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1. A multicenter, open‐label, single‐arm trial of the long‐term safety of empagliflozin treatment for refractory diabetes mellitus with insulin resistance (EMPIRE‐02)

Author: Yushi Hirota, Yasumasa Kakei, Junta Imai, Hideki Katagiri, Ken Ebihara, Jun Wada, Junichi Suzuki, Tatsuhiko Urakami, Takashi Omori, and Wataru Ogawa
Subjects: Genetic insulin resistance syndrome, Lipoatrophic diabetes, SGLT2 inhibitor, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: ABSTRACT Aims/Introduction Insulin resistance syndrome and lipoatrophic diabetes are rare conditions characterized by the development of treatment‐refractory diabetes with severe insulin resistance. We recently conducted a 24 week, multicenter, single‐arm trial (EMPIRE‐01) that demonstrated a certain level of effectiveness and safety of empagliflozin for these conditions. To evaluate treatment safety over a longer period, we have now performed an additional 28 week trial (EMPIRE‐02) that followed on from EMPIRE‐01. Materials and Methods The primary and secondary outcomes were safety and efficacy evaluations, respectively. All eight subjects of the EMPIRE‐01 trial participated in EMPIRE‐02. Results Twenty adverse events (AEs) were recorded among five individuals during the combined 52 week treatment period of both trials. Whereas one case of chronic hepatitis B was moderate in severity, all other AEs were mild. There were thus no serious AEs or events necessitating discontinuation or suspension of treatment or a reduction in drug dose. Whereas ketoacidosis or marked increases in serum ketone body levels were not observed, the mean body mass of the subjects was decreased slightly after completion of EMPIRE‐02. The improvement in mean values of glycemic parameters observed in EMPIRE‐01 was not sustained in EMPIRE‐02, mostly because of one individual whose parameters deteriorated markedly, likely as a result of nonadherence to diet therapy. The improvement in glycemic parameters was sustained during EMPIRE‐02 after exclusion of this subject from analysis. Conclusions Empagliflozin demonstrated a certain level of safety and efficacy for the treatment of insulin resistance syndrome and lipoatrophic diabetes over 52 weeks, confirming its potential as a therapeutic option.
Published: 2024
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2. Effects of soy or whey protein on weight reduction in patients with obesity: An exploratory, three-arm, placebo-controlled, double-blind, randomized clinical trial

Author: Michiko Takahashi, Takumi Imai, Tomoko Yamada, Naokazu Muramae, Kai Yoshimura, Yuji Mitomo, Hironori Bando, Kenji Sugawara, Shun-Ichiro Asahara, Yushi Hirota, Yoshikazu Tamori, Yutaka Takahashi, and Wataru Ogawa
Subjects: Obesity, Weight loss program, High-protein diet, Soy protein, Hunger, Satisfaction, Nutrition. Foods and food supply, TX341-641
Abstract: Summary: Background & aim: Although weight loss programs including diet and exercise targeting patients with obesity are essential, the percentage of patients who successfully achieve weight loss is less than 10%. One cause of failure to achieve weight loss is a strong sense of hunger, which is difficult to sustain. Additionally, it is important to prevent a decrease in muscle mass. Various protein supplements have been used to overcome these problems. However, there is insufficient evidence to support this theory. This study aimed to evaluate the effect of soy or whey protein beverages in conjunction with general dietary and exercise therapies on weight loss. Methods: This placebo-controlled, double-blind, randomized clinical trial was conducted at Kobe University Hospital. Patients with obesity and at least one obesity-related complication were enrolled. Three arms of soy, whey protein, or a placebo were supplemented once a day for 12 weeks, in addition to the general guidance on dietary and exercise therapies in a weight loss program. Energy intake during the trial was calculated using the Food Frequency Questionnaire. The primary outcome was percentage change in body weight from baseline to 12 weeks. Results: Between March 2021 and April 2022, 44 patients were enrolled. No significant differences were observed in body weight, waist circumference, body composition parameters, resting energy expenditure, blood pressure, or metabolic indicators. However, the energy, protein, and lipid intakes calculated from the prescribed nutritional intake in the weight loss program were significantly lower in the soy protein group (control group vs. soy group; total energy [kcal] −121.0 ± 416.6 vs. −340.0 ± 487.0, respectively P = 0.016; protein [g] 8.5 ± 11.9 vs. −5.1 ± 14.7, P = 0.023; lipid [g] −5.1 ± 16.1 vs. −19.8 ± 18.2, P = 0.018). Conclusions: No significant weight loss was observed in the soy or whey protein group. However, in the soy protein group, it was possible to maintain a lower energy intake, and protein and lipid intakes decreased in post-hoc analysis. Although further investigation is necessary, extending the administration period may result in significant weight loss. Clinical trial registration: Japan Registry of Clinical Trials (identifier: jRCTs051200103).
Published: 2024
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3. Definition, criteria, and core concepts of guidelines for the management of obesity disease in Japan

Author: Wataru Ogawa, Yushi Hirota, Shigeru Miyazaki, Tadashi Nakamura, Yoshihiro Ogawa, Iichiro Shimomura, Toshimasa Yamauchi, Koutaro Yokote, and on behalf of the Creation Committee for Guidelines for the Management of Obesity Disease 2022 by Japan Society for the Study of Obesity (JASSO)
Subjects: obesity, obesity disease, management guideline, visceral fat obesity, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: To identify those who might benefit from weight reduction within a large population of obese individuals, Japan Society for the Study of Obesity (JASSO) advocated the concept of “obesity disease.” Here we summarize the definition, criteria, and core concepts for the management of obesity disease based on JASSO’s latest guideline. JASSO defines obesity as excessive fat storage in adipose tissue associated with a BMI of ≥25 kg/m2. The threshold BMI of obesity is low as compared to Western countries given that Japanese individuals tend to develop obesity-related health disorders at lower BMI. Obesity with a BMI of ≥35 kg/m2 is referred to as “high-degree obesity” as treatment strategies vary based on the degree of obesity. Obesity is diagnosed as “obesity disease” if accompanied by any of the 11 specific obesity-related health disorders that weight reduction can prevent or alleviate, or if it meets the criteria for visceral fat obesity with a visceral fat area of ≥100 cm2. The initial weight reduction goals for high-degree obesity disease range from 5% to 10% of their current body weight, depending on the associated health disorders. That for those with obesity disease who do not qualify as high-degree is 3% or more. If these initial goals are not achieved, intensifying dietary therapy or introducing drug therapy (or both) may be necessary. While surgical treatment is primarily indicated for high-degree obesity disease, it might be appropriate for cases of obesity disease with a BMI
Published: 2023
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4. Advantages of sensor‐augmented insulin pump therapy for pregnant women with type 1 diabetes mellitus

Author: Hitomi Imafuku, Kenji Tanimura, Naohisa Masuko, Masako Tomimoto, Yutoku Shi, Akiko Uchida, Masashi Deguchi, Kazumichi Fujioka, Akane Yamamoto, Kei Yoshino, Yushi Hirota, Wataru Ogawa, and Yoshito Terai
Subjects: Pregnant women, Sensor‐augmented pump, Type 1 diabetes mellitus, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Aims/Introduction To evaluate the efficacy of sensor‐augmented pump (SAP) for improving obstetric and neonatal outcomes among pregnant women with type 1 diabetes mellitus by comparing it with continuous subcutaneous insulin infusion plus self‐monitoring of blood glucose (continuous subcutaneous insulin infusion [CSII]/SMBG). Materials and Methods This retrospective cohort study included 40 cases of pregnancy complicated by type 1 diabetes mellitus treated with SAP (SAP group), and 29 cases of pregnancy complicated by type 1 diabetes mellitus treated with CSII/SMBG (CSII/SMBG group). The obstetric and neonatal outcomes were compared between the two groups. Results The median of the glycoalbumin levels in the first (18.8% vs 20.9%; P
Published: 2023
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5. Composite paraganglioma-ganglioneuroma with atypical catecholamine profile and phenylethanolamine N-methyltransferase expression: a case report and literature review

Author: Yuriko Sasaki, Maki Kanzawa, Masaaki Yamamoto, Keitaro Kanie, Hironori Bando, Kei Yoshino, Yushi Hirota, Katsumi Shigemura, Masato Fujisawa, Wataru Ogawa, and Hidenori Fukuoka
Subjects: composite tumors, phenylethanolamine n-methyltransferase, pheochromocytomas and paragangliomas, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Pheochromocytomas and paragangliomas (PPGLs) are rare tumors that secrete catecholamines and arise from the adrenal medulla or extra-adrenal sympathetic ganglia. These tumors secrete adrenaline and noradrenaline, but paragangliomas usually produce only noradrenaline because of the lack of phenylethanolamine N-methyltransferase (PNMT) expression. Composite paragangliomas, which are complex tumors consisting of multiple types of neuroblastic cells, are extremely rare. We present the case of a 46-year-old woman with an atypical catecholamine profile who was preoperatively diagnosed with pheochromocytoma. However, postoperative pathology revealed that the patient had an extra-adrenal paraganglioma accompanied by a ganglioneuroma, which led to the diagnosis of a composite tumor. Interestingly, PNMT is expressed in both paragangliomas and ganglioneuromas. In addition, we reviewed reported composite paragangliomas and compared their clinical features with those of composite pheochromocytomas. We also discuss various aspects of the etiology of composite paragangliomas and the mechanism by which PNMT is expressed in tumors.
Published: 2023
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6. Impact of COVID‐19 pandemic on behavioral changes and glycemic control and a survey of telemedicine in patients with diabetes: A multicenter retrospective observational study

Author: Ryotaro Bouchi, Takehiro Sugiyama, Atsushi Goto, Mitsuru Ohsugi, Narihito Yoshioka, Hideki Katagiri, Tomoya Mita, Yushi Hirota, Hiroshi Ikegami, Munehide Matsuhisa, Eiichi Araki, Hiroki Yokoyama, Masae Minami, Katsuya Yamazaki, Hideaki Jinnouchi, Hiroki Ikeda, Hitomi Fujii, Miyuki Nogawa, Masahiro Kaneshige, Kengo Miyo, and Kohjiro Ueki
Subjects: COVID‐19, glycemic control, lifestyle changes, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: ABSTRACT Aims/Introduction To investigate whether the COVID‐19 pandemic affected behavioral changes and glycemic control in patients with diabetes and to conduct a survey of telemedicine during the pandemic. Materials and Methods In this retrospective study, a total of 2,348 patients were included from 15 medical facilities. Patients were surveyed about their lifestyle changes and attitudes toward telemedicine. Hemoglobin A1c (HbA1c) levels were compared among before (from June 1 to August 31, 2019) and in the first (from June 1 to August 31, 2020) and in the second (from June 1 to August 31, 2021) year of the pandemic. A survey of physician attitudes toward telemedicine was also conducted. Results The HbA1c levels were comparable between 2019 (7.27 ± 0.97%), 2020 (7.28 ± 0.92%), and 2021 (7.25 ± 0.94%) without statistical difference between each of those 3 years. Prescriptions for diabetes medications increased during the period. The frequency of eating out was drastically reduced (51.7% in 2019; 30.1% in 2020), and physical activity decreased during the pandemic (48.1% in 2019; 41.4% in 2020; 43.3% in 2021). Both patients and physicians cited increased convenience and reduced risk of infection as their expectations for telemedicine, while the lack of physician–patient interaction and the impossibility of consultation and examination were cited as sources of concern. Conclusions Our data suggest that glycemic control did not deteriorate during the COVID‐19 pandemic with appropriate intensification of diabetes treatment in patients with diabetes who continued to attend specialized diabetes care facilities, and that patients and physicians shared the same expectations and concerns about telemedicine.
Published: 2023
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7. A family with type A insulin resistance syndrome caused by a novel insulin receptor mutation

Author: Osamu Horikawa, Satoshi Ugi, Tomofumi Takayoshi, Yasushi Omura, Maya Yonishi, Daisuke Sato, Yukihiro Fujita, Tomoya Fuke, Yushi Hirota, Wataru Ogawa, and Hiroshi Maegawa
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: A 17-year-old boy was referred to our endocrinology clinic for a clinical investigation of hyperinsulinemia. An oral glucose tolerance test showed plasma glucose concentrations in the normal range. However, insulin concentrations were considerably elevated (0 min: 71 μU/mL; 60 min: 953 μU/mL), suggesting severe insulin resistance. An insulin tolerance test confirmed that he had insulin resistance. There was no apparent hormonal or metabolic cause, including obesity. The patient had no outward features of hyperinsulinemia, including acanthosis nigricans or hirsutism. However, his mother and grandfather also had hyperinsulinemia. Genetic testing showed that the patient (proband), his mother, and his grandfather had a novel p.Val1086del heterozygous mutation in exon 17 of the insulin receptor gene (INSR). Although all three family members have the same mutation, their clinical courses have been different. The onset of the mother’s diabetes was estimated at 50 years, whereas the grandfather developed diabetes at 77 years.
Published: 2023
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8. Factors associated with hemoglobin glycation index in adults with type 1 diabetes mellitus: The FGM‐Japan study

Author: Naoki Sakane, Yushi Hirota, Akane Yamamoto, Junnosuke Miura, Hiroko Takaike, Sari Hoshina, Masao Toyoda, Nobumichi Saito, Kiminori Hosoda, Masaki Matsubara, Atsuhito Tone, Satoshi Kawashima, Hideaki Sawaki, Tomokazu Matsuda, Masayuki Domichi, Akiko Suganuma, Seiko Sakane, and Takashi Murata
Subjects: Continuous glucose monitoring, Glycated hemoglobin A1c, Glycemic variability, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: ABSTRACT Aims/Introduction The discrepancy between HbA1c and glucose exposure may have significant clinical implications; however, the association between the hemoglobin glycation index (HGI) and clinical parameters in type 1 diabetes remains controversial. This study aimed to find the factors associated with HGI (laboratory HbA1c − predicted HbA1c derived from the continuous glucose monitoring [CGM]). Materials and Methods We conducted a cross‐sectional study of adults with type 1 diabetes (n = 211, age 50.9 ± 15.2 years old, female sex = 59.2%, duration of CGM use = 2.1 ± 1.0 years). All subjects wore the CGM for 90 days before HbA1c measurement. Data derived from the FreeStyle Libre sensor were used to calculate the glucose management indicator (GMI) and glycemic variability (GV) parameters. HGI was defined as the difference between the GMI and the laboratory HbA1c levels. The participants were divided into three groups according to the HGI tertile (low, moderate, and high). Multivariate regression analyses were performed. Results The female sex ratio, HbA1c, and % coefficient of variation (%CV) significantly increased over the HGI tertile, while eGFR and Hb decreased over the HGI tertile. In multivariate analysis, the factors associated with HGI were %CV and eGFR, after adjusting for HbA1c level and sex (R2 = 0.44). Conclusions This study demonstrated that HGI is associated with female sex, eGFR, and some glycemic variability indices, independently of HbA1c. Minimizing glycemic fluctuations might reduce HGI. This information provides diabetic health professionals and patients with personalized diabetes management for adults with type 1 diabetes.
Published: 2023
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9. Impact of body mass index on in-hospital mortality for six acute cardiovascular diseases in Japan

Author: Naofumi Yoshida, Masato Ogawa, Michikazu Nakai, Koshiro Kanaoka, Yoko Sumita, Takuo Emoto, Yoshihiro Saito, Hiroyuki Yamamoto, Kazuhiro P. Izawa, Yoshitada Sakai, Yushi Hirota, Wataru Ogawa, Yoshitaka Iwanaga, Yoshihiro Miyamoto, Tomoya Yamashita, and Ken-ichi Hirata
Subjects: Medicine, Science
Abstract: Abstract Body mass index (BMI) distribution and its impact on cardiovascular disease (CVD) vary between Asian and western populations. The study aimed to reveal time-related trends in the prevalence of obesity and underweight and safe ranges of BMI in Japanese patients with CVD. We analyzed 5,020,464 records from the national Japanese Registry of All Cardiac and Vascular Diseases—Diagnosis Procedure Combination dataset over time (2012–2019) and evaluated BMI trends and the impact on in-hospital mortality for six acute CVDs: acute heart failure (AHF), acute myocardial infarction (AMI), acute aortic dissection (AAD), ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Patients were categorized into five groups using the WHO Asian-BMI criteria: underweight (
Published: 2022
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10. Relation between the insulin lowering rate and changes in bone mineral density: Analysis among subtypes of type 1 diabetes mellitus

Author: Masaki Suzuki, Shin Urai, Hidenori Fukuoka, Yushi Hirota, Masaaki Yamamoto, Yuko Okada, Naoki Yamamoto, Hiroki Shichi, Yasunori Fujita, Keitaro Kanie, Genzo Iguchi, Yutaka Takahashi, and Wataru Ogawa
Subjects: Bone mineral density, Subtypes, Type 1 diabetes mellitus, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Aims/Introduction The bone mineral density in patients with type 1 diabetes mellitus is reduced due to impaired insulin secretion. However, it is unclear whether the rate of bone mineral density reduction is affected by the type 1 diabetes mellitus subtype. This study aimed to clarify the difference in bone mineral density across type 1 diabetes mellitus subtypes: slowly progressive (SP), acute‐onset (AO), and fulminant (F). Methods This was a retrospective, single‐center, cross‐sectional study conducted on 98 adult type 1 diabetes mellitus patients. The main outcome included the bone mineral density Z‐score (BMD‐Z) measured at the lumbar spine and femoral neck. Results The lumbar spine BMD‐Z was lower in the acute‐onset than in the slowly progressive subtype (P = 0.03). No differences were observed when compared with the fulminant subtype. The femoral neck BMD‐Z tended to be higher in the slowly progressive than in the acute‐onset and fulminant subtypes. Multiple regression analyses showed that the lumbar spine BMD‐Z was associated with subtypes (AO vs SP) (P = 0.01), but not subtypes (F vs SP), adjusted for sex, duration, retinopathy, and C‐peptide immunoreactivity (CPR). When the patients were divided into disease duration tertiles, in the first and second tertiles, the CPR levels were lower in the acute‐onset or fulminant than in the slowly progressive subtype. In contrast, the lumbar spine and femoral neck BMD‐Z differed between the acute‐onset and slowly progressive only in the second tertiles (both P
Published: 2022
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11. Relation of cardiac function to insulin resistance as evaluated by hyperinsulinemic‐euglycemic clamp analysis in individuals with type 2 diabetes

