Papers - ITOH Hiroshi

2型糖尿病患者に非定型抗精神病薬リスペリドンを使用し高血糖高浸透圧症候群を発症した1例

宇都 飛鳥, 税所 芳史, 入江 潤一郎, 田中 正巳, 目黒 周, 伊藤 裕

日本抗加齢医学会総会プログラム・抄録集 ((一社)日本抗加齢医学会)  19回   246 - 246 2019.06

Accepted

2型糖尿病患者における血中総ビリルビン濃度と網膜症および大血管障害との関連

田中 正巳, 西村 健志, 目黒 周, 入江 潤一郎, 税所 芳史, 三石 正憲, 川野 義長, 伊藤 裕

日本抗加齢医学会総会プログラム・抄録集 ((一社)日本抗加齢医学会)  19回   249 - 249 2019.06

Accepted

2型糖尿病患者における短時間作用型GLP-1製剤から長時間作用型GLP-1製剤への切替えの有効性及び安全性についての検討

税所 芳史, 渡辺 雄祐, 稲石 淳, 侯 金成, 山内 晃, 金澤 寧彦, 大久保 佳昭, 徳井 幹也, 今井 孝俊, 村上 理恵, 土屋 多美, 佐々木 裕伸, 菊地 理恵子, 正岡 建洋, 入江 潤一郎, 目黒 周, 伊藤 裕

日本抗加齢医学会総会プログラム・抄録集 ((一社)日本抗加齢医学会)  19回   231 - 231 2019.06

CKDにおけるdysbiosisは、筋萎縮およびミトコンドリア機能低下を伴う運動耐容能の低下を惹起する

内山 清貴, 脇野 修, 入江 潤一郎, 伊藤 裕

日本抗加齢医学会総会プログラム・抄録集 ((一社)日本抗加齢医学会)  19回   194 - 194 2019.06

Accepted

Foxo1-CoF Repressor (FCoR) Regulates Pancreatic Alpha- and Beta-Cell Identity by both DNA and Histone Methylation

Noriko Kodani, Masaki Kobayashi, Osamu Kikuchi, Tadahiro Kitamura, Hiroshi Itoh, Jun Nakae

DIABETES (AMER DIABETES ASSOC)  68 2019.06

ISSN  0012-1797

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ケトジェニック環境下におけるGPR43の機能解析

宮本 潤基, 北野 隆司[大植], 五十嵐 美樹, 入江 潤一郎, 伊藤 裕, 木村 郁夫

日本抗加齢医学会総会プログラム・抄録集 ((一社)日本抗加齢医学会)  19回   220 - 220 2019.06

Accepted

高齢者透析患者に合併した小腸angioectasiaの一例

木内 謙一郎, 脇野 修, 二木 功治, 徳山 博文, 細江 直樹, 菅野 義彦, 林 松彦, 林 晃一, 伊藤 裕

日本抗加齢医学会総会プログラム・抄録集 ((一社)日本抗加齢医学会)  19回   251 - 251 2019.06

減量外科術が日本人肥満症患者の腸内細菌叢と糖代謝指標に与える影響

入江 潤一郎, 菊池 理恵子, 後藤 伸子, 吉川 絵梨, 関 洋介, 笠間 和典, 伊藤 裕

日本抗加齢医学会総会プログラム・抄録集 ((一社)日本抗加齢医学会)  19回   244 - 244 2019.06

Accepted

糖尿病・肥満症、慢性腎臓病と腸内細菌叢

入江 潤一郎, 内山 清貴, 木村 郁夫, 脇野 修, 伊藤 裕

日本抗加齢医学会総会プログラム・抄録集 ((一社)日本抗加齢医学会)  19回   271 - 271 2019.06

Accepted

肝脂肪蓄積・糖代謝異常に対するGLP-1治療におけるTリンパ球の意義

田中 久美子, 入江 潤一郎, 伊藤 新, 田川 裕恒, 楠本 幸恵, 加藤 麻里, 小林 奈奈, 菊池 理恵子, 藤田 正隆, 中島 裕也, 山田 悟, 河合 俊英, 伊藤 裕

日本抗加齢医学会総会プログラム・抄録集 ((一社)日本抗加齢医学会)  19回   259 - 259 2019.06

Accepted

腸管内胆汁酸代謝を介した腸内細菌制御と体脂肪蓄積抑制の解明

楠本 幸恵, 入江 潤一郎, 岩部 佳穂, 田川 裕恒, 伊藤 新, 加藤 麻里, 田中 久美子, 菊地 理恵子, 藤田 真隆, 森本 耕吉, 山田 悟, 河合 俊英, 渡辺 光博, 尾池 雄一, 伊藤 裕

