bluuebunny/crossref_metadata_2025_split huggingface dataset:
1514-P: Suboptimal Glycemic Control and High Prevalence of Diabetes Complications in Adults with Type 1 Diabetes (T1D) in the SAGE Study
Authors: RENARD ERIC , BOSNYAK ZSOLT , LAUAND FELIPE , POZZILLI PAOLO , IKEGAMI HIROSHI , KESAVADEV JOTHYDEV , VIANNA ANDRE G. 
Published: June 2020

Poor glycemic control is a risk factor for many diabetes-related complications, but global real-world data on diabetes management in adults with T1D is limited. SAGE was a multinational, observational, cross-sectional study to describe glycemic control of participants aged ≥26 years with T1D for ≥1 year.
Of 3858 participants from 17 countries, 54.6% were female, with mean (standard deviation [SD]) age 47.4 (14.0) years, T1D duration 20.7 (12.6) years, and age at T1D onset 26.7 (14.4) years. Childhood-onset T1D was most common (48%) in the 26-44 years age group. Mean (SD) HbA1c was 7.95 (1.42) % (63.4 [15.6] mmol/mol), and similar across predefined age groups (Table). Only 20.9% of participants reached their individualized HbA1c target. Prevalence of microvascular complications was 36-63%, increasing with age and duration of diabetes. Incidence of diabetic ketoacidosis was similar in all age groups and consistent with previous reports.
SAGE shows that the prevalence of microvascular complications remains high, affecting over half of the study population aged ≥65 years, and is more prevalent in those with a longer duration of diabetes.

Disclosure
E. Renard: Board Member; Self; Abbott, Insulet Corporation, Novo Nordisk A/S, Roche Diabetes Care. Consultant; Self; Air Liquide, Eli Lilly and Company, Sanofi. Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. Z. Bosnyak: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. F. Lauand: Employee; Self; Sanofi. P. Pozzilli: Advisory Panel; Self; Abbott, AstraZeneca, Eli Lilly and Company. Research Support; Self; Medtronic, Sanofi. H. Ikegami: None. J. Kesavadev: Speaker’s Bureau; Self; Biocon, Novo Nordisk Inc., Sanofi-Aventis. A.G. Vianna: Board Member; Self; Abbott, Medtronic, Novo Nordisk A/S. Research Support; Self; Sanofi. Speaker’s Bureau; Self; Lilly Diabetes.

Funding
Sanofi
1517-P: Characteristics and Burden of Macro, Micro, and Normoalbuminuria in Patients with Type 2 Diabetes (T2D)
Authors: BLONDE LAWRENCE , WILK ALAN , BOGDANOV ALINA , VASEY JOE , KALLENBACH LEE , DURKIN MICHAEL 
Published: June 2020

Individuals with T2D and diabetic nephropathy are at higher risk for adverse cardiovascular events. This study compared patient characteristics and disease burden by severity of albuminuria (normoalbuminuria [NOR], microalbuminuria [MIU], macroalbuminuria [MAU]) among T2D patients tested for albuminuria and initiating new diabetes pharmacotherapy not dispensed in the prior 6 months.
From a U.S. database of linked electronic health records and insurance claims, we identified adults with T2D initiating a new DPP-4, GLP-1, or sulfonylurea between June 2016 and June 2019 (index event), with a lab value for urinary albumin: creatinine ratio (UACR) or albumin excretion rate (AER). Albuminuria was defined as NOR if UACR (in mg/g) or AER (in mg/day) &lt;30, MIU if 30≤UACR/AER≤300, and MAU if 300&lt;UACR/AER&lt;5,000. Baseline characteristics and healthcare resource utilization for 6 months pre-index were compared among cohorts.
Patients with an available UACR/AER value (n=127,405) represented ∼12% of adult T2D therapy initiators. Severity of albuminuria was NOR (54.9%), MIU (37.0%), and MAU (8.1%). As severity increased, the percentage of patients with baseline cardiovascular conditions and medications and with baseline hospitalizations also increased (Table). More research is needed into the unique needs of the T2D with MAU population.

Disclosure
L. Blonde: Advisory Panel; Self; AstraZeneca, Gilead Sciences, Inc. Consultant; Self; Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Janssen Scientific Affairs, LLC., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc., Sanofi. A. Wilk: Employee; Self; Veradigm. A. Bogdanov: None. J. Vasey: None. L. Kallenbach: None. M. Durkin: Employee; Self; Janssen Scientific Affairs, LLC.

