المؤلفون: R. Myers, Muhammad Y. Sheikh, Ramy Younes, David A. Shapiro, Robert Riccio, Arie Regev, Melissa Palmer, Richard Torstenson, Detlef Schuppan, Steven Bollipo, Minjun Chen, Puneet S. Arora, Henrik Landgren, Rajarshi Banerjee, Yasser Fouad, Martin Blake, Bradley Freilich, Dina Attia, Alastair D. Smith, Morten A. Karsdal, Hans-Juergen Gruss, Robert G. Gish

المصدر: Journal of Clinical and Translational Hepatology. 10:374-382

مصطلحات موضوعية: education.field_of_study, medicine.medical_specialty, Hepatology, business.industry, Public health, Fatty liver, Population, Disease, Public relations, medicine.disease, Terminology, Drug development, Nonalcoholic fatty liver disease, medicine, Regulatory science, business, education

الوصف: Metabolic (dysfunction)-associated fatty liver disease (MAFLD) affects a third of the population and is a leading cause of liver-related death. Since no effective treatments exist, novel approaches to drug development are required. Unfortunately, outdated terminology and definitions of the disease are hampering efforts to develop new drugs and treatments. An international consensus panel has put forth an influential proposal for the disease to be renamed from nonalcoholic fatty liver disease (NAFLD) to MAFLD, including a proposal for how the disease should be diagnosed. As allies with the many stakeholders in MAFLD care―including patients, patients’ advocates, clinicians, researchers, nurse and allied health groups, regional societies, and others―we are aware of the negative consequences of the NAFLD term and definition. We share the sense of urgency for change and will act in new ways to achieve our goals. Although there is much work to be done to overcome clinical inertia and reverse worrisome recent trends, the MAFLD initiative provides a firm foundation to build on. It provides a roadmap for moving forward toward more efficient care and affordable, sustainable drug and device innovation in MAFLD care. We hope it will bring promising new opportunities for a brighter future for MAFLD care and improve care and outcomes for patients of one of the globe’s largest and costliest public health burdens. From this viewpoint, we have revisited this initiative through the perspectives of drug development and regulatory science.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a4ec305dfc4190b37a162d4c4d7e1d06Test
https://doi.org/10.14218/jcth.2021.00408Test

المؤلفون: Chin Wong, Thomas Gelzleichter, Junichiro Sonoda, Amos Baruch, Linda Morrow, Suresh Dheerendra, Leslie W. Chinn, Richard Boismenu, Eric Wakshull, Maria E. Wilson, Puneet S. Arora, Shan Chen, Anjali Vaze, Johnny Gutierrez, Nicholas Lewin-Koh

المصدر: Proceedings of the National Academy of Sciences of the United States of America

مصطلحات موضوعية: Male, 0301 basic medicine, obesity, Medical Sciences, FGF21, Adipose tissue, Mice, 0302 clinical medicine, Weight loss, Homeostasis, Medicine, Multidisciplinary, biology, Middle Aged, Biological Sciences, Adipose Tissue, Female, Adiponectin, Antibody, medicine.symptom, FGF21 receptor activation, Adult, Agonist, medicine.medical_specialty, Adolescent, medicine.drug_class, 030209 endocrinology & metabolism, Antibodies, Food Preferences, Young Adult, 03 medical and health sciences, Internal medicine, Weight Loss, Animals, Humans, Receptor, Fibroblast Growth Factor, Type 1, Aged, business.industry, Fibroblast growth factor receptor 1, Body Weight, medicine.disease, Obesity, Fibroblast Growth Factors, stomatognathic diseases, Macaca fascicularis, 030104 developmental biology, Endocrinology, biology.protein, food preference, business, metabolism, Biomarkers