Author: Natsu Otowa‐Suematsu, Kazuhiko Sakaguchi, Akihiro Kaneko, Jun Ito, Yasuko Morita, Hiroshi Miura, Tomoko Yamada, Anna So, Hisako Komada, Yuko Okada, Yushi Hirota, Yoshikazu Tamori, and Wataru Ogawa
Subjects: glucose clamp, insulin resistance, left ventricular cardiac dysfunction, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Aims Whereas homeostasis model assessment of insulin resistance (HOMA‐IR), an easily measured but limited index of insulin resistance, has been shown to correlate with impairment of cardiac function in individuals without diabetes, the pathological relevance of insulin resistance to the development of cardiac dysfunction in individuals with type 2 diabetes has remained unclear. Here we investigated the relation between left ventricular (LV) function as assessed by echocardiography and insulin resistance as evaluated by hyperinsulinemic‐euglycemic clamp analysis, the gold standard for measurement of this parameter, in individuals with type 2 diabetes. Methods This retrospective study included 34 individuals with type 2 diabetes who underwent both hyperinsulinemic‐euglycemic clamp analysis and echocardiography. Both the insulin sensitivity index (ISI) as determined by glucose clamp analysis as well as HOMA‐IR were determined as measures of insulin resistance. The ratio of the peak early‐ to late‐diastolic mitral inflow velocities (E/A) and the LV ejection fraction (LVEF) were determined as measures of diastolic and systolic function, respectively. Results The ISI was significantly correlated with both the E/A ratio and LVEF (correlation coefficients of 0.480 and 0.360, respectively), whereas HOMA‐IR was not correlated with either cardiac parameter. Multivariate analysis revealed that ISI was an independent predictor for both a high log [E/A] (P = 0.031) and a high LVEF (P = 0.045). Conclusions Insulin resistance as evaluated by hyperinsulinemic‐euglycemic clamp analysis may be causally related to LV diastolic and systolic dysfunction in individuals with type 2 diabetes.
Published: 2021
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12. Association of left ventricular longitudinal myocardial function with subclinical right ventricular dysfunction in type 2 diabetes mellitus

Author: Saki Todo, Hidekazu Tanaka, Yuki Yamauchi, Shun Yokota, Yasuhide Mochizuki, Hiroaki Shiraki, Kentaro Yamashita, Ayu Shono, Makiko Suzuki, Keiko Sumimoto, Yusuke Tanaka, Yushi Hirota, Wataru Ogawa, and Ken-ichi Hirata
Subjects: Type 2 diabetes mellitus, Right ventricular systolic function, Global longitudinal strain, Echocardiography, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background Left ventricular (LV) involvement in diabetic cardiomyopathy has been reported; however, only limited data exist on right ventricular (RV) involvement. Therefore, our purpose was to investigate RV systolic dysfunction and its association with LV longitudinal myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM) and preserved LV ejection fraction (LVEF). Methods We studied 177 T2DM patients with preserved LVEF and 79 age-, sex-, and LVEF-matched healthy volunteers. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS), and RV systolic function was assessed as RV free-wall strain, and predefined cutoff values for subclinical dysfunction were set at GLS
Published: 2021
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13. Impact of daily glucose fluctuations on cardiovascular outcomes after percutaneous coronary intervention for patients with stable coronary artery disease undergoing lipid‐lowering therapy

Author: Hiroyuki Yamamoto, Toshiro Shinke, Hiromasa Otake, Hiroyuki Kawamori, Takayoshi Toba, Masaru Kuroda, Yushi Hirota, Kazuhiko Sakaguchi, Wataru Ogawa, and Ken‐ichi Hirata
Subjects: Cardiovascular event, Glucose fluctuation, Stable coronary artery disease, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Aims/Introduction Glucose fluctuation (GF) is a residual risk factor for coronary artery disease (CAD). We investigated whether GF influenced clinical outcomes and progression of coronary stenosis in stable CAD patients. Materials and Methods In this prospective study, 101 consecutive lipid‐controlled stable CAD patients underwent percutaneous coronary intervention were enrolled, and GF was expressed as the mean amplitude of glycemic excursion (MAGE) obtained by continuous glucose monitoring before the procedure was evaluated. At 9 months after enrollment, culprit and non‐culprit (mild‐to‐moderate stenosis without ischemia) lesions were serially assessed by angiography. Cardiovascular events (CVE) consisting of cardiovascular death, non‐fatal myocardial infarction or ischemia‐driven revascularization during 2‐year follow up, rapid progression in non‐culprit lesions (defined as ≥10% luminal narrowing progression in lesions with stenosis ≥50%, ≥30% luminal narrowing progression in non‐culprit lesions with stenosis
Published: 2021
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14. Effect of heart rate on left ventricular longitudinal myocardial function in type 2 diabetes mellitus

Author: Yuki Yamauchi, Hidekazu Tanaka, Shun Yokota, Yasuhide Mochizuki, Yuko Yoshigai, Hiroaki Shiraki, Kentaro Yamashita, Yusuke Tanaka, Ayu Shono, Makiko Suzuki, Keiko Sumimoto, Kensuke Matsumoto, Yushi Hirota, Wataru Ogawa, and Ken-ichi Hirata
Subjects: Type 2 diabetes mellitus, Heart rate, Global longitudinal strain, Echocardiography, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background Left ventricular (LV) longitudinal myocardial dysfunction is considered a marker of preclinical LV dysfunction in patients with type 2 diabetes mellitus (T2DM). High heart rate (HR) is associated with cardiovascular outcomes, but the effect of HR on LV longitudinal myocardial function in T2DM patients is uncertain. Methods We studied 192 T2DM patients with preserved LV ejection fraction (LVEF), and 81 age-, sex-, and LVEF-matched healthy volunteers. HR was measured as the average HR during echocardiography, and high HR was defined as resting HR ≥ 70 beats/minute. LV longitudinal myocardial function was assessed as global longitudinal strain (GLS). The predefined cutoff for subclinical LV dysfunction was set at GLS
Published: 2021
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15. The impact of vildagliptin on the daily glucose profile and coronary plaque stability in impaired glucose tolerance patients with coronary artery disease: VOGUE—A multicenter randomized controlled trial

Author: Hiroyuki Yamamoto, Akihide Konishi, Toshiro Shinke, Hiromasa Otake, Masaru Kuroda, Tsuyoshi Osue, Takahiro Sawada, Tomofumi Takaya, Hiroya Kawai, Naoko Hashimoto, Takeshi Ohara, Yushi Hirota, Kazuhiko Sakaguchi, Takashi Omori, Wataru Ogawa, and Ken-ichi Hirata
Subjects: Vildagliptin, Fibrous cap thickness, Mean amplitude of glycemic excursion, Impaired glucose tolerance, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background The impact of reduction in glycemic excursion on coronary plaques remains unknown. This study aimed to elucidate whether a dipeptidyl peptidase 4 inhibitor could reduce the glycemic excursion and stabilize the coronary plaques compared with conventional management in coronary artery disease (CAD) patients with impaired glucose tolerance (IGT). Methods This was a multicenter, randomized controlled trial including CAD patients with IGT under lipid-lowering therapy receiving either vildagliptin (50 mg once a day) or no medication (control group) regarding glycemic treatment. The primary endpoint was changes in the minimum fibrous cap thickness and lipid arc in non-significant native coronary plaques detected by optical coherence tomography at 6 months after intervention. Glycemic variability expressed as the mean amplitude of glycemic excursion (MAGE) measured with a continuous glucose monitoring system was evaluated before and 6 months after intervention. Results A total of 20 participants with 47 lesions were allocated to either the vildagliptin group (10 participants, 22 lesions) or the control group (10 participants, 25 lesions). The adjusted difference of mean changes between the groups was − 18.8 mg/dl (95% confidence interval, − 30.8 to − 6.8) (p = 0.0064) for the MAGE (vildagliptin, − 20.1 ± 18.0 mg/dl vs. control, 2.6 ± 12.7 mg/dl), − 22.8° (− 40.6° to − 5.1°) (p = 0.0012) for the mean lipid arc (vildagliptin, − 9.0° ± 25.5° vs. control, 15.8° ± 16.8°), and 42.7 μm (15.3 to 70.1 μm) (p = 0.0022) for the minimum fibrous cap thickness (vildagliptin, 35.7 ± 50.8 μm vs. control, − 15.1 ± 25.2 μm). Conclusions Vildagliptin could reduce the MAGE at 6 months and may be associated with the decreased lipid arc and increased minimum FCT of the coronary plaques in CAD patients with IGT as compared with the control group. These findings may represent its potential stabilization effect on coronary plaques, which are characteristic in this patient subset. Trial registration Registered in the UMIN clinical trial registry (UMIN000008620), Name of the registry: VOGUE trial, Date of registration: Aug 6, 2012, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000010058
Published: 2021
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16. Patients with pheochromocytoma exhibit low aldosterone renin ratio-preliminary reports

Author: Tomoko Yamada, Hidenori Fukuoka, Yusei Hosokawa, Yukiko Odake, Kenichi Yoshida, Ryusaku Matsumoto, Hironori Bando, Yuko Okada, Yushi Hirota, Genzo Iguchi, Wataru Ogawa, and Yutaka Takahashi
Subjects: Pheochromocytoma, Adrenal incidentaloma, Renin, Aldosterone, ARR, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Background Plasma renin activity (PRA) is generally increased in patients with pheochromocytoma (PCC) due to low circulating plasma volume and activation of β-1 adrenergic receptor signaling. However, there has been no study on the aldosterone renin ratio (ARR) in patients with PCC. To elucidate the issue, this study aimed to determine the PRA, plasma aldosterone concentration (PAC), and ARR in patients with PCC and compare them with those in patients with subclinical Cushing’s syndrome (SCS) and non-functioning adrenal adenoma (NFA). Methods In this retrospective single-center, cross-sectional study, 67 consecutive patients with adrenal tumors (PCC (n = 18), SCS (n = 18), and NFA (n = 31)) diagnosed at Kobe University Hospital between 2008 and 2014 were enrolled. Results PRA was significantly higher in patients with PCC than in those with SCS and NFA (2.1 (1.3 ~ 2.8) vs. 0.7 (0.5 ~ 1.8) and 0.9 (0.6 ~ 1.4) ng/mL/h; p = 0.018 and p = 0.025). Although PACs were comparable among the three groups, ARR was significantly lower in patients with PCC than in those with SCS and NFA (70.5 (45.5 ~ 79.5) vs. 156.0 (92.9 ~ 194.5) and 114.9 (90.1 ~ 153.4); p = 0.001 and p 1.55 ng/mL/h showed a sensitivity of 70.0% and specificity of 80.6%. Interestingly, ARR
Published: 2020
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17. Relationship between metformin use and vitamin B12 status in patients with type 2 diabetes in Japan

Author: Kenji Sugawara, Yuko Okada, Yushi Hirota, Kazuhiko Sakaguchi, and Wataru Ogawa
Subjects: Homocysteine, Metformin, Vitamin B12, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Aims/Introduction Metformin therapy has been associated with vitamin B12 (VB12) deficiency, but information regarding this adverse effect in Asian populations is limited. We have now examined the relationship between metformin use and VB12 status in individuals with type 2 diabetes mellitus in Japan. Materials and Methods This cross‐sectional study was carried out with type 2 diabetes mellitus patients treated (Met group, n = 122) or not treated (control group, n = 63) with metformin. The primary end‐point was the difference in the serum concentration of homocysteine, a marker of VB12 activity, between the two groups. The serum concentrations of VB12, blood hemoglobin level and mean corpuscular volume were also compared between the groups. Subset analysis was carried out with individuals aged ≥70 years. The potential correlation between the daily dose or duration of metformin treatment and the other measured parameters was also examined. Results The level of homocysteine, as well as the VB12 level, hemoglobin concentration and mean corpuscular volume, did not differ significantly between the control and treated with metformin groups. The level of homocysteine was positively and that of VB12 negatively correlated with the daily dose of metformin. Among elderly individuals, the hemoglobin level was significantly lower in the treated with metformin group than in the control group, although the mean corpuscular volume was similar in the two groups. Conclusions The risk of VB12 deficiency during metformin treatment appears to be low in Japanese type 2 diabetes mellitus patients. However, high doses of metformin might result in a moderate decrease in the circulating VB12 level, as well as in anemia in elderly individuals.
Published: 2020
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18. Clinical characteristics of insulin resistance syndromes: A nationwide survey in Japan

Author: Takehito Takeuchi, Yasushi Ishigaki, Yushi Hirota, Yutaka Hasegawa, Tohru Yorifuji, Hiroko Kadowaki, Takashi Akamizu, Wataru Ogawa, and Hideki Katagiri
Subjects: Insulin resistance syndrome, Nationwide survey, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Aims/Introduction Insulin resistance syndrome (IRS) of type A or B is triggered by gene abnormalities of or autoantibodies to the insulin receptor, respectively. Rabson–Mendenhall/Donohue syndrome is also caused by defects of the insulin receptor gene (INSR), but is more serious than type A IRS. Here, we carried out a nationwide survey of these syndromes in Japan. Materials and Methods We sent questionnaires to a total of 1,957 academic councilors or responsible individuals at certified facilities of the Japan Diabetes Society, as well as at the department pediatrics or neonatology in medical centers with >300 beds. Results We received 904 responses with information on 23, 30 and 10 cases of type A or B IRS and Rabson–Mendenhall/Donohue syndrome, respectively. Eight cases with type A IRS‐like clinical features, but without an abnormality of INSR, were tentatively designated type X IRS, with five of these cases testing positive for PIK3R1 mutations. Fasting serum insulin levels at diagnosis (mean ± standard deviation) were 132.0 ± 112.4, 1122.1 ± 3292.5, 2895.5 ± 3181.5 and 145.0 ± 141.4 μU/mL for type A IRS, type B IRS, Rabson–Mendenhall/Donohue syndrome and type X IRS, respectively. Type A and type X IRS, as well as Rabson–Mendenhall/Donohue syndrome were associated with low birthweight. Type B IRS was diagnosed most frequently in older individuals, and was often associated with concurrent autoimmune conditions and hypoglycemia. Conclusions Information yielded by this first nationwide survey should provide epidemiological insight into these rare conditions and inform better healthcare for affected patients.
Published: 2020
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19. Relationship between glycated hemoglobin level and duration of hypoglycemia in type 2 diabetes patients treated with sulfonylureas: A multicenter cross‐sectional study

Author: Atsuko Matsuoka, Yushi Hirota, Akihiko Takeda, Minoru Kishi, Naoko Hashimoto, Takeshi Ohara, Satomi Higo, Hiroyuki Yamada, Tomoaki Nakamura, Tetsushi Hamaguchi, Takehito Takeuchi, Yasushi Nakagawa, Yuko Okada, Kazuhiko Sakaguchi, and Wataru Ogawa
Subjects: Continuous glucose monitoring, Hypoglycemia, Sulfonylureas, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Aims/Introduction Sulfonylurea‐related hypoglycemia increases the risk of cardiovascular sequela, such as cardiac arrhythmia. This study aimed to clarify the relationship between the level of glycated hemoglobin (HbA1c) and the duration of hypoglycemia in type 2 diabetes patients treated with sulfonylureas. Materials and Methods Glucose levels in the enrolled patients (n = 300) were investigated with a professional continuous glucose monitoring device in the outpatient setting at six diabetes centers in Japan. Results A total of 269 participants completed the study. The duration of hypoglycemia with glucose values of 10% of the time in daily life (6.8 ± 5.6 min/h). The duration of hypoglycemia with glucose values of
Published: 2020
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20. Serum Orosomucoid Is Associated with Serum Adiponectin, Adipose Tissue Insulin Resistance Index, and a Family History of Type 2 Diabetes in Young Normal Weight Japanese Women

Author: Mari Honda, Ayaka Tsuboi, Satomi Minato-Inokawa, Mika Takeuchi, Miki Kurata, Tomofumi Takayoshi, Yushi Hirota, Bin Wu, Tsutomu Kazumi, and Keisuke Fukuo
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Introduction. Adipose tissue (AT) expandability may be facilitated by adiponectin and suppressed by orosomucoid, and reduced AT expandability may be associated with first-degree relatives of type 2 diabetes. We tested the hypothesis that orosomucoid may be associated not only with adiponectin and adipose tissue insulin resistance but also with a family history of type 2 diabetes (FHD). Research Design and Methods. Anthropometric and metabolic variables, adipokines, and measures of inflammatory and insulin resistance were cross-sectionally investigated in 153 young normal weight Japanese women. Stepwise multivariate linear regression analyses were used to identify the most important determinants of orosomucoid. Results. Orosomucoid was higher in women with positive (n=57) compared to women with negative FHD and was associated positively with FHD (both p=0.01). Orosomucoid also showed positive associations with fasting glucose (p
Published: 2022
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21. Association of glycemic variability with left ventricular diastolic function in type 2 diabetes mellitus