Funding
Janssen Scientific Affairs, LLC
152-OR: Postabsorptive Splanchnic and Leg Glucagon Metabolism in Healthy Subjects: Use of 13C 15N Glucagon
Authors: RUCHI FNU , YADAV YOGESH R. , ROMERES DAVIDE , SAWLEH SAFIA , BENSON LINDA M. , JOHNSON KENNETH L. , MAN CHIARA DALLA , COBELLI CLAUDIO , MCCORMICK DANIEL J. , WILKINS LUKE R. , BASU RITA , BASU ANANDA 
Published: June 2020

Glucagon metabolism in humans is poorly understood and is currently under active investigation. We have recently developed a novel isotope dilution method using nonradioactive, stable human glucagon (Phe 6 13C9, 15N; Phe 22 13C9, 15N) tracer to measure glucagon turnover. In this study we combined this method with organ catheterization technique to estimate splanchnic and leg glucagon extraction and uptake. We present data from the first 6 healthy subjects (age 25±3.6 yrs; BMI 26.7±4.5 kg/m2; fasting glucose 4.6±0.5 mM; HbA1c 5.1±0.3%) completed thus far. After IRB approval and informed consent, subjects were admitted in the morning after an overnight fast to Interventional Radiology, where catheters were placed in the right femoral artery and vein under local anesthesia with aseptic precautions. Under fluoroscopic guidance, a hepatic venous catheter was positioned through the femoral vein. Glucagon tracer was infused intravenously and Indocyanine Green infused via the femoral artery sheath to measure splanchnic and femoral plasma flows. Plasma samples were collected periodically from femoral artery, femoral vein and hepatic vein for concentrations of glucagon tracer (Tandem Mass Spectrometry), glucagon, glucose and Indocyanine Green (Spectrophotometry) concentrations. Fractional splanchnic glucagon extraction was 24.0±12.5 % while total splanchnic glucagon uptake was 214.3±56.1 ng/kg total body weight/min. Net splanchnic glucagon balance was -34.4±10.0 ng/kg total body weight/min implying net splanchnic glucagon production. Fractional leg glucagon extraction was 13.5±3.8% while total leg glucagon uptake was 53.0±21.2 pg/kg total body weight/min. To the best of our knowledge, these initial data provide the first direct assessment of regional glucagon metabolism in healthy humans in the post absorptive fasting state.

Disclosure
F. Ruchi: None. Y.R. Yadav: None. D. Romeres: None. S. Sawleh: None. L.M. Benson: None. K.L. Johnson: None. C. Dalla Man: Research Support; Self; Sanofi-Aventis Deutschland GmbH. C. Cobelli: None. D.J. McCormick: None. L.R. Wilkins: None. R. Basu: Consultant; Self; GENFIT. Research Support; Self; AstraZeneca. A. Basu: Consultant; Spouse/Partner; GENFIT. Research Support; Spouse/Partner; AstraZeneca.

Funding
National Institutes of Health (R01DK029953 to R.B.), (R01DK085516 to A.B.), (DK059637, DK020593)
1522-P: High Incidence of Hospital-Onset Clostridium Difficile Infection in Diabetic Foot Syndrome Patients: Data from a Single Tertiary Diabetes Care Clinic in Poland
Authors: HOHENDORFF JERZY , SERAFIN MARIA , WITEK PRZEMYSLAW W. , BORYS SEBASTIAN , KATRA BARBARA , MALECKI MACIEJ 
Published: June 2020

