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Diabetes Core Update – March 2019

Diabetes Core Update is a monthly podcast that presents and discusses the latest clinically relevant articles from the American Diabetes Association’s four science and medical journals – Diabetes, Diabetes Care, Clinical Diabetes, and Diabetes Spectrum. Each episode is approximately 20 minutes long and presents 5-6 recently published articles from ADA journals.

Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

This month we review articles on:

  1. Association of body mass index, fitness, and mortality in patients with diabetes
  2. Cognitive deficits and traditional diabetic complications in the severely obese
  3. Late Relapse of Diabetes after Bariatric Surgery
  4. Hypoglycemia in Type 1 Diabetes and Subsequent Cognitive Deficits
  5. Nutrient Induced Beta Cell Stress
  6. Topical Oxygen Therapy in the Treatment of Diabetic Foot Ulcers

For more information about each of ADA’s science and medical journals, please visit www.diabetesjournals.org.

Presented by:

Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health

John J. Russell, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Director, Family Medicine Residency Program, Abington Jefferson Health

 




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Diabetes Core Update – COVID-19 UPDATE: March 2019

This is a special issue focusing on Covid-19 and Diabetes:

  1. Characteristics of and Important Lessons From
    the Coronavirus Disease 2019 (COVID-19) Outbreak in China
  2. Clinical course and risk factors for mortality
  3. Diabetes and Hypertension: Are ACE’s, ARBs and NSAIDs OK to Use?

Diabetes Core Update is a monthly podcast that presents and discusses the latest clinically relevant articles from the American Diabetes Association’s four science and medical journals – Diabetes, Diabetes Care, Clinical Diabetes, and Diabetes Spectrum. Each episode is approximately 20 minutes long and presents 5-6 recently published articles from ADA journals.

Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

For more information about each of ADA’s science and medical journals, please visit www.diabetesjournals.org.

Presented by:

Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health

John J. Russell, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Director, Family Medicine Residency Program, Abington Jefferson Health




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Diabetes Core Update – April 2019

Diabetes Core Update is a monthly podcast that presents and discusses the latest clinically relevant articles from the American Diabetes Association’s four science and medical journals – Diabetes, Diabetes Care, Clinical Diabetes, and Diabetes Spectrum. Each episode is approximately 20 minutes long and presents 5-6 recently published articles from ADA journals.

Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

This issue will review:

  1. Normalization of functional beta cell capacity after weight loss in type 2 diabetes
  2. Screening for glucose intolerance and diabetes in patients with coronary artery disease
  3. Trends Prescribing Preferences for SGLT2 Inhibitors and GLP-1 Receptor Agonists, 2013–2018
  4. Impact of a Telephone Intervention to Improve Diabetes Control on Healthcare Utilization and Cost for Adults in South Bronx, New York –
  5. Efficacy and Safety of Dapagliflozin Plus Saxagliptin Versus Insulin Glargine Over 52 Weeks as Add‐on to Metformin With or Without Sulfonylurea in Patients With Type 2 Diabetes
  6. The Association Between Poor Glycemic Control and Health Care Costs in People With Diabetes

For more information about each of ADA’s science and medical journals, please visit www.diabetesjournals.org.

Presented by:

Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health

John J. Russell, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Director, Family Medicine Residency Program, Chair-Department of Family Medicine, Abington Jefferson Health




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Diabetes Core Update: Therapeutic Inertia – April 2020

In this first episode of a three-part series on “Disrupting Therapeutic Inertia in Diabetes Management,” Drs. John Russell and Neil Skolnik examine a case study of a 55-year-old man with type 2 diabetes (3 years duration, A1C 8.2%). In so doing, they review six articles that define achievement gaps in reaching A1C goals and the reasons for why those gaps exist. In episodes 2 and 3 of this series, Drs. Russell and Skolnik we will look at additional causes of therapeutic inertia and solutions for overcoming it. This special three-part series on therapeutic inertia is supported by independent educational grant from Sanofi (https://www.sanofi.com).

