Faculty Profiles - SONE, Hirohito

Isolated Adrenocorticotropic Hormone Deficiency Presenting with Severe Hyponatremia and Rhabdomyolysis: A Case Report and Literature Review. Reviewed International journal

Takeshi Komatsu, Nobumasa Ohara, Naoko Hirota, Yuichiro Yoneoka, Takashi Tani, Keishi Terajima, Tetsutaro Ozawa, Hirohito Sone

The American journal of case reports 20 1857 - 1863 2019.12

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND Isolated adrenocorticotropic hormone deficiency (IAD) is a rare disorder characterized by central adrenal insufficiency (AI) but normal secretion of pituitary hormones other than adrenocorticotropic hormone. IAD usually presents with unspecific symptoms of AI, such as anorexia and fatigue, but some patients present with a variety of atypical manifestations. Rhabdomyolysis is a potentially life-threatening clinical syndrome caused by skeletal muscle injury with the release of muscle cell contents into the circulation. A wide variety of disorders can cause rhabdomyolysis. Herein, we report an unusual case of IAD presenting with hyponatremia and rhabdomyolysis. CASE REPORT A 67-year-old Japanese woman with a 2-month history of anorexia and fatigue was diagnosed with severe hyponatremia (serum sodium, 118 mEq/L) and rhabdomyolysis (serum creatine phosphokinase, 6968 IU/L), after 2 days of vomiting and muscle weakness. Physical and laboratory findings did not show dehydration or peripheral edema. Her rhabdomyolysis resolved with normalization of serum sodium levels during administration of sodium chloride. However, her anorexia and fatigue remained unresolved. After reducing the amount of sodium chloride administered, the patient still had hyponatremia. Detailed endocrinological examinations indicated IAD; her hyponatremia was associated with inappropriately high plasma arginine vasopressin levels. The patient received corticosteroid replacement therapy, which resolved her anorexia, fatigue, excessive arginine vasopressin, and hyponatremia. CONCLUSIONS This case highlights the importance of considering the possibility of central AI in patients with hyponatremia and excessive arginine vasopressin levels. In addition, rhabdomyolysis associated with hyponatremia can be an important manifestation of IAD.

DOI： 10.12659/AJCR.918427

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Risk of coronary artery disease according to glucose abnormality status and prior coronary artery disease in Japanese men. Reviewed International journal

Masaru Kitazawa, Kazuya Fujihara, Taeko Osawa, Masahiko Yamamoto, Mayuko Harada Yamada, Masanori Kaneko, Yasuhiro Matsubayashi, Takaho Yamada, Nauta Yamanaka, Hiroyasu Seida, Hirohito Sone

Metabolism: clinical and experimental 101 153991 - 153991 2019.12

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Although glucose abnormality status (GAS), prior coronary artery disease (CAD), and other traditional risk factors affect the incidence of subsequent CAD, their impact in the same cohort has been scantly studied. RESEARCH DESIGN AND METHODS: We analyzed data from a nationwide claims database in Japan that was accumulated during 2008-2016 involving 138,162 men aged 18-72 years. Participants were classified as having normoglycemia, borderline glycemia, or diabetes mellitus (DM) with prior CAD (CAD+) or without prior CAD (CAD-). Cox regression model identified variables related to the incidence of CAD. RESULTS: Among CAD-, management of traditional risks differed from those with and without subsequent CAD events. On the other hand, such differences were weaker in borderline glycemia and DM CAD+, and the influence of traditional risk factors on subsequent CAD was not observed. Cox regression model showed that borderline glycemia and DM confer approximately 1.2- and 2.8-fold excess risks of CAD, respectively, compared with CAD- with normoglycemia. CAD+ confers approximately a 5- to 8-fold increased risk. The impacts of DM and prior CAD additively reached a hazard ratio (HR) of 15.74 (95% confidence interval [CI]: 11.82-21.00). However, the HR in those with borderline glycemia and CAD+ was 7.20 (95% CI: 5.01-10.34), which was not different from those with normoglycemia and CAD+. CONCLUSION: Control status of traditional risk factors and impact on subsequent CAD differ among categories of glycemic status with and without prior CAD. Individualizing treatment strategies is needed in consideration of risk factors, such as GAS and CAD+.

