詳細

武友　保憲 （タケトモ　ヤスノリ）

  • 医学科　医学部講師
Last Updated :2024/04/19

コミュニケーション情報 byコメンテータガイド

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    糖尿病を始めとする内分泌代謝領域の研究、診療を行っています。

研究者情報

学位

  • 博士（医学）（2017年03月 近畿大学）
  • 学士（医学）（2007年03月 近畿大学）

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J-Global ID

現在の研究分野（キーワード）

    糖尿病を始めとする内分泌代謝領域の研究、診療を行っています。

研究分野

  • ライフサイエンス / 代謝、内分泌学

研究活動情報

論文

  • Shuzo Imamura; Fumimaru Niwano; Naru Babaya; Yoshihisa Hiromine; Ippei Matsumoto; Keiko Kamei; Yuta Yoshida; Yasunori Taketomo; Sawa Yoshida; Yoshifumi Takeyama; Shinsuke Noso; Norikazu Maeda; Hiroshi Ikegami
    The Journal of Clinical Endocrinology & Metabolism 109 3 619 - 630 2024年03月 [査読有り]
     
    Abstract Context Glucose tolerance worsens after distal pancreatectomy (DP); however, the long-term incidence and factors affecting interindividual variation in this worsening are unclear. Objective To investigate the changes in diabetes-related traits before and after DP and to clarify the incidence of diabetes and its predictors. Methods Among 493 registered patients, 117 underwent DP. Among these, 56 patients without diabetes before surgery were included in the study. Glucose and endocrine function were prospectively assessed using a 75-g oral glucose tolerance test preoperatively, 1 month after DP, and every 6 months thereafter for up to 36 months. Pancreatic volumetry was performed using multidetector row computed tomography before and after surgery. Results Insulin secretion decreased and blood glucose levels worsened after DP. Residual pancreatic volume was significantly associated with the reserve capacity of insulin secretion but not with blood glucose levels or the development of diabetes. Among 56 patients, 33 developed diabetes mellitus. The cumulative incidence of diabetes at 36 months after DP was 74.1%. Multivariate Cox regression analysis showed that impaired glucose tolerance as a preoperative factor as well as a decreased insulinogenic index and impaired glucose tolerance at 1 month postoperatively were identified as risk factors for diabetes following DP. Conclusion Impaired glucose tolerance and reduced early-phase insulin response to glucose are involved in the development of new-onset diabetes after DP; the latter is an additional factor in the development of diabetes and becomes apparent when pancreatic beta cell mass is reduced after DP.
  • Naru Babaya; Shinsuke Noso; Yoshihisa Hiromine; Yasunori Taketomo; Fumimaru Niwano; Sawa Yoshida; Sara Yasutake; Yumiko Kawabata; Norikazu Maeda; Hiroshi Ikegami
    Scientific Reports 14 1 1 - 8 2024年03月 [査読有り]
     
    Abstract Continuous glucose monitoring (CGM) values obtained from CGM systems using the same sensor but with different internal algorithms (the first- and third-generation FreeStyle Libre (1st-gen-libre and 3rd-gen-libre, respectively)) were compared. We used 19,819 paired and simultaneously measured CGM values of 13 patients with diabetes. The average CGM value was significantly higher (P < 0.0001) and the time below range (CGM value < 70 mg/dL) was significantly lower (P < 0.0001) with the 3rd-gen-libre than with the 1st-gen-libre. There was a significant correlation (P < 0.0001) between the CGM values of the 3rd-gen-libre (y-axis, mg/dL) and 1st-gen-libre (x-axis, mg/dL) using the following formula: y = 0.9728x + 10.024. On assessing the association between glycated hemoglobin (HbA1c (%), y-axis) and the average CGM values (x-axis, mg/dL) by applying the obtained equation to previously reported 1st-gen-libre data and converting it to 3rd-gen-libre data, we obtained the equation y = 0.02628x + 3.233, indicating that the glucose management indicator reported in the West may be underestimated compared with the laboratory-measured HbA1c in the Japanese population. Glucose values from the same sensor were found to be significantly different between readers with different algorithms, and the calculation of CGM-related indices may need to be individualized for each device.
  • Yoshihisa Hiromine; Shinsuke Noso; Naru Babaya; Yasunori Taketomo; Fumimaru Niwano; Yuki Okuda; Sara Yasutake; Tatsuro Minohara; Naonobu Tsuda; Yuichiro Hama; Hiroshi Ikegami
    Internal Medicine 62 7 1023 - 1029 2023年04月 [査読有り]
  • Shinsuke Noso; Naru Babaya; Yoshihisa Hiromine; Yasunori Taketomo; Fumimaru Niwano; Sawa Yoshida; Hiroshi Ikegami
    Journal of Diabetes Investigation 14 1 48 - 57 2023年01月 [査読有り]
  • Fumimaru Niwano; Naru Babaya; Yoshihisa Hiromine; Ippei Matsumoto; Keiko Kamei; Yasunori Taketomo; Sawa Yoshida; Yoshifumi Takeyama; Shinsuke Noso; Hiroshi Ikegami
    The Journal of Clinical Endocrinology & Metabolism 107 12 3362 - 3369 2022年12月 [査読有り]
     