Diabetic Foot Syndrome (DFS) commonly occurs with infected ulceration and is associated with a high rate of amputation and excessive mortality. Antibiotic therapy increases the risk of Clostridium difficile infection (CDI). The mean CDI rate in European hospitals is 7.0 cases (country range 0.7-28.7) per 10 000 patient-bed days (PBD). The risk of hospital-acquired CDI (HA-CDI) among patients with diabetes mellitus (DM) and DFS may be much higher than in the general hospitalized population. The aim of the study is to define the incidence of HA-CDI in patients with DM and DFS. We performed a retrospective analysis using 2018 data from a tertiary diabetes care hospital which provides medical care mostly to patients with diabetes, including those admitted from the emergency department. We included patients with CDI confirmed by positive test result for toxins A/B. In 2018, CDI occurred in 22 cases, including 9 in patients with DFS. Overall, the CDI incidence rate was 21.6 cases per 10 000 PBD. The rate was much higher among patients with DFS than among patients department-wide (IRR: 3.73, 95% CI: 1.59-8.71). Prior to testing for toxins A/B, antibiotics were used in all DM patients with DFS who developed HA-CDI (9/9) and in 83.8% (109/130) DFS cases not complicated by CDI. Patients with DFS and CDI were characterized by lower mean BMI (28.3±0.4 vs. 30.3±0.6 kg/m2, p=0.01) than patients with DFS and without CDI. Between these two groups, no statistically significant differences were found in sex (male: 96/130 vs. 6/9, p=0.70), median age at hospitalization (65.0 (57.0-70.0) vs. 62.0 (52.0-67.0) yrs., p=0.30), HbA1c (68.3 (42.1-80.3) vs. 60.7 (49.7-78.1) mmol/mol, p=0.93) and eGFR (78.0 (62.0-93.0) vs. 84.5 (54.0-97.0) ml/min/1,73m2, p=0.91). Our results showed that DM patients with DFS had a higher risk of CDI than patients department-wide.

Disclosure
J. Hohendorff: None. M. Serafin: None. P.W. Witek: None. S. Borys: None. B. Katra: None. M. Malecki: None.
1528-P: Blood Level of Alpha-1 Antitrypsin in the Course of Acute Myocardial Infarction in Diabetic Patients: A Possible Clinical Significance
Authors: KHATIB SAID Y. 
Published: June 2020

Introduction: Alpha-1 antitrypsin (A1AT) is known to protect lung tissue from damage. Such protection is extended to myocardial tissues during myocardial ischemia/infarction.
Objective: The aim of the study was to determine the time course of A1AT levels in the plasma of myocardial infarction patients over 96 hours and compare it with healthy individuals.
Methods: Blood samples were collected from patients (n=40, age 58 ± 11 yrs, males 29 and females 11), at 1, 4, 24, 48 and 96 hrs after confirmed diagnosis and admission to King Salman Cardiac Center in King Fahad Medical City, Riyadh, Saudi Arabia. IRB approval and consent was signed by all patients. The patients were divided into diabetics (n=19) and nondiabetic (21). Blood samples were collected in purple top tubes containing EDTA to prevent blood coagulation and immediately centrifuged at 6000 rpm at 4 C for 20 min. Plasma was decanted and stored at - 20 C until analyzed. AlAT was determined in plasma using Eliza kits (abcam, USA). Control blood samples were collected from 20 healthy individuals (age 46±10 yrs.
Results: A1AT were significantly less in MI patients (1025±77 ug/ml at 96 hrs, P&lt;001, n=40) compared to (1655±128 ug/ml, n=20) (mean ±SEM) in controls. Those patients in whom the decrease in A1AT was greater than 50 % of control values, they did not survive and deceased (673+71 ug/ml, approx 40%, n=3). The decrease was significantly greater in nondiabetic patients as compared to diabetics. A1AT after an MI attack was comparable in hypertensive and non-hypertensive and in STEMI and Non-STEMI patients.
Conclusion: A1AT seem to be important in providing some protection to myocardial cells during an MI attack. A1AT levels seem to drop following an MI attack. The drop is larger in nondiabetic as compared to diabetics. In those patients in whom the level of A1AT drops to more than 50 % of normal values they are less likely to survive the MI attack. More studies are needed to confirm the above findings.

Disclosure
S.Y. Khatib: None.