日本抗加齢医学会総会プログラム・抄録集 ((一社)日本抗加齢医学会)  19回   194 - 194 2019.06

Accepted

免疫チェックポイント阻害剤投与後に劇症1型糖尿病を発症した1例

稲石 淳, 税所 芳史, 渡辺 雄祐, 三石 正憲, 入江 潤一郎, 田中 正巳, 目黒 周, 伊藤 裕

日本抗加齢医学会総会プログラム・抄録集 ((一社)日本抗加齢医学会)  19回   232 - 232 2019.06

Accepted

ステロイドによる血糖悪化に対し、週1回投与のGLP-1受容体作動薬と持効型インスリンでコントロールしえた高齢2型糖尿病患者の1例

三石 正憲, 斎藤 洸平, 中島 裕也, 稲石 淳, 税所 芳史, 入江 潤一郎, 田中 正巳, 目黒 周, 伊藤 裕

日本抗加齢医学会総会プログラム・抄録集 ((一社)日本抗加齢医学会)  19回   246 - 246 2019.06

Accepted

Acquired partial lipodystrophy with metabolic disease in children following hematopoietic stem cell transplantation: a report of two cases and a review of the literature.

Mayumi Hosokawa, Hironori Shibata, Takahiro Hosokawa, Junichiro Irie, Hiroshi Ito, Tomonobu Hasegawa

Journal of pediatric endocrinology & metabolism : JPEM 32 ( 5 ) 537 - 541 2019.05

Accepted

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Hematopoietic stem cell transplantation (HSCT) has been newly identified as an etiology underlying acquired lipodystrophy (ALD). We report about two children with leukemia who underwent HSCT and later manifested aberrant fat distributions consistent with acquired partial lipodystrophy (APL). Both patients manifested graft-versus-host disease (GVHD), suggesting that GVHD may trigger lipodystrophy. The patients exhibited diabetic blood glucose patterns in the oral glucose tolerance test (OGTT) with high homeostasis model assessment ratios (HOMA-Rs), hypertriglyceridemia, fatty liver, and decreased serum leptin and adiponectin levels. Both patients were diagnosed with APL with metabolic disease. A review of the data of patients with ALD after HSCT revealed common clinical features, including aberrant fat distribution, impaired glucose tolerance (IGT) or diabetes and dyslipidemia. Based on previous reports and our two cases, we speculate that GVHD in the adipose tissue supports the development of ALD after HSCT. In conclusion, children may develop APL after HSCT. Therefore, evaluations of fat distribution and metabolic disease may be important during the long-term follow-up of these patients.

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High prevalence of diabetes in patients with primary aldosteronism (PA) associated with subclinical hypercortisolism and prediabetes more prevalent in bilateral than unilateral PA: A large, multicenter cohort study in Japan

Akehi Y., Yanase T., Motonaga R., Umakoshi H., Tsuiki M., Takeda Y., Yoneda T., Kurihara I., Itoh H., Katabami T., Ichijo T., Wada N., Shibayama Y., Yoshimoto T., Ashida K., Ogawa Y., Kawashima J., Sone M., Inagaki N., Takahashi K., Fujita M., Watanabe M., Matsuda Y., Kobayashi H., Shibata H., Kamemura K., Otsuki M., Fujii Y., Yamamoto K., Ogo A., Okamura S., Miyauchi S., Fukuoka T., Izawa S., Hashimoto S., Yamada M., Yoshikawa Y., Kai T., Suzuki T., Kawamura T., Naruse M.

Diabetes Care (Diabetes Care)  42 ( 5 ) 938 - 945 2019.05

ISSN  01495992

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© 2019 by the American Diabetes Association. OBJECTIVE To investigate the prevalence and causes of diabetes in patients with primary aldosteronism (PA) in a multi-institutional cohort study in Japan. RESEARCH DESIGN AND METHODS The prevalence of diabetes was determined in 2,210 patients with PA (diagnosed or glycated hemoglobin [HbA1c] ‡6.5% [‡48 mmol/mol]; NGSP) and compared with that of the Japanese general population according to age and sex. In 1,386 patients with PA and clear laterality (unilateral or bilateral), the effects of plasma aldosterone concentration (PAC), hypokalemia (<3.5 mEq/L), suspected subclinical hypercortisolism (SH; serum cortisol ‡1.8 mg/dL after 1-mg dexamethasone suppression test), and PA laterality on the prevalence of diabetes or prediabetes (5.7% £ HbA1c <6.5% [39 mmol/mol £ HbA1c <48 mmol/mol]) were examined. RESULTS Of the 2,210 patients with PA, 477 (21.6%) had diabetes. This prevalence is higher than that in the general population (12.1%) or in 10-year cohorts aged 30–69 years. Logistic regression or x2 test revealed a significant contribution of suspected SH to diabetes. Despite more active PA profiles (e.g., higher PAC and lower potassium concentrations) in unilateral than bilateral PA, BMI and HbA1c values were significantly higher in bilateral PA. PA laterality had no effect on the prevalence of diabetes; however, the prevalence of prediabetes was significantly higher in bilateral than unilateral PA. CONCLUSIONS Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA.