Author: Shun Yokota, Hidekazu Tanaka, Yasuhide Mochizuki, Fumitaka Soga, Kentaro Yamashita, Yusuke Tanaka, Ayu Shono, Makiko Suzuki, Keiko Sumimoto, Jun Mukai, Makiko Suto, Hiroki Takada, Kensuke Matsumoto, Yushi Hirota, Wataru Ogawa, and Ken-ichi Hirata
Subjects: Type 2 diabetes mellitus, Glycemic variability, Diastolic function, Echocardiography, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background Type 2 diabetes mellitus (T2DM) is a major cause of heart failure (HF) with preserved ejection fraction (HFpEF), usually presenting as left ventricular (LV) diastolic dysfunction. Thus, LV diastolic function should be considered a crucial marker of a preclinical form of DM-related cardiac dysfunction. However, the impact of glycemic variability (GV) on LV diastolic function in such patients remains unclear. Methods We studied 100 asymptomatic T2DM patients with preserved LV ejection fraction (LVEF) without coronary artery disease (age: 60 ± 14 years, female: 45%). GV was evaluated as standard deviation of blood glucose level using continuous glucose monitoring system for at least 72 consecutive hours. LV diastolic function was defined as mitral inflow E and mitral e’ annular velocities (E/e’), and > 14 was determined as abnormal. Results E/e’ in patients with high GV (≥ 35.9 mg/dL) was significantly higher than that in patients with low GV (11.3 ± 3.9 vs. 9.8 ± 2.8, p = 0.03) despite similar age, gender-distribution, and hemoglobin A1c (HbA1c). Multivariate logistic regression analysis showed that GV ≥ 35.9 mg/dL (odds ratio: 3.67; 95% confidence interval: 1.02–13.22; p 14. In sequential logistic models for the associations of LV diastolic dysfunction, one model based on clinical variables including age, gender and hypertension was not improved by addition of HbA1c (p = 0.67) but was improved by addition of high GV (p = 0.04). Conclusion Since HFpEF is a syndrome caused by diverse agents, reducing GV may represent a potential new therapeutic strategy for the prevention of the development of HFpEF in T2DM patients.
Published: 2019
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22. Bacteroides spp. promotes branched-chain amino acid catabolism in brown fat and inhibits obesity

Author: Naofumi Yoshida, Tomoya Yamashita, Tatsunori Osone, Tetsuya Hosooka, Masakazu Shinohara, Seiichi Kitahama, Kengo Sasaki, Daisuke Sasaki, Takeshi Yoneshiro, Tomohiro Suzuki, Takuo Emoto, Yoshihiro Saito, Genki Ozawa, Yushi Hirota, Yasuyuki Kitaura, Yoshiharu Shimomura, Yuko Okamatsu-Ogura, Masayuki Saito, Akihiko Kondo, Shingo Kajimura, Takeshi Inagaki, Wataru Ogawa, Takuji Yamada, and Ken-ichi Hirata
Subjects: Computer systems organization, Energy engineering, Energy systems, Science
Abstract: Summary: The gut microbiome has emerged as a key regulator of obesity; however, its role in brown adipose tissue (BAT) metabolism and association with obesity remain to be elucidated. We found that the levels of circulating branched-chain amino acids (BCAA) and their cognate α-ketoacids (BCKA) were significantly correlated with the body weight in humans and mice and that BCAA catabolic defects in BAT were associated with obesity in diet-induced obesity (DIO) mice. Pharmacological systemic enhancement of BCAA catabolic activity reduced plasma BCAA and BCKA levels and protected against obesity; these effects were reduced in BATectomized mice. DIO mice gavaged with Bacteroides dorei and Bacteroides vulgatus exhibited improved BAT BCAA catabolism and attenuated body weight gain, which were not observed in BATectomized DIO mice. Our data have highlighted a possible link between the gut microbiota and BAT BCAA catabolism and suggest that Bacteroides probiotics could be used for treating obesity.
Published: 2021
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23. Effects of ipragliflozin on glycemic control, appetite and its related hormones: A prospective, multicenter, open‐label study (SOAR‐KOBE Study)

Author: Hiroshi Miura, Kazuhiko Sakaguchi, Yuko Okada, Tomoko Yamada, Natsu Otowa‐Suematsu, Anna So, Hisako Komada, Yushi Hirota, Takeshi Ohara, Yasuo Kuroki, Kenta Hara, Tomokazu Matsuda, Minoru Kishi, Akihiko Takeda, Kazuki Yokota, Yoshikazu Tamori, and Wataru Ogawa
Subjects: Appetite, Ipragliflozin, Leptin, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Aims/Introduction Sodium–glucose cotransporter 2 (SGLT‐2) inhibitors improve blood glucose control, as well as reducing bodyweight by promoting urinary glucose excretion. The weight loss is less than expected from urinary glucose loss, however, likely because of an increase in food intake. To investigate whether SGLT‐2 inhibitors might increase appetite by affecting related hormones, we examined the effects of the SGLT‐2 inhibitor, ipragliflozin, including those on appetite‐regulating hormones, in individuals with suboptimally controlled type 2 diabetes. Materials and Methods The present prospective, multicenter, open‐label study was carried out with 96 patients with a body mass index of ≥22 kg/m2 who were treated with ipragliflozin (50 mg/day) for 16 weeks. Parameters including glycated hemoglobin level, bodyweight, circulating leptin and active ghrelin concentrations, and appetite as assessed with a visual analog scale were measured before and during treatment. Results Both glycated hemoglobin level (from 7.9 ± 0.8 to 7.1 ± 0.7%) and bodyweight (from 75.2 ± 12.6 to 72.6 ± 12.4 kg) were significantly decreased after treatment for 16 weeks. The fasting serum leptin level was significantly decreased after 2 weeks (from 19.5 ± 13.1 to 18.1 ± 12.4 ng/mL) and remained decreased up to 16 weeks, even after adjustment for bodyweight, whereas the plasma active ghrelin level showed no significant change. The visual analog scale score for hunger was significantly increased at 2 and 8 weeks. Conclusions The present results suggest that ipragliflozin improved glycemic control and reduced bodyweight, but also reduced serum leptin levels and might thereby have increased appetite.
Published: 2019
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24. Sodium–glucose cotransporter 2 inhibitor‐associated diabetic ketoacidosis in patients with type 1 diabetes: Metabolic imbalance as an underlying mechanism

Author: Wataru Ogawa and Yushi Hirota
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Published: 2019
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25. Phenotypic differences and similarities of monozygotic twins with maturity‐onset diabetes of the young type 5

Author: Yasuko Ohara, Yuko Okada, Tomoko Yamada, Kenji Sugawara, Masayuki Kanatani, Hidenori Fukuoka, Yushi Hirota, Takaki Maeda, Naoya Morisada, Kazumoto Iijima, and Wataru Ogawa
Subjects: Hepatocyte nuclear factor 1β gene, Maturity‐onset diabetes of the young type 5, Monozygotic twins, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Here, we report phenotypic differences and similarities of monozygotic twins with maturity‐onset diabetes of the young type 5 harboring a partial deletion of chromosome 17q12. The proband and her twin sister manifested complete aplasia and marked hypoplasia, respectively, of the body and tail of the pancreas. Whereas both twins showed marked hypoplasia of the right kidney and multiple cysts in both kidneys, only the proband's sister showed hydronephrosis in the left kidney. The proband had profound defects in insulin and glucagon secretion, as well as mild renal dysfunction, whereas her sister had pronounced renal dysfunction accompanied by mild defects in insulin and glucagon secretion. Both twins manifested hypomagnesemia and hyperuricemia, but no apparent liver dysfunction or intellectual disability. The severity of renal and pancreatic defects differed between monozygotic twins with maturity‐onset diabetes of the young type 5, suggesting that the phenotypes of this condition are determined not solely by genetic factors.
Published: 2019
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26. In silico and in vitro analyses of the pathological relevance of the R258H mutation of hepatocyte nuclear factor 4α identified in maturity‐onset diabetes of the young type 1

Author: Kenji Sugawara, Kazuhiro Nomura, Yuko Okada, Aki Sugano, Masaaki Matsumoto, Toru Takarada, Atsuko Takeuchi, Hiroyuki Awano, Yushi Hirota, Hisahide Nishio, Yutaka Takaoka, and Wataru Ogawa
Subjects: Hepatocyte nuclear factor 4α, Insulin secretion, Maturity‐onset diabetes of the young type 1, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract: Abstract Mutations of the hepatocyte nuclear factor 4α (HNF4α) gene give rise to maturity‐onset diabetes of the young type 1. Although many such mutations have been identified in affected individuals, part of these mutations has been characterized with regard to their pathological relevance. We here identified a missense mutation (c.773G>A, p.R258H) of HNF4A in a mother and daughter with early‐onset diabetes and impaired insulin secretion. In silico simulation and in vitro luciferase reporter analyses showed that the mutation impairs the stability of self‐dimerization and the transactivation activity of HNF4α. Although arginine‐258 does not appear to participate directly in dimerization, its mutation alters the electrostatic surface potential of the dimer interface. Our results thus suggest that this mutation impairs the function of HNF4α and thereby contributes to the pathogenesis of maturity‐onset diabetes of the young type 1.
Published: 2019
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27. Usefulness of hemoglobin A1c and glycated albumin measurements for insulinoma screening: an observational case-control study

Author: Keiichi Torimoto, Yosuke Okada, Yoshiya Tanaka, Atsuko Matsuoka, Yushi Hirota, Wataru Ogawa, Yoshifumi Saisho, Isao Kurihara, Hiroshi Itoh, Shinya Inada, and Masafumi Koga
Subjects: Insulinoma, HbA1c, Glycated albumin, Hypoglycemia, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Insulinoma represents hypoglycemia as a predominant symptom; the autonomic symptoms may be resolved by chronically recurrent hypoglycemia resulting in the persistence of non-specific symptoms alone. Therefore, it has been estimated that there are many patients in whom the disease takes longer to diagnose and has remained undiagnosed. Although some parameters exist for the definitive diagnosis of the disease, there are currently no indices for early screening. Indices of glycemic control, hemoglobin A1c (HbA1c), and glycated albumin (GA) may be useful for the screening of patients with insulinoma having chronic hypoglycemia because the values become low in such a condition. Because there are no articles that have reported the point, we examine the effective cutoff values of HbA1c and GA for the diagnosis of insulinoma in the present study. Methods In a multicenter cross-sectional study, 31 patients with insulinoma were included for comparison with 120 control subjects with normal glucose tolerance based on 75 g oral glucose tolerance tests whose characteristics were matched to the patients. The primary outcomes were optimal cutoff values of HbA1c and GA for the screening of insulinoma. Results HbA1c was significantly lower in the insulinoma group at 4.7 ± 0.4% compared to the healthy control group at 5.7 ± 0.3% (p
Published: 2019
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28. Data on impact of monocytes and glucose fluctuation on plaque vulnerability in patients with coronary artery disease

Author: Hiroyuki Yamamoto, Naofumi Yoshida, Toshiro Shinke, Hiromasa Otake, Masaru Kuroda, Kazuhiko Sakaguchi, Yushi Hirota, Takayoshi Toba, Hachidai Takahashi, Daisuke Terashita, Kenzo Uzu, Natsuko Tahara, Yuto Shinkura, Kouji Kuroda, Yoshinori Nagasawa, Yuichiro Nagano, Yoshiro Tsukiyama, Ken-ichi Yanaka, Takuo Emoto, Naoto Sasaki, Tomoya Yamashita, Wataru Ogawa, and Ken-ichi Hirata
Subjects: Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract: Data presented in this article are supplementary material to our research article entitled “Impact of CD14++CD16+ monocytes on coronary plaque vulnerability assessed by optical coherence tomography in coronary artery disease patients” [1]. This article contains the data of study population, diagnostic ability of CD14++CD16+ monocytes to identify thin-cap fibroatheromas, and association between laboratory variables and plaque properties.
Published: 2018
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29. Impact of overweight on left ventricular function in type 2 diabetes mellitus

Author: Makiko Suto, Hidekazu Tanaka, Yasuhide Mochizuki, Jun Mukai, Hiroki Takada, Fumitaka Soga, Kumiko Dokuni, Yutaka Hatani, Keiko Hatazawa, Hiroki Matsuzoe, Hiroyuki Sano, Hiroyuki Shimoura, Junichi Ooka, Kensuke Matsumoto, Yushi Hirota, Wataru Ogawa, and Ken-ichi Hirata
Subjects: Diabetes mellitus, Left ventricular longitudinal function, Left ventricular diastolic function, Obesity, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background Coexistence of left ventricular (LV) longitudinal myocardial systolic dysfunction with LV diastolic dysfunction could lead to heart failure with preserved ejection fraction (HFpEF). Diabetes mellitus (DM) is known as a significant factor associated with HFpEF. Although the mechanisms of DM-related LV myocardial injury are complex, it has been postulated that overweight contributes to the development of LV myocardial injury in type 2 diabetes mellitus (T2DM) patients. However, the precise impact of overweight on LV longitudinal myocardial systolic function in T2DM patients remains unclear. Methods We studied 145 asymptomatic T2DM patients with preserved LV ejection fraction (LVEF) without coronary artery disease. LV longitudinal myocardial systolic function was assessed by global longitudinal strain (GLS), which was defined as the average peak strain of 18-segments obtained from standard apical views. Overweight was defined as body mass index (BMI) ≥ 25 kg/m2. Ninety age-, gender- and LVEF-matched healthy volunteers served as controls. Results GLS of overweight T2DM patients was significantly lower than that of non-overweight patients (17.9 ± 2.4% vs. 18.9 ± 2.6%, p
Published: 2017
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30. Impact of CD14++CD16+ monocytes on plaque vulnerability in diabetic and non-diabetic patients with asymptomatic coronary artery disease: a cross-sectional study

Author: Naofumi Yoshida, Hiroyuki Yamamoto, Toshiro Shinke, Hiromasa Otake, Masaru Kuroda, Daisuke Terashita, Hachidai Takahashi, Kazuhiko Sakaguchi, Yushi Hirota, Takuo Emoto, Hilman Zulkifli Amin, Taiji Mizoguchi, Tomohiro Hayashi, Naoto Sasaki, Tomoya Yamashita, Wataru Ogawa, and Ken-ichi Hirata
Subjects: CD14++CD16+ monocytes, Coronary plaque vulnerability, Thin-cap fibroatheroma, Glucose fluctuations, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background Previously, we have reported that daily glucose fluctuations could affect coronary plaque vulnerability, but the underlying mechanisms remained unclear. This study sought to investigate the impact of CD14++CD16+ monocytes on plaque vulnerability, as assessed by virtual histology intravascular ultrasound (VH-IVUS), as well as their relationship to fluctuating glucose levels in patients with asymptomatic coronary artery disease (CAD). Methods Fifty-one patients with asymptomatic CAD, who were undergoing lipid-lowering therapy and underwent VH-IVUS evaluation for angiographically mild to moderate lesions, were enrolled in the study. Standard VH-IVUS parameters, including the percentage volume of the necrotic core (%NC) within the plaque and the presence of a virtual histology thin-cap fibroatheroma (VH-TCFA), were then evaluated. Additionally, monocyte subsets were assessed by flow cytometry, and daily glucose fluctuations were analyzed by measuring the mean amplitude of glycemic excursion (MAGE). Results Among 82 plaques from 22 diabetes mellitus (DM) patients and 29 non-DM patients, 15 VH-TCFAs were identified. CD14++CD16+ monocyte counts significantly correlated with both %NC and the presence of VH-TCFA (%NC: r = 0.339, p = 0.002; VH-TCFA: p = 0.003). Multivariate logistic regression analysis revealed that CD14++CD16+ monocyte counts were independently associated with VH-TCFA (odds ratio = 1.029, p = 0.004). Furthermore, CD14++CD16+ monocyte counts were significantly correlated with the MAGE score in the non-DM patients (r = 0.544, p = 0.005). Conclusions CD14++CD16+ monocyte levels are associated with coronary plaque vulnerability and can serve as a biomarker for VH-TCFA in patients with CAD undergoing lipid-lowering therapy. In patients without DM, glucose fluctuations may alter the balance of monocyte subsets. Trial registration UMIN Registry number: UMIN000021228
Published: 2017
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31. Impact of Self-Reported Sitting Time and Transtheoretical Model Based on Exercise Behavior Change on Glycemic and Weight Control in Japanese Adults with Type 1 Diabetes: A Cross-Sectional Study

Author: Hiroto Honda, Makoto Igaki, Shin-ichiro Tanaka, Kumiko Ono, and Yushi Hirota
Subjects: sitting time, transtheoretical model, self-administered questionnaire, glycemic control, weight control, type 1 diabetes, Medicine
Abstract: This cross-sectional study aimed to examine the associations among self-reported sitting time (ST), transtheoretical model (TTM) based on exercise behavior change, and glycemic and weight control in Japanese adults with type 1 diabetes (T1D). Forty-two adults (age, 44.0 (33.3–56.8) years) with uncomplicated T1D answered questions regarding their lifestyles, including ST per day, and TTM using self-administered questionnaires. The glycated hemoglobin (HbA1c) level correlated with age and ST (p < 0.05, p < 0.01, respectively), whereas body mass index correlated with duration of T1D and TTM (p < 0.05, p < 0.01, respectively). Logistic regression analysis showed that poor glycemic control (HbA1c, >7%) was associated with ST (odds ratio, 3.53 (95% confidence interval, 1.54–8.11), p < 0.01). In addition, the cut-off points for quartiles of ST were 4.6, 6.0, and 8.0 h/day, and the HbA1c level in the lowest quartile was 15% lower than that in the highest quartile (p < 0.01). Although further studies with larger samples are needed, these results implied that expanded self-reported ST might be related to poor glycemic control in Japanese T1D adults, most of whom were lean, young and middle-aged, regardless of TTM based on exercise behavior change.
Published: 2020
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32. Caution is required for the evaluation of the accuracy of continuous glucose monitoring devices

Author: Yushi Hirota, Masao Toyoda, Takashi Murata, and Junnosuke Miura
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Published: 2020
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33. Glucagon secretions are impaired in patients with fulminant type 1 diabetes

Author: Hisako Komada, Yushi Hirota, and Wataru Ogawa
Subjects: Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Published: 2019
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34. Definition, criteria, and core concepts of guidelines for the management of obesity disease in Japan.

