Impact of COVID-19 pandemic on healthcare service use for non-COVID-19 patients in Japan: retrospective cohort study.

OBJECTIVES: We aimed to investigate the impact of the first and second waves of the COVID-19 pandemic on healthcare service use by non-COVID-19 patients. DESIGN: Retrospective cohort study. SETTING: Hospital-based claims database from anonymised hospitals in Japan. PARTICIPANTS: Patients (n=785 495) who visited and/or were hospitalised in 26 anonymised hospitals in Japan between January 2017 and November 2020. OUTCOME MEASURES: We compared changes in the monthly number of hospitalisations (overall or by diagnosis), outpatient visits, endoscopic fibrescopies (EFs), rehabilitations, outpatient chemotherapy treatments, maintenance haemodialysis treatments and outpatient prescriptions between pre-COVID-19 years and the same period in 2020. RESULTS: The overall number of hospitalisations and outpatient visits decreased by 27% and 22%, respectively, in May 2020, of which the most substantial decrease was observed in the paediatrics department (65% and 51%, respectively). The number of hospitalisations for respiratory diseases, circulatory diseases, malignant neoplasms and digestive diseases decreased by a maximum of 55%, 32%, 10% and 26%, respectively, in 2020. The number of hospitalisations for non-COVID-19 pneumonia in patients aged <16 years, patients aged ≥16 years and patients with asthma decreased by 93%, 43% and 80%, respectively, in May 2020. EFs and outpatient rehabilitations decreased by >30%. In contrast, outpatient chemotherapy and maintenance haemodialysis treatments decreased by <10%, if at all. Outpatient prescriptions decreased by a maximum of 20% in 2020, with the largest decrease observed in drugs for obstructive airway diseases and cough and cold preparations. CONCLUSIONS: The use of healthcare services by non-COVID-19 patients was most affected during the first wave of the COVID-19 pandemic in May 2020. The number of hospitalisations for respiratory diseases, particularly non-COVID-19 pneumonia and asthma, drastically decreased, while the number of hospitalisations and outpatient chemotherapies for malignant neoplasms or maintenance haemodialysis was less affected.

Blood Glucose Control Strategy for Type 2 Diabetes Patients With COVID-19.

Since December 2019, coronavirus disease 2019 (COVID-19) caused by a novel coronavirus has spread all over the world affecting tens of millions of people. Another pandemic affecting the modern world, type 2 diabetes mellitus is among the major risk factors for mortality from COVID-19. Current evidence, while limited, suggests that proper blood glucose control may help prevent exacerbation of COVID-19 even in patients with type 2 diabetes mellitus. Under current circumstances where the magic bullet for the disease remains unavailable, it appears that the role of blood glucose control cannot be stressed too much. In this review the profile of each anti-diabetic agent is discussed in relation to COVID-19.

Immune Regulation of Postprandial Glycemia and Whole-Body Insulin Sensitivity through Myeloid Production of IL-10

As feeding increases signals that potently induce gene expression in immune cells, we aimed to elucidate the role of myeloid cells in normal postprandial metabolism. Feeding increased serum levels of LPS, which is known to induce multiple genes in immune cells. Notably, LPS together with insulin potently induced IL-10 in macrophages, which could also be detected in the postprandial portal vein in vivo. In cultured hepatocytes, physiological levels of insulin alone did not suppress gluconeogenic gene expression, although when added together with medium from macrophages stimulated with LPS and insulin, they were markedly suppressed. This suppression was not seen in medium from macrophages of IL-10 knockout mice, showing this to be an IL-10 dependent process. Plasma glucose concentration ad libitum was elevated in mice injected with adenovirus encoding shRNA targeting the IL-10 receptor, and the normal postprandial suppression of gluconeogenic genes in liver was compromised, showing the importance of the IL-10 signal in postprandial glucose metabolism. Furthermore, myeloid-specific knockout of Akt1 and Akt2 resulted in similar phenotypes that were rescued by incrementing mTOR signaling, pointing to an Akt-mTOR dependent mechanism. As whole-body deficiency of IL-10 has been reported to decrease body weight and increase insulin sensitivity, we assessed the effect of myeloid deficiency of IL-10 by conducting bone marrow transfer from IL-10 knockout mice to wild type mice. While these phenotypes were recapitulated, postprandial glucose production was not improved despite markedly increased whole-body insulin sensitivity. These results pointed to the differential actions of myeloid IL-10 where baseline production maintains normal body weight, while postprandial increases in the hepatic-portal system suppresses hepatic gluconeogenic gene expression, collectively showing the need for context-dependent administration of IL-10 based therapies. Disclosure: G. Toda: None. K. Soeda: None. N. Arakawa: None. Y. Masuda: None. N. Kobayashi: None. H. Suwanai: None. Y. Izumida: None. T. Yamauchi: Research Support;Self;AeroSwitch, Asahi Mutual Life Insurance Company, Astellas Pharma Inc., AstraZeneca K.K., Boehringer Ingelheim International GmbH, Daiichi Sankyo Company, Limited, Kowa Pharmaceutical company,limited., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Corporation Life Sciences Limited, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Novo Nordisk Inc., NTT Docomo Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, TOSOH CORPORATION. Other Relationship;Self;Covidien Japan Inc. (Medtronic Japan Co., Ltd.), Eli Lilly Japan K.K., Johnson & Johnson, Kissei Pharmaceutical Co., Ltd. T. Kadowaki: Research Support;Self;Astellas Pharma Inc., Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau;Self;Abbott, Astellas Pharma Inc., AstraZeneca K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Cosmic Corporation, Daiichi Sankyo, Eli Lilly Japan K.K., FUJIFILM, Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Medscape Education, Medtronic, Mitsubishi Tanabe Pharma Corporation, MSD Corporation, NIPRO Medical Corporation, Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Other Relationship;Self;Asahi Mutual Life Insurance. K. Ueki: None. Funding: Japan Society for the Promotion of Science (16K15488, 17K16141, 19K17954) [ABSTRACT FROM AUTHOR] Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