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β-hydroxybutyrate attenuates renal ischemia-reperfusion injury through its anti-pyroptotic effects

Tajima T., Yoshifuji A., Matsui A., Itoh T., Uchiyama K., Kanda T., Tokuyama H., Wakino S., Itoh H.

Kidney International (Kidney International)  95 ( 5 ) 1120 - 1137 2019.05

ISSN  00852538

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© 2019 International Society of Nephrology Ketone bodies including β-hydroxybutyrate (β-OHB) have been shown to protect against ischemic tissue injury when present at low concentrations. We evaluated the impact of β-OHB on renal ischemia/reperfusion injury (IRI). Mice were treated with a continuous infusion of β-OHB using an osmotic mini-pump before and after IRI. We also tested the effects of increasing endogenous serum β-OHB levels by fasting. Renal IRI was attenuated by β-OHB treatment compared to saline control, with similar results in the fasting condition. β-OHB treatment reduced the number of terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling (TUNEL)-positive cells and increased expression of forkhead transcription factor O3 (FOXO3), an upstream regulator of pyroptosis. Although β-OHB treatment did not impact markers of apoptosis, it decreased the expression of caspase-1 and proinflammatory cytokines, indicating that β-OHB blocked pyroptosis. In a human proximal tubular cell line exposed to hypoxia and reoxygenation, β-OHB reduced cell death in a FOXO3-dependent fashion. Histone acetylation was decreased in kidneys exposed to IRI and in proximal tubular cells exposed to hypoxia and reoxygenation, and this effect was ameliorated by β-OHB through the inactivation of histone deacetylases. In vitro, β-OHB treatment restored histone acetylation at the FOXO3 promoter. Consistent with epigenetic molecular effects, the renoprotective effects of β-OHB were still observed when the continuous infusion was stopped at the time of IRI. Thus, β-OHB attenuates renal IRI through anti-pyroptotic effects, likely mediated by an epigenetic effect on FOXO3 expression.

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CKDにおけるdysbiosisは腸管tight junctionの発現低下及び尿毒素蓄積からインスリン抵抗性とサルコペニアを惹起する

内山 清貴, 脇野 修, 入江 潤一郎, 伊藤 裕

日本腎臓学会誌 ((一社)日本腎臓学会)  61 ( 3 ) 400 - 400 2019.05

Accepted,  ISSN  0385-2385

Role of Nampt-Sirt6 Axis in Renal Proximal Tubules in Extracellular Matrix Deposition in Diabetic Nephropathy

Muraoka H., Hasegawa K., Sakamaki Y., Minakuchi H., Kawaguchi T., Yasuda I., Kanda T., Tokuyama H., Wakino S., Itoh H.

Cell Reports (Cell Reports)  27 ( 1 ) 199 - 212.e5 2019.04

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© 2019 The Author(s) Nicotinamide adenine dinucleotide (NAD + ) metabolism plays a critical role in kidneys. We previously reported that decreased secretion of a NAD + precursor, nicotinamide mononucleotide (NMN), from proximal tubules (PTs) can trigger diabetic albuminuria. In the present study, we investigated the role of NMN-producing enzyme nicotinamide phosphoribosyltransferase (Nampt) in diabetic nephropathy. The expression of Nampt in PTs was downregulated in streptozotocin (STZ)-treated diabetic mice when they exhibited albuminuria. This albuminuria was ameliorated in PT-specific Nampt-overexpressing transgenic (TG) mice. PT-specific Nampt-conditional knockout (Nampt CKO) mice exhibited TBM thickening and collagen deposition, which were associated with the upregulation of the profibrogenic gene TIMP-1. Nampt CKO mice also exhibited the downregulation of sirtuins, particularly in Sirt6. PT-specific Sirt6-knockout mice exhibited enhanced fibrotic phenotype resembling that of Nampt CKO mice with increased Timp1 expression. In conclusion, the Nampt-Sirt6 axis in PTs serves as a key player in fibrogenic extracellular matrix remodeling in diabetic nephropathy. Muraoka et al. reveal that the Nampt-Sirt6 axis in proximal tubules serves as a key player in fibrogenic extracellular matrix remodeling in diabetic nephropathy.