Author: Wataru Ogawa, Yushi Hirota, Shigeru Miyazaki, Tadashi Nakamura, Yoshihiro Ogawa, Iichiro Shimomura, Toshimasa Yamauchi, and Koutaro Yokote
Published: 2024
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35. Changes in Physical Activity and Glycemic Control before and after the Declaration of the State of Emergency Due to the COVID-19 Pandemic in Japanese Adult Females with Type 1 Diabetes: A 1-Year Follow-Up Study

Author: Hiroto Honda, Naoko Hashimoto, Masako Zenibayashi, Akihiko Takeda, Takehito Takeuchi, Akane Yamamoto, and Yushi Hirota
Subjects: Applied Mathematics
Abstract: This preliminary study aimed to investigate physical activity (PA) and glycemic control changes in Japanese adult females with type 1 diabetes (T1D) before the COVID-19 pandemic and one year later. Twelve females with T1D who used continuous glucose monitoring devices and initially volunteered for the study between February and March 2020 were included. PA data, obtained using a triaxial accelerometer, and glycemic control, including glycated hemoglobin (HbA1c), glycoalbumin (GA), mean 24-h sensor glucose (SG), time above range (TAR > 180 mg/dL), time in range (TIR 70–180 mg/dL), and time below range (TBR < 70 mg/dL), were analyzed. One year later, long (≥10 min) bouts of moderate-to-vigorous-intensity PA and daily steps decreased by 35.1% and 6.0%, respectively, and TAR increased from 23.5% to 29.0%. Additionally, an increase in prolonged (≥30 min) sedentary behavior correlated with a decrease in TBR and an increase in mean 24-h SG, GA, and the GA/HbA1c ratio. Furthermore, a decrease in daily energy consumption correlated with a decrease in TIR. These results indicate that some forms of PA in Japanese T1D adults have not returned to their pre-pandemic status, even in the same season one year later, which could worsen glycemic control.
Published: 2022

36. Type 1 diabetes iron‐deficiency anaemia case report and the clinical relevance of <scp>red blood cell</scp> lifespan‐adjusted <scp>glycated haemoglobin</scp>

Author: Yushi Hirota, Yongjin Xu, Akane Yamamoto, Atsuko Matsuoka, Timothy C. Dunn, and Wataru Ogawa
Subjects: Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine
Published: 2022

37. Composite paraganglioma-ganglioneuroma with atypical catecholamine profile and phenylethanolamine N-methyltransferase expression: a case report and literature review.

Author: Yuriko Sasaki, Maki Kanzawa, Masaaki Yamamoto, Keitaro Kanie, Hironori Bando, Kei Yoshino, Yushi Hirota, Katsumi Shigemura, Masato Fujisawa, Wataru Ogawa, and Hidenori Fukuoka
Published: 2024
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38. Impact of <scp>COVID</scp> ‐19 pandemic on behavioral changes and glycemic control and a survey of telemedicine in patients with diabetes: A multicenter retrospective observational study

Author: Ryotaro Bouchi, Takehiro Sugiyama, Atsushi Goto, Mitsuru Ohsugi, Narihito Yoshioka, Hideki Katagiri, Tomoya Mita, Yushi Hirota, Hiroshi Ikegami, Munehide Matsuhisa, Eiichi Araki, Hiroki Yokoyama, Masae Minami, Katsuya Yamazaki, Hideaki Jinnouchi, Hiroki Ikeda, Hitomi Fujii, Miyuki Nogawa, Masahiro Kaneshige, Kengo Miyo, and Kohjiro Ueki
Subjects: Endocrinology, Diabetes and Metabolism, Internal Medicine, General Medicine
Published: 2023

39. Association between diabetic nephropathy and left ventricular longitudinal myocardial function in type 1 diabetes mellitus patients with preserved ejection fraction

Author: Eri Ota, Hidekazu Tanaka, Yasuhide Mochizuki, Yuki Yamauchi, Hiroaki Shiraki, Kentaro Yamashita, Ayu Shono, Makiko Suzuki, Keiko Sumimoto, Aisha Yokoi, Shin Urai, Yushi Hirota, Wataru Ogawa, and Ken-ichi Hirata
Subjects: Global longitudinal strain, LV longitudinal myocardial dysfunction, Echocardiography, Type 1 diabetes mellitus, Radiology, Nuclear Medicine and imaging, Diabetic nephropathy, Cardiology and Cardiovascular Medicine
Published: 2022

40. Predictive factors for postpartum glucose intolerance in women with gestational diabetes mellitus

Author: Naohisa Masuko, Kenji Tanimura, Nobue Kojima, Hitomi Imafuku, Masashi Deguchi, Yuko Okada, Yushi Hirota, Wataru Ogawa, and Hideto Yamada
Subjects: Blood Glucose, Postpartum Period, Obstetrics and Gynecology, Glucose Tolerance Test, gestational diabetes mellitus, oral disposition index, Diabetes, Gestational, glucose intolerance, Pregnancy, Risk Factors, Humans, Female, Prospective Studies, postpartum, 75-g oral glucose tolerance test
Abstract: Aim The aim of this prospective cohort study was to evaluate the risk factors for postpartum glucose intolerance (GI) in women with gestational diabetes mellitus (GDM). Method A total of 140 women with GDM were enrolled. Of these, 115 underwent a 75-g oral glucose tolerance test (OGTT) at 12 weeks after delivery. Clinical factors and parameters in the antepartum 75-g OGTT associated with postpartum GI were evaluated by logistic regression analyses. Results Twenty-two (19.1%) of the 115 women with GDM developed postpartum GI. The univariate and multivariable logistic regression analyses revealed that low oral disposition index (DI) was a risk factor for postpartum GI (OR, 0.2; 95% CI, 0.04-0.7; p < 0.05), and that no clinical factors were associated with postpartum GI. Conclusions Lower oral DI on the antepartum 75-g OGTT may be a useful marker for identifying GDM women who are at high risk for postpartum GI.
Published: 2022

41. To Use or Not to Use a Self-monitoring of Blood Glucose System? Real-world Flash Glucose Monitoring Patterns Using a Cluster Analysis of the FGM-Japan Study.

Author: Naoki Sakane, Yushi Hirota, Akane Yamamoto, Junnosuke Miura, Hiroko Takaike, Sari Hoshina, Masao Toyoda, Nobumichi Saito, Kiminori Hosoda, Masaki Matsubara, Atsuhito Tone, Satoshi Kawashima, Hideaki Sawaki, Tomokazu Matsuda, Masayuki Domichi, Akiko Suganuma, Seiko Sakane, and Takashi Murata
Published: 2023
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42. Possible Relationship between the Deteriorated Accuracy of Intermittent-Scanning Continuous Glucose Monitoring Device and the Contact Dermatitis: Post-hoc analysis of the ISCHIA Study.

Author: Masao TOYODA, Takashi MURATA, Yushi HIROTA, Kiminori HOSODA, Ken KATO, Kunichi KOUYAMA, Ryuji KOUYAMA, Akio KURODA, Yuka MATOBA, Munehide MATSUHISA, Shu MEGURO, Junnosuke MIURA, Kunihiro NISHIMURA, Akira SHIMADA, Shota SUZUKI, Atsuhito TONE, and Naoki SAKANE
Subjects: CONTACT dermatitis, MEDICAL equipment, GLYCEMIC control, BLOOD sugar, TYPE 1 diabetes
Abstract: Objective: We previously reported the mean average relative difference (MARD) of the sensor glucose (SG) of the first-generation FreeStyle Libre with the original algorithm, an intermittent scanning continuous glucose monitoring (isCGM) device, was 15.6% in the Effect of Intermittent-Scanning Continuous Glucose Monitoring to Glycemic Control Including Hypoglycemia and Quality of Life of Patients with Type 1 Diabetes Mellitus Study (ISCHIA Study). In the present study, we aimed to further analyze its accuracy in detail by conducting a post-hoc analysis of the study. Methods: The ISCHIA Study was a multicenter, randomized, cross-over trial to assess the efficacy of isCGM. The SG levels of isCGM and the measured capillary blood glucose (BG) levels of 91 participants were used for the analysis. Results: Bland-Altman analysis showed bias of -13.0 mg/dl when the SG levels were compared to the BG levels, however no proportional bias was observed (r = 0.085). MARD of the participants without and with contact dermatitis were 15.0 ± 6.0% and 27.4 ± 21.4% (P = 0.001), respectively. Conclusion: There was negative bias in the SG levels of isCGM compared to the BG levels. There is a possibility that the complication of the contact dermatitis during isCGM use may be related with deteriorated accuracy of the SG levels. [ABSTRACT FROM AUTHOR]
Published: 2023

43. Glycated albumin (GA) and the GA/HbA1c ratio are higher in diabetic patients positive for insulin antibodies with high binding capacity and low affinity

Author: Wataru Ogawa, Takehito Takeuchi, Masafumi Koga, Tetsushi Hamaguchi, Yuko Okada, Kazuhiko Sakaguchi, Atsuko Matsuoka, Yasushi Nakagawa, and Yushi Hirota
Subjects: medicine.medical_specialty, HbA1c, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Type 2 diabetes, Insulin Antibody, Glycated albumin, Low affinity, Insulin antibodies, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Binding site, Type 1 diabetes, business.industry, Insulin, Diabetes, nutritional and metabolic diseases, medicine.disease, Insulin autoimmune syndrome, Endocrinology, Original Article, business
Abstract: Patients with diabetes mellitus having insulin antibodies (InsAb) with properties of high binding capacity and low affinity, which are observed in insulin autoimmune syndrome (IAS), are known to have greater plasma glucose fluctuations. Glycated albumin (GA) and the GA/HbA1c ratio have been demonstrated to reflect plasma glucose fluctuations. Hence, we hypothesized that GA or the GA/HbA1c ratio in diabetic patients having InsAb with properties of high binding capacity and low affinity may be higher than those in InsAb-negative diabetic patients, and we verified this hypothesis. Subjects were 12 diabetic patients who had InsAb noted while being treated with insulin and were subjected to Scatchard analysis and whose InsAb had properties similar to those of patients with IAS (affinity constant K1 < 0.24 x 1/10(-8) M, number of binding sites R1 ≥ 11.5 x 10(-8) M) [four cases of type 1 diabetes (T1D) and eight cases of type 2 diabetes (T2D)]. The control group consisted of T1D and T2D cases matched to the T1D and T2D cases, respectively, according to sex, age, BMI, and HbA1c. GA and the GA/HbA1c ratio were compared between both groups. GA and the GA/HbA1c ratio in InsAb-positive patients was significantly higher than that in the control group for both T1D and T2D patients. Diabetic patients having InsAb with properties of high binding capacity and low affinity had higher GA and the GA/HbA1c ratio than those of InsAb-negative patients. Greater plasma glucose fluctuations were suggested in InsAb-positive diabetic patients.
Published: 2022