    Abstract Context The glucose tolerance of patients changes considerably from before to after pancreaticoduodenectomy wherein approximately half of the pancreas is resected. Purpose The aim of this prospective study was to investigate the incidence of and risk factors for diabetes after pancreaticoduodenectomy. Methods This study is a part of an ongoing prospective study, the Kindai Prospective Study on Metabolism and Endocrinology after Pancreatectomy (KIP-MEP) study. Of the 457 patients enrolled to date, 96 patients without diabetes who underwent pancreaticoduodenectomy were investigated in this study. Preoperatively, 1-month post-pancreaticoduodenectomy, and every 6 months thereafter, the glucose metabolism and endocrine function were evaluated using the 75-g oral glucose tolerance test. Various other metabolic, endocrine, and exocrine indices were also examined over a period of up to 36 months. Results Of the 96 patients analyzed in this study, 33 were newly diagnosed with diabetes. The cumulative diabetes incidence at 36 months following pancreaticoduodenectomy was 53.8%. The preoperative insulinogenic index and ΔC-peptide in the glucagon stimulation test were significantly lower in the progressors than in the non-progressors to diabetes. Multivariate Cox regression analysis demonstrated that the insulinogenic index was the only significant risk factor for new-onset diabetes. Conclusions The majority of patients developed new-onset diabetes after pancreaticoduodenectomy, and a low value of the insulinogenic index was suggested to be a risk factor for diabetes. Preoperative assessment for the prediction of the onset of diabetes serves as useful information for patients and is important for postoperative glycemic control and diabetes management in patients who require pancreaticoduodenectomy.
  • Naru Babaya; Shinsuke Noso; Yoshihisa Hiromine; Yasunori Taketomo; Fumimaru Niwano; Sawa Yoshida; Sara Yasutake; Yumiko Kawabata; Hiroshi Ikegami
    Scientific Reports 11 1 1 - 9 2021年12月 [査読有り]
     
    AbstractThe targets for continuous glucose monitoring (CGM)-derived metrics were recently set; however, studies on CGM data over a long period with stable glycemic control are limited. We analyzed 194,279 CGM values obtained from 19 adult Japanese patients with type 1 diabetes. CGM data obtained during stable glycemic control over four months were analyzed. CGM-related metrics of different durations “within 120, 90, 60, 30, and 7 days” were calculated from baseline. Time in range (TIR; glucose 70–180 mg/dL), time above range (TAR; glucose ≥ 181 mg/dL), and average glucose levels, but not time below range (TBR; glucose ≤ 69 mg/dL), strongly correlated with glycated hemoglobin (HbA1c) values (P < 0.0001). TBR correlated with glucose coefficient of variation (CV) (P < 0.01). Fasting serum C-peptide levels negatively correlated with glucose CV (P < 0.01). HbA1c of approximately 7% corresponded to TIR of 74% and TAR of 20%. The shorter the CGM period, the weaker was the relationship between HbA1c and CGM-related metrics. TIR, TAR, and average glucose levels accurately reflected HbA1c values in Japanese patients with type 1 diabetes with stable glycemic control. Glucose CV and TBR complemented the limitation of HbA1c to detect glucose variability and hypoglycemia. Stable glycemic control with minimal hypoglycemia depended on residual β-cell function.
  • Naru Babaya; Shinsuke Noso; Yoshihisa Hiromine; Yasunori Taketomo; Fumimaru Niwano; Keisuke Monobe; Shuzo Imamura; Kazuki Ueda; Yuto Yamazaki; Hironobu Sasano; Hiroshi Ikegami
    Journal of the Endocrine Society 5 11 1 - 8 2021年11月 [査読有り]
     
