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Papers - ITOH Hiroshi

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落葉状天疱瘡と水疱性類天疱瘡の合併症例に対し血漿交換が奏功した一例

高橋利奈, 水口斉, 吉田理, 伊藤裕, 大家基嗣

日本透析医学会雑誌 ((一社)日本透析医学会) 53 ( Suppl.1 ) 544 - 544 2020.10

ISSN 1340-3451

Asperuloside Improves Obesity and Type 2 Diabetes through Modulation of Gut Microbiota and Metabolic Signaling.

Anna Nakamura, Yoko Yokoyama, Kazuki Tanaka, Giorgia Benegiamo, Akiyoshi Hirayama, Qi Zhu, Naho Kitamura, Taichi Sugizaki, Kohkichi Morimoto, Hiroshi Itoh, Shinji Fukuda, Johan Auwerx, Kazuo Tsubota, Mitsuhiro Watanabe

iScience 23 ( 9 ) 101522 - 101522 2020.09

Asperuloside (ASP) is an iridoid glycoside that is extracted from Eucommia leaves. Eucommia is used in traditional Chinese medicine and has a long history of benefits on health and longevity. Here, we investigated the impact of ASP on obesity-related metabolic disorders and show that ASP reduces body weight gain, glucose intolerance, and insulin resistance effectively in mice fed with a high-fat diet (HFD). Intestinal dysbiosis is closely linked with metabolic disorders. Our data indicate that ASP achieves these benefits on metabolic homeostasis by reversing HFD-induced gut dysbiosis and by changing gut-derived secondary metabolites and metabolic signaling. Our results indicate that ASP may be used to regulate gut microbiota for the treatment of obesity and type 2 diabetes.

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Contribution of uremic dysbiosis to insulin resistance and sarcopenia.

Kiyotaka Uchiyama, Shu Wakino, Junichiro Irie, Junki Miyamoto, Ayumi Matsui, Takaya Tajima, Tomoaki Itoh, Yoichi Oshima, Ayumi Yoshifuji, Ikuo Kimura, Hiroshi Itoh

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 35 ( 9 ) 1501 - 1517 2020.09

ISSN 0931-0509

BACKGROUND: Chronic kidney disease (CKD) leads to insulin resistance (IR) and sarcopenia, which are associated with a high mortality risk in CKD patients; however, their pathophysiologies remain unclear. Recently, alterations in gut microbiota have been reported to be associated with CKD. We aimed to determine whether uremic dysbiosis contributes to CKD-associated IR and sarcopenia. METHODS: CKD was induced in specific pathogen-free mice via an adenine-containing diet; control animals were fed a normal diet. Fecal microbiota transplantation (FMT) was performed by oral gavage in healthy germ-free mice using cecal bacterial samples obtained from either control mice (control-FMT) or CKD mice (CKD-FMT). Vehicle mice were gavaged with sterile phosphate-buffered saline. Two weeks after inoculation, mice phenotypes, including IR and sarcopenia, were evaluated. RESULTS: IR and sarcopenia were evident in CKD mice compared with control mice. These features were reproduced in CKD-FMT mice compared with control-FMT and vehicle mice with attenuated insulin-induced signal transduction and mitochondrial dysfunction in skeletal muscles. Intestinal tight junction protein expression and adipocyte sizes were lower in CKD-FMT mice than in control-FMT mice. Furthermore, CKD-FMT mice showed systemic microinflammation, increased concentrations of serum uremic solutes, fecal bacterial fermentation products and elevated lipid content in skeletal muscle. The differences in gut microbiota between CKD and control mice were mostly consistent between CKD-FMT and control-FMT mice. CONCLUSIONS: Uremic dysbiosis induces IR and sarcopenia, leaky gut and lipodystrophy.

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A new normal for hypertension medicine with coronavirus disease-2019 (COVID-19): proposal from the president of the Japanese Society of Hypertension.

Hiroshi Itoh

Hypertension research : official journal of the Japanese Society of Hypertension 43 ( 9 ) 857 - 858 2020.09

ISSN 0916-9636

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Low birth weight trends: possible impacts on the prevalences of hypertension and chronic kidney disease.