44. Empagliflozin in Patients with Chronic Kidney Disease

Author: Herrington, William G, Staplin, Natalie, Wanner, Christoph, Green, Jennifer B, Hauske, Sibylle J, Emberson, Jonathan R, Preiss, David, Judge, Parminder, Mayne, Kaitlin J, Ng, Sarah Y A, Sammons, Emily, Zhu, Doreen, Hill, Michael, Stevens, Will, Wallendszus, Karl, Brenner, Susanne, Cheung, Alfred K, Liu, Zhi-Hong, Li, Jing, Hooi, Lai Seong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Maggioni, Aldo P, Pontremoli, Roberto, Deo, Rajat, Goto, Shinya, Rossello, Xavier, Tuttle, Katherine R, Steubl, Dominik, Petrini, Michaela, Massey, Dan, Eilbracht, Jens, Brueckmann, Martina, Landray, Martin J, Baigent, Colin, Haynes, Richard, The EMPA-KIDNEY Collaborative Group: Colin Baigent, Martin J Landray, Christoph Wanner, William G Herrington, Richard Haynes, Jennifer B Green, Sibylle J Hauske, Martina Brueckmann, Mark Hopley, Maximillian von-Eynatten, Jyothis George, Susanne Brenner, Alfred K Cheung, David Preiss, Zhi-Hong Liu, Jing Li, Laiseong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Roberto Pontremoli, Aldo P Maggioni, Natalie Staplin, Jonathan Emberson, Stefan Hantel, Shinya Goto, Rajat Deo, Katherine R Tuttle, Michael Hill, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Xavier Rossello, Emily Sammons, Doreen Zhu, Peter Sandercock, Rudolf Bilous, Charles Herzog, Paul Whelton, Janet Wittes, Derrick Bennett, Patricia Achiri, Chrissie Ambrose, Cristina Badin, Jill Barton, Richard Brown, Andy Burke, Sebastian Butler, Rejive Dayanandan, Pia Donaldson, Robert Dykas, Lucy Fletcher, Kate Frederick, Hannah Kingston, Mo Gray, Emily Harding, Akiko Hashimoto, Lyn Howie, Susan Hurley, Ryonfa Lee, Nik Luker, Kevin Murphy, Mariko Nakahara, John Nolan, Michelle Nunn, Sorcha Mulligan, Akiko Omata, Sandra Pickworth, YanRu Qiao, Shraddha Shah, Karen Taylor, Alison Timadjer, Monique Willett, Liz Wincott, Qin Yan, Hui Yu, Louise Bowman, Fang Chen, Robert Clarke, Michelle Goonasekera, Waseem Karsan, Marion Mafham, Christina Reith, Mohammed Zayed, Ritva Ellison, Rowan Moys, Will Stevens, Kevin Verdel, Karl Wallendszus, Chris Bowler, Anna Brewer, Andy Measor, Guanguo Cui, Charles Daniels, Angela Field, Bob Goodenough, Ashley Lawson, Youcef Mostefai, Dheeptha Radhakrishnan, Samee Syed, Shuang Xia, Ruth Adewuyi-Dalton, Thomas Arnold, Anne-Marie Beneat, Anoushka Bhatt, Chloe Bird, Andrew Breach, Laura Brown, Mark Caple, Tatyana Chavagnon, Karen Chung, Sarah Clark, Luminita Condurache, Katarzyna Eichstadt, Marta Espino Obrero, Scarlett Forest, Helen French, Nick Goodwin, Andrew Gordon, Joanne Gordon, Cat Guest, Tina Harding, Michal Hozak, Matthew Lacey, David MacLean, Louise Messinger, Stewart Moffat, Martin Radley, Claire Shenton, Sarah Tipper, Jon Tyler, Lesley Weaving, James Wheeler, Elissa Williams, Tim Williams, Hamish Woodhouse, Angela Chamberlain, Jo Chambers, Joanne Davies, Denise Donaldson, Pati Faria-Shayler, Denise Fleming-Brown, Jennifer Ingell, Carol Knott, Anna Liew, Helen Lochhead, Juliette Meek, Isabel Rodriguez-Bachiller, Andrea Wilson, Patrick Zettergren, Rach AitSadi, Ian Barton, Alex Baxter, Yonghong Bu, Lukasz Danel, Sonja Grotjahn, Rijo Kurien, Michael Lay, Archie Maskill, Aleksandra Murawska, Rachel Raff, Allen Young, Rebecca Sardell, Vladimir Cejka, Marcela Fajardo-Moser, Christian Hartner, Doris Poehler, Janina Renner, Franziska Scheidemantel, Miya Bryant, Anita Hepditch, Cassandra Johnson, Erin Latore, Yolanda Miller, Lauren Price, Merilee Whalen, Ashleigh Wheeler, Jenny Ingell, Yu An, Yinghua Chen, Peiling Chen, Hao Dai, Hong Du, Fang Feng, Qing Guo, Libo Hou, Wuhanbilige Hundei, Binbin Jin, Yan Li, Jiamin Liu, Xia Song, Yanping Wang, Yanwu Yu, Ning Zhang, Lingshan Zhao, Hui Zhong, Cheng Beng Goh, Ye Mun Low, Soon Yi Sor, Farah Hanis Zulkipli, Sarojini Sivanandam, Natsuki Arai, Ai Fukasawa, Mizue Furukawa, Keisuke Habuki, Shoko Hayashi, Wakako Isari, Saki Kanegae, Maria Kawai, Reiki Kobayashi, Takako Kuramae, Chika Kuribayashi, Sawako Maeno, Satoshi Masumoto, Tomoko Morisaki, Minoru Oda, Kazue Sawada, Kenta Sugamori, Ayana Tatsuzawa, Aiko Tomita, Kazuyuki Yuasa, Hiroko Inazawa, Amanda Axler, Kerri Gallo, Ester Baldini, Barbara Bartolomei Mecatti, Francesca Bianchini, Martina Ceseri, Laura Cipressa, Gianna Fabbri, Andrea Lorimer, Donata Lucci, Sharang Ghavampour, Anja Knoppe, Hans Schmidt-Gurtler, Hubert Dumann, Sybille Merscher, Margret Patecki, Georg Rainer Schlieper, Anke Torp, Bianca Weber, Maja Zietz, Bernd Hohenstein, Urs Benck, Diliana Draganova, Thomas Weinreich, Lothar Wolf, Jasmine Gaidu, Hanna Reiner, Mandy Visnjic, Daniel Steffl, Marie Breitenfeldt, Annette Kraemer-Guth, Christine Braun, Simone Hagge, Michael Schomig, Stephan Matthias, Dominik Stoffler, Beate Schumacher, Thomas Sitter, Louise Fuessl, Julia Krappe, Jerome Loutan, Volker Vielhauer, Luciano Andriaccio, Magdalena Maurer, Bernhard Winkelmann, Martin Dursch, Linda Seifert, Linda Tenbusch, Julia Weinmann-Menke, Simone Boedecker, Wiebke Kaluza-Schilling, Daniel Kraus, Carina Krieger, Margit Schmude, Anne Schreiber, Ewelina Eckrich, Diethelm Tschope, Abdulwahab Arbi, Young Lee-Barkey, Bernd Stratmann, Natalie Prib, Sina Rolfsmeier, Irina Schneider, Lars Rump, Johannes Stegbauer, Christine Pötz, Mara Schemmelmann, Claudia Schmidt, Michael Koch, Sendogan Aker, Annika Küpper, Manuela Martin, Thiemo Pfab, Christian Albert, Michael Haase, Barbara Zander, Claudia Schneider-Danwitz, Wolfgang Seeger, Wolf-Adam Seeger, Britta Zemann, Christoph Stellbrink, Kristin Marx, Ekaterina Stellbrink, Britta Brettschneider, Stephanie Watson, Marion Iselt, Gerhard Klausmann, Inga-Nadine Kummer, Auguste Kutschat, Simone Streitenberger, Matthias Girndt, Silke Markau, Ina Girakossyan, Claudia Hanf, Joachim Beige, Ralph Wendt, Ulrike Schmidt, Andreas Schneider, Roland Veelken, Claudia Donhauser, Luis Becker, Nexhat Miftari, Ricarda Wolfling, Sarah Morlok, Christian Hugo, Alexander Paliege, Jens Passauer, Julian Stumpf, Annegret Fleischer, Kerstin Haaser, Bernhard Kraemer, Jan Jochims, Bernd Kruger, Claudia Foellinger, Anastassiya Reisler, Frank Strutz, Stefan Haack, Ursula Hohenstatt, Martin Busch, Konstantin Herfurth, Gunter Wolf, Rainer Paul, Hermann Haller, Jessica Kaufeld, Jan Menne, Elisabeth Bahlmann-Kroll, Angela Bergner, Horst Weihprecht, Aydin Er, Florian Sonntag, Elif Turan, Michael Wittmann, Franziska Klauser, Eva Voigt, Volker Schettler, Egbert Schulz, Madlen Rohnstock, Elke Schettler, Bernd Schroppel, Rene van Erp, Martin Kachele, Ulla Ludwig, Lena Schulte-Kemna, Waltraud Kmietschak, Elke Preiss, Martina Ruocco, Gunnar Heine, Martin Brzoska, Sebastian Gabel, Christina Büttner, Asma Sabarai, Bernhard Banas, Tobias Bergler, Yvonne Ehrl, Franz Putz, Antonia Schuster, Stefanie Kuhn, Torsten Schramm, Stefan Degenhardt, Gerhard Schmidt, Lea Weiland, Ulrike Giebeln-Hudnell, Jan Kielstein, Gabriele Eden, Brigitte Fuchs, Gina Morig, Manuela Winkler, Harald Darius, Charalampos Kriatselis, Carl-Philipp Roesch, Astrid Maselli, Dominik Alscher, Markus Ketteler, Moritz Schanz, Severin Schricker, Bianka Rettenmaier, Andrea Schwab, Pablo Pergola, Irene Leal, Melissa Cagle, Anna Romo, Anthony Torres, Sucharit Joshi, Kulli Barrett, Alexis Africano, Vicki Dodds, Dorleena Gowen, Ashlee Morris, Juan Fernandez, Guillermo Jimenez, Ricardo Viera, Kendaling Bruce, Ryan Barrios, Maylin Garcia, Kerelyn Garcia, Iradis Leal, David Tietjen, David Bains, Carlo Castillo, Genielle Brewer, Justin Davis, Natalie Freking, Brittany Golson, Sally Ham, Jesslyn Roesch, Pusadee Suchinda, Shameem Beigh, Usah Lilavivat, Joyce Bilton, Kim Bocchicchia, Jeffrey Turner, Neera Dahl, Aldo Peixoto, Yasemin Kavak, Lauren Liberti, Hari Nair, Nicolas Page, Stephanie Rosenberg, Kathryn Simmons, Tamara Isakova, Rebecca Frazier, Rupal Mehta, Anand Srivastava, Patrick Fox, Jonathan Hecktman, Alexander Hodakowski, Carlos Martinez, Rachel Phillips, Alexis Stevenson, Reem Mustafa, Kyle Jansson, Cassandra Kimber, Jason Stubbs, Ahmad Tuffaha, Sri Yarlagadda, Debbie Griffin, Elisabeth Laundy, Zhuo Tang, Radica Alicic, Ann Cooper, Lisa Davis, Ashwini Gore, Rebecca Goldfaden, Leslie Harvill, Lisa Hichkad, Barry Johns, Thomas Jones, Kayla Merritt, Jennifer Sheldon, Jennifer Stanfield, Lindsay Alexander, Kaitlyn Preston, Lindsey Wood, Rajesh Pradhan, Roger DeRaad, Kelli McIntosh, Louis Raymond, Michael Shepperd, Susan McLaughlin, Mary Seifert, Andrew Shepherd, Joseph Aiello, William Durham, Laurie Loudermilk, John Manley, Sabrina Burnette, Stephanie Evans, Tara Johnson, Lance Sloan, Judy Ann Acosta, Stacy Gillham, Katia Sloan, SueAnn Squyres, Michael Rocco, Amret Hawfield, Ben Bagwell, Lauren Richmond, Joseph Soufer, Subha Clarke, Amanda Aliu, Kristine Calabrese, Amanda Davis, Veronica Poma, Tracy Spinola, James Magee, Ricardo Silva, Rushab Choksi, Lorraine Dajani, John Evans, Anil George, Prasanth Krish, Gerard Martins, Mae Sheikh-Ali, David Sutton, Freda Driver, Abraham Hanburry, Laura Hume, Amber Hurst, Matthew Taddeo, Marla Turner, Veronica Yousif, Srinivasan Beddhu, Laith Al-Rabadi, Nikita Abraham, Amalia Caamano, Judy Carle, Victoria Gonce, Kaitlyn Staylor, Na Zhou, Shweta Bansal, Manoj Bhattarai, Kumar Sharma, Subrata Debnath, Aliseiya Garza, Chakradhar Velagapudi, Sergio Rovner, Javier Almeida, Pablo Casares, Verlaine Stewart-Ray, Rene Almaraz, Renata Dayrell, Ana Moncada, Ricardo Pulido, Roxana Rodriquez, Wasim Deeb, Kathryn DeGoursey, Rodel Gloria, Trevor Greene, Robert Miller, Edward Pereira, Miguel Roura, Debbie Domingo, Sasha Dorestin, William Hodge, Cathy Jackson, Deborah Lund, Katrina Taylor, Kenneth Boren, Brittany Cleveland, Sandra Gaiser, Mandeep Sahani, Logan Aldrich, Exodus Edmerson, Edmond Limon, Cole Valletta, Patricia Vasquez, Christopher Provenzano, Navkiranjot Brar, Heather Henderson, Bellovich Keith, Qur Khai, Quresh Khairullah, Gail Makos, Joel Topf, Sherry Gasko, Rosemarie Henschel, Kaitlin Knapp, Teresa Kozlowski, Paula LaFleur, Ashwathy Varughese, Hui Xue, Patricia Wu, Olga Arechiga, Shan Darbeau, Michael Fechter, Stephanie Martinez, Lenita Hanson, Nyla Cooper, Arelis Madera, Jay Cadorna, Rita Sheridan, Helen Sparks, Bradley Eilerman, Susanne Bodine, Wael Eid, Rebecca Flora, Amber Avery, Cashmere Hardy, Mihaela Biscoveanu, Steven Nagelberg, Tracey Cummins, Frederic Rahbari-Oskoui, Anju Oommen, Zohreh Forghani, Stacie Hitchcock, Darya Hosein, Diane Watkins, Minesh Patel, Anthony Lambert, Elizabeth Newman, Autumn Wood, Tammy Ross, Stephany Topping, Jeffrey Mulhern, Lorna Murphy, Ann Vasseur, Gregory Greenwood, Alexander Hadley, Denise Laurienti, Christopher Marshall, Nicholas McLean, Scott Satko, Brandy Caudill, Jacob Maris, Janice Rogers, Cindy Vanhoy, George Thomas, Georges Nakhoul, John O'Toole, Jonathan Taliercio, Leslie Cooperman, Marina Markovic, Barbara Tucky, Devasmita Dev, Alia Hasan, Hima Yalamanchili, Namita Jain, Lesley McNeil, Eric Wines, Jean Park, Adline Ghazi, Mia Hamm, Tejas Patel, Amy Mottl, Emily Chang, Vimal Derebail, Emmie Cole, Anne Froment, Sara Kelley, Jordan Osmond Foster, Vahid Mahabadi, Golriz Jafari, Anita Kamarzarian, Wendy Arriaga, Daisy Arteaga, Rosario Machicado, Genesis Naverrete, Prashant Kumar, Imran Nazeer, Karina Urquia, Tammi Glider, Vickie Jones, Savannah Rucker, Jennifer Wiley, Rahul Pandey, Jesus Arroyo, Harish Pariani, Mohammad Ahmad, Shahin Mozaffari, Erika Perez, Matthew Budoff, Sion Roy, Divya Birudaraju, Ahmed Ghanem, Sajad Hamal, Stephen Aronoff, Elisa Joye Petr, Richard Sachson, Jaime Wiebel, Sana Akram, Laurie Jones, Curtis Knight, Maurie Tarlac, Shahbaz Ahmed, Harold Szerlip, Akinwande Akinfolarin, Ankit Mehta, Shana Camp, Cindy Castro, Zanaida Cooper, Jessica Terry, Ahmed Awad, Bhavya Kothapalli, Ryan Lustig, Serine Alfaress, Hyder Jasim, Mary Parrigon, Dennis Karounos, Sadiq Ahmed, Maggie Berry, Ruth Oremus, Carlos Hernandez-Cassis, Elias Ugwu, Nazia Junejo, Nancy Suazo, Mark Segal, Amir Kazory, Sherry Brown, Tristan Daniels, Sofia Dayi, Renee Hogan, Kathy McCray, Jennifer Stickley, Mahboob Rahman, Mirela Dobre, Lavinia Negrea, Aparna Padiyar, Nishigandha Pradhan, Arash Rashidi, Nagaraju Sarabu, Vicki Donley, Tricia Young, Godson Oguchi, Judepatricks Onyema, Kahla Damianik, Jack Dienes, Judith Plummer-Morgan, Marilyn Roman, Mauver Skipper, Stacey-Ann Villaruel, Krystle Williams, Danny Sugimoto, Jeffrey Dugas, Ismeal Ahmed, Jamie Bhairoo, Dolores Rijos, Huzaifa Salim, Madita Gavrila, Kathryn Lafferty, Ria Rabara, Sally Ruse, Maria Weetman, James Bushnell, Albert Power, Alison Jenkins, Stefanie Jones, Amanda Scott, Cath Byrne, Mark Jesky, Alison Cowley, Emma McHaffie, Holly Waterfall, Jo Taylor, Laura Bough, Thomas Phillips, Barbara Winter-Goodwin, Sui Phin Kon, Iain MacDougall, Eirini Lioudaki, Sapna Shah, Claire Sharpe, Francisco Aguilar, Abegail Hernandez Pena, Conception Pugay, Amelia Te, Hugh Finn, Wasim Hanif, Samiul Mostafa, Alice Aitken, Katharine Draxlbauer, Evelina Grobovaite, Jennifer Kearney, Theresa McCarthy, Giorgio Gentile, Duncan Browne, Palanichamy Chellamuthu, Tabinda Dugal, Terri Chant, Laura Jones, Emily Laity, Megan Miners, James Muir, Elizabeth Swanson, Andrew Frankel, James Tomlinson, Marlon Alegata, Rashid Almasarwah, Anthoula Apostolidi, Maria Vourvou, Thomas Walters, Maarten Taal, Hari Dukka, Nitin Kolhe, Carly McDonald, Kelly White, Shiva Ugni, Smita Gunda, Rotimi Oluyombo, Vicki Brindle, Ping Coutts, Tracy Fuller, Evelyn Nadar, Suresh Ramadoss, Nichola Motherwell, Susannah Pajak, Louise Tonks, Sunil Bhandari, Richard Bodington, Adil Hazara, Dominic Fellowes, Christopher Wong, Christopher Goldsmith, Sherald Barnes, Ann Bennett, Claire Burston, Samantha Hope, Nicola Hunt, Lini Kurian, Richard Fish, Daniela Farrugia, Judy Lee, Emma Sadler, Hannah Turner, Christopher Hill, Henry Brown, Agnes Masengu, Peter Maxwell, Nina Bleakley, Hugh Murtagh, William Petchey, Vivian Yiu, Joanne Kellett, Angharad Williams, Helen Clarke, Victoria Carnall, Sarah Benyon, Caroline Blake, Stephanie Estcourt, Jane Piper, Neal Morgan, Carolyn Hutchinson, Teresa McKinley, Alastair Woodman, Judi Graham, Niall Leonard, John Smyth, Vicki Adell, Samantha Hagan, Ben Caplin, Amin Oomatia, Eleanor Damian, Toluleyi Sobande, Tim Doulton, Michael Delaney, Mahmoud Montasser, Jenny Hansen, David Loader, Angela Moon, Frances Morris, Smeeta Sinha, Chukwuma Chukwu, Amy Hudson, Diane Campbell, Melanie Kershaw, Stephanie Whittaker, Ayesha Irtiza-Ali, Farid Ghalli, Heba Nosseir, Allison Leslie, Kate Trivedi, Donald Fraser, Mohammad Alhadj Ali, Sian Griffin, Farah Latif, Justyna Witczak, Alexa Wonnacott, Lynda Jeffers, Yvette Webley, Paul Phelan, Eve Miller-Hodges, Ailsa Geddes, Margaret Glenwright, Amy Hunter, Thomas Pickett, Jim Moriarty, Linda Hill, Amanda Tyler, Waqar Ayub, Gail Evans, Sue Hewins, Davina Hewitt, Kerry Read, Samira Bell, Leanne Cosgrove, Rachel Craik, Shona Murray, Nitin Bhandary, Holly Coles, Rashmi Easow, Maya Joseph, Arif Khwaja, Yvonne Jackson, Angeline Mbuyisa, Rachel Sellars, Nihil Chitalia, Cynthia Mohandas, Anca Gherman, Charlotte Kamundi, Olumide Olufuwa, Kieran