    Abstract Adrenocortical carcinoma (ACC) is a rare tumor, and some histological variants (oncocytic, myxoid, and sarcomatoid ACCs) have been reported in addition to the conventional ACC. Among these subtypes, oncocytic ACC is histologically characterized by the presence of abundant eosinophilic granular cytoplasm in the carcinoma cells owing to the accumulation of mitochondria, which generally yields high 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET). Herein, we report the case of a 21-year-old woman with oncocytic ACC with low FDG uptake on PET scan. Her circulating levels of androgens were high, and androgen-synthesis enzymes were detected in carcinoma cells. The patient also had hypocholesterolemia. However, glucose transporter 1 (GLUT1) was not detected in the tumor, which was considered to account for the low FDG uptake by the tumor. To the best of our knowledge, this is the first case of low FDG uptake by oncocytic ACC without GLUT1 expression. Additionally, since hypocholesterolemia was reported in 3 previous reports of androgen-producing tumors, a possible correlation between androgenicity in adrenal tumors and the development of hypocholesterolemia could be postulated; however, further investigations are needed for clarification. This case highlights important information regarding the diversity of ACC and its impact on hypocholesterolemia.
  • Sawa Yoshida; Naru Babaya; Hiroyuki Ito; Yoshihisa Hiromine; Yasunori Taketomo; Fumimaru Niwano; Shuzo Imamura; Yuto Yamazaki; Hironobu Sasano; Yumiko Kawabata; Shinsuke Noso; Hiroshi Ikegami
    Journal of the Endocrine Society 5 10 1 - 7 2021年10月 [査読有り]
     
    Abstract Mixed corticomedullary tumors (MCMTs) are rare and comprise medullary and cortical cells in a single adrenal tumor. The mechanisms underlying their development have not been fully elucidated. Here, we report a case of MCMT in a 42-year-old woman. Based on the preoperative clinical findings, the patient was diagnosed as having a pheochromocytoma with subclinical Cushing syndrome. Postoperative pathological diagnosis revealed that the tumor demonstrated morphologically distinct medullary and cortical components, which produced catecholamines and cortisol, respectively. Hybrid tumor cells producing both catecholamines and cortisol were not detected. Adrenocorticotropin (ACTH)-positive tumor cells were identified to be present in the pheochromocytoma. This ectopic production of ACTH can contribute to an autonomous cortisol production in a paracrine manner. In addition, micronodules producing aldosterone were detected in the adrenal tissue adjacent to the tumor. The simultaneous development of these 2 lesions may not be correlated with each other; however, this case confirms the importance of a detailed histopathological examination of the adrenal lesions harboring complicated hormonal abnormalities by providing pivotal and indispensable information on their pathogenesis and the possible interaction of the hormones produced in the adrenal gland.
  • Tatsuro Minohara; Shinsuke Noso; Naru Babaya; Yoshihisa Hiromine; Yasunori Taketomo; Fumimaru Niwano; Yukako Makutani; Sawa Yoshida; Sara Yasutake; Shuzo Imamura; Hiroshi Ikegami
    Geriatrics & Gerontology International 21 10 932 - 938 2021年10月 [査読有り]
  • Fumimaru Niwano; Naru Babaya; Yoshihisa Hiromine; Ippei Matsumoto; Keiko Kamei; Shinsuke Noso; Yasunori Taketomo; Yoshifumi Takeyama; Yumiko Kawabata; Hiroshi Ikegami
    The Journal of Clinical Endocrinology & Metabolism 106 5 e2203 - e2214 2021年05月 [査読有り]
     