Funding
King Fahad Medical City Research Center (016-2018)
1530-P: Metabolic Characteristics in Chinese Sarcopenia Patients with Type 2 Diabetes
Authors: HE QINGHUA , GUO LIXIN 
Published: June 2020

Objective: To evaluate glucose metabolism characteristics in middle-aged and elderly sarcopenia patients with type 2 diabetes.
Methods: Data were collected from a multicenter, cross-sectional survey study. Eligible patients aged 50 years or older with a previous diagnosis of type 2 diabetes were recruited from the endocrinology department of nine different hospitals in Beijing, China. All participants were grouped into a probable sarcopenia group with low muscle strength and a nonsarcopenia group with normal muscle strength according to the recommendations from EWGSOP2 (2018). Body composition, glucose metabolism, laboratory and nutritional index were compared between two groups.
Results: A total of 1125 diabetic participants were included, with 405 in probable sarcopenia group and 720 in nonsarcopenia control group. Compared to the controls, the probable sarcopenia participants were older and had lower waist-to-hip ratio and BMI, higher fasting plasma glucose level and glycosylated hemoglobin (HbA1c), decreased estimated glomerular filtration rate, and lower bone mineral content, basal metabolic rate, fatless upper arm circumference, appendicular skeletal muscle mass index (ASMI) and muscle quality in both men and women. The prevalence of low muscle mass was obviously elevated in probable sarcopenia group in both sexes (men: 11.0% vs. 25.4%, women: 6.8% vs. 19.1%). Multivariable logistic regression analysis showed that aged, male sex, low BMI, increased HbA1c, diabetic nephropathy and decreased serum albumin level were risk factors associated with low muscle strength in diabetes patients.
Conclusions: Sarcopenic diabetic patients were older and had lower BMI, worse nutritional status and glucose metabolism, decreased renal function and reduced muscle quality and mass with a greater likelihood of osteoporosis. Clinically, diabetic aged patients should receive an assessment on muscle strength and muscle quality to optimize their treatment program.

Disclosure
Q. He: None. L. Guo: None.
154-LB: Cardiac MRI Findings in Young Adults with Childhood-Onset Type 2 Diabetes
Authors: DIAZ SANDRA VAZQUEZ , KATZ LORRAINE E. , GIDDING SAMUEL , WITSCHEY WALTER , CAPELLA COURTNEY , LITT HAROLD 
Published: June 2020

Left ventricular (LV) hypertrophy and left atrial dilation are present at echocardiography in youth with T2D, however limited cardiac MRI data exist. We compared cardiac MRI findings in young adults with childhood- onset T2D (n=10) age 19-24 years, with published controls. History, physical exam and HbA1c were obtained. Hemodynamics were evaluated from cine imaging. For myocardial fibrosis, extracellular volume (ECV) fraction and native T1 relaxation times were assessed using a Modified Look-Locker Imaging sequence. Subjects were 8 females and 2 males, 7 black, 1 white, 1 mixed race and 1 Hispanic. Median (interquartile range IQR) age, diabetes duration, SBP, BMI and HbA1c were 19.9 (1.39) years, 7.8 (4.7) years, 121.5 (25) mmHg, 32.7 (9.5) kg/m2 and 10.3 (3.04)%, respectively. Subjects had a higher median (IQR) end systolic volume (ESV) index than published mean (SD) for healthy 20-29 year olds: 40.81 (5.74) ml/m2 vs. 29 (5.1) ml/m2 (p=0.007). However, they had lower LV mass index: 54.61 (9.01) g/m2 vs. 69 (8.1) g/m2 (p=0.01) and ejection fraction (EF): 50 (2.8)% vs. 66 (4.6)% (p=0.0049). Higher median (IQR) myocardial T1 of 1030.35 (44.6) msec vs. 965.6 (30.2) msec (p=0.005) and ECV fraction of 27.5 (1.5)% vs. 25 (3)% (p=0.012) were present. LV mass index directly correlated with HbA1c (rs= 0.69, p=0.03). Females had a higher median (IQR) ESV index of 40.81 (4.08) ml/m2 than published mean (SD) for females age 16-20 years of 29 (7.5) ml/m2 (p= 0.01), but lower EF of 50 (2.65)% vs. 64.3 (7.3)% (p= 0.01) and cardiac index of 3.08 (0.425) L/min/m2 vs. 3.85 (0.86) L/min/m2 (p= 0.01). ESV index positively correlated with HbA1c (rs=0.762, p=0.03). Males had a median (IQR) ESV index of 39.94 (25.7) ml/m2, LV mass index of 67.46 (13.9) g/m2 and EF of 54.95 (9.9)%. In this pilot study, young adult subjects with youth-onset T2D had a different myocardial phenotype compared to published normal values, characterized by undersized hearts relative to larger body size, poorer systolic performance and evidence for early onset myocardial fibrosis.