Takeshi Kanda, Ayano Murai-Takeda, Hiroshi Kawabe, Hiroshi Itoh

Hypertension research : official journal of the Japanese Society of Hypertension 43 ( 9 ) 859 - 868 2020.09

ISSN 0916-9636

Worldwide, hypertension and chronic kidney disease (CKD) are highly prevalent disorders and are strong risk factors for cardiovascular disease and end-stage renal disease (ESRD). The developmental origins of health and disease (DOHAD) concept suggests that undesirable perinatal environmental conditions, such as malnutrition, contribute to disease development in adults. Among the known hypertension and CKD risk factors, DOHAD plays a potential role in determining susceptibility to the onset of these diseases in later adulthood. Since low birth weight (LBW) is a surrogate marker for adverse fetal environmental conditions, the high incidence of LBW in developing countries and its increasing incidence in most developed countries (attributed to multiple pregnancies and prepregnancy maternal factors, such as undernutrition, advanced maternal age, and smoking) is concerning. Thus, LBW is an important public health problem not only because of the associated infant mortality and morbidity but also because it is a risk factor for adult-onset hypertension/CKD. During their reproductive years, pregnant women who were born with LBWs have an increased risk of hypertensive disorders of pregnancy, which contribute to the risk of developing cardiovascular disease and ESRD. The offspring of LBW females are also likely to be LBW, which suggests that susceptibility to hypertension/CKD may reflect transgenerational inheritance. Therefore, there is global concern about the increasing prevalence of LBW-related diseases. This review summarizes the relevance of hypertension and CKD in conjunction with DOHAD and discusses recent studies that have examined the impact of the upward LBW trend on renal function and blood pressure.

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Relationship between daily and visit-to-visit glycemic variability in patients with type 2 diabetes.

Tami Tsuchiya, Yoshifumi Saisho, Rie Murakami, Yuusuke Watanabe, Jun Inaishi, Hiroshi Itoh

Endocrine journal 67 ( 8 ) 877 - 881 2020.08

ISSN 0918-8959

The aim of the study was to explore the relationship between daily glycemic variability (GV) and visit-to-visit glycemic variability (VVV) in patients with type 2 diabetes (T2DM). A total of 156 outpatients with T2DM who had undergone continuous glucose monitoring (CGM) for 5 days were included in this study. Indices of GV, i.e., standard deviation and coefficient of variation (CV) of glucose, mean amplitude of glycemic excursion (MAGE) and mean of the daily differences (MODD) were calculated from the CGM data. VVV was calculated as CV of HbA1c or glycated albumin (GA) from HbA1c or GA measured for 3 years. Relationships among clinical parameters, GV and VVV were evaluated. Age was positively, and BMI and C-peptide index were inversely correlated with GV such as CV glucose and MAGE, while BMI was positively correlated with VVV. Mean glucose rather than GV was correlated with VVV. In contrast, time in range (TIR, 70-180 mg/dL) was correlated with both mean HbA1c or GA and VVV. In conclusion, GV and VVV were differently correlated with clinical parameters and were hardly correlated with each other. TIR was correlated with both mean HbA1c and VVV, suggesting that efforts to achieve optimal TIR are practical strategies to reduce VVV in patients with T2DM.

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エキセナチド1日2回製剤から週1回製剤への切り替えによる血糖変動・胃排出速度・血管内皮機能の変化 Twin-exenatide試験(第2報)

渡辺雄祐, 税所芳史, 稲石淳, 土屋多美, 佐々木裕伸, 正岡建洋, 入江潤一郎, 目黒周, 伊藤裕

糖尿病 ((一社)日本糖尿病学会) 63 ( Suppl.1 ) S - 213 2020.08

ISSN 0021-437X

原発性アルドステロン症における腎障害は心血管イベントと異なり血中アルドステロン値と直接相関する

川島彰透, 曽根正勝, 稲垣暢也, 武田仁勇, 伊藤裕, 栗原勲, 一城貴政, 方波見卓行, 和田典男, 小川佳宏, 宮内省蔵, 鈴木知子, 成瀬光栄

日本内分泌学会雑誌 ((一社)日本内分泌学会) 96 ( 1 ) 241 - 241 2020.08

ISSN 0029-0661

Appropriate timing for a biochemical evaluation after adrenalectomy for unilateral aldosterone-producing adenoma.