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A Case Report of Autosomal Dominant Polycystic Kidney Disease Under Peritoneal Dialysis With Cyst Infection and Culture-Positive Peritoneal Fluid

Yasuda I., Hasegawa K., Tokuyama H., Washida N., Shinozuka K., Yasuda M., Ryuzaki M., Urai H., Wakino S., Itoh H.

Clinical Medicine Insights: Case Reports (Clinical Medicine Insights: Case Reports)  12 2019.04

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© The Author(s) 2019. Background: Cyst infection is a complication sometimes seen in patients with autosomal dominant polycystic kidney disease (ADPKD) and often shows through a positive blood culture. However, there have been no reports of ADPKD patients whose cyst infection propagate to peritoneal fluid leading to positive peritoneal fluid culture. Case presentation: A 74-year-old Japanese man with ADPKD under peritoneal dialysis (PD) was presented with left flank pain, fever, and chills at our hospital. He did not show any symptoms or signs suggestive of peritonitis. There were no elevated cell counts or polymorphonuclear leucocytes in his PD fluid. There were some complicated cysts found in computed tomography and magnetic resonance imaging examinations. We clinically diagnosed him as having a renal cyst infection rather than PD-related peritonitis. We initiated treatment by administering ceftriaxone with an immediate favorable response. As the possibility of accompanying prostatitis still remained, we switched to intravenous levofloxacin on the second day. On the 10th day, Helicobacter cinaedi was detected in 2 sets of blood culture as well as in PD fluid. We switched back to ceftriaxone and this treatment was entirely successful. Conclusions: This is the first report of H cinaedi cyst infection which propagates to peritoneal fluid in a patient with ADPKD.

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Achieving LDL cholesterol target levels &lt;1.81 mmol/L may provide extra cardiovascular protection in patients at high risk: Exploratory analysis of the Standard Versus Intensive Statin Therapy for Patients with Hypercholesterolaemia and Diabetic Retinopathy study

Itoh H., Komuro I., Takeuchi M., Akasaka T., Daida H., Egashira Y., Fujita H., Higaki J., Hirata K., Ishibashi S., Isshiki T., Ito S., Kashiwagi A., Kato S., Kitagawa K., Kitakaze M., Kitazono T., Kurabayashi M., Miyauchi K., Murakami T., Murohara T., Node K., Ogawa S., Saito Y., Seino Y., Shigeeda T., Shindo S., Sugawara M., Sugiyama S., Terauchi Y., Tsutsui H., Ueshima K., Utsunomiya K., Yamagishi M., Yamazaki T., Yo S., Yokote K., Yoshida K., Yoshimura M., Yoshimura N., Nakao K., Nagai R.

Diabetes, Obesity and Metabolism (Diabetes, Obesity and Metabolism)  21 ( 4 ) 791 - 800 2019.04

ISSN  14628902

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© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. Aims: To assess the benefits of intensive statin therapy on reducing cardiovascular (CV) events in patients with type 2 diabetes complicated with hyperlipidaemia and retinopathy in a primary prevention setting in Japan. In the intension-to-treat population, intensive therapy [targeting LDL cholesterol <1.81 mmol/L (<70 mg/dL)] was no more effective than standard therapy [LDL cholesterol ≥2.59 to <3.10 mmol/L (≥100 to <120 mg/dL)]; however, after 3 years, the intergroup difference in LDL cholesterol was only 0.72 mmol/L (27.7 mg/dL), and targeted levels were achieved in <50% of patients. We hypothesized that the intergroup difference in CV events would have been statistically significant if more patients had been successfully treated to target. Materials and Methods: This exploratory post hoc analysis focused on intergroup data from patients who achieved their target LDL cholesterol levels. The primary endpoint was the composite incidence of CV events. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for incidence of the primary endpoint in patients who achieved target LDL cholesterol levels in each group. Results: Data were analysed from 1909 patients (intensive: 703; standard: 1206) who achieved target LDL cholesterol levels. LDL cholesterol at 36 months was 1.54 ± 0.30 mmol/L (59.7 ± 11.6 mg/dL) in the intensive group and 2.77 ± 0.46 mmol/L (107.1 ± 17.8 mg/dL) in the standard group (P < 0.05). After adjusting for baseline prognostic factors, the composite incidence of CV events or deaths associated with CV events was significantly lower in the intensive than the standard group (HR 0.48; 95% confidence interval 0.28-0.82; P = 0.007). Conclusions: This post hoc analysis suggests that achieving LDL cholesterol target levels <1.81 mmol/L may more effectively reduce CV events than achieving target levels ≥2.59 to <3.10 mmol/L in patients with hypercholesterolaemia and diabetic retinopathy.

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