Disclosure
S. Vazquez Diaz: None. L.E. Katz: None. S. Gidding: None. W. Witschey: None. C. Capella: None. H. Litt: None.

Funding
University of Pennsylvania; National Institutes of Health (3T32DK7314-39S1)
1545-P: Associations of Carotenoids with Hyperuricemia: Results from a National Population Study
Authors: ZHANG NAN , ZHANG NAN , CHEN LULU 
Published: June 2020

Background: Carotenoid are strong antioxidants rich in fruits and vegetables. Plasma carotenoids are good markers of fruit and vegetable intakes. We aimed to investigate the associations of plasma carotenoid levels with uric acid concentrations and hyperuricemia.
Method: A cross-sectional study using data from United States National Health and Nutrition Examination Survey from 2001 to 2006 was conducted. After excluding missing data of uric acid and carotenoids levels, 19124 participants aged 0-85 were included in the study. Associations of carotenoids with uric acid or hyperuricemia were conducted using multivariate linear regression or logistic regression.
Results: In the study, 1992 participants had hyperuricemia. After adjustments of age, gender, race, education, cotinine, physical activity, alcohol drinking, energy intake, body mass index, C-reactive protein, estimated glomerular filtration rate (eGFR), non-high-density lipoprotein cholesterol (nonHDL-C), HDL-C and hypertension, each unit increase of a-carotene, trans-b-carotene, cis-b-carotene, trans-lycopene, combined lutein/zeaxanthin, and b-cryptoxanthin was associated with 33.01 (95% CI= -50.57 to -15.44), 10.59 (95% CI= -14.76 to -6.41), 169.40 (95% CI=-235.98 to -102.83), 13.05 (95% CI=-24.53 to -1.57), 27.99 (95% CI=-43.84 to -12.14), and 36.14 (95% CI=-55.16 to -17.12) mmol/L decrease of uric acid, respectively and odds ratios of above carotenoids and hyperuricemia were 0.05 (95% CI= 0.01 to 0.5), 0.31 (95% CI= 0.14 to 0.68), &lt;0.001 (95% CI=&lt;0.001 to 0.003), 0.37 (95% CI=0.20 to 0.66), 0.22 (95% CI=0.07 to 0.77), and 36.14 (95% CI=0.02 to 0.20) respectively.
Conclusion: Carotenoids were inversely associated with uric acid levels and hyperuricemia risk. Higher plasma carotenoids may be beneficial against hyperuricemia. Increasing carotenoids concentrations, for instance by fruits and vegetables intake, as a novel preventive treatment for hyperuricemia deserves further investigation.

Disclosure
N. Zhang: None. N. Zhang: None. L. Chen: Consultant; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S.
155-OR: ADA Presidents’ Select Abstract: Symptom Responses to Hypoglycemia Are Related to Connectivity Change between the Thalamus and Frontal Lobes
Authors: JACOB PETER , NWOKOLO MUNACHISO , ODALY OWEN , ZELAYA FERNANDO O. , AMIEL STEPHANIE A. , CHOUDHARY PRATIK 
Published: June 2020

Neuroimaging studies highlight the importance of thalamic activation in response to hypoglycemia in people with and without type 1 diabetes (T1D). This activation is characteristically attenuated in impaired awareness of hypoglycaemia (IAH), a major risk factor for severe hypoglycemia. We investigated changes in connectivity of the thalamus with other brain regions during hypoglycemia.
Methods: Fourteen people without diabetes (no diabetes, ND), 15 with T1D and normal awareness of hypoglycemia (NAH) and 22 with IAH, all right-handed, age, sex and gender matched, underwent a hyperinsulinemic glucose clamp during which we acquired blood oxygen level dependent fMRI at euglycemia (90mg/dL) and at onset of hypoglycemia (48mg/dL). Connectivity was studied using the CONN toolbox in SPM12. A thalamic seed was used in a seed-to-voxel analysis with and without the increase in symptoms at hypoglycemia as an explanatory regressor variable.
Results: Symptom scores in response to hypoglycemia rose earliest and to the greatest levels in NAH (11.0 to 18.3, p= 0.029). The rise in symptom scores in ND was not significant at this timepoint (9.2 to 13.8, p= 0.057), whilst IAH showed no symptom change (10.5 to 9.8, p= 0.7). In ND, hypoglycemia increased thalamic connectivity with the right frontal pole (pFDR = 0.018). This did not occur in diabetes, either in NAH or IAH. The NAH group demonstrated a positive relationship between change in symptoms with change in connectivity of the thalamus and a left frontal pole region (pFDR = 0.035), whereas an overlapping area had a negative correlation in ND (pFDR = 0.001). There was no correlation in IAH.
Conclusion: During hypoglycemia, those with T1D display aberrantly enhanced thalamic connectivity with brain regions responsible for complex behavior. Disruption of this network occurs in IAH and may be the mechanism for failure of perception of the onset of hypoglycemia and reduced hypoglycemia avoidance behaviors, increasing severe hypoglycemia risk.