Kimiharu Takamatsu, Toshikazu Takeda, Seiya Hattori, Nobuyuki Tanaka, Shinya Morita, Kazuhiro Matsumoto, Takeo Kosaka, Ryuichi Mizuno, Toshiaki Shinojima, Eiji Kikuchi, Hiroshi Asanuma, Isao Kurihara, Hiroshi Itoh, Mototsugu Oya

Clinical endocrinology 92 ( 6 ) 503 - 508 2020.06

ISSN 0300-0664

CONTEXT: The oversecretion of plasma aldosterone by unilateral aldosterone-producing adenoma (APA) can be cured by adrenalectomy. However, the time needed for the endocrine environment to normalize remains unclear. OBJECTIVE: To clarify adequate timing for a biochemical evaluation in unilateral APA patients after adrenalectomy. DESIGN AND PATIENTS: A total of 166 unilateral APA patients were retrospectively reviewed. We evaluated the plasma aldosterone concentration (PAC) (pg/mL), active renin concentration (ARC) (pg/mL), aldosterone-renin ratio (ARR; PAC/ARC), serum potassium concentration and estimated glomerular filtration rate (eGFR) at 1, 3 and 6 postoperation months (POM). RESULTS: PAC was significantly lower at 1POM than at presurgery (presurgery; 407.2, 1 POM; 90.0 pg/mL, P < .001). ARC did not increase from baseline at 1POM, but significantly increased at 3POM (presurgery; 4.43, 1POM; 4.87, 3POM; 11.3 pg/mL, P < .001). ARR significantly decreased at 1POM (presurgery; 146.9, 1 POM; 26.3, P < .001) although ARC did not increase at 1POM. Among the 34 patients who had hypokalaemia presurgery, it was resolved in 28 (82%) at 1POM and in all (100%) at 3POM. The biochemical outcomes at 1POM were 131 (79%) complete, 20 (12%) partial and 15 (9%) absent successes, while at 3POM, 147 (89%) were complete, 9 (5%) partial and 10 (6%) absent. Twenty-three (14%) patients were reclassified into different biochemical outcomes between 1 and 3POM, whereas only 5 (3%) changed between 3 and 6POM. CONCLUSION: The appropriate timing for a biochemical evaluation of unilateral APA patients treated with laparoscopic adrenalectomy appears to be 3 months or more after surgery.

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A case of cerebral infarction caused by painless acute aortic dissection in autosomal dominant polycystic kidney disease.

Shintaro Yamaguchi, Shu Wakino, Hirobumi Tokuyama, Hiroshi Itoh

CEN case reports 9 ( 2 ) 177 - 181 2020.05

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder, characterized by the progressive formation of renal cysts. Although ADPKD is strongly associated with cerebral and cardiovascular complications, cerebral ischemia caused by dissection of thoracic and carotid arteries has rarely been reported. We report the case of a 71-year-old Japanese woman who complained of hemiparesis. She required maintenance hemodialysis therapy with a background of ADPKD. Cerebral infarction was initially diagnosed by excluding intracranial hemorrhage and aneurysm rupture that are recognized as common complications of ADPKD and thereby anticoagulation therapy was initiated. However, the patient was suspected as having painless aortic dissection because a chest X-ray examination showed expanded upper mediastinum. Sequential vascular imagings revealed dissection of the aorta, originating from brachiocephalic trunk to the right common carotid artery with mediastinal hematoma. The patient died from progression of dissection. Herein, we described a case of the ADPKD patient that an acute aortic dissection without any pain induced the occlusion of supplying vessels to the brain, resulting in cerebral ischemic symptoms. A high level of clinical vigilance for an acute aortic dissection should be maintained in the ADPKD population with sudden onset of neurological symptoms even in the absence of pain. Furthermore, the initiation of anticoagulation treatment for cerebral ischemia which may aggravate the risk of further dissection requires careful consideration.