    Abstract Context The rate of glucose metabolism changes drastically after partial pancreatectomy. Objective This work aims to analyze changes in patients’ glucose metabolism and endocrine and exocrine function before and after partial pancreatectomy relative to different resection types (Kindai Prospective Study on Metabolism and Endocrinology after Pancreatectomy: KIP-MEP study). Methods A series of 278 consecutive patients with scheduled pancreatectomy were enrolled into our prospective study. Of them, 109 individuals without diabetes, who underwent partial pancreatectomy, were investigated. Data were compared between patients with pancreaticoduodenectomy (PD, n = 73) and those with distal pancreatectomy (DP, n = 36). Results Blood glucose levels during the 75-g oral glucose tolerance test (75gOGTT) significantly decreased after pancreatectomy in the PD group (area under the curve [AUC] –9.3%, P &lt; .01), and significantly increased in the DP population (AUC + 16.8%, P &lt; .01). Insulin secretion rate during the 75gOGTT and glucagon stimulation test significantly decreased after pancreatectomy both in the PD and DP groups (P &lt; .001). Both groups showed similar homeostasis model assessment of insulin resistance (HOMA-IR) values after pancreatectomy. Decrease in exocrine function quality after pancreatectomy was more marked in association with PD than DP (P &lt; .01). Multiple regression analysis indicated that resection type and preoperative HOMA-IR independently influenced glucose tolerance-related postoperative outcomes. Conclusions Blood glucose levels after the OGTT differed markedly between PD and DP populations. The observed differences between PD and DP suggest the importance of individualization in the management of metabolism and nutrition after partial pancreatectomy.
  • Keisuke Monobe; Shinsuke Noso; Naru Babaya; Yoshihisa Hiromine; Yasunori Taketomo; Fumimaru Niwano; Sawa Yoshida; Sara Yasutake; Tatsuro Minohara; Yumiko Kawabata; Hiroshi Ikegami
    Journal of Diabetes Investigation 12 5 728 - 737 2021年05月 [査読有り]
  • Naru Babaya; Yuki Okuda; Shinsuke Noso; Yoshihisa Hiromine; Yasunori Taketomo; Fumimaru Niwano; Kazuki Ueda; Yumiko Tanaka; Yuto Yamazaki; Hironobu Sasano; Yumiko Kawabata; Yasuhiro Ohno; Hiroshi Ikegami
    Journal of the Endocrine Society 5 2 1 - 9 2021年02月 [査読有り]
     
    Abstract Characterization of adrenocortical disorders is challenging because of varying origins, laterality, the presence or absence of hormone production, and unclarity about the benign or malignant nature of the lesion. Histopathological examination in conjunction with immunohistochemistry is generally considered mandatory in this characterization. We report a rare case of bilateral adrenocortical adenomas associated with unilateral adrenal endothelial cysts in a 65-year-old woman whose condition was not diagnosed before surgery. Detailed histological examination of the resected adrenal glands revealed hyperplasia in the zona glomerulosa. Despite hyperplasia, the patient had normal serum aldosterone levels and renin activity without clinical evidence of hypertension. The patient was treated with a sodium-glucose cotransporter protein 2 (SGLT2) inhibitor. This may have stimulated the renin-angiotensin-aldosterone system. To the best of our knowledge, this is the first case in which both relatively large bilateral adrenocortical adenomas and unilateral adrenal endothelial cysts were detected. This case also highlights the complexity and difficulty of preoperative diagnosis. Furthermore, this case reports the first detailed histopathological examination of adrenal lesions with SGLT2 treatment and the possibility of SGLT2 inhibitor treatment resulting in histological hyperplasia in the zona glomerulosa; however, it is difficult to prove a causative relationship between SGLT2 inhibitors and hyperplasia of the zona glomerulosa based on the data of this case. It can be confirmed only under limited conditions; therefore, further studies on adrenal gland histology employing SGLT2 inhibition are warranted.
  • Naru Babaya; Shinsuke Noso; Yoshihisa Hiromine; Yasunori Taketomo; Fumimaru Niwano; Sawa Yoshida; Sara Yasutake; Yumiko Kawabata; Hiroshi Ikegami
    Journal of Diabetes Investigation 11 5 1222 - 1229 2020年09月 [査読有り]
  • Noso S; Babaya N; Hiromine Y; Ito H; Taketomo Y; Yoshida S; Niwano F; Monobe K; Minohara T; Okada T; Tsugawa M; Kawabata Y; Ikegami H
    The Journal of Clinical Endocrinology & Metabolism 104 12 6338 - 6344 2019年12月 [査読有り]
  • Babaya N; Noso S; Hiromine Y; Ito H; Taketomo Y; Yamamoto T; Kawabata Y; Ikegami H
    Journal of Endocrine Society 2 10 1207 - 1213 2018年10月 [査読有り]
  • Kousei Kanto; Hiroyuki Ito; Shinsuke Noso; Naru Babaya; Yoshihisa Hiromine; Yasunori Taketomo; Junko Toma; Fumimaru Niwano; Sara Yasutake; Yumiko Kawabata; Hiroshi Ikegami
    Journal of Diabetes Investigation 9 3 587 - 593 2018年05月 [査読有り]
     