This issue will review:

  1. Achievement of target therapeutic goals in persons with T2DM
  2. Achievement of therapeutic goals from 2005 – 2015
  3. Clinical Inertia in Newly Diagnosed Type 2 DM
  4. Clinical Inertia over Time in Type 2 DM
  5. Gap Between Efficacy in Randomized Controlled Trials and Effectiveness in Real-World Use
  6. Difference between Clinical Trial and Real-World Studies Achievement of Target A1C <7.0% in Patients Treated with Basal Insulin in RCTs and Clinical Practice

For more information about each of ADA’s science and medical journals, please visit www.diabetesjournals.org.

Presented by:

Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health

John J. Russell, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Director, Family Medicine Residency Program, Chair-Department of Family Medicine, Abington Jefferson Health




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Diabetes Core Update: Covid-19 - Planning Sick Days April 2019

This special issue focuses on Diabetes, Covid-19 and managing patient’s diabetes when they are sick.

Recorded April 1, 2020.

This podcast will cover:

  1. How do we help our patients with diabetes stay safe
  2. Helping patient negotiate safety issues in the workplace
  3. Safety Issues when people do not come in for care
  4. Managing SGLT-2 inhibitors during the pandemic
  5. Home detection and care of DKA
  6. Renewing Medications
  7. Telemedicine Visits

Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

Presented by:

Louis Philipson, MD, PhD, ADA Past President, Medicine & Science, University of Chicago

Anne Peters, MD, Diabetologist, University of Southern California




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Diabetes Core Update: Covid-19 – Inpatient Management of Persons with Diabetes April 2019

This special issue focuses on Diabetes, Covid-19 and Inpatient Management.

Recorded April 3, 2020.

This podcast will cover:

  1. Risk with Diabetes of Covid-19 and Complications of Covid-19
  2. Management of Hyperglycemia during Covid-19 Infection
  3. Sub-cutaneous Insulin for DKA
  4. CGM in the Hospital Setting
  5. Diabetes Education in the Hospital During Covid-19

Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

Presented by:

Irl Hirsch, MD, Professor of Medicine, University of Washington, Seattle

Guillermo E. Umpierrez, MD, CDE, Professor of Medicine, Emory University, Atlanta Georgia




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Diabetes Core Update: Covid-19 – Deep Dive into Medication Management April 2019

This special issue focuses on Diabetes, Covid-19 and Inpatient Management.

Recorded April 14, 2020.

This podcast will cover:

  1. Inpatient Medication Management for Persons Admitted with Diabetes
  2. Outpatient Medication Management for Persons with Diabetes
    1. Hypoglycemic Medication Management
    2. ACE and ARBs
    3. NSAIDs

Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

Presented by:

Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Associate Director, Family Medicine Residency Program, Abington Jefferson Health

Dr. Joshua Neumiller, Vice Chair & Allen I. White Distinguished Associate Professor of Pharmacotherapy at Washington State University




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Diabetes Core Update: Covid-19 and Diabetes – Considerations for Health Care Professionals - April 2019

Diabetes Core Update: Covid-19 and Diabetes – Considerations for Health Care Professionals - April 2019

This special issue is an audio version of the American Diabetes Associations Covid-19 leadership team discussing a range of issues on Covid-19 and Diabetes.

Recorded March 31, 2020.