McCafferty, Adedolapo Adeleke, Cara Healy, Damini Jeyarajah, Edward Kinsella-Perks, Richard Smith, Brian Camilleri, Carol Buckman, Jenny Finch, Vanessa Rivers, Andrew Connor, Sheila Carr, Lisa Shainberg, Andrew Lewington, Richard Baker, Suzannah Dorey, Kay Tobin, Rosalyn Wheatley, Debasish Banerjee, Richard Hull, Sharirose Abat, Riny Paul, Mahzuz Karim, Zay Htet, Saad Tufail, Ravi Varma, Karen Convery, Deirdre Fottrell-Gould, Lisa Hudig, Emily Tropman, Thahir Abdul-Samad, Anne Grace, Marie Phipps, Rebecca Suckling, Subash Somalanka, Bhrigu Sood, Pauline Swift, Sarah Acheampong, Kwame Ansu, Martia Augustin, Anna Sampson, Lynn Vinall, Kim Wren, Shamila Wanninayake, Nicholas Wooding, Heather Edwards, Lydia Owen, Stephanie Bolton, Marion Carson, Michael Matthews, Nigel Brunskill, Jorge Jesus-Silva, Alex Howson, Mary Quashie-Akponeware, Hilary Tindall, Chidambaram Nethaji, Helen Eldon, Rajan Patel, Patrick Mark, Alastair Rankin, Michael Sullivan, Kirsty Forsyth, Rowan McDougall, Tanaji Dasgupta, Louisa Davies, Maggie Ryder, Philip Grimmer, Clare Macdonald, Mary Webster, Newcastle Newcastle, Timothy Ellam, Edwin Wong, Christine Meshykhi, Andrea Webster, Peter Wilson, Enric Vilar, Jocelyn Berdeprado, Eunice Doctolero, Lily Wilkinson, Frank McCarroll, Hesham Ammar, Ying Kuan, Conor Moran, Girish Shivashankar, Ryan Campbell, Deborah Glowski, Paula McDermott, Amar Ali, Zuber Patel, Christine Bond, Gillian Whalley, Haitao Zhang, Liu Yang, Lihua Zhang, Tingting Kan, Ling Zhu, Jinghong Zhao, Weiping Hou, Jing Wu, Hong Cheng, Weijing Bian, Zhirui Zhao, Fengmin Shao, Huixia Cao, Xiaojing Jiao, Peiyuan Niu, Jianying Niu, Yu Chen, Lihong Zhang, Shenglang Zhu, Haiyan Lin, Shaopeng Yao, Jiehui Chen, Ying Jiang, Ying Hu, Huaying Xiao, Fuye Yang, Xinzhou Zhang, Baochun Guo, Qiu Jin, Lixia Liu, Xiangcheng Xiao, Yanyun Xie, Ting Meng, Chuanwen Xu, Jie Huang, Yanmei Xu, Weixin Kong, Xiaoliang Wang, Qianpan Liu, Xueying Wang, Ming Gao, Xiumei Hu, Ying Lu, Li Wang, Kun Peng, Wei Wang, Qiuhong Gong, Jianfang Cai, Xiaojue Li, Xuejiao Liu, Shuhan Zhou, Hong Liu, Yao Weng, Shuai Tang, Yao Yao, Shi Zhao, Chen Cheng, Wei Wei, Na Li, Sadanah Aqashiah Mazlan, Alia Zubaidah Bahtar, Elliyyin Katiman, Noraini Othman, Lily Mushahar, Nurdiana Mazlan, Nur Sharafina Safiee, Sarasa Ramasamy, Hin Seng Wong, Hajar Ahmad Rosdi, Esther Zhao Zhi Tan, Ju Fan Tay, Kok Seng Teng, Hasnah Yahaya, Wen Jiun Liu, Lik Wee Ee, Kenneth Kay Leong Khoo, Yuana Mohd Yusoff, Fariz Safhan Mohamad Nor, Mohd Kamil Ahmad, Mohd Ramli Seman, Clare Hui Hong Tan, Laura Lui Sian Ngu, Jaime Yoke May Chan, Javelin Peji, Chek Loong Loh, Yee Yan Lee, Sridhar Ramanaidu, Kah Mean Thong, Yik Hong Wong, Suria Junus, Chen Hua Ching, Mohammad Faisal Asmee, Ku Ruziana Ku Md Razi, Chun Leong Low, Christopher Sze Bing Sim, Zhang Duan Tham, Noor Kamila Abdullah, Tai Meng Chen, Yong Chieh Chan, Eason Chang, Huan Yean Kang, Kai Quan Lee, Sue Ann Lee, Aik Kheng Lee, Jeevika Vinathan, Rizna Abdul Cader, Ruslinda Mustafar, Lydia Kamaruzaman, Rozita Mohd, Rahimah Ismail, Chong Men Leong, Chee Koon Low, Liang Wei Wong, Norlezah Adnan, Sabariah Ibrahim, Mohamad Zaimi Abdul Wahab, Sunita Bavanandan, Yik Shen Lim, Wan Hazlina Wan Mohamad, Siti Munirah Jaafar, Nur Ashykeen Mohd Fauzi, Aziee Sudin, Soo Kun Lim, Chye Chung Gan, Albert Hing, Wan Ahmad Faizal Alaidin Razali, Yew Fong Liew, Chelsia Bao Tyng Chan, Mei Chih Cheng, Yu Chen Ong, Loke Meng Ong, Farah Amalina Mohamed Affandi, Korina Rahmat, Ban Chai Peng, Masayu Amat, Nuzaimin Hadafi Ahmad, Doo Yee Mah, Yi Loon Tye, Zaid Azhari, Siti Nabilah Mohamad Zaini, Mohd Aidil Musa, Norazinizah Ahmad Miswan, Rafizanur Ramli, Nor Aziah Ahmad, Bak Leong Goh, Nurul Izah Ahmad, Fairol Huda Ibrahim, Tze Jian Ng, Malini Shanmuganathan, Li Lian Tay, Zaiha Harun, Salmi Ramli, Nurul 'Ain Yusof, Rossenizal Abd Rahman, Muhammad Iqbal Abdul Hafidz, Nur Hidayati Mohd Sharif, Irda Yasmoon Awang, Eitaro Nakashima, Rui Imamine, Makiko Minatoguchi, Yukari Miura, Miduki Nakaoka, Yoshiki Suzuki, Hitomi Yoshikawa, Koki Shin, Kanae Fujita, Misuzu Iwasa, Haruka Sasajima, Airi Sato, Yoshiyuki Hamamoto, Yuki Fujita, Takuya Haraguchi, Takanori Hyo, Kiyohiro Izumi, Toshiyuki Komiya, Sodai Kubota, Takeshi Kurose, Hitoshi Kuwata, Susumu Nakatani, Kaori Oishi, Saki Okamoto, Kaori Okamura, Jun Takeoka, Nagaaki Tanaka, Katsuya Tanigaki, Naohiro Toda, Koin Watanabe, Hiromi Komori, Rika Kumuji, Asako Takesada, Aya Tanaka, Shoichi Maruyama, Tomonori Hasegawa, Akiko Ishiguro, Takuji Ishimoto, Kazuhiro Ito, Yutaka Kamimura, Noritoshi Kato, Sawako Kato, Hiroshi Kojima, Tomoki Kosugi, Kayaho Maeda, Masasi Mizuno, Shoji Saito, Hitomi Sato, Yuka Sato, Yasuhiro Suzuki, Akihito Tanaka, Yoshinari Yasuda, Fujiko Hasegawa, Maiko Hayashi, Shizuka Higashi, Kaho Shimamura, Momoko Sumi, Kazuki Tajima, Chimaki Unekawa, Kana Wakayama, Yukiko Wakita, Takatoshi Otani, Ayako Imai, Sayaka Kawashima, Eri Kogure, Tomoe Sato, Misato Takezawa, Shinya Yoshida, Hideo Araki, Yuko Katsuda, Masahiro Konishi, Takahiro Matsunaga, Masashi Oe, Kunihiro Ogane, Masato Sakai, Tomoko Takahashi, Takahiro Yamano, Takuya Yokoyama, Hitomi Ito, Masayo Katayama, Emi Kuroda, Toru Ikeda, Takuma Kojo, Etsuo Yoshidome, Rieko Mizumachi, Akane Yamamoto, Narihisa Yamasaki, Yoshihiko Yamasaki, Jun Wada, Jun Eguchi, Chigusa Higuchi, Akihiro Katayama, Masaru Kinomura, Masashi Kitagawa, Shinji Kitamura, Satoshi Miyamoto, Hiroshi Morinaga, Atsuko Nakatsuka, Ichiro Nojima, Kenichi Shikata, Hitoshi Sugiyama, Katsuyuki Tanabe, Kenji Tsuji, Haruhito Uchida, Mayu Watanabe, Chie Hashimoto, Takahiro Kato, Sayaka Yamamoto, Takehiko Wada, Masafumi Fukagawa, Naoto Hamano, Masahiro Koizumi, Hirotaka Komaba, Yosuke Nakagawa, Michiyo Iwamoto, Kosuke Masutani, Akane Katanosaka, Mayu Kiyota, Hikari Uchi, Yuka Ueda, Sonoka Yamamoto, Hajime Nagasu, Seiji Itano, Tsukasa Iwakura, Hiroyuki Kadoya, Eiichiro Kanda, Naoki Kashihara, Kengo Kidokoro, Megumi Kondo, Tamaki Sasaki, Minoru Satoh, Atsuyuki Tokuyama, Reina Umeno, Yoshihisa Wada, Toshiya Yamamoto, Yu Yamanouchi, Masumi Abe, Yoko Inukai, Wataru Ogawa, Shunichiro Asahara, Hideki Fujii, Shunsuke Goto, Yushi Hirota, Tetsuya Hosooka, Keiji Kono, Shinichi Nishi, Yuko Okada, Kazuhiko Sakaguchi, Kenji Sugawara, Michiko Takahashi, Tomoko Takai, Yoshikazu Tamori, Kentaro Watanabe, Miyu Kitajima, Misaki Nishi, Junko Wada, Yasuhiko Ito, Hideki Kamiya, Akimasa Asai, Nao Asai, Saeko Asano, Shogo Banno, Yohei Ejima, Hanako Hase, Tomohide Hayami, Tatsuhito Himeno, Takahiro Ishikawa, Mayumi Ito, Shiho Iwagaitsu, Rina Kasagi, Yoshiro Kato, Makoto Kato, Koichi Kato, Takayuki Katsuno, Miyuka Kawai, Hiroshi Kinashi, Masaki Kondo, Masako Koshino, Naoya Matsuoka, Yoshiaki Morishita, Mikio Motegi, Jiro Nakamura, Hiromi Shimoda, Hirokazu Sugiyama, Shin Tsunekawa, Makoto Yamaguchi, Kazuyo Takahashi, Hirotaka Watada, Takashi Funayama, Yasuhiko Furukawa, Tomohito Gohda, Hiromasa Goto, Hideyoshi Kaga, Yasuhiko Kanaguchi, Akio Kanazawa, Kayo Kaneko, Toshiki Kano, Masao Kihara, Shogo Kimura, Takashi Kobayashi, Masayuki Maiguma, Yuko Makita, Satoshi Mano, Tomoya Mita, Takeshi Miyatsuka, Maki Murakoshi, Masahiro Muto, Masami Nakata, Junichiro Nakata, Yuya Nishida, Nao Nohara, Takeshi Ogihara, Daisuke Sato, Junko Sato, Hiroaki Sato, Yusuke Suzuki, Ruka Suzuki, Hitoshi Suzuki, Miyuki Takagi, Yoshifumi Tamura, Toyoyoshi Uchida, Seiji Ueda, Miki Asawa, Minako Miyaji, Eri Nagashima, Yoshie Shibata, Eri Yanagisawa, Toshimasa Yamauchi, Yosuke Hirakawa, Hiroshi Nishi, Nobuhiro Shojima, Satoko Horikawa, Yukiko Nakayama, Naoko Yamada, Yuki Omori, Shintaro Yano, Miyabi Ioka, Nahoko Kuwabara, Remi Nagano, Megumi Nozawa, Yumi Osawa, Hiroshi Maegawa, Shinji Kume, Shinichi Araki, Itsuko Miyazawa, Katsutaro Morino, Ikuko Kawai, Masumi Sobata, Motoko Takaoka, Yasushi Iwaita, Takashi Udagawa, Ami Inamori, Aya Kawase, Aya Yamanaka, Hitoshi Shimano, Akiko Fujita, Hitoshi Iwasaki, Hirayasu Kai, Yoshinori Osaki, Chie Saito, Motohiro Sekiya, Ryoya Tsunoda, Kunihiro Yamagata, Rikako Nakamura, Aiko Yamada, Mitsuru Ohsugi, Motoharu Awazawa, Ryotaro Bouchi, Shota Hashimoto, Makiko Hashimoto, Tomoko Hisatake, Noriko Ihana, Koko Ishizuka, Kazuo Izumi, Hiroshi Kajio, Michi Kobayashi, Noriko Kodani, Koji Maruyama, Michihiro Matsumoto, Maya Matsushita, Tomoka Nakamura, Takehiro Sugiyama, Akiyo Tanabe, Aiko Terakawa, Kojiro Ueki, Yuko Orimo, Takako Ozawa, Eriko Takahira, Yoshimitsu Yamasaki, Masakazu Haneda, Tadahiro Tomita, Saori Akimoto, Akihiro Fujimoto, Kenji Ishihara, Chiho Murakami, Akiyo Nishiyama, Yukiko Toyonaga, Kana Uozumi, Yukihiro Yamaji, Tetsuya Shigehara, Jun Okajyo, Yukihiro Shimizu, Shingo Iwasaki, Yuki Fukao, Megumi Furusho, Shintaro Nunokawa, Hideki Katagiri, Tomohito Izumi, Keizo Kaneko, Shinjiro Kodama, Mariko Miyazaki, Yuichiro Munakata, Tasuku Nagasawa, Yuji Oe, Hiroto Sugawara, Kei Takahashi, Kazushige Hirata, Keiko Inomata, Shoko Otomo, Taeko Uchida, Chigusa Yamashita, Arihiro Kiyosue, Ryota Tamura, Francois Dube, Marilene Bolduc, Marie-Christine Talbot, Leslie Cham, Vesta Lai, Josephine Tse, Shivinder Jolly, Tabbatha Duck, Scott Lyle, Rachel Epp, Camille Galloway, Susan Haskett, Elizabeta Matvienko, Liam Paulsen, Louise Moist, Zabrina Lozon, Tina Ramsey, Brittany Whitmore, Bader Al-Zeer, Paula Macleod, Aoife O'Sullivan, Zainab Sheriff, Sam Tholl, Amritanshu Pandey, Samantha Armstrong, Bethelihem Gebeyehu, Patrick Toth, Ronald Goldenberg, Mahsa Jahangiriesmaili, Shariff Sanguila, Neethi Suresh, Tanvi Talsania, Nadia Zalunardo, Mohsen Agharazii, Marie-Pier Roussel, Annie Saillant, France Samson, Harpreet Bajaj, Miken Bhavsar, Parul Dhall, Gagandeep Dhillon, Bhupinder Grewal, Taniya Nimbkar, Francois Madore, Guylaine Marcotte, Oren Steen, Mathura Bullen, Shayani Raguwaran, Andre Valleteau, Marie-France Langlois, Christine Brown, Andrew Steele, Melissa Garrity, Taneera Ghate, Holly Robinson, Michael Tolibas, Chetna Tailor, Lauren Elliott, Christine McClary-Wright, Fadia Boreky, Sameh Fikry, Ayesha Ali, Chintankumar Barot, Wagdy Basily, Thisun Saram, Vinay Varad, Hasnain Khandwala, Alex Aguilera, Patricia Alvarez, Balwinder Gill, Nazihah Huda, Aamir Navivala, Daniel Pinto, Micheli Bevilacqua, Elaine Fung, Geraldine Hernandez, Puneet Mann, Jaskiran Saini, Remi Rabasa-Lhoret, Danijela Bovan, Marie Devaux, Cecilia Barnini, Giovanna Leoncini, Luca Manco, Giulia Nobili, Matteo Piemontese, Filippo Aucella, Rachele Grifa, Francesco Totaro, Gaetano La Manna, Irene Capelli, Giuseppe Cianciolo, Sarah Lerario, Fulvia Zappulo, Alberto Rosati, Filippo Fani, Giuseppe Spatoliatore, Loreto Gesualdo, Francesco Pesce, Maria Russo, Maria Zippo, Cesira Cafiero, Daria Motta, Simona Bianco, Donatella Bilucaglia, Piergiorgio Messa, Laura Pavone, Federica Tripodi, Simone Vettoretti, Paola Fioretto, Gianni Carraro, Filippo Farnia, Anna Postal, Alessandro D'Amelio, Antonio Cardone, Giovanni Piccinni, Annalisa Aloisi, Francesco Scolari, Federico Alberici, Alice Guerini, Chiara Saccà, Chiara Salviani, Roberta Zani, Luca De Nicola, Carlo Garofalo, Maria Elena Liberti, Roberto Minutolo, Luigi Pennino, Lucio Polese, Paolo Mené, Simona Barberi, Clorinda Falcone, Francesco Russo, Maurizio Caroppo, Gennaro Santorelli, Rodolfo Rivera, Domenico Santoro, Alfio Giuffrida, Fortunata Zirino, Cristina Calvi, Luca Estienne, Giovanni Gambaro, Concetta Gangemi, Vittorio Ortalda, Giuseppina Pessolano, Giuseppe Grandaliano, Rocco Baccaro, Pietro Ferraro, Roberto Mangiacapra, Marco Melandri, Nadia Foligno, Rita Quartagno, Giuseppe Vezzoli, Elena Brioni, William G, Herrington, Natalie, Staplin, Christoph, Wanner, Jennifer B, Green, Sibylle J, Hauske, Jonathan R, Emberson, David, Prei, Parminder, Judge, Kaitlin J, Mayne, Sarah Y A, Ng, Emily, Sammon, Doreen, Zhu, Michael, Hill, Will, Steven, Karl, Wallendszu, Susanne, Brenner, Alfred K, Cheung, Zhi-Hong, Liu, Jing, Li, Lai Seong, Hooi, Wen, Liu, Takashi, Kadowaki, Masaomi, Nangaku, Adeera, Levin, David, Cherney, Aldo P, Maggioni, Roberto, Pontremoli, Rajat, Deo, Shinya, Goto, Xavier, Rossello, Katherine R, Tuttle, Dominik, Steubl, Michaela, Petrini, Dan, Massey, Jens, Eilbracht, Martina, Brueckmann, Martin J, Landray, Colin, Baigent, Richard, Hayne, EMPA-KIDNEY Collaborative Group: Colin Baigent, The, J Landray, Martin, Wanner, Christoph, G Herrington, William, Haynes, Richard, B Green, Jennifer, J Hauske, Sibylle, Brueckmann, Martina, Hopley, Mark, von-Eynatten, Maximillian, George, Jyothi, Brenner, Susanne, K Cheung, Alfred, Preiss, David, Liu, Zhi-Hong, Li, Jing, Hooi, Laiseong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Pontremoli, Roberto, P Maggioni, Aldo, Staplin, Natalie, Emberson, Jonathan, Hantel, Stefan, Goto, Shinya, Deo, Rajat, R Tuttle, Katherine, Hill, Michael, Judge, Parminder, J Mayne, Kaitlin, A Ng, Sarah Y, Rossello, Xavier, Sammons, Emily, Zhu, Doreen, Sandercock, Peter, Bilous, Rudolf, Herzog, Charle, Whelton, Paul, Wittes, Janet, Bennett, Derrick, Achiri, Patricia, Ambrose, 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Andrea, Pergola, Pablo, Leal, Irene, Cagle, Melissa, Romo, Anna, Torres, Anthony, Joshi, Sucharit, Barrett, Kulli, Africano, Alexi, Dodds, Vicki, Gowen, Dorleena, Morris, Ashlee, Fernandez, Juan, Jimenez, Guillermo, Viera, Ricardo, Bruce, Kendaling, Barrios, Ryan, Garcia, Maylin, Garcia, Kerelyn, Leal, Iradi, Tietjen, David, Bains, David, Castillo, Carlo, Brewer, Genielle, Davis, Justin, Freking, Natalie, Golson, Brittany, Ham, Sally, Roesch, Jesslyn, Suchinda, Pusadee, Beigh, Shameem, Lilavivat, Usah, Bilton, Joyce, Bocchicchia, Kim, Turner, Jeffrey, Dahl, Neera, Peixoto, Aldo, Kavak, Yasemin, Liberti, Lauren, Nair, Hari, Page, Nicola, Rosenberg, Stephanie, Simmons, Kathryn, Isakova, Tamara, Frazier, Rebecca, Mehta, Rupal, Srivastava, Anand, Fox, Patrick, Hecktman, Jonathan, Hodakowski, Alexander, Martinez, Carlo, Phillips, Rachel, Stevenson, Alexi, Mustafa, Reem, Jansson, Kyle, Kimber, Cassandra, Stubbs, Jason, Tuffaha, Ahmad, Yarlagadda, Sri, Griffin, Debbie, Laundy, Elisabeth, 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Lesley, Wines, Eric, Park, Jean, Ghazi, Adline, Hamm, Mia, Patel, Teja, Mottl, Amy, Chang, Emily, Derebail, Vimal, Cole, Emmie, Froment, Anne, Kelley, Sara, Osmond Foster, Jordan, Mahabadi, Vahid, Jafari, Golriz, Kamarzarian, Anita, Arriaga, Wendy, Arteaga, Daisy, Machicado, Rosario, Naverrete, Genesi, Kumar, Prashant, Nazeer, Imran, Urquia, Karina, Glider, Tammi, Jones, Vickie, Rucker, Savannah, Wiley, Jennifer, Pandey, Rahul, Arroyo, Jesu, Pariani, Harish, Ahmad, Mohammad, Mozaffari, Shahin, Perez, Erika, Budoff, Matthew, Roy, Sion, Birudaraju, Divya, Ghanem, Ahmed, Hamal, Sajad, Aronoff, Stephen, Joye Petr, Elisa, Sachson, Richard, Wiebel, Jaime, Akram, Sana, Jones, Laurie, Knight, Curti, Tarlac, Maurie, Ahmed, Shahbaz, Szerlip, Harold, Akinfolarin, Akinwande, Mehta, Ankit, Camp, Shana, Castro, Cindy, Cooper, Zanaida, Terry, Jessica, Awad, Ahmed, Kothapalli, Bhavya, Lustig, Ryan, Alfaress, Serine, Jasim, Hyder, Parrigon, Mary, Karounos, Denni, Ahmed, Sadiq, Berry, Maggie, Oremus, 