    Aims/Introduction: Differences in the efficacy and safety of antidiabetic drugs among different ethnic groups are well documented. Metformin is widely used in the treatment of type 2 diabetes in Western countries, but high doses of metformin have been approved only recently for clinical use in Japan. The aim of the present study was to investigate the effects of dosage and dosing frequency on the efficacy and safety of high-dose metformin in Japanese patients. Materials and Methods: A total of 71 Japanese patients with type 2 diabetes were prospectively studied for the effects of dosage and dosing frequency on the efficacy and safety of metformin during hospitalization. Dose effects were studied in 27 patients treated with 0, 500, 1,000, 1,500 and 2,250 mg/day of metformin. The effect of dosing frequency was compared in 56 patients with 1,500 mg/day of metformin administered either two or three times per day. Results: Significant dose-dependent improvement in daily profiles of blood glucose was observed with metformin dosages up to 1,500 mg/day, with a trend towards further improvement observed at 2,250 mg/day. The efficacy of 1,500 mg of metformin was comparable when the drug was administered either two or three times per day. The most frequently reported side-effects were gastrointestinal symptoms, which were not affected by the dosage or dosing frequency of metformin. Conclusions: These results show that the efficacy of high-dose metformin is dose-dependent in Japanese patients. The efficacy and safety of metformin were similar when the drug was administered either two or three times per day.
  • Naru Babaya; Yukako Makutani; Shinsuke Noso; Yoshihisa Hiromine; Hiroyuki Ito; Yasunori Taketomo; Kazuki Ueda; Hokuto Ushijima; Yoshifumi Komoike; Yuto Yamazaki; Hironobu Sasano; Yumiko Kawabata; Hiroshi Ikegami
    BMC ENDOCRINE DISORDERS 17 1 1 - 6 2017年12月 [査読有り]
     
    Background: We report a rare case of a juxta-adrenal schwannoma that could not be discriminated from an adrenal tumor before surgical resection and was complicated by bilateral hyperaldosteronism. To the best of our knowledge, this is first case in which both a juxta-adrenal schwannoma and hyperaldosteronism co-existed. Case presentation: A 69-year-old male treated for hypertension was found to have a left supra-renal mass (5.8 x 5.2 cm) by abdominal computed tomography. His laboratory data showed that his plasma aldosterone concentration (PAC) was within the normal range, but his plasma renin activity (PRA) was reduced, resulting in an increased aldosterone/renin ratio (ARR). Load tests of captopril or furosemide in the standing position demonstrated autonomous aldosterone secretion and renin suppression. Adrenal venous sampling (AVS) with ACTH stimulation indicated bilateral hypersecretion of aldosterone. A left supra-renal tumor was resected because of the possibility of malignancy and was found to be a benign schwannoma arising from the juxta-adrenal region together with an adrenal gland. The dissected left adrenal gland was morphologically hyperplastic in the zona glomerulosa, but was immunohistochemically negative for CYP11B2 (aldosterone synthase). Multiple CYP11B2positive adrenocortical micronodules were detected in the adrenal gland, indicating micronodular hyperplasia. Although bilateral aldosteronism was indicated by AVS before the operation, the PRA, PAC and ARR values were within their respective reference ranges after resection of the unilateral tumor, suggesting that the slight increase in hormone secretion from the remaining right-sided lesion could not be detected after resection. Conclusion: A clinical and morphologic diagnosis of juxta-adrenal schwannoma is difficult, particularly in a case of hyperaldosteronism, as shown in this case. These data suggest the complexity and difficulty diagnosing adrenal incidentaloma.
  • Yasunori Taketomo; Shinsuke Noso; Naru Babaya; Yoshihisa Hiromine; Hiroyuki Ito; Kousei Kanto; Fumimaru Niwano; Naoki Oiso; Akira Kawada; Yumiko Kawabata; Hiroshi Ikegami
    HUMAN IMMUNOLOGY 78 2 185 - 189 2017年02月 [査読有り]
     