Disclosure
P. Jacob: None. M. Nwokolo: Other Relationship; Self; Sanofi. O. ODaly: None. F.O. Zelaya: None. S.A. Amiel: Advisory Panel; Self; Medtronic, Novo Nordisk A/S, Roche Pharma. Other Relationship; Self; Diabetes UK. P. Choudhary: Advisory Panel; Self; Abbott, Eli Lilly and Company, Insulet Corporation, Medtronic. Research Support; Self; European Union, JDRF. Speaker’s Bureau; Self; Dexcom, Inc., Novartis AG, Novo Nordisk A/S, Sanofi-Aventis.

Funding
JDRF (3-SRA-2017-484-S-B)
1553-P: Combination of Diabetes Mellitus and Lack of Habitual Physical Activity Is a Risk Factor for Functional Disability in Japanese
Authors: FUJIHARA KAZUYA , YAMADA MAYUKO H. , MATSUBAYASHI YASUHIRO , KITAZAWA MASARU , KANEKO MASANORI , YAMAMOTO MASAHIKO , YAGUCHI YUTA , YAHIRO TAKUYA , KODAMA SATORU , KATO KIMINORI , SONE HIROHITO 
Published: June 2020

Declining healthy life expectancy due to functional disability is relevant and urgent not only because of its association with decreased quality of life but also for its enormous socioeconomic impact. Thus, we analyzed a population-based retrospective cohort study including 9,673 community dwelling Japanese adults (4,420, men) aged 39-98 years in 2012-2017. Functional disability was defined as a condition meeting Japan’s new long-term care insurance certification requirements for the need of assistance in the activities of daily living whether by caregivers or assistive devices. Cox proportional hazards regression model identified variables related to functional disability. Median follow-up was 3.7 years. During the study period, 165 disabilities occurred in the overall study population. Multivariate analysis showed that diabetes (hazard ratio [HR] 1.74 (95% CI: 1.12-2.68)), no physical activity habit (HR 1.83 (1.27-2.65)), and low BMI category (18.5 kg/m2 &gt;) (HR 1.63 (1.02-2.63)) presented increased risks for disability. The prevalence ratio of 0, 1, 2, 3 and 4 conditions (diabetes, hypertension, dyslipidemia, and physical activity habits) was 12.8%, 40.0%, 32.6%, 12.9 and 1.7%, respectively. HR for disability increased with the number of risk factors (HR of individuals with 1, 2, 3 and 4 conditions, 1.34 (0.71-2.52), 1.95 (1.04-3.63), 2.11 (1.07-4.15), and 3.96 (1.59-9.99) vs. individuals with none of those conditions as a ref.). HR for disability among diabetes patients with and without a physical activity habit was 1.68 (0.70-4.04) and 3.19 (1.79-5.70), respectively, compared to individuals without diabetes with a physical activity habit. This shows that the combination of diabetes and lack of habitual physical activity is predictive of functional disability in Japanese. Habitual physical activity attenuates the risk of functional disability in patients with diabetes.

Disclosure
K. Fujihara: None. M.H. Yamada: None. Y. Matsubayashi: None. M. Kitazawa: None. M. Kaneko: None. M. Yamamoto: None. Y. Yaguchi: None. T. Yahiro: None. S. Kodama: None. K. Kato: None. H. Sone: Research Support; Self; Kyowa Hakko Kirin Co., Ltd., Novartis AG, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.

Funding
Japan Society for the Promotion of Science (18K17897)