DOI： 10.1016/j.metabol.2019.153991

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Relationship Between Number of Multiple Risk Factors and Coronary Artery Disease Risk With and Without Diabetes Mellitus. Reviewed International journal

Mayuko Yamada-Harada, Kazuya Fujihara, Taeko Osawa, Masahiko Yamamoto, Masanori Kaneko, Masaru Kitazawa, Yasuhiro Matsubayashi, Takaho Yamada, Nauta Yamanaka, Hiroyasu Seida, Wataru Ogawa, Hirohito Sone

The Journal of clinical endocrinology and metabolism 104 ( 11 ) 5084 - 5090 2019.11

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To determine the degree of control of multiple risk factors under real-world conditions for coronary artery disease (CAD) according to the presence or absence of diabetes mellitus (DM) and to determine whether reaching multifactorial targets for blood pressure (BP), low-density lipoprotein-cholesterol (LDL-C), HbA1c, and current smoking is associated with lower risks for CAD. METHODS: We investigated the effects on subsequent CAD of the number of controlled risk factors among BP, LDL-C, HbA1c, and current smoking in a prospective cohort study using a nationwide claims database of 220,894 individuals in Japan. Cox regression examined risks over a 4.8-year follow-up. RESULTS: The largest percentage of participants had two risk factors at target in patients with DM (39.6%) and subjects without DM (36.4%). Compared with those who had two targets achieved, the risks of CAD among those who had any one and no target achieved were two and four times greater, respectively, regardless of the presence of DM. The effect of composite control was sufficient to bring CAD risk in patients with DM below that for subjects without DM with any two targets achieved, whereas the risk of CAD in the DM group with all four risk factors uncontrolled was 9.4 times more than in the non-DM group who had achieved two targets. CONCLUSIONS: These findings show that composite control of modifiable risk factors has a large effect in patients with and without DM. The effect was sufficient to bring CAD risk in patients with DM below that in the non-DM group who had two targets achieved.

DOI： 10.1210/jc.2019-00168

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2型糖尿病発症予防のための妊娠糖尿病妊婦への非薬物的強化介入の試み

川崎麻紀, 荒田尚子, 和栗雅子, 飯村祐子, 山本周美, 川嵜有紀, 牧尉太, 玉田祥子, 青山友子, 田中茂穂, 秦健一郎, 宮越敬, 橋本貢士, 杉山隆, 安日一郎, 曽根博仁, 菊池透, 瀧本秀美, 安田和基, 小川佳宏, 大田えりか, 井上永介, 平松祐司

糖尿病と妊娠 19 ( 3 ) S - 96 2019.11

Association between Helicobacter pylori infection, eradication and diabetes mellitus. Reviewed

Masayuki Kato, Akiko Toda, Ritsuko Yamamoto-Honda, Yasuji Arase, Hirohito Sone

Journal of diabetes investigation 10 ( 5 ) 1341 - 1346 2019.9

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

AIMS/INTRODUCTION: It is suspected that Helicobacter pylori is associated with extradigestive diseases including diabetes. So far, a number of studies have examined the association between H. pylori and diabetes, and the results were conflicting. The aim of the present study was to examine the association between H. pylori infection, eradication and diabetes. MATERIALS AND METHODS: The present cross-sectional study was carried out using data from annual health checkups carried out at the Toranomon Hospital Health Management Center. The status of H. pylori infection, determined by serum antibodies and history of eradication, was categorized into three groups as "never," "current" and "past." The association between H. pylori infection and diabetes was examined using logistic regression. RESULTS: Of 21,634 participants, 6,530 (30.2%) had a current or past history of H. pylori infection, and 1,184 (5.5%) were identified as having diabetes. Multivariate adjusted odds ratios for diabetes compared with the "never" group were 1.36 (95% confidence interval 1.10-1.67) for the "current" group and 0.92 (95% confidence interval 0.79-1.07) for the "past" group. The association between H. pylori infection and diabetes was also observed among participants without a history of eradication. CONCLUSIONS: We found that current H. pylori infection was associated with an increased risk of diabetes, and the increased risk was not observed among participants after eradication. The results were concordant with the hypothesis that H. pylori infection increases the risk of diabetes. Further studies are necessary to validate the present results.

DOI： 10.1111/jdi.13011

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Patient-based prediction algorithm of relapse after allo-HSCT for acute Leukemia and its usefulness in the decision-making process using a machine learning approach. Reviewed International journal

Kyoko Fuse, Shun Uemura, Suguru Tamura, Tatsuya Suwabe, Takayuki Katagiri, Tomoyuki Tanaka, Takashi Ushiki, Yasuhiko Shibasaki, Naoko Sato, Toshio Yano, Takashi Kuroha, Shigeo Hashimoto, Tatsuo Furukawa, Miwako Narita, Hirohito Sone, Masayoshi Masuko

Cancer medicine 8 ( 11 ) 5058 - 5067 2019.9

Language：English Publishing type：Research paper (scientific journal)