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Nadir Aldosterone Levels After Confirmatory Tests Are Correlated With Left Ventricular Hypertrophy in Primary Aldosteronism.

Youichi Ohno, Masakatsu Sone, Nobuya Inagaki, Akiyuki Kawashima, Yoshiyu Takeda, Takashi Yoneda, Isao Kurihara, Hiroshi Itoh, Mika Tsuiki, Takamasa Ichijo, Takuyuki Katabami, Norio Wada, Ryuichi Sakamoto, Yoshihiro Ogawa, Takanobu Yoshimoto, Tetsuya Yamada, Junji Kawashima, Yuichi Matsuda, Hiroki Kobayashi, Kohei Kamemura, Koichi Yamamoto, Michio Otsuki, Shintaro Okamura, Shoichiro Izawa, Ryuji Okamoto, Kouichi Tamura, Akiyo Tanabe, Mitsuhide Naruse

Hypertension (Dallas, Tex. : 1979) 75 ( 6 ) HYPERTENSIONAHA11914601 - 1482 2020.04

Accepted, ISSN 0194-911X

Left ventricular hypertrophy (LVH) is often seen in patients with primary aldosteronism (PA), and the prevalence of LVH is reportedly higher among patients with PA than patients with essential hypertension. However, the correlation between aldosterone levels and LVH is undefined, and how aldosterone affects LVH in patients with PA remains unclear. We, therefore, retrospectively assessed a large PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) to reveal the factors associated with LVH in patients with PA without suspected autonomous cortisol secretion. In the 1186 patients with PA studied, the basal plasma aldosterone concentration, plasma renin activity, and the aldosterone-to-renin ratio did not significantly correlate with left ventricular LV mass index (LVMI) in single or multiple regression analyses. However, the plasma aldosterone concentration after the captopril challenge test or saline-infusion test, which are associated with autonomous aldosterone secretion, correlated significantly with LVMI, even after adjusting for patients' backgrounds, including age and blood pressure. In addition, hypokalemia and the unilateral subtype also correlated with LVMI. Longitudinal subanalysis of medically or surgically treated patients with PA showed significant reductions in LVMI in both the surgery (63.0±18.1 to 55.3±19.5 g/m2.7, P<0.001) and drug treatment (56.8±14.1 to 52.1±13.5 g/m2.7, P<0.001) groups. Our results suggest the autonomous aldosterone secretion level, not the basal aldosterone level itself, is relevant to LVH in patients with PA. In addition, the elevated LVMI seen in patients with PA is at least partially reversible with surgical or medical treatment.

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Associations of birthweight and history of childhood obesity with beta cell mass in Japanese adults.

Hironobu Sasaki, Yoshifumi Saisho, Jun Inaishi, Yuusuke Watanabe, Tami Tsuchiya, Masayoshi Makio, Midori Sato, Minoru Kitago, Taketo Yamada, Hiroshi Itoh

Diabetologia 63 ( 6 ) 1199 - 1210 2020.04

Accepted, ISSN 0012-186X

AIMS/HYPOTHESIS: Low birthweight is associated with a high risk of diabetes, but there are no reports discussing birthweight and pancreatic tissues in humans. The purpose of this study was to examine the correlation between birthweight and beta and alpha cell mass in humans. METHODS: Sixty-four Japanese adults with and without diabetes who underwent pancreatectomy and were able to recall their weight history including birthweight were included. Pancreatic tissues were stained for insulin and glucagon, and fractional beta cell area (BCA) and alpha cell area (ACA) were quantified. Islet size and density and beta cell replication were also quantified and their associations with birthweight were evaluated. RESULTS: In participants without diabetes, there was a weak positive correlation between birthweight and BCA (R = 0.34, p = 0.03). The group with a history of childhood obesity, but not the group with a history of obesity in adulthood only, showed higher BCA compared with those without a history of obesity (1.78 ± 0.74% vs 0.99 ± 0.53%, p = 0.01), and the correlation coefficient between birthweight and BCA increased after excluding those with a history of childhood obesity (R = 0.51, p < 0.01). In those with diabetes, there was no correlation between birthweight and BCA. No correlation was found between birthweight and ACA in either those with or without diabetes. CONCLUSIONS/INTERPRETATION: Birthweight and beta, but not alpha, cell mass are positively correlated in non-diabetic adults, and a history of childhood obesity may affect beta cell mass. Graphical abstract.