    Our previous observations clarified that Graves' disease (GD) is the most frequent autoimmune disease in patients with alopecia areata (AA), and 42.7% of patients with AA were positive for thyrotropin receptor antibody (TRAb). A class II HLA haplotype DRB1*15:01-DQB1*06:02 was suggested to contribute to autoimmunity against the thyroid gland in M. To further clarify the genetic factors contributing to organ specificity in autoimmune diseases, we studied the contribution of non-HLA genes to organ specificity in GD and AA. A high frequency of AA (13.4%) was observed in patients with GD, indicating strong phenotypic association between GD and AA. CTLA4 and TSHR were significantly associated with GD (Pc = 0.007 and Pc < 0.002, respectively), but not with AA, even in TRAb-positive patients. The difference in the association between GD and AA suggests that the CTLA4 and TSHR are not main factors contributing to determining common genetic basis among GD and AA. (C) 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
  • Tomohiko Narita; Naoki Oiso; Yasunori Taketomo; Kazunori Okahashi; Kohei Yamauchi; Masako Sato; Shusuke Uchida; Hiromasa Matsuda; Akira Kawada
    JOURNAL OF DERMATOLOGY 43 2 210 - 214 2016年02月 [査読有り]
     
    Nivolumab, a blockade of programmed cell death 1, is now administrated for advanced malignant melanomas. Nivolumab-associated adverse events include organ-specific autoimmune disorders; autoimmune thyroid disease, vitiligo and insulin-dependent diabetes. However, predisposed persons are currently unknown. Here, we report serological aggravation of autoimmune thyroid disease in two cases receiving nivolumab: one with Hashimoto disease and another with probable subclinical Hashimoto disease. We should verify if nivolumab-related hypothyroidism and hyperthyroidism are predisposed to occur in euthyroid individuals with subclinical autoimmune thyroid disease.
  • Shinsuke Noso; Choongyong Park; Naru Babaya; Yoshihisa Hiromine; Takeshi Harada; Hiroyuki Ito; Yasunori Taketomo; Kousei Kanto; Naoki Oiso; Akira Kawada; Tamio Suzuki; Yumiko Kawabata; Hiroshi Ikegami
    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 100 5 1976 - 1983 2015年05月 [査読有り]
     
    Context: Multiple autoimmune diseases, such as autoimmunity against the thyroid gland and pancreatic islets, are often observed in a single patient. Although alopecia areata (AA) is one of the most frequent organ-specific autoimmune diseases, the association of AA with other autoimmune diseases and the genetic basis of the association remain to be analyzed. Objective: The aim of this study was to clarify the similarities and differences in HLA and clinical characteristics of thyroid and islet autoimmunity in patients with AA. Participants: A total of 126 patients with AA were newly recruited. Anti-islet and antithyroid autoantibodies were tested, and genotypes of HLA genes were determined. Results: Among the autoimmune diseases associated with AA, autoimmune thyroid disease was most frequent (10.0%), followed by vitiligo (2.7%) and rheumatoid arthritis (0.9%) but not type 1 diabetes (0.0%). The prevalence of thyroid-related autoantibodies in patients with AA was significantly higher than that in controls (TSH receptor antibody [TRAb]: 42.7% vs 1.2%, P = 1.6 x 10(-46); thyroid peroxidase antibody: 29.1% vs 11.6%; P = 1.7 x 10(-6)), whereas the prevalence of islet-related autoantibodies was comparable between patients with AA and control subjects. The frequency of DRB1*15:01-DQB1*06:02, a protective haplotype for type 1 diabetes, was significantly higher in TRAb-positive (12.8%, P = .0028, corrected P value [P-c] = .02) but not TRAb-negative (7.1%, not significant) patients with AA than in control subjects (4.5%). The frequency of DRB1*04:05-DQB1*04: 01, a susceptible haplotype for type 1 diabetes, was significantly lower in patients with AA (TRAb-positive: 8.5%; TRAb-negative: 11.9%) than in those with type 1 diabetes (29.5%, P-c = .0003 and P-c = .0008, respectively). Conclusion: AA was associated with thyroid autoimmunity but not islet autoimmunity, which correlated with class II HLA haplotypes susceptible or resistant to each autoimmune disease.
  • 朴忠勇; 能宗伸輔; 川畑由美子; 山内孝哲; 馬場谷成; 原田剛史; 廣峰義久; 伊藤裕進; 村田佳織; 武友保憲; 貫戸幸星; 當間純子; 末吉功治; 吉田左和; 大磯直毅; 川田暁; 池上博司
    近畿大学医学雑誌(Medical Journal of Kinki University) 38 3,4 107 - 114 近畿大学医学会 2013年12月 [査読有り]
     