Topics include:

  1. Access to medications
  2. Effect on Diabetes Self-management
  3. Can Patients take their own Supplies if they are an inpatient in the hospital – particularly insulin pumps and CGM
  4. Considerations for Specific Hypoglycemic Medications during Inpatient Hospitalization
  5. Differences in Management for Persons with Type 1 and Type 2 Diabetes
  6. SGLT-2 inhibitors and GLP-1 Receptor Agonists use During Covid-19 Infection
  7. Diabetes and Cardiovascular Disease during Covid-19
  8. ACEs and ARBs
  9. Stress among Healthcare Professionals

Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

Presented by:

Robert Eckel, MD
ADA President, Medicine & Science
University of Colorado

Mary de Groot, PhD
ADA President, Health Care & Education
Indiana University

Irl Hirsch, MD
University of Washington

Anne Peters, MD
University of Southern California    

Louis Philipson, MD, PhD
ADA Past President, Medicine & Science
University of Chicago

Neil Skolnik, MD
Abington Jefferson Health




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Diabetes Core Update: COVID-19 – Inpatient Management # 2 April 2019

This special issue focuses on Answering Questions about Inpatient Care During Covid 19, a follow-up discussion to the Townhall meeting discussing inpatient care. 

Recorded April 15, 2020.

This podcast will cover:

  1. Subcutaneous Insulin Infusions
  2. CGM use in the inpatient setting
  3. Insulin Infusion pumps in the inpatient setting
  4. Inpatient Glycemic Control - what are the recommendations?
  5. Oral Medications
  6. Hydroxychloroquine adverse effects in persons with diabetes

Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

Presented by:

Robert Eckel, MD
ADA President, Medicine & Science

Irl Hirsch, MD
University of Washington

Mary Korytkowski, MD
University of Pittsburgh




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Diabetes Core Update: COVID-19 – Inpatient Townhall April 2019

This special issue focuses on Answering Questions about Inpatient Care During Covid 19, a follow-up discussion to the Townhall meeting discussing inpatient care. 

Recorded April 7, 2020.

This is a part of the American Diabetes Associations ongoing project providing resources for practicing clinicians on the care of Diabetes during the Covid-19 pandemic.  Todays discussion is an audio version of a webinar recorded on April 17th, 2020 where the panel answered questions submitted during and after the last webinar/townhall a week prior on inpatient management of patients with diabetes with Covid-19.

Presented by:

Shivani Agarwal, MD, MPH
Albert Einstein College of Medicine

Jennifer Clements, PharmD, FCCP, BCPS, CDE, BCACP
American Pharmacists Association

Robert Eckel, MD
ADA President, Medicine & Science

Irl Hirsch, MD
University of Washington

Melanie Mabrey, DNP 
Co-Chair - American Association of Nurse Practitioners - Endocrine Specialty Practice Group

Jane Jeffrie-Seley, DNP, BC-ADM, CDCES
Association of Diabetes Care and Education Specialists 




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Diabetes Core Update: COVID-19 – Telehealth and COVID-19 , April 2019

This special issue focuses on Telehealth and COVID-19.

Recorded March 31, 2020.

Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

Presented by:

Neil Skolnik, MD
Sidney Kimmel Medical College, Thomas Jefferson University

Eric Johnson, MD
University of North Dakota School of Medicine and Health Sciences




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Diabetes Core Update: COVID-19 – Caring for Ourselves while Caring for Others, April 2019

This special issue focuses on caring for ourselves while caring for others. 

Recorded April 1, 2020.

This is a part of the American Diabetes Associations ongoing project providing resources for practicing clinicians on the care of Diabetes during the Covid-19 pandemic.  Todays discussion is an audio version of a webinar recorded on April 1, 2020.

Presented by:

Neil Skolnik, M.D.

Abington Jefferson Health

 

Aaron Sutton

Behavioral Health Consultant

Abington Jefferson Health

 




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Diabetes Core Update: COVID-19 - Empowering Patients with Diabetes During Covid-19 April 2019

This special issue focuses on Empowering Patients with Diabetes During Covid-19

Recorded April 9, 2020.

