.001). 4-h postprandial ApoB48 at endpoint was lower in the linagliptin group (p = 0.007), and positive correlation was detected between change of ApoB48 and changes in both triglyceride (r = 0.67, p < 0.001) and RLP-C (r = 0.73, p < 0.001) at 4 h. This study revealed that in drug-naïve Japanese patients with relatively mild type 2 diabetes mellitus, linagliptin improves not only postprandial blood glucose level but also levels of lipids such as TG and RLP-C by reducing the ApoB48 level compared with voglibose.

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  • Xuan Shu, Shenyou Shu, Shijie Tang, Lvjun Yang, Dan Liu, Ke Li, Zejun ...
    Type: Original
    Article ID: EJ17-0424
    [Advance publication] Released: January 22, 2018
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    Diabetic foot ulcer is a chronic, refractory, frequent complication in diabetic patient. Its treatment often requires multidisciplinary joint efforts, diverse strategies have been adopted to address this annoying issue, including stem cell-based therapy/acellular dermal matrix/negative pressure wound therapy etc. However, consensus has not been reached. To assess the current evidence regarding the efficiency and potential advantages of stem cell-based therapy compared with conventional standard treatment and/or placebo in the treatment of diabetic foot ulcer. A comprehensive search in PubMed, EmBase, Cochrane Central and Web of Science databases was conducted during December 2016 and a systematic review and meta-analysis of all relevant studies were performed. A total of 7 studies that involved 224 diabetic foot patients, classified as Wagner grades 1–5, were analyzed. The pooled results confirmed the benefits of using the stem cell treatment. Partial and/or complete healing were significantly higher in the stem cell group compared with the control group (77.4% vs. 31.9%; RR: 2.22; 95% CI, 1.65–2.98). Subgroup analysis on ABI and TCP02 also confirmed the results. The present meta-analysis indicates that stem cell-based therapy can enhance the healing of diabetic foot ulcers and is associated with lesser pain, lower amputation rate and improved prognosis compared with normal treatment. Well-designed randomized controlled trials are required in the future in order to confirm and update these findings.

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  • Nuri Karadurmus, Mehmet Ilkin Naharci, Sinasi Erol Bolu, Aydogan Aydog ...
    Article ID: RET10-1
    [Advance publication] Released: November 12, 2010
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    This article released online on September 22, 2010 as advance publication was withdrawn at the request of the authors.
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  • Nuri Karadurmus, Mehmet Ilkin Naharci, Sinasi Erol Bolu, Aydogan Aydog ...
    Article ID: K10E-195
    [Advance publication] Released: September 22, 2010
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    This article was retracted. See the Notification.
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  • Chengjiang LI, Mingzhi XU, Qing GU
    Article ID: K08E-187
    [Advance publication] Released: November 20, 2008
    JOURNALS FREE ACCESS ADVANCE PUBLICATION
    This article was retracted. See the Notification.
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