    [抄録]目的: 円形脱毛症患者における甲状腺自己免疫および膵島自己免疫の臨床的・遺伝的実態を明らかにする. 方法: 円形脱毛症患者110例について臨床的特徴および自己免疫疾患の合併率を検討し, 血清学的に抗サイログロブリン（Tg）抗体, 抗甲状腺ペルオキシダーゼ（TPO）抗体, 甲状腺刺激ホルモン受容体抗体（TRAb)抗glutamic acid decarboxylase（GAD）抗体, 抗insulinoma-associated antigen2（IA-2抗体）, インスリン自己抗体（IAA）を測定した. またHLA-DRB1, -DQB1, -A, -B, -C 遺伝子型を決定した. 結果: 円形脱毛症患者は健常対照者に比し, 抗Tg抗体, 抗IA-2抗体, IAA, 抗GAD抗体陽性率は同等であったが, 抗TPO抗体（29.1％ vs. 11.6％, P＜0.001）, TRAb（42.7％ vs. 1.2％, P＜0.001）の陽性率は有意に高値を示した. 膵島関連自己抗体価の比較では抗GAD抗体, 抗IA-2抗体, IAAはいずれも健常対照者との間に差を認めず, 自己免疫性甲状腺疾患患者に比し有意に低値であった. 遺伝子解析において円形脱毛症患者は健常対照者に比し, A, 33: 03 が有意に低頻度であり（3.2％ vs. 9.7％, Pc＝0.036）, DRB1, 04: 05 -DQB1, 04:01 は低頻度の傾向, DRB1, 15: 01-DQB1, 06: 02 は高頻度の傾向を示した. 結語: 円形脱毛症には甲状腺自己免疫を高率に合併するが, 膵島自己免疫・１型糖尿病の合併は稀であること、遺伝子解析でも円形脱毛症では１型糖尿病の疾患感受性ハプロタイプが低頻度、疾患抵抗性ハプロタイプが高頻度であるという今回の結果から、円形脱毛症が自己免疫性甲状腺疾患とは共通性を有するのに対し、１型糖尿病とは臨床的にも遺伝的にも異質性を有することが示唆された.
  • 村田佳織; 川畑由美子; 能宗伸輔; 山内孝哲; 馬場谷成; 原田剛史; 廣峰義久; 伊藤裕進; 朴忠勇; 武友保憲; 貫戸幸星; 板家純子; 末吉功治; 吉田左和; 池上博司
    近畿大学医学雑誌(Medical Journal of Kinki University) 38 1,2 55 - 61 近畿大学医学会 2013年06月 [査読有り]
     
    [抄録]目的：自己免疫性甲状腺疾患（AITD）発症へのHLAクラスII領域とクラスI領域の関与を明らかにする． 方法：AITD患者281人と健常対照者198人を対象に，HLAクラスII領域のDRB1 とDQB1 アリルおよびクラスI領域のA，B とC アリルを決定し，アリル頻度およびハプロタイプ頻度を比較検討した．成績：DRB1 についてはDRB1*08:03 がAITD患者において有意に高頻度（14.4％ vs.7.6％，Pc＜0.01），DRB1*01:01 は有意に低頻度（2.3％ vs.8.8％，Pc＜0.0001）であった．DQB1 については，DQB1*05:01 が患者群において有意に低頻度（2.7％ vs.10.6％，Pc＜0.00001）であった．DRB1-DQB1 ハプロタイプについては，DRB1*08:03 -DQB1*06:01 が患者群において有意に高頻度（14.2％ vs.7.3％，Pc＜0.01），DRB1*01:01-DQB1*05:01が有意に低頻度（2.3％ vs.8.8％，Pc＜0.0001）であった．A については，いずれのアリルについても統計学的有意差を認めなかった．B についてはB *35:01 が患者群において有意に高頻度（13.2％ vs.6.8％，Pc＝0.04），B*07:02 が有意に低頻度（1.6％ vs.6.8％，Pc＜0.01）であった．C については，C *03:03 が患者群において有意に高頻度（17.4％ vs.8.1％，Pc＜0.01）であった．B -C ハプロタイプについては，B*35:01-C*03:03 が患者群において有意に高頻度（11.9％ vs.4.7％，Pc＜0.001），B *07:02 -C*07:02 が患者群で有意に低頻度（1.6％ vs.6.6％，Pc＝0.02）であった．DRB1
  • 武友保憲; 廣峰義久; 川畑由美子; 山内孝哲; 能宗伸輔; 原田剛史; 小牧克守; 馬場谷成; 伊藤裕進; 錦野真理子; 守口将典; 村田佳織; 山片里美; 東本貴弘; 朴忠勇; 大野恭裕; 池上博司
    近畿大学医学雑誌(Med Kindai Univ) 35 2 135 - 137 近畿大学医学会 2010年06月 [査読有り]
     