This podcast will cover:

  1. Defining terms and talking with patients about the epidemiology of COVID-19
  2. How should providers talk with patients about the risk of COVID-19 – The impact of testing
  3. COVID-19 infection and its impact on self-care
  4. Barriers to Problem Solving
  5. Diabetes Self Care Helping to Create a Sense of Normalcy
  6. Self-Care – “Its OK not to be OK” – Acknowledging our feelings
  7. Coping with Stress

Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

Presented by:

Mary de Groot, PhD
President, Health Care & Education, ADA

Jane Jeffrie-Seley, DNP, MPH
New York Presbyterian/Weill Cornell Medicine

Jean M. Lawrence, ScD, MPH, MSSA, FACE
Southern California Permanente Medical Group
Kaiser Permanente Research




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Diabetes Core Update: COVID-19 – Cardiovascular Concerns, April 2019

This special issue focuses on Cardiovascular Concerns with Diabetes an COVID-19. 

Recorded April 19, 2020.

This is a part of the American Diabetes Associations ongoing project providing resources for practicing clinicians on the care of Diabetes during the Covid-19 pandemic.  Todays discussion is an audio version of a webinar recorded on April 19, 2020.

Presented by:

Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health

John J. Russell, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Director, Family Medicine Residency Program, Chair-Department of Family Medicine, Abington Jefferson Health




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Diabetes Core Update: COVID-19 – Older Adults with Diabetes and Covid-19 April 2019

This special issue focuses on Older Adults with Diabetes and Covid-19.

Recorded April 20, 2020.

This podcast will cover:

  1. Risk of COVID-19 in Older Adults
  2. What are the recommendations for glucose control during the pandemic
  3. Telemedicine
  4. Challenges to home care
  5. Long-term care settings

Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

Presented by:

Irl Hirsch, MD
University of Washington
 
Elbert Huang, MD, MPH, FACP
University of Chicago
 
Stacie Levine, MD
University of Chicago

 




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Diabetes Core Update: COVID-19 – Impact on Youth and their Families, May 2019

This special issue focuses on the impact COVID-19 is having on youth with diabetes and their families. 

Recorded April 30, 2020.

This is a part of the American Diabetes Associations ongoing project providing resources for practicing clinicians on the care of Diabetes during the Covid-19 pandemic.  Today’s discussion is an audio version of a webinar recorded on April 30, 2020.

Presented by:

Barry Conrad, MPH, RD, CDE
Stanford Children's Health

Tamara S. Hannon, MD, MS
Indiana University

Marisa Hilliard, PhD
Baylor College of Medicine and Texas Children's Hospital

Cynthia Munoz, PhD, MPH
President-Elect, Helath Care & Education, American Diabetes Association

Jennifer Raymond, MD, MCR
Children's Hospital Los Angelas

 




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Diabetes Core Update – May 2019

Diabetes Core Update is a monthly podcast that presents and discusses the latest clinically relevant articles from the American Diabetes Association’s four science and medical journals – Diabetes, Diabetes Care, Clinical Diabetes, and Diabetes Spectrum. Each episode is approximately 20 minutes long and presents 5-6 recently published articles from ADA journals.

Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

This issue will review:

  1. Incidence and Risk Factors for Chronic Kidney Disease in the Community
  2. Efficacy and Safety of Liraglutide 3.0 mg in Individuals With Overweight or Obesity and Type 2 Diabetes Treated With Basal Insulin
  3. Initial Glycemic Control and Care Among Adults Diagnosed With Type 2 Diabetes at a Younger Age
  4. Treatment and prevention of severe hypoglycaemia: Current and new formulations of glucagon – Diabetes Obesity and Metabolism
  5. Long-term Effects of Metformin on Patients With Type 2 Diabetic Kidney Disease
  6. Breakfast skipping is associated with persistently increased arterial stiffness in patients with type 2 diabetes – BMJ Open Diabetes Research and Care

For more information about each of ADA’s science and medical journals, please visit www.diabetesjournals.org.