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Effect of cosyntropin during adrenal venous sampling on subtype of primary aldosteronism: analysis of surgical outcome.

Hiroki Kobayashi, Yoshihiro Nakamura, Masanori Abe, Isao Kurihara, Hiroshi Itoh, Takamasa Ichijo, Yoshiyu Takeda, Takashi Yoneda, Takuyuki Katabami, Mika Tsuiki, Norio Wada, Yoshihiro Ogawa, Ryuichi Sakamoto, Junji Kawashima, Masakatsu Sone, Nobuya Inagaki, Takanobu Yoshimoto, Tetsuya Yamada, Ryuji Okamoto, Yuichi Matsuda, Megumi Fujita, Minemori Watanabe, Kouichi Tamura, Akiyo Tanabe, Mitsuhide Naruse

European journal of endocrinology 182 ( 3 ) 265 - 273 2020.03

Accepted, ISSN 0804-4643

Objectives: We investigated the clinical significance of ACTH stimulation during adrenal venous sampling (AVS) by surgical outcome of primary aldosteronism (PA). Design: Multicenter retrospective study by Japan PA study. Method: We allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to three groups: basal lateralization index (LI) ≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n = 245); basal LI <2 with ACTH-stimulated LI ≥4 (Bilateral (B) to U group, n = 15); and basal LI ≥2 with ACTH-stimulated LI <4 (U to B group, n = 54). We compared surgical outcomes among the groups using the Primary Aldosteronism Surgical Outcome (PASO) criteria. Results: Compared with U to U group, U to B group had poor clinical and biochemical outcomes and low rates of adrenal adenoma as pathological findings (P = 0.044, 0.006, and 0.048, respectively), although there were no significant differences between U to U and B to U groups. All patients in U to B group with clinical and biochemical benefits, however, had adrenal adenoma as pathological findings and could be well differentiated from those with poor surgical outcomes via basal LI (>8.3), but not ACTH-stimulated LI. These results were similar even when we defined each group based on a cut-off value of 4 for basal LI. Conclusions: Although PA patients in U to B group had worse surgical outcomes than did those in U to U group, basal LI could discriminate among patients with better surgical outcomes in U to B group.

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【糖尿病患者における感染症】合併症と感染症、その治療について糖尿病と腸内細菌

中島裕也, 入江潤一郎, 伊藤裕

月刊糖尿病 ((株)医学出版) 12 ( 3 ) 61 - 69 2020.03

Accepted

原発性アルドステロン症に対する副腎静脈サンプリングの経年的変化と施設間の差異

藤井雄一, 武田仁勇, 栗原勲, 伊藤裕, 方波見卓行, 一城貴政, 和田典男, 柴山唯, 吉本貴宣, 小川佳宏, 河島淳司, 曽根正勝, 稲垣暢也, 高橋克敏, 渡邉峰守, 松田祐一, 小林洋輝, 柴田洋孝, 亀村幸平, 大月道夫, 山本浩一, 小河淳, 柳瀬敏彦, 岡村慎太郎, 宮内省蔵, 藤田恵, 鈴木知子, 馬越洋宜, 小笠原辰樹, 立木美香, 成瀬光栄

広島医学 (広島医学会) 73 ( 3 ) 164 - 165 2020.03

ISSN 0367-5904

DNA damage and expression of DNA methylation modulators in urine-derived cells of patients with hypertension and diabetes.