الوصف: Significance Fibroblast growth factor 21 (FGF21) controls metabolic organ homeostasis and eating behavior via FGF receptor 1/Klothoβ (FGFR1/KLB) complexes. Here we show that a bispecific anti-FGFR1/KLB agonist antibody, BFKB8488A, mimics the actions of FGF21 in monkeys and humans. BFKB8488A induced marked weight loss in obese monkeys while elevating expression of FGFR1 target genes in adipose tissue. A clinical study in overweight human participants demonstrated that a single dose of BFKB8488A caused transient body weight reduction, sustained improvement in cardiometabolic parameters, and a trend toward reduction in preference for sweet taste and carbohydrate intake. These data suggest that antibody-mediated activation of the FGFR1/KLB complex in humans recapitulates the effects of FGF21 and can be used as therapy for obesity-related metabolic defects.
Fibroblast growth factor 21 (FGF21) controls metabolic organ homeostasis and eating/drinking behavior via FGF receptor 1/Klothoβ (FGFR1/KLB) complexes expressed in adipocytes, pancreatic acinar cells, and the nervous system in mice. Chronic administration of recombinant FGF21 or engineered variants improves metabolic health in rodents, nonhuman primates, and humans; however, the rapid turnover of these molecules limits therapeutic utility. Here we show that the bispecific anti-FGFR1/KLB agonist antibody BFKB8488A induced marked weight loss in obese cynomolgus monkeys while elevating serum adiponectin and the adipose expression of FGFR1 target genes, demonstrating its action as an FGF21 mimetic. In a randomized, placebo-controlled, single ascending-dose study in overweight/obese human participants, subcutaneous BFKB8488A injection caused transient body weight reduction, sustained improvement in cardiometabolic parameters, and a trend toward reduction in preference for sweet taste and carbohydrate intake. These data suggest that specific activation of the FGFR1/KLB complex in humans can be used as therapy for obesity-related metabolic defects.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ecb1e6fc5999a3fd66bc3ad16e368b18Test
https://doi.org/10.1073/pnas.2012073117Test

المؤلفون: Sara J. Achenbach, Farhad Zangeneh, Peter James Dyck, Ann L. Oberg, Robert A. Rizza, Lynn M. Bekris, Puneet S. Arora, Åke Lernmark

المصدر: Endocrine Practice. 12:388-393

مصطلحات موضوعية: Blood Glucose, Male, medicine.medical_specialty, Time Factors, Diabetic neuropathy, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Glucagon, Body Mass Index, Endocrinology, Diabetes mellitus, Internal medicine, Insulin Secretion, Humans, Insulin, Medicine, Glycemic, Glycated Hemoglobin, C-Peptide, business.industry, Type 2 Diabetes Mellitus, General Medicine, medicine.disease, Diabetes Mellitus, Type 2, Creatinine, Injections, Intravenous, Female, Hemoglobin, business, Body mass index, Follow-Up Studies

الوصف: Objective: To gain insight into the effects of duration of type 2 diabetes on insulin secretion in patients with type 2 diabetes mellitus. Methods: C-peptide concentrations were measured every 2 years before and after intravenous injection of 1 mg of glucagon in 89 patients with type 2 diabetes (51 men and 38 women) as part of the Rochester Diabetic Neuropathy Study in those subjects who participated in follow-up (median, 12 years; range, 6 to 14). Results: Although insulin secretion decreased over time (P

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7d34f8ef96ec01145ef296fc8e9fe6bbTest
https://doi.org/10.4158/ep.12.4.388Test

المؤلفون: Thy P. Do, Aarthi Arasu, Peggy M. Cawthon, Steven R. Cummings, Li-Yung Lui, Kristine E. Ensrud, Puneet S. Arora, Jane A. Cauley