Presented by:

Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health

John J. Russell, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Director, Family Medicine Residency Program, Chair-Department of Family Medicine, Abington Jefferson Health




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Serotonin Regulates Adult {beta}-Cell Mass by Stimulating Perinatal {beta}-Cell Proliferation

A sufficient β-cell mass is crucial for preventing diabetes, and perinatal β-cell proliferation is important in determining the adult β-cell mass. However, it is not yet known how perinatal β-cell proliferation is regulated. Here, we report that serotonin regulates β-cell proliferation through serotonin receptor 2B (HTR2B) in an autocrine/paracrine manner during the perinatal period. In β-cell–specific Tph1 knockout (Tph1 βKO) mice, perinatal β-cell proliferation was reduced along with the loss of serotonin production in β-cells. Adult Tph1 βKO mice exhibited glucose intolerance with decreased β-cell mass. Disruption of Htr2b in β-cells also resulted in decreased perinatal β-cell proliferation and glucose intolerance in adulthood. Growth hormone (GH) was found to induce serotonin production in β-cells through activation of STAT5 during the perinatal period. Thus, our results indicate that GH-GH receptor-STAT5-serotonin-HTR2B signaling plays a critical role in determining the β-cell mass by regulating perinatal β-cell proliferation, and defects in this pathway affect metabolic phenotypes in adults.




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Tacrolimus-Induced BMP/SMAD Signaling Associates With Metabolic Stress-Activated FOXO1 to Trigger {beta}-Cell Failure

Active maintenance of β-cell identity through fine-tuned regulation of key transcription factors ensures β-cell function. Tacrolimus, a widely used immunosuppressant, accelerates onset of diabetes after organ transplantation, but underlying molecular mechanisms are unclear. Here we show that tacrolimus induces loss of human β-cell maturity and β-cell failure through activation of the BMP/SMAD signaling pathway when administered under mild metabolic stress conditions. Tacrolimus-induced phosphorylated SMAD1/5 acts in synergy with metabolic stress–activated FOXO1 through formation of a complex. This interaction is associated with reduced expression of the key β-cell transcription factor MAFA and abolished insulin secretion, both in vitro in primary human islets and in vivo in human islets transplanted into high-fat diet–fed mice. Pharmacological inhibition of BMP signaling protects human β-cells from tacrolimus-induced β-cell dysfunction in vitro. Furthermore, we confirm that BMP/SMAD signaling is activated in protocol pancreas allograft biopsies from recipients on tacrolimus. To conclude, we propose a novel mechanism underlying the diabetogenicity of tacrolimus in primary human β-cells. This insight could lead to new treatment strategies for new-onset diabetes and may have implications for other forms of diabetes.




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HB-EGF Signaling Is Required for Glucose-Induced Pancreatic {beta}-Cell Proliferation in Rats

The molecular mechanisms of β-cell compensation to metabolic stress are poorly understood. We previously observed that nutrient-induced β-cell proliferation in rats is dependent on epidermal growth factor receptor (EGFR) signaling. The aim of this study was to determine the role of the EGFR ligand heparin-binding EGF-like growth factor (HB-EGF) in the β-cell proliferative response to glucose, a β-cell mitogen and key regulator of β-cell mass in response to increased insulin demand. We show that exposure of isolated rat and human islets to HB-EGF stimulates β-cell proliferation. In rat islets, inhibition of EGFR or HB-EGF blocks the proliferative response not only to HB-EGF but also to glucose. Furthermore, knockdown of HB-EGF in rat islets blocks β-cell proliferation in response to glucose ex vivo and in vivo in transplanted glucose-infused rats. Mechanistically, we demonstrate that HB-EGF mRNA levels are increased in β-cells in response to glucose in a carbohydrate-response element–binding protein (ChREBP)–dependent manner. In addition, chromatin immunoprecipitation studies identified ChREBP binding sites in proximity to the HB-EGF gene. Finally, inhibition of Src family kinases, known to be involved in HB-EGF processing, abrogated glucose-induced β-cell proliferation. Our findings identify a novel glucose/HB-EGF/EGFR axis implicated in β-cell compensation to increased metabolic demand.