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Francisco, Hernandez Pena, Abegail, Pugay, Conception, Te, Amelia, Finn, Hugh, Hanif, Wasim, Mostafa, Samiul, Aitken, Alice, Draxlbauer, Katharine, Grobovaite, Evelina, Kearney, Jennifer, Mccarthy, Theresa, Gentile, Giorgio, Browne, Duncan, Chellamuthu, Palanichamy, Dugal, Tabinda, Chant, Terri, Jones, Laura, Laity, Emily, Miners, Megan, Muir, Jame, Swanson, Elizabeth, Frankel, Andrew, Tomlinson, Jame, Alegata, Marlon, Almasarwah, Rashid, Apostolidi, Anthoula, Vourvou, Maria, Walters, Thoma, Taal, Maarten, Dukka, Hari, Kolhe, Nitin, Mcdonald, Carly, White, Kelly, Ugni, Shiva, Gunda, Smita, Oluyombo, Rotimi, Brindle, Vicki, Coutts, Ping, Fuller, Tracy, Nadar, Evelyn, Ramadoss, Suresh, Motherwell, Nichola, Pajak, Susannah, Tonks, Louise, Bhandari, Sunil, Bodington, Richard, Hazara, Adil, Fellowes, Dominic, Wong, Christopher, Goldsmith, Christopher, Barnes, Sherald, Bennett, Ann, Burston, Claire, Hope, Samantha, Hunt, Nicola, Kurian, Lini, Fish, Richard, Farrugia, Daniela, Lee, Judy, Sadler, Emma, Turner, Hannah, Hill, Christopher, Brown, Henry, Masengu, Agne, Maxwell, Peter, Bleakley, Nina, Murtagh, Hugh, Petchey, William, Yiu, Vivian, Kellett, Joanne, Williams, Angharad, Clarke, Helen, Carnall, Victoria, Benyon, Sarah, Blake, Caroline, Estcourt, Stephanie, Piper, Jane, Morgan, Neal, Hutchinson, Carolyn, Mckinley, Teresa, Woodman, Alastair, Graham, Judi, Leonard, Niall, Smyth, John, Adell, Vicki, Hagan, Samantha, Caplin, Ben, Oomatia, Amin, Damian, Eleanor, Sobande, Toluleyi, Doulton, Tim, Delaney, Michael, Montasser, Mahmoud, Hansen, Jenny, Loader, David, Moon, Angela, Morris, France, Sinha, Smeeta, Chukwu, Chukwuma, Hudson, Amy, Campbell, Diane, Kershaw, Melanie, Whittaker, Stephanie, Irtiza-Ali, Ayesha, Ghalli, Farid, Nosseir, Heba, Leslie, Allison, Trivedi, Kate, Fraser, Donald, Alhadj Ali, Mohammad, Griffin, Sian, Latif, Farah, Witczak, Justyna, Wonnacott, Alexa, Jeffers, Lynda, Webley, Yvette, Phelan, Paul, Miller-Hodges, Eve, Geddes, Ailsa, Glenwright, Margaret, Hunter, Amy, Pickett, Thoma, Moriarty, Jim, Hill, Linda, Tyler, Amanda, Ayub, Waqar, Evans, Gail, Hewins, Sue, Hewitt, Davina, Read, Kerry, Bell, Samira, Cosgrove, Leanne, Craik, Rachel, Murray, Shona, Bhandary, Nitin, Coles, Holly, Easow, Rashmi, Joseph, Maya, Khwaja, Arif, Jackson, Yvonne, Mbuyisa, Angeline, Sellars, Rachel, Chitalia, Nihil, Mohandas, Cynthia, Gherman, Anca, Kamundi, Charlotte, Olufuwa, Olumide, Mccafferty, Kieran, Adeleke, Adedolapo, Healy, Cara, Jeyarajah, Damini, Kinsella-Perks, Edward, Smith, Richard, Camilleri, Brian, Buckman, Carol, Finch, Jenny, Rivers, Vanessa, Connor, Andrew, Carr, Sheila, Shainberg, Lisa, Lewington, Andrew, Baker, Richard, Dorey, Suzannah, Tobin, Kay, Wheatley, Rosalyn, Banerjee, Debasish, Hull, Richard, Abat, Sharirose, Paul, Riny, Karim, Mahzuz, Htet, Zay, Tufail, Saad, Varma, Ravi, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Tropman, Emily, Abdul-Samad, Thahir, Grace, Anne, Phipps, Marie, Suckling, Rebecca, Somalanka, Subash, Sood, Bhrigu, Swift, Pauline, Acheampong, Sarah, Ansu, Kwame, Augustin, Martia, Sampson, Anna, Vinall, Lynn, Wren, Kim, Wanninayake, Shamila, Wooding, Nichola, Edwards, Heather, Owen, Lydia, Bolton, Stephanie, Carson, Marion, Matthews, Michael, Brunskill, Nigel, Jesus-Silva, Jorge, Howson, Alex, Quashie-Akponeware, Mary, Tindall, Hilary, Nethaji, Chidambaram, Eldon, Helen, Patel, Rajan, Mark, Patrick, Rankin, Alastair, Sullivan, Michael, Forsyth, Kirsty, Mcdougall, Rowan, Dasgupta, Tanaji, Davies, Louisa, Ryder, Maggie, Grimmer, Philip, Macdonald, Clare, Webster, Mary, Newcastle, Newcastle, Ellam, Timothy, Wong, Edwin, Meshykhi, Christine, Webster, Andrea, Wilson, Peter, Vilar, Enric, Berdeprado, Jocelyn, Doctolero, Eunice, Wilkinson, Lily, Mccarroll, Frank, Ammar, Hesham, Kuan, Ying, Moran, Conor, Shivashankar, Girish, Campbell, Ryan, Glowski, Deborah, Mcdermott, Paula, Ali, Amar, Patel, Zuber, Bond, Christine, Whalley, Gillian, Zhang, Haitao, Yang, Liu, Zhang, Lihua, Kan, Tingting, Zhu, Ling, Zhao, Jinghong, Hou, Weiping, Wu, Jing, Cheng, Hong, Bian, Weijing, Zhao, Zhirui, Shao, Fengmin, Cao, Huixia, Jiao, Xiaojing, Niu, Peiyuan, Niu, Jianying, Chen, Yu, Zhang, Lihong, Zhu, Shenglang, Lin, Haiyan, Yao, Shaopeng, Chen, Jiehui, Jiang, Ying, Hu, Ying, Xiao, Huaying, Yang, Fuye, Zhang, Xinzhou, Guo, Baochun, Jin, Qiu, Liu, Lixia, Xiao, Xiangcheng, Xie, Yanyun, Meng, Ting, Xu, Chuanwen, Huang, Jie, Xu, Yanmei, Kong, Weixin, Wang, Xiaoliang, Liu, Qianpan, Wang, Xueying, Gao, Ming, Hu, Xiumei, Lu, Ying, Wang, Li, Peng, Kun, Wang, Wei, Gong, Qiuhong, Cai, Jianfang, Li, Xiaojue, Liu, Xuejiao, Zhou, Shuhan, Liu, Hong, Weng, Yao, Tang, Shuai, Yao, Yao, Zhao, Shi, Cheng, Chen, Wei, Wei, Li, Na, Aqashiah Mazlan, Sadanah, Zubaidah Bahtar, Alia, Katiman, Elliyyin, Othman, Noraini, Mushahar, Lily, Mazlan, Nurdiana, Sharafina Safiee, Nur, Ramasamy, Sarasa, Seng Wong, Hin, Ahmad Rosdi, Hajar, Zhao Zhi Tan, Esther, Fan Tay, Ju, Seng Teng, Kok, Yahaya, Hasnah, Jiun Liu, Wen, Wee Ee, Lik, Kay Leong Khoo, Kenneth, Mohd Yusoff, Yuana, Safhan Mohamad Nor, Fariz, Kamil Ahmad, Mohd, Ramli Seman, Mohd, Hui Hong Tan, Clare, Lui Sian Ngu, Laura, Yoke May Chan, Jaime, Peji, Javelin, Loong Loh, Chek, Yan Lee, Yee, Ramanaidu, Sridhar, Mean Thong, Kah, Hong Wong, Yik, Junus, Suria, Hua Ching, Chen, Faisal Asmee, Mohammad, Ruziana Ku Md Razi, Ku, Leong Low, Chun, Sze Bing Sim, Christopher, Duan Tham, Zhang, Kamila Abdullah, Noor, Meng Chen, Tai, Chieh Chan, Yong, Chang, Eason, Yean Kang, Huan, Quan Lee, Kai, Ann Lee, Sue, Kheng Lee, Aik, Vinathan, Jeevika, Abdul Cader, Rizna, Mustafar, Ruslinda, Kamaruzaman, Lydia, Mohd, Rozita, Ismail, Rahimah, Men Leong, Chong, Koon Low, Chee, Wei Wong, Liang, Adnan, Norlezah, Ibrahim, Sabariah, Zaimi Abdul Wahab, Mohamad, Bavanandan, Sunita, Shen Lim, Yik, Hazlina Wan Mohamad, Wan, Munirah Jaafar, Siti, Ashykeen Mohd Fauzi, Nur, Sudin, Aziee, Kun Lim, Soo, Chung Gan, Chye, Hing, Albert, Ahmad Faizal Alaidin Razali, Wan, Fong Liew, Yew, Bao Tyng Chan, Chelsia, Chih Cheng, Mei, Chen Ong, Yu, Meng Ong, Loke, Amalina Mohamed Affandi, Farah, Rahmat, Korina, Chai Peng, Ban, Amat, Masayu, Hadafi Ahmad, Nuzaimin, Yee Mah, Doo, Loon Tye, Yi, Azhari, Zaid, Nabilah Mohamad Zaini, Siti, Aidil Musa, Mohd, Ahmad Miswan, Norazinizah, Ramli, Rafizanur, Aziah Ahmad, Nor, Leong Goh, Bak, Izah Ahmad, Nurul, Huda Ibrahim, Fairol, Jian Ng, Tze, Shanmuganathan, Malini, Lian Tay, Li, Harun, Zaiha, Ramli, Salmi, 'Ain Yusof, Nurul, Abd Rahman, Rossenizal, Iqbal Abdul Hafidz, Muhammad, Hidayati Mohd Sharif, Nur, Yasmoon Awang, Irda, Nakashima, Eitaro, Imamine, Rui, Minatoguchi, Makiko, Miura, Yukari, Nakaoka, Miduki, Suzuki, Yoshiki, Yoshikawa, Hitomi, Shin, Koki, Fujita, Kanae, Iwasa, Misuzu, Sasajima, Haruka, Sato, Airi, Hamamoto, Yoshiyuki, Fujita, Yuki, Haraguchi, Takuya, Hyo, Takanori, Izumi, Kiyohiro, Komiya, Toshiyuki, Kubota, Sodai, Kurose, Takeshi, Kuwata, Hitoshi, Nakatani, Susumu, Oishi, Kaori, Okamoto, Saki, Okamura, Kaori, Takeoka, Jun, Tanaka, Nagaaki, Tanigaki, Katsuya, Toda, Naohiro, Watanabe, Koin, Komori, Hiromi, Kumuji, Rika, Takesada, Asako, Tanaka, Aya, Maruyama, Shoichi, Hasegawa, Tomonori, Ishiguro, Akiko, Ishimoto, Takuji, Ito, Kazuhiro, Kamimura, Yutaka, Kato, Noritoshi, Kato, Sawako, Kojima, Hiroshi, Kosugi, Tomoki, Maeda, Kayaho, Mizuno, Masasi, Saito, Shoji, Sato, Hitomi, Sato, Yuka, Suzuki, Yasuhiro, Tanaka, Akihito, Yasuda, Yoshinari, Hasegawa, Fujiko, Hayashi, Maiko, Higashi, Shizuka, Shimamura, Kaho, Sumi, Momoko, Tajima, Kazuki, Unekawa, Chimaki, Wakayama, Kana, Wakita, Yukiko, Otani, Takatoshi, Imai, Ayako, Kawashima, Sayaka, Kogure, Eri, Sato, Tomoe, Takezawa, Misato, Yoshida, Shinya, Araki, Hideo, Katsuda, Yuko, Konishi, Masahiro, Matsunaga, Takahiro, Oe, Masashi, Ogane, Kunihiro, Sakai, Masato, Takahashi, Tomoko, Yamano, Takahiro, Yokoyama, Takuya, Ito, Hitomi, Katayama, Masayo, Kuroda, Emi, Ikeda, Toru, Kojo, Takuma, Yoshidome, Etsuo, Mizumachi, Rieko, Yamamoto, Akane, Yamasaki, Narihisa, Yamasaki, Yoshihiko, Wada, Jun, Eguchi, Jun, Higuchi, Chigusa, Katayama, Akihiro, Kinomura, Masaru, Kitagawa, Masashi, Kitamura, Shinji, Miyamoto, Satoshi, Morinaga, Hiroshi, Nakatsuka, Atsuko, Nojima, Ichiro, Shikata, Kenichi, Sugiyama, Hitoshi, Tanabe, Katsuyuki, Tsuji, Kenji, Uchida, Haruhito, Watanabe, Mayu, Hashimoto, Chie, Kato, Takahiro, Yamamoto, Sayaka, Wada, Takehiko, Fukagawa, Masafumi, Hamano, Naoto, Koizumi, Masahiro, Komaba, Hirotaka, Nakagawa, Yosuke, Iwamoto, Michiyo, Masutani, Kosuke, Katanosaka, Akane, Kiyota, Mayu, Uchi, Hikari, Ueda, Yuka, Yamamoto, Sonoka, Nagasu, Hajime, Itano, Seiji, Iwakura, Tsukasa, Kadoya, Hiroyuki, Kanda, Eiichiro, Kashihara, Naoki, Kidokoro, Kengo, Kondo, Megumi, Sasaki, Tamaki, Satoh, Minoru, Tokuyama, Atsuyuki, Umeno, Reina, Wada, Yoshihisa, Yamamoto, Toshiya, Yamanouchi, Yu, Abe, Masumi, Inukai, Yoko, Ogawa, Wataru, Asahara, Shunichiro, Fujii, Hideki, Goto, Shunsuke, Hirota, Yushi, Hosooka, Tetsuya, Kono, Keiji, Nishi, Shinichi, Okada, Yuko, Sakaguchi, Kazuhiko, Sugawara, Kenji, Takahashi, Michiko, Takai, Tomoko, Tamori, Yoshikazu, Watanabe, Kentaro, Kitajima, Miyu, Nishi, Misaki, Wada, Junko, Ito, Yasuhiko, Kamiya, Hideki, Asai, Akimasa, Asai, Nao, Asano, Saeko, Banno, Shogo, Ejima, Yohei, Hase, Hanako, Hayami, Tomohide, Himeno, Tatsuhito, Ishikawa, Takahiro, Ito, Mayumi, Iwagaitsu, Shiho, Kasagi, Rina, Kato, Yoshiro, Kato, Makoto, Kato, Koichi, Katsuno, Takayuki, Kawai, Miyuka, Kinashi, Hiroshi, Kondo, Masaki, Koshino, Masako, Matsuoka, Naoya, Morishita, Yoshiaki, Motegi, Mikio, Nakamura, Jiro, Shimoda, Hiromi, Sugiyama, Hirokazu, Tsunekawa, Shin, Yamaguchi, Makoto, Takahashi, Kazuyo, Watada, Hirotaka, Funayama, Takashi, Furukawa, Yasuhiko, Gohda, Tomohito, Goto, Hiromasa, Kaga, Hideyoshi, Kanaguchi, Yasuhiko, Kanazawa, Akio, Kaneko, Kayo, Kano, Toshiki, Kihara, Masao, Kimura, Shogo, Kobayashi, Takashi, Maiguma, Masayuki, Makita, Yuko, Mano, Satoshi, Mita, Tomoya, Miyatsuka, Takeshi, Murakoshi, Maki, Muto, Masahiro, Nakata, Masami, Nakata, Junichiro, Nishida, Yuya, Nohara, Nao, Ogihara, Takeshi, Sato, Daisuke, Sato, Junko, Sato, Hiroaki, Suzuki, Yusuke, Suzuki, Ruka, Suzuki, Hitoshi, Takagi, Miyuki, Tamura, Yoshifumi, Uchida, Toyoyoshi, Ueda, Seiji, Asawa, Miki, Miyaji, Minako, Nagashima, Eri, Shibata, Yoshie, Yanagisawa, Eri, Yamauchi, Toshimasa, Hirakawa, Yosuke, Nishi, Hiroshi, Shojima, Nobuhiro, Horikawa, Satoko, Nakayama, Yukiko, Yamada, Naoko, Omori, Yuki, Yano, Shintaro, Ioka, Miyabi, Kuwabara, Nahoko, Nagano, Remi, Nozawa, Megumi, Osawa, Yumi, Maegawa, Hiroshi, Kume, Shinji, Araki, Shinichi, Miyazawa, Itsuko, Morino, Katsutaro, Kawai, Ikuko, Sobata, Masumi, Takaoka, Motoko, Iwaita, Yasushi, Udagawa, Takashi, Inamori, Ami, Kawase, Aya, Yamanaka, Aya, Shimano, Hitoshi, Fujita, Akiko, Iwasaki, Hitoshi, Kai, Hirayasu, Osaki, Yoshinori, Saito, Chie, Sekiya, Motohiro, Tsunoda, Ryoya, Yamagata, Kunihiro, Nakamura, Rikako, Yamada, Aiko, Ohsugi, Mitsuru, Awazawa, Motoharu, Bouchi, Ryotaro, Hashimoto, Shota, Hashimoto, Makiko, Hisatake, Tomoko, Ihana, Noriko, Ishizuka, Koko, Izumi, Kazuo, Kajio, Hiroshi, Kobayashi, Michi, Kodani, Noriko, Maruyama, Koji, Matsumoto, Michihiro, Matsushita, Maya, Nakamura, Tomoka, Sugiyama, Takehiro, Tanabe, Akiyo, Terakawa, Aiko, Ueki, Kojiro, Orimo, Yuko, Ozawa, Takako, Takahira, Eriko, Yamasaki, Yoshimitsu, Haneda, Masakazu, Tomita, Tadahiro, Akimoto, Saori, Fujimoto, Akihiro, Ishihara, Kenji, Murakami, Chiho, Nishiyama, Akiyo, Toyonaga, Yukiko, Uozumi, Kana, Yamaji, Yukihiro, Shigehara, Tetsuya, Okajyo, Jun, Shimizu, Yukihiro, Iwasaki, Shingo, Fukao, Yuki, Furusho, Megumi, Nunokawa, Shintaro, Katagiri, Hideki, Izumi, Tomohito, Kaneko, Keizo, Kodama, Shinjiro, Miyazaki, Mariko, Munakata, Yuichiro, Nagasawa, Tasuku, Oe, Yuji, Sugawara, Hiroto, Takahashi, Kei, Hirata, Kazushige, Inomata, Keiko, Otomo, Shoko, Uchida, Taeko, Yamashita, Chigusa, Kiyosue, Arihiro, Tamura, Ryota, Dube, Francoi, Bolduc, Marilene, Talbot, Marie-Christine, Cham, Leslie, Lai, Vesta, Tse, Josephine, Jolly, Shivinder, Duck, Tabbatha, Lyle, Scott, Epp, Rachel, Galloway, Camille, Haskett, Susan, Matvienko, Elizabeta, Paulsen, Liam, Moist, Louise, Lozon, Zabrina, Ramsey, Tina, Whitmore, Brittany, Al-Zeer, Bader, Macleod, Paula, O'Sullivan, Aoife, Sheriff, Zainab, Tholl, Sam, Pandey, Amritanshu, Armstrong, Samantha, Gebeyehu, Bethelihem, Toth, Patrick, Goldenberg, Ronald, Jahangiriesmaili, Mahsa, Sanguila, Shariff, Suresh, Neethi, Talsania, Tanvi, Zalunardo, Nadia, Agharazii, Mohsen, Roussel, Marie-Pier, Saillant, Annie, Samson, France, Bajaj, Harpreet, Bhavsar, Miken, Dhall, Parul, Dhillon, Gagandeep, Grewal, Bhupinder, Nimbkar, Taniya, Madore, Francoi, Marcotte, Guylaine, Steen, Oren, Bullen, Mathura, Raguwaran, Shayani, Valleteau, Andre, Langlois, Marie-France, Brown, Christine, Steele, Andrew, Garrity, Melissa, Ghate, Taneera, Robinson, Holly, Tolibas, Michael, Tailor, Chetna, Elliott, Lauren, McClary-Wright, Christine, Boreky, Fadia, Fikry, Sameh, Ali, Ayesha, Barot, Chintankumar, Basily, Wagdy, Saram, Thisun, Varad, Vinay, Khandwala, Hasnain, Aguilera, Alex, Alvarez, Patricia, Gill, Balwinder, Huda, Nazihah, Navivala, Aamir, Pinto, Daniel, Bevilacqua, Micheli, Fung, Elaine, Hernandez, Geraldine, Mann, Puneet, Saini, Jaskiran, Rabasa-Lhoret, Remi, Bovan, Danijela, Devaux, Marie, Barnini, Cecilia, Leoncini, Giovanna, Manco, Luca, Nobili, Giulia, Piemontese, Matteo, Aucella, Filippo, Grifa, Rachele, Totaro, Francesco, La Manna, Gaetano, Capelli, Irene, Cianciolo, Giuseppe, Lerario, Sarah, Zappulo, Fulvia, Rosati, Alberto, Fani, Filippo, Spatoliatore, Giuseppe, Gesualdo, Loreto, Pesce, Francesco, Russo, Maria, Zippo, Maria, Cafiero, Cesira, Motta, Daria, Bianco, Simona, Bilucaglia, Donatella, Messa, Piergiorgio, Pavone, Laura, Tripodi, Federica, Vettoretti, Simone, Fioretto, Paola, Carraro, Gianni, Farnia, Filippo, Postal, Anna, D'Amelio, Alessandro, Cardone, Antonio, Piccinni, Giovanni, Aloisi, Annalisa, Scolari, Francesco, Alberici, Federico, Guerini, Alice, Saccà, Chiara, Salviani, Chiara, Zani, Roberta, DE NICOLA, Luca, Garofalo, Carlo, Elena Liberti, Maria, Minutolo, Roberto, Pennino, Luigi, Polese, Lucio, Mené, Paolo, Barberi, Simona, Falcone, Clorinda, Russo, Francesco, Caroppo, Maurizio, Santorelli, Gennaro, Rivera, Rodolfo, Santoro, Domenico, Giuffrida, Alfio, Zirino, Fortunata, Calvi, Cristina, Estienne, Luca, Gambaro, Giovanni, Gangemi, Concetta, Ortalda, Vittorio, Pessolano, Giuseppina, Grandaliano, Giuseppe, Baccaro, Rocco, Ferraro, Pietro, Mangiacapra, Roberto, Melandri, Marco, Foligno, Nadia, Quartagno, Rita, Vezzoli, Giuseppe, Brioni, Elena, and Group, EMPA-KIDNEY Collaborative
Subjects: chronic renal disease, empagliflozin, empa-kidney, General Medicine
Abstract: Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; PConclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110. opens in new tab; EudraCT number, 2017-002971-24. opens in new tab.)
Published: 2023