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for high-risk acute leukemia (AL), some patients still relapse. Since patients simultaneously have many prognostic factors, difficulties are associated with the construction of a patient-based prediction algorithm of relapse. The alternating decision tree (ADTree) is a successful classification method that combines decision trees with the predictive accuracy of boosting. It is a component of machine learning (ML) and has the capacity to simultaneously analyze multiple factors. Using ADTree, we attempted to construct a prediction model of leukemia relapse within 1 year of transplantation. With the model of training data (n = 148), prediction accuracy, the AUC of ROC, and the κ-statistic value were 78.4%, 0.746, and 0.508, respectively. The false positive rate (FPR) of the relapse prediction was as low as 0.134. In an evaluation of the model with validation data (n = 69), prediction accuracy, AUC, and FPR of the relapse prediction were similar at 71.0%, 0.667, and 0.216, respectively. These results suggest that the model is generalized and highly accurate. Furthermore, the output of ADTree may visualize the branch point of treatment. For example, the selection of donor types resulted in different relapse predictions. Therefore, clinicians may change treatment options by referring to the model, thereby improving outcomes. The present results indicate that ML, such as ADTree, will contribute to the decision-making process in the diversified allo-HSCT field and be useful for preventing the relapse of leukemia.

DOI： 10.1002/cam4.2401

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Attenuation of Weight Loss Through Improved Antilipolytic Effect in Adipose Tissue Via the SGLT2 Inhibitor Tofogliflozin Reviewed International journal

Akihiro Yoshida, Yasuhiro Matsubayashi, Toshiaki Nojima, Hideki Suganami, Takahiro Abe, Masahiro Ishizawa, Kazuya Fujihara, Shiro Tanaka, Kohei Kaku, Hirohito Sone

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 104 ( 9 ) 3647 - 3660 2019.9

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：ENDOCRINE SOC

Context: Although calorie loss from increased urinary glucose excretion continues after long-term treatment with sodium-glucose cotransporter 2 inhibitors (SGLT2is), the mechanisms of the attenuated weight loss due to SGLT2is are not well known.Objective: To examine the mechanism of the attenuated weight loss during long-term treatment with an SGLT2i, tofogliflozin, focusing on the antilipolytic effect of insulin on adipose tissue.Design and Participants: An integrated analysis was performed using data from two phase 3 studies of 52 weeks of tofogliflozin administration. The antilipolytic effect was evaluated using adipose tissue insulin resistance (Adipo-IR) calculated from the product of the levels of fasting insulin (f-IRI) and fasting free fatty acids (f-FFAs).Results: Data from 774 patients with type 2 diabetes (mean age, 58.5 years; glycosylated hemoglobin, 8.1%; body mass index, 25.6 kg/m(2); estimated glomerular filtration rate, 83.9 mUmin/1.73m(2); 66% men) were analyzed. Weight loss plateaued between weeks 24 and 52 after decreasing significantly. f-IRI levels decreased significantly from baseline to week 24, and the decrease was maintained until Week 52. f-FFA levels significantly increased, peaked at week 24, then declined from weeks 24 to 52. Adipo-IR levels declined progressively throughout the 52 weeks (-3.6 mmol/L.pmol/L and -6.2 mmol/L.pmol/L at weeks 24 and 52, respectively; P < 0.001 baseline vs weeks 24 and 52 and week 24 vs week 52). Higher baseline Adipo-IR levels were independently associated with greater weight loss at week 52.Conclusion: The improved antilipolytic effect in adipose tissue may attenuate progressive lipolysis, leading to attenuating future weight loss induced by an SGLT2i in patients with type 2 diabetes.

DOI： 10.1210/jc.2018-02254

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大血管障害耐糖能状態及び心血管疾患既往の有無で層別化した、心血管疾患発症リスクの検討 Reviewed

北澤勝, 藤原和哉, 山田万祐子, 大澤妙子, 山本正彦, 矢口雄大, 金子正儀, 松林泰弘, 山田貴穂, 清田浩康, 曽根博仁

糖尿病合併症 33 ( Suppl.1 ) 242 - 242 2019.9

青少年期の体格と代謝指標の関連 Reviewed

森川咲子, 治田麻理子, 平澤玲子, 谷内洋子, 堀川千嘉, 曽根博仁

New Diet Therapy 35 ( 2 ) 151 - 151 2019.9

眼科処置を要する重症糖尿病性眼疾患発生リスクと血液学的因子の関係についての検討 Reviewed

山本正彦, 藤原和哉, 大澤妙子, 山田万祐子, 石澤正博, 石黒創, 鈴木浩史, 松林泰弘, 児玉暁, 長谷部日, 曽根博仁

糖尿病合併症 33 ( Suppl.1 ) 263 - 263 2019.9

大血管障害糖尿病、非糖尿患者における血糖・血圧・脂質・喫煙の管理目標の達成状況と冠動脈疾患発症の関連 Reviewed

山田万祐子, 藤原和哉, 大澤妙子, 山本正彦, 石澤正博, 金子正儀, 松林泰弘, 清田浩康, 山田貴穂, 曽根博仁

糖尿病合併症 33 ( Suppl.1 ) 241 - 241 2019.9

Effect of family-oriented diabetes programs on glycemic control: A meta-analysis. Reviewed International journal