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PRMT1 Is Required for the Maintenance of Mature {beta}-Cell Identity

Loss of functional β-cell mass is an essential feature of type 2 diabetes, and maintaining mature β-cell identity is important for preserving a functional β-cell mass. However, it is unclear how β-cells achieve and maintain their mature identity. Here we demonstrate a novel function of protein arginine methyltransferase 1 (PRMT1) in maintaining mature β-cell identity. Prmt1 knockout in fetal and adult β-cells induced diabetes, which was aggravated by high-fat diet–induced metabolic stress. Deletion of Prmt1 in adult β-cells resulted in the immediate loss of histone H4 arginine 3 asymmetric dimethylation (H4R3me2a) and the subsequent loss of β-cell identity. The expression levels of genes involved in mature β-cell function and identity were robustly downregulated as soon as Prmt1 deletion was induced in adult β-cells. Chromatin immunoprecipitation sequencing and assay for transposase-accessible chromatin sequencing analyses revealed that PRMT1-dependent H4R3me2a increases chromatin accessibility at the binding sites for CCCTC-binding factor (CTCF) and β-cell transcription factors. In addition, PRMT1-dependent open chromatin regions may show an association with the risk of diabetes in humans. Together, our results indicate that PRMT1 plays an essential role in maintaining β-cell identity by regulating chromatin accessibility.




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Lamin C Counteracts Glucose Intolerance in Aging, Obesity, and Diabetes Through {beta}-Cell Adaptation

Aging-dependent changes in tissue function are associated with the development of metabolic diseases. However, the molecular connections linking aging, obesity, and diabetes remain unclear. Lamin A, lamin C, and progerin, products of the Lmna gene, have antagonistic functions on energy metabolism and life span. Lamin C, albeit promoting obesity, increases life span, suggesting that this isoform is crucial for maintaining healthy conditions under metabolic stresses. Because β-cell loss during obesity or aging leads to diabetes, we investigated the contribution of lamin C to β-cell function in physiopathological conditions. We demonstrate that aged lamin C only–expressing mice (LmnaLCS/LCS) become obese but remain glucose tolerant due to adaptive mechanisms including increased β-cell mass and insulin secretion. Triggering diabetes in young mice revealed that LmnaLCS/LCS animals normalize their fasting glycemia by both increasing insulin secretion and regenerating β-cells. Genome-wide analyses combined to functional analyses revealed an increase of mitochondrial biogenesis and global translational rate in LmnaLCS/LCS islets, two major processes involved in insulin secretion. Altogether, our results demonstrate for the first time that the sole expression of lamin C protects from glucose intolerance through a β-cell–adaptive transcriptional program during metabolic stresses, highlighting Lmna gene processing as a new therapeutic target for diabetes treatment.




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Insulin-Deficient Diabetic Condition Upregulates the Insulin-Secreting Capacity of Human Induced Pluripotent Stem Cell-Derived Pancreatic Endocrine Progenitor Cells After Implantation in Mice

The host environment is a crucial factor for considering the transplant of stem cell–derived immature pancreatic cells in patients with type 1 diabetes. Here, we investigated the effect of insulin (INS)-deficient diabetes on the fate of immature pancreatic endocrine cell grafts and the underlying mechanisms. Human induced pluripotent stem cell–derived pancreatic endocrine progenitor cells (EPCs), which contained a high proportion of chromogranin A+ NK6 homeobox 1+ cells and very few INS+ cells, were used. When the EPCs were implanted under the kidney capsule in immunodeficient mice, INS-deficient diabetes accelerated increase in plasma human C-peptide, a marker of graft-derived INS secretion. The acceleration was suppressed by INS infusion but not affected by partial attenuation of hyperglycemia by dapagliflozin, an INS-independent glucose-lowering agent. Immunohistochemical analyses indicated that the grafts from diabetic mice contained more endocrine cells including proliferative INS-producing cells compared with that from nondiabetic mice, despite no difference in whole graft mass between the two groups. These data suggest that INS-deficient diabetes upregulates the INS-secreting capacity of EPC grafts by increasing the number of endocrine cells including INS-producing cells without changing the graft mass. These findings provide useful insights into postoperative diabetic care for cell therapy using stem cell–derived pancreatic cells.