NFIA Differentially Regulates Adipogenesis and Myogenesis through Distinct Molecular Pathways to Ensure Adipocyte Differentiation

Brown and beige fat dissipate chemical energy in the form of heat through uncoupling protein-1 (Ucp1) on the mitochondrial inner membrane as well as through the other pathways, while white fat generally stores energy in the form of lipid. Stimulating development and/or function of brown fat is highly anticipated as a novel strategy for the treatment of obesity and its complications including type 2 diabetes. Previously, we identified a transcription factor nuclear factor I-A (NFIA) as a crucial regulator of brown fat. NFIA binds to and activates the brown-fat-specific enhancers even before differentiation and later facilitates the binding of PPARgamma (peroxisome proliferator-activated receptor gamma—a master transcription factor of adipogenesis), to control the brown fat gene program. Here we show that the C-terminal 17 amino acid residues of NFIA (which we call pro#3 domain) are required for the transcriptional activity of NFIA. Full-length NFIA—but not deletion mutant lacking pro#3 domain—rescued impaired Pparg expression and adipogenesis in NFIA-knockout cells. However, the deletion mutant still binds to Myod1 enhancer to represses Myod1 expression via competition with KLF5 in terms of enhancer binding, leading to suppression of myogenic gene program. Therefore, the negative effect of NFIA on the myogenic gene program is, at least partly, independent of the positive effect on Pparg expression and its downstream adipogenic gene program. Overall, our results uncover multiple ways of action of NFIA to ensure optimal regulation of brown adipocyte differentiation. Disclosure: Y. Hiraike: Research Support;Self;Daiichi Sankyo, Daiichi Sankyo, Novo Nordisk Inc., Novo Nordisk Inc. H. Waki: Research Support;Self;Astellas Pharma Inc., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Takeda Science Foundation, The Cell Science Research Foundation. Speaker's Bureau;Self;AstraZeneca K.K., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Kyowa Hakko Kirin Co., Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K. K. Miyake: Research Support;Self;NTT DOCOMO, INC. M. Oguchi: None. T. Yamauchi: Research Support;Self;AeroSwitch, Asahi Mutual Life Insurance Company, Astellas Pharma Inc., AstraZeneca K.K., Boehringer Ingelheim International GmbH, Daiichi Sankyo Company, Limited, Kowa Pharmaceutical company,limited., Kyowa Hakko Kirin Co., Ltd., Merck Sharp & Dohme Corp., Mitsubishi Corporation Life Sciences Limited, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Novo Nordisk Inc., NTT Docomo Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, TOSOH CORPORATION. Other Relationship;Self;Covidien Japan Inc. (Medtronic Japan Co., Ltd.), Eli Lilly Japan K.K., Johnson & Johnson, Kissei Pharmaceutical Co., Ltd. T. Kadowaki: Research Support;Self;Astellas Pharma Inc., Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau;Self;Abbott, Astellas Pharma Inc., AstraZeneca K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Cosmic Corporation, Daiichi Sankyo, Eli Lilly Japan K.K., FUJIFILM, Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Medscape Education, Medtronic, Mitsubishi Tanabe Pharma Corporation, MSD Corporation, NIPRO Medical Corporation, Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Other Relationship;Self;Asahi Mutual Life Insurance. [ABSTRACT FROM AUTHOR] Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Voices: Insulin and beyond.

Marking insulin's centennial, we share stories of researchers and clinicians whose seminal work has advanced our understanding of insulin, islet biology, insulin resistance, and diabetes. The past century of pursuing the "hormone of hormones" and advancing diabetes therapies is replete with stories of collaboration, perseverance, and triumph.

The Japanese Medical Science Federation COVID-19 Expert Opinion English Version.

In 2020, the COVID-19 pandemic has had unprecedented impacts on various aspects of the world. Each academic society has published a guide and/or guidelines on how to cope with COVID-19 separately. As the one and only nationwide association of academic societies that represent medical science in Japan, JMSF has decided to publish the expert opinion to help patients and care providers find specifically what they want. This expert opinion is a summary of recommendations by many academic societies and will be updated when necessary. Patients that each academic society targets differ even though they suffer from the same COVID-19, and recommendations can be different in a context-dependent manner. Readers are supposed to be flexible and adjustable when they use this expert opinion.

Diabetes and COVID-19: IDF perspective in the Western Pacific region.

The World Health Organization (WHO) declared a pandemic, the highest risk level in the infectious disease alert phase, on 11 March 2020. In the Western Pacific Region (WPR), 192,016 confirmed cases with 7125 deaths had been reported as of 8 June 2020. In people with diabetes COVID-19 can be more difficult to treat due to the wide fluctuations in blood glucose levels or presence of comorbidities such as diabetes complications, including cardiovascular disease and renal damage, which are recognized risks for adverse outcomes. National diabetes associations and governments have established guidelines for subjects with diabetes in relation to COVID-19, and are trying to supply emergency and their regularly required medical products for them. The WPR is so large and composed of such diverse countries and COVID-19 situations, no one conclusion or program applies. Instead we could see a diverse COVID-19 pandemic profile in the WPR, and several creative diagnostic and therapeutic measures undertaken. This includes drive-through screening facilities, high-speed RT-PCR technologies, convalescent patients' plasma therapy, which potentially had some positive contributions in combatting COVID-19 in the WPR as well as globally. Although the numbers of confirmed cases are currently decreasing in the region, the COVID-19 pandemic is not over, and many experts are recommending to prepare measures for potential second or third waves of COVID-19.