Satoru Kodama, Sakiko Morikawa, Chika Horikawa, Dai Ishii, Kazuya Fujihara, Masahiko Yamamoto, Taeko Osawa, Masaru Kitazawa, Takaho Yamada, Kiminori Kato, Shiro Tanaka, Hirohito Sone

Family practice 36 ( 4 ) 387 - 394 2019.7

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Efficacy of programs for patients with diabetes mellitus (DM) that have promoted family members to help with patients' self-care activities has been largely inconsistent. This meta-analysis aims to assess the effect of family-oriented diabetes programs for glycemic control (GC). METHODS: Electronic literature searches were conducted for clinical trials with a parallel design wherein there were two groups according to whether family members were included (intervention group) or not included (control group) and changes in glycohemoglobin A1C (A1C) were assessed as a study outcome. Each effect size (i.e. difference in A1C change between the intervention and control group) was pooled with a random-effects model. RESULTS: There were 31 eligible trials consisting of 1466 and 1415 patients in the intervention and control groups, respectively. Pooled A1C change [95% confidence interval (CI)] was -0.45% (-0.64% to -0.26%). Limiting analyses to 21 trials targeted at patients with type 1 DM or 9 trials targeted at patients with type 2 DM, the pooled A1C changes (95% CI) were -0.35% (-0.55% to -0.14%) and -0.71% (-1.09% to -0.33%), respectively. CONCLUSION: This meta-analysis suggests that focusing on the family as well as the individual patient in self-management diabetes programs to improve the performance of self-care activities of patients with DM is effective in terms of proper GC.

DOI： 10.1093/fampra/cmy112

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Blake's pouch cystに伴う水頭症の治療により若年性認知症の改善を認めた糖尿病の1例 Reviewed

種村聡, 山本正彦, 石黒創, 岩永みどり, 松林泰弘, 山田貴穂, 藤原和哉, 渡邊賢一, 曽根博仁

糖尿病 62 ( 7 ) 441 - 441 2019.7

Overt Proteinuria, Moderately Reduced eGFR and Their Combination Are Predictive of Severe Diabetic Retinopathy or Diabetic Macular Edema in Diabetes. Reviewed International journal

Masahiko Yamamoto, Kazuya Fujihara, Masahiro Ishizawa, Taeko Osawa, Masanori Kaneko, Hajime Ishiguro, Yasuhiro Matsubayashi, Hiroyasu Seida, Nauta Yamanaka, Shiro Tanaka, Satoru Kodama, Hiruma Hasebe, Hirohito Sone

Investigative ophthalmology & visual science 60 ( 7 ) 2685 - 2689 2019.6

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Purpose: Since the combined effects of proteinuria and a moderately decreased eGFR on incident severe eye complications in patients with diabetes are still largely unknown, these associations were determined in a large historical cohort of Japanese patients with diabetes mellitus. Methods: We evaluated the effects of overt proteinuria (OP) (dipstick 1+ and over) and/or moderately reduced estimated glomerular filtration rate (eGFR) (MG) (baseline eGFR 30.0-54.9 mL/min/1.73 m2) on the incidence of treatment-required diabetic eye diseases (TRDED). We divided 7709 patients into four groups according to the presence or absence of OP and MG: no OP without MG (NP[MG-]), OP without MG (OP[MG-]), no OP with MG (NP[MG+]), and OP with MG (OP[MG+]). Multivariate Cox analyses were performed to calculate hazard ratios (HRs) with 95% confidence intervals for combinations of the presence and/or absence of OP and MG on the risk of developing TRDED. Results: During the median follow-up period of 5.6 years, 168 patients developed TRDED. HRs for OP and MG for incident TRDED were 1.91 (95% confidence interval, 1.27-2.87) and 1.90 (1.11-3.23), respectively. HRs for incident TRDED were 1.73 (1.11-2.69) and 5.57 (2.40-12.94) for OP(MG-) and OP(MG+), respectively, in comparison with NP(MG-). Conclusions: In Japanese patients with diabetes, OP and MG were separately as well as additionally associated with higher risks of TRDED. Results indicate the necessity of the simultaneous assessment of proteinuria and eGFR for appropriate evaluation of risks of severe eye complications in patients with diabetes.

DOI： 10.1167/iovs.19-26749

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Papers - SONE, Hirohito