Akihito Hishikawa, Kaori Hayashi, Norifumi Yoshimoto, Ran Nakamichi, Koichiro Homma, Hiroshi Itoh

Scientific reports 10 ( 1 ) 3377 - 3377 2020.02

Diabetes and hypertension have become the primary causes of chronic kidney disease worldwide. However, there are no established markers for early diagnosis or predicting renal prognosis. Here, we investigated the expression profiles of DNA repair and DNA methylation factors in human urine-derived cells as a possible diagnostic or renal prognosis-predicting marker. A total of 75 subjects, aged 63.3 ± 1.9 years old, were included in this study. DNA and RNA were extracted from 50 mL of urine samples. We evaluated DNA double-strand breaks (DSBs) by the quantitative long distance-PCR method and performed real-time RT-PCR analysis to analyze the expression of renal cell-specific markers, DNA DSB repair factor KAT5, DNA methyltransferases DNMTs, and demethylation enzymes TETs. In patients with hypertension and diabetes, DNA DSBs of the nephrin gene increased with decreased urine KAT5/nephrin expression, consistent with our previous study (Cell Rep 2019). In patients with hypertension, DNA DSBs of the AQP1 gene were increased with elevated urine DNMTs/AQP1 and TETs/AQP1 expression. Moreover, urine DNMTs/AQP1 expression was significantly correlated with the annual eGFR decline rate after adjustment for age, baseline eGFR, the presence of diabetes and the amount of albuminuria, suggesting a possible role as a renal prognosis predictor.

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Association of glucose tolerance status with pancreatic β- and α-cell mass in community-based autopsy samples of Japanese individuals: The Hisayama Study.

Jun Inaishi, Yoshifumi Saisho, Yoichiro Hirakawa, Daigo Yoshida, Jun Hata, Naoko Mukai, Yuusuke Watanabe, Yoshinao Oda, Hiroshi Itoh, Toshiharu Ninomiya

Journal of diabetes investigation 11 ( 5 ) 1197 - 1206 2020.02

Accepted, ISSN 2040-1116

AIMS/INTRODUCTION: Changes in histologically quantified β- and α-cell mass during the development of glucose intolerance have not been fully elucidated. The aim of the present study was to explore differences in β- and α-cell mass according to the glucose tolerance status. MATERIALS AND METHODS: Autopsy samples from a total of 103 individuals (40 with normal glucose tolerance, 31 with prediabetes and 32 with type 2 diabetes mellitus) who underwent a 75-g oral glucose tolerance test within 5 years before death were selected from 643 community-based autopsy samples collected from 2002 to 2016. Fractional β-cell area (BCA) and α-cell area were quantified with Image Pro Plus software. Associations of BCA and α-cell area with glucose tolerance status were assessed using a linear regression analysis, and Spearman's correlation coefficients between glycemic markers and β-cell function were estimated. RESULTS: The mean values of BCA decreased significantly with worsening glucose tolerance status (mean ± standard error 1.85 ± 0.10% in normal glucose tolerance, 1.59 ± 0.11% in prediabetes and 1.17 ± 0.11% in type 2 diabetes mellitus, P for trend < 0.001), whereas there was no significant association between α-cell area and glucose tolerance status. BCA was inversely correlated with fasting and 2-h plasma glucose levels during oral glucose tolerance test and glycated hemoglobin measurement, and positively correlated with disposition index (all P < 0.01). CONCLUSIONS: β-Cell mass decreased significantly with worsening glucose tolerance, from the stage of prediabetes, in the Japanese population. Prevention of declining β-cell mass before the onset of glucose intolerance is important to reduce the burden of type 2 diabetes mellitus.

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Fasting and Non-Fasting Triglycerides and Risk of Cardiovascular Events in Diabetic Patients Under Statin Therapy.