45. Metabolic surgery in treatment of obese Japanese patients with type 2 diabetes: a joint consensus statement from the Japanese Society for Treatment of Obesity, the Japan Diabetes Society, and the Japan Society for the Study of Obesity

Author: Wataru Ogawa, Nobuya Inagaki, Michio Shimabukuro, K Ueki, Nobuhiro Shojima, Motoyoshi Tsujino, Junji Fujikura, Hiroaki Masuzaki, Eri Kikkawa, Koutaro Yokote, Satoshi Ugi, Hitoshi Nishizawa, Atsuhito Saiki, Takehiro Nozaki, Hiroaki Watada, Karin Hayashi, Yushi Hirota, Iichiro Shimomura, Yasushi Ishigaki, Akira Sasaki, Hidenori Koyama, Ichiro Tatsuno, Yosuke Seki, Takashi Kadowaki, Takeshi Naitoh, Masayuki Ohta, Toshimasa Yamauchi, Takashi Yamaguchi, Shinichi Okazumi, Kazunori Kasama, and Takeshi Miyatsuka
Subjects: Bariatric surgery, Sleeve gastrectomy, medicine.medical_specialty, business.industry, Statement (logic), Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Metabolic surgery, Diabetes, Report of the Committee, Type 2 diabetes, Duodenojejunal bypass, medicine.disease, Obesity, Scientific evidence, Family medicine, Diabetes mellitus, Internal Medicine, medicine, business, Beneficial effects
Abstract: Bariatric surgery has been shown to have a variety of metabolically beneficial effects for patients with type 2 diabetes (T2D), and is now also called metabolic surgery. At the 2nd Diabetes Surgery Summit held in 2015 in London, the indication for bariatric and metabolic surgery was included in the “algorithm for patients with type T2D”. With this background, the Japanese Society for Treatment of Obesity (JSTO), the Japan Diabetes Society (JDS) and the Japan Society for the Study of Obesity (JASSO) have formed a joint committee to develop a consensus statement regarding bariatric and metabolic surgery for the treatment of Japanese patients with T2D. Eventually, the consensus statement was announced at the joint meeting of the 38th Annual Meeting of JSTO and the 41st Annual Meeting of JASSO convened in Toyama on March 21, 2021. In preparing the consensus statement, we used Japanese data as much as possible as scientific evidence to consider the indication criteria, and set two types of recommendation grades, “recommendation” and “consideration”, for items for which recommendations are possible. We hope that this statement will be helpful in providing evidence-based high-quality care through bariatric and metabolic surgery for the treatment of obese Japanese patients with T2D. Supplementary Information The online version contains supplementary material available at 10.1007/s13340-021-00551-0.
Published: 2021

46. Author response for 'Type 1 diabetes iron‐deficiency anemia case report and the clinical relevance of RBC lifespan adjusted A1C'

Author: null Yushi Hirota, null Yongjin Xu, null Akane Yamamoto, null Atsuko Matsuoka, null Timothy C Dunn, and null Wataru Ogawa
Published: 2022

47. Relation of cardiac function to insulin resistance as evaluated by hyperinsulinemic‐euglycemic clamp analysis in individuals with type 2 diabetes

Author: Hiroshi Miura, Anna So, Yasuko Morita, Wataru Ogawa, Kazuhiko Sakaguchi, Natsu Otowa-Suematsu, Akihiro Kaneko, Yushi Hirota, Hisako Komada, Yoshikazu Tamori, Jun Ito, Tomoko Yamada, and Yuko Okada
Subjects: Adult, Blood Glucose, Male, Cardiac function curve, medicine.medical_specialty, Diabetic Cardiomyopathies, Endocrinology, Diabetes and Metabolism, Diastole, Type 2 diabetes, Diseases of the endocrine glands. Clinical endocrinology, Ventricular Function, Left, Ventricular Dysfunction, Left, Insulin resistance, insulin resistance, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Insulin, glucose clamp, Aged, Retrospective Studies, Ejection fraction, business.industry, Stroke Volume, Retrospective cohort study, Articles, General Medicine, Middle Aged, RC648-665, medicine.disease, Clinical Science and Care, Cross-Sectional Studies, Clamp, Diabetes Mellitus, Type 2, Echocardiography, Multivariate Analysis, Glucose Clamp Technique, Cardiology, Original Article, Female, business, left ventricular cardiac dysfunction
Abstract: Aims Whereas homeostasis model assessment of insulin resistance (HOMA‐IR), an easily measured but limited index of insulin resistance, has been shown to correlate with impairment of cardiac function in individuals without diabetes, the pathological relevance of insulin resistance to the development of cardiac dysfunction in individuals with type 2 diabetes has remained unclear. Here we investigated the relation between left ventricular (LV) function as assessed by echocardiography and insulin resistance as evaluated by hyperinsulinemic‐euglycemic clamp analysis, the gold standard for measurement of this parameter, in individuals with type 2 diabetes. Methods This retrospective study included 34 individuals with type 2 diabetes who underwent both hyperinsulinemic‐euglycemic clamp analysis and echocardiography. Both the insulin sensitivity index (ISI) as determined by glucose clamp analysis as well as HOMA‐IR were determined as measures of insulin resistance. The ratio of the peak early‐ to late‐diastolic mitral inflow velocities (E/A) and the LV ejection fraction (LVEF) were determined as measures of diastolic and systolic function, respectively. Results The ISI was significantly correlated with both the E/A ratio and LVEF (correlation coefficients of 0.480 and 0.360, respectively), whereas HOMA‐IR was not correlated with either cardiac parameter. Multivariate analysis revealed that ISI was an independent predictor for both a high log [E/A] (P = 0.031) and a high LVEF (P = 0.045). Conclusions Insulin resistance as evaluated by hyperinsulinemic‐euglycemic clamp analysis may be causally related to LV diastolic and systolic dysfunction in individuals with type 2 diabetes., Our study suggested that insulin resistance as evaluated by glucose clamp analysis is associated with LV diastolic and systolic dysfunction in individuals with type 2 diabetes.
Published: 2021

48. Prevention of hypoglycemia by intermittent-scanning continuous glucose monitoring device combined with structured education in patients with type 1 diabetes mellitus: A randomized, crossover trial

Author: Takashi Murata, Kiminori Hosoda, null Kunihiro Nishimura, Yoshihiro Miyamoto, Naoki Sakane, Noriko Satoh-Asahara, Masao Toyoda, Yushi Hirota, Munehide Matsuhisa, Akio Kuroda, Ken Kato, Ryuji Kouyama, Junnosuke Miura, Atsuhito Tone, Masato Kasahara, Shu Kasama, Shota Suzuki, Yukie Ito, Tomokazu Watanabe, Akiko Suganuma, Zhuo Shen, Hiroko Kobayashi, Satoshi Takagi, Sari Hoshina, Kanako Shimura, Yukiko Tsuchida, Moritsugu Kimura, Nobumichi Saito, Akira Shimada, Yoichi Oikawa, Atsushi Satomura, Akifumi Haisa, Satoshi Kawashima, Shu Meguro, Hiroshi Itoh, Yoshifumi Saisho, Junichiro Irie, Masami Tanaka, Masanori Mitsuishi, Yuya Nakajima, Jun Inaishi, Kenichiro Kinouchi, Shintaro Yamaguchi, Arata Itoh, Kazutoshi Sugiyama, Kazuma Yagi, Tami Tsuchiya, Noriko Kodani, Ikki Shimizu, Tetsuya Fukuda, Yoshiki Kusunoki, Tomoyuki Katsuno, Yuka Matoba, Yumi Hitaka, Kentaro Abe, Natsuko Tanaka, Ryoko Taniguchi, Toshihiko Nagao, Kazuyuki Hida, Izumi Iseda, Masaya Takeda, Yuichi Matsushita, Masafumi Tenta, Tsuyoshi Tanaka, Kunichi Kouyama, and Michiru Fukunaga
Subjects: Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine, General Medicine
Abstract: We conducted a randomized, crossover trial to compare intermittent-scanning continuous glucose monitoring (isCGM) device with structured education (Intervention) to self-monitoring of blood glucose (SMBG) (Control) in the reduction of time below range.This crossover trial involved 104 adults with type 1 diabetes mellitus (T1DM) using multiple daily injections. Participants were randomly allocated to either sequence Intervention/Control or sequence Control/Intervention. During the Intervention period which lasted 84 days, participants used the first-generation FreeStyle Libre (Abbott Diabetes Care, Alameda, CA, USA) and received structured education on how to prevent hypoglycemia based on the trend arrow and by frequent sensor scanning (≥10 times a day). Confirmatory SMBG was conducted before dosing insulin. The Control period lasted 84 days. The primary endpoint was the decrease in the time below range (TBR;70 mg/dL).The time below range was significantly reduced in the Intervention arm compared to the Control arm (2.42 ± 1.68 h/day [10.1 %±7.0 %] vs 3.10 ± 2.28 h/day [12.9 %±9.5 %], P = 0.012). The ratio of high-risk participants with low blood glucose index 5 was significantly reduced (8.6 % vs 23.7 %, P 0.001).The use of isCGM combined with structured education significantly reduced the time below range in patients with T1DM.
Published: 2022

49. 670-P: Iron-Deficiency Anemia Case Report Showing the Clinical Relevance of RBC-Lifespan–Adjusted A1C

Author: YUSHI HIROTA, YONGJIN XU, AKANE YAMAMOTO, ATSUKO MATSUOKA, TIMOTHY DUNN, and WATARU OGAWA
Subjects: Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract: Laboratory A1C does not precisely reflect glycemic control in those with altered RBC lifespan and our aim was to evaluate an adjusted A1C, a glycemic measure that adjusts A1C to a reference RBC lifespan. By removing the individual RBC lifespan variation, adjusted A1C better reflects intracellular glucose exposure in RBCs and perhaps other organs susceptible to complications. Iron-deficiency anemia and treatment is known to affect RBC lifespan and therefore provides opportunity to evaluate the model. The patient was a 53-year-old woman with iron-deficiency anemia and type 1 diabetes utilizing sensor-augmented pump therapy. Longitudinal A1C and CGM were evaluated with a novel kinetic model to estimate RBC lifespan and glucose uptake rate. During the six months before iron therapy, the RBC lifespan was estimated at 151 days and 93% of a reference glucose uptake. During six months of iron therapy, the RBC lifespan decreased to 122 days, while the RBC glucose uptake increased slightly to 101% of reference value. The RBC lifespan change explains the observed laboratory A1C change (Figure) and can be attribute to the iron therapy and supported by Hb, RDW and Ferritin data. The adjusted A1C based on these two different RBC lifespans agree with the stable CGM mean glucose of this patient. In this case study, we confirmed the clinical relevance of adjusted A1C to account for variations in RBC lifespan. Disclosure Y.Hirota: Speaker's Bureau; Abbott Japan Co., Ltd., Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Lilly, Medtronic, Mochida Pharmaceutical Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Terumo Corporation. Y.Xu: Employee; Abbott Diabetes. A.Yamamoto: None. A.Matsuoka: None. T.Dunn: Employee; Abbott. W.Ogawa: Advisory Panel; Abbott Japan Co., Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk, Other Relationship; Abbott Japan Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Research Support; Abbott, Astellas Pharma Inc., Eli Lilly and Company, Kowa Company, Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Funding Abbott Diabetes Care
Published: 2022

50. Combined Hypophysitis and Type 1 Diabetes Mellitus Related to Immune Checkpoint Inhibitors

Author: Yasunori Fujita, Fumika Kamitani, Masaaki Yamamoto, Hidenori Fukuoka, Yushi Hirota, Nobuharu Nishiyama, Naho Goda, Yuko Okada, Yuiko Inaba, Hiroki Nakajima, Yukako Kurematsu, Keitaro Kanie, Hiroki Shichi, Shin Urai, Masaki Suzuki, Naoki Yamamoto, Hironori Bando, Genzo Iguchi, Hirotaka Suto, Yohei Funakoshi, Naomi Kiyota, Yutaka Takahashi, and Wataru Ogawa
Subjects: immune checkpoint inhibitors, HLA haplotype, Endocrinology, Diabetes and Metabolism, diabetes mellitus, hypophysitis, combined endocrinopathies
Abstract: Context The occurrence of multiple endocrinopathies due to immune checkpoint inhibitors (ICIs) is a relatively common adverse event. However, the occurrence of a combination of hypophysitis and type 1 diabetes mellitus (T1DM) is extremely rare, and its clinical features are unclear. Objective We comparatively analyzed the clinical features of this combination and each individual ICI-induced endocrinopathy. Methods We reported 3 cases that we encountered and reviewed previously reported cases of patients with combined hypophysitis and T1DM due to ICIs. Results Anti-programmed cell death-1 (anti-PD-1) antibodies were prescribed to all 3 cases. The duration from ICI initiation to the onset of endocrine disease was 12 to 48 weeks. Several human leukocyte antigen (HLA) haplotypes that have disease susceptibility to hypophysitis were detected in all 3 patients. With the 17 previously reported cases, combined endocrinopathies were more common in men (85%). The onset age was in the 60s for both combined and single endocrinopathies. Anti-PD-1 antibodies were used in most of the cases (90%). The time from ICI initiation to the onset of endocrinopathies was 24 (8-76) weeks for hypophysitis and 32 (8-76) weeks for T1DM in patients with combined endocrinopathies, which was not significantly different from that for each single endocrinopathy. Conclusion We presented 3 cases of patients with combined endocrinopathies of hypophysitis and T1DM that may have been caused by anti-PD-1 antibodies. There was no difference in the time from ICI initiation to the onset of endocrinopathies between combined and single endocrinopathies. Further case accumulation and pathogenic investigations are required.
Published: 2023

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