مصطلحات موضوعية: Genetic Markers, medicine.medical_specialty, Bone density, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Context (language use), Biochemistry, White People, Cohort Studies, chemistry.chemical_compound, Endocrinology, Bone Density, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Adaptor Proteins, Signal Transducing, Aged, Proportional Hazards Models, Bone mineral, Aged, 80 and over, Hip fracture, business.industry, Endocrine Care, Hip Fractures, Incidence, Biochemistry (medical), medicine.disease, chemistry, Cohort, Bone Morphogenetic Proteins, Physical therapy, Sclerostin, Female, business, Cohort study, Follow-Up Studies

الوصف: Sclerostin, a protein secreted by osteocytes, inhibits bone formation. Individuals with genetic mutations that decrease the availability of sclerostin have very high bone mass.The aim of this study was to examine the hypothesis that elevated serum sclerostin levels are associated with increased risk of hip fracture in older women.This was a case-cohort study of a prospective, community-based cohort of 9704 women aged 65 yr or older. Sclerostin levels were measured in serum collected in 1989-1990 in 228 women with incident hip fractures and 227 women in a randomly selected sample; average follow-up time was 9.8 yr.Serum sclerostin levels were correlated with total hip bone mineral density (BMD; r = 0.27, P0.001). The risk of hip fracture increased across quartiles of serum sclerostin (test for trend, P0.001) and was significantly elevated among those in the fourth quartile (hazard risk 3.4, 95% confidence interval 1.7-7.0) compared with women in the lowest quartile, after adjusting for age, body mass index, estrogen use, history of fracture since age 50 yr, and total hip BMD. When dividing the cohort into eight groups by sclerostin quartile and median hip BMD, women with lower total hip BMD in the highest sclerostin quartile had a 22.3-fold (95% confidence interval 5.8-86.3) increased risk of fracture compared with women with higher total hip BMD in the lowest sclerostin quartile.We conclude that higher serum sclerostin levels are associated with a greater risk of hip fractures in older women. In addition, the risk of hip fracture is amplified when high sclerostin levels are combined with lower BMD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09bade73e5f082b50df3e3f8971960b0Test
https://europepmc.org/articles/PMC3387417Test/

المؤلفون: Puneet S. Arora

المصدر: Endocrine Practice. 12:7

مصطلحات موضوعية: medicine.medical_specialty, Endocrinology, business.industry, Endocrinology, Diabetes and Metabolism, Family medicine, Medicine, General Medicine, Primary care, business, medicine.disease, Obesity

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::e6b9e92c320a13f07e760dfe6e69490cTest
https://doi.org/10.1016/s1530-891xTest(20)44079-0

المؤلفون: Puneet S. Arora

المصدر: Endocrine Practice. 11:81

مصطلحات موضوعية: medicine.medical_specialty, Endocrinology, business.industry, Endocrinology, Diabetes and Metabolism, medicine, Metastatic thyroid cancer, General Medicine, Radiology, business, Imaging modalities

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::e0fd5230179f97a22f7ea95d8c338df8Test
https://doi.org/10.1016/s1530-891xTest(20)43720-6

المؤلفون: Manfred Blum, Puneet S. Arora

المصدر: Endocrine Practice. 9:21

مصطلحات موضوعية: medicine.medical_specialty, Endocrinology, Lactating breast, business.industry, Endocrinology, Diabetes and Metabolism, medicine, Whole Body Scan, General Medicine, Radiology, business, medicine.disease, Thyroid cancer

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::783691fe08ac6ff277f9afcee39ffaafTest
https://doi.org/10.1016/s1530-891xTest(20)43901-1

المؤلفون: Peter J. Dyck, Puneet S. Arora, Ann L. Oberg, Farhad Zangeneh, Claudia C. Powell, Robert A. Rizza

المصدر: Endocrine Practice. 9:25

مصطلحات موضوعية: medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, General Medicine, Type 2 diabetes, medicine.disease, Natural history, Endocrinology, Internal medicine, Medicine, In patient, business, Insulin secretion

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::a9dc1057f4ccc5f3b64255d99d9a152cTest
https://doi.org/10.1016/s1530-891xTest(20)43913-8