Hayato Tada, Akihiro Nomura, Kenichi Yoshimura, Hiroshi Itoh, Issei Komuro, Masakazu Yamagishi, Masayuki Takamura, Masa-Aki Kawashiri

Circulation journal : official journal of the Japanese Circulation Society 84 ( 3 ) 509 - 515 2020.02

Accepted, ISSN 1346-9843

BACKGROUND: Few data specifically investigate associations between fasting/non-fasting triglycerides (TG) and cardiovascular (CV) events under statin therapy among Japanese diabetic patients.Methods and Results:We recruited 4,988 participants with diabetes from the EMPATHY study. Median follow-up was 3 years. We evaluated associations between serum fasting/non-fasting TG and first CV events in Cox-regression hazard models adjusted by classical risk factors. CV events were defined as (1) major adverse cardiac events (MACE) including myocardial infarction, stroke, or cardiac death; and (2) CV diseases (CVD) including myocardial infarction, unstable angina, ischemic stroke, or large artery disease or peripheral arterial disease. Fasting as well as non-fasting TG were associated with MACE (adjusted hazard ratio [HR]: 1.017 per 10 mg/dL; 95% confidence interval [CI]: 1.000-1.037; P=0.046, adjusted HR: 1.028 per 10 mg/dL; 95% CI: 1.006-1.050; P=0.0091) and CVD (adjusted HR: 1.024 per 10 mg/dL; 95% CI: 1.011-1.038; P=4.4×10-3, adjusted HR: 1.028 per 10 mg/dL; 95% CI: 1.010-1.046; P=4.9×10-3). Comparing the top quartile with the bottom quartile of non-fasting TG, adjusted HR significantly increased 5.18 (95% CI: 1.38-18.3, P=0.014) for MACE, and 2.40 (95% CI: 1.11-4.75, P=0.021) for CVD, while adjusted HR did not change when divided into quartile of fasting TG. CONCLUSIONS: Non-fasting TG could be considered as a substitute for fasting TG as a risk stratification for future CV events among Japanese diabetic patients.

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Usefulness of the index calculated as the product of levels of fasting plasma glucose and hemoglobin A1c for insulinoma screening.

Keiichi Torimoto, Yosuke Okada, Yoshiya Tanaka, Atsuko Matsuoka, Yushi Hirota, Wataru Ogawa, Yoshifumi Saisho, Isao Kurihara, Hiroshi Itoh, Shinya Inada, Masafumi Koga

Endocrine journal 67 ( 5 ) 509 - 513 2020.02

Accepted, ISSN 0918-8959

Hypoglycemia is the major symptom of insulinoma. Chronic and recurrent hypoglycemia leads to the disappearance of autonomic symptoms and persistence of non-specific symptoms alone, possibly contributing to the delayed diagnosis of insulinoma and accounting for several undiagnosed cases. We previously reported the usefulness of hemoglobin A1c (HbA1c) and glycated albumin as markers for early insulinoma screening; however, their diagnostic prediction performance and diagnostic performance were not satisfactory. We hypothesized that the product of fasting plasma glucose (FPG) and HbA1c levels (FPG × HbA1c index) is low in insulinoma, and this index may be a useful marker for screening. This cross-sectional multicenter study compared 82 insulinoma patients with 100 age-, sex-, and body mass index-matched controls with normal glucose tolerance based on 75-g oral glucose tolerance test. The FPG × HbA1c index was significantly lower in the insulinoma group than in the control group. Receiver operating curve analysis showed that the optimal cutoff point of the FPG × HbA1c index to diagnose insulinoma was 447.1, and the area under the curves (AUCs) of the FPG × HbA1c index and HbA1c were 0.998 and 0.966, respectively. The AUC of the index was significantly higher than that of HbA1c (p = 0.010). Conversely, no significant difference existed between the AUC of the FPG × HbA1c index and that of the FPG/fasting immunoreactive insulin index. Thus, in apparently healthy population, the product of FPG and HbA1c yields a useful index for insulinoma screening in terms of accuracy and versatility.

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原発性アルドステロン症における腎障害は心血管イベントと異なり血中アルドステロン値と直接相関する

川島彰透, 曽根正勝, 稲垣暢也, 武田仁勇, 伊藤裕, 栗原勲, 一城貴政, 方波見卓行, 小川佳宏, 鈴木知子, 成瀬光栄, JPAS and JRAS Study group

日本内分泌学会雑誌 ((一社)日本内分泌学会) 95 ( 4 ) 1515 - 1515 2020.02

ISSN 0029-0661

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