    [抄録] 低Na血症は臨床上遭遇する電解質異常のなかでも頻度が高く，軽症では倦怠感や食欲不振の訴えにとどまるが，ひとたび重症化すると，けいれんや意識障害をきたし，生命維持に危機に関わる重要な病態である．今回我々は著明な低Na血症に加えて低血糖を伴った症例を経験し，速やかに加療を開始すると共に鑑別診断を行い，下垂体性副腎皮質機能低下症と診断し得たので報告する．

書籍

  • 糖尿病ケア＜特集＞糖尿病の検査値20 早わかりポイントノート
    武友保憲; 馬場谷成; 池上博司 (担当:共著範囲:6 ケトン体（血中・尿中）)メディカ出版 2018年01月 22-23

講演・口頭発表等

MISC

共同研究・競争的資金等の研究課題

  • 日本学術振興会：科学研究費助成事業 若手研究
    研究期間 : 2022年04月 -2024年03月 
    代表者 : 武友 保憲
  • 日本学術振興会：科学研究費助成事業 基盤研究(C)
    研究期間 : 2021年04月 -2024年03月 
    代表者 : 池上 博司; 馬場谷 成; 武友 保憲; 廣峰 義久; 能宗 伸輔
     
    本研究では、１型糖尿病において治療困難の原因となる膵β細胞機能の完全廃絶を規定する遺伝因子を同定し、その分子メカニズムを明らかにするとともに、膵β細胞機能の完全廃絶を予知・予測するバイオマーカーを探索・同定することにより、内因性インスリンの完全廃絶阻止に資する基盤情報を得ることを目的として研究を進めている。 １）膵β細胞機能の完全廃絶を規定する遺伝因子の解析： 膵β細胞が発症時から完全廃絶する劇症１型糖尿病のゲノムワイド関連解析（GWAS）でゲノムワイド有意水準をクリアしたHLA領域とCSAD領域のターゲットリシークエンスを進め、劇症化・膵β細胞機能完全廃絶の直接原因となる変異・多型の同定・抽出を進めている。また、自己免疫性１型糖尿病（急性発症・緩徐進行）を対象としたGWASを新たに進めており、劇症１型糖尿病のGWAS結果と対比した解析を行うことで、１型糖尿病の劇症化・膵β細胞機能の完全廃絶に関与する遺伝子を抽出・同定し、膵β細胞機能完全廃絶を規定する体質・遺伝子の全貌解明へと展開する。 ２）膵β細胞機能の完全廃絶を予知・予測するバイオマーカーの探索： 劇症１型糖尿病のGWASで同定した染色体12q13.13のCSADがコードする遺伝子の機能に関連する血中バイオマーカーの探索を進めた結果、CSADが律速酵素として生合成する産物Taurineがバイオマーカーとなりうる可能性が示唆された。これと並行して血中メタボローム解析を施行し、アミノ酸以外の各種メタボライトも含めた解析で膵β細胞完全廃絶に関与するバイオマーカーの探索を進めている。
  • 日本学術振興会：科学研究費助成事業 若手研究
    研究期間 : 2020年04月 -2022年03月 
    代表者 : 武友 保憲
     
    内分泌臓器を標的とする免疫関連有害事象（irAE）の頻度は、甲状腺、下垂体、膵β細胞（1型糖尿病）の順で高頻度であった。甲状腺irAEにおける甲状腺自己抗体陽性率は62.5％であった。irAEによる１型糖尿病の膵島関連自己抗体陽性率は33.3％であり、全例でインスリン依存状態となった。下垂体irAEでは、ACTH単独欠損が54.8％と最多であった。HLA疾患感受性ハプロタイプについて、甲状腺irAEは自己免疫性甲状腺疾患と、irAEによる１型糖尿病は自然発症1型糖尿病とそれぞれ同程度に保有しており、irAEは標的臓器を同じくする自然発症自己免疫疾患と遺伝的に類似性を有する可能性が示唆された。

その他

  • 2018年04月 - 2019年03月  免疫チェックポイント分子阻害に伴う内分泌細胞破壊の機序ならびに予測因子の解明 
    近畿大学学内研究助成金 奨励研究助成金 SR11 研究内容：免疫チェックポイント阻害による特異的内分泌細胞破壊の実態と病態を解明し予知法を確立するとともに、自己免疫疾患の根本メカニズム解明に資する基盤情報を得る

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