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Pancreas Pathology of Latent Autoimmune Diabetes in Adults (LADA) in Patients and in a LADA Rat Model Compared With Type 1 Diabetes

Approximately 10% of patients with type 2 diabetes suffer from latent autoimmune diabetes in adults (LADA). This study provides a systematic assessment of the pathology of the endocrine pancreas of patients with LADA and for comparison in a first rat model mimicking the characteristics of patients with LADA. Islets in human and rat pancreases were analyzed by immunohistochemistry for immune cell infiltrate composition, by in situ RT-PCR and quantitative real-time PCR of laser microdissected islets for gene expression of proinflammatory cytokines, the proliferation marker proliferating cell nuclear antigen (PCNA), the anti-inflammatory cytokine interleukin (IL) 10, and the apoptosis markers caspase 3 and TUNEL as well as insulin. Human and rat LADA pancreases showed differences in areas of the pancreas with respect to immune cell infiltration and a changed ratio between the number of macrophages and CD8 T cells toward macrophages in the islet infiltrate. Gene expression analyses revealed a changed ratio due to an increase of IL-1β and a decrease of tumor necrosis factor-α. IL-10, PCNA, and insulin expression were increased in the LADA situation, whereas caspase 3 gene expression was reduced. The analyses into the underlying pathology in human as well as rat LADA pancreases provided identical results, allowing the conclusion that LADA is a milder form of autoimmune diabetes in patients of an advanced age.




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Patient spotlight - How can we get better at providing patient centred care?

Participants in our discussion on person centred care in January agreed that a change in culture and better use of technology could benefit both patients and doctors. At the roundtable: Fiona Godlee (chair), editor in chief, The BMJ Tessa Richards, senior editor, patient partnership, The BMJ Rosamund Snow, patient editor, The BMJ Navjoyt Ladher,...




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"I thought I was the worst person with type I..." - Self management of diabetes

Nick Oliver, consultant diabetologist at Imperial Healthcare NHS Trust and Philippa Cooper, who has type I diabetes, join us to explain how structured education works for patients, and give tips on self management. Read the full review: http://www.bmj.com/content/352/bmj.i998




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Late effects of anticancer chemotherapy: It's hard to trust your body, after it's betrayed you

Lily was diagnosed at 14 years old with stage four Hodgkin's lymphoma and received six rounds of chemotherapy and two weeks of radiotherapy. She survived but now lives with the long term effects of that therapy - and joins us to discuss how it has impacted her quality of life. We're also joined by Saif Ahmad and Thankamma Ajithkumar, oncologists...




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The evidence manifesto - better trials, better use of trial data

We're creating a manifesto for better evidence. The centre for Evidence Based Medicine at the University of Oxford, and the BMJ, are asking what are the problem with medical evidence, and how can we fix them? In this second discussion we went to Nottingham​ University, to find out what the people who create the bread and butter of EBM -...




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Diabetes remission - "treating blood glucose, when the disease process is to do with body fat"

In the UK - type 2 diabetes now affects between 5-10% of the population - and accounts for around 10% of our total NHS budget. For the individuals affected, treatments are effective at helping control glucose levels - however, the sequela associated with the disease - vascular problems, and a life expectancy that’s 6 years shorter - are still an...




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What forced migration can tell us about diabetes

Worldwide, the rate of type II diabetes is estimated to be around 1 in 11 people - about 9%. For the Pima people of Arizona, 38% of the adult population have the condition - but across the border in Mexico, the rate drops down to 7%. The difference between the groups is their life experience - one side displaced, the other on their traditional...




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Diabetes Insipidus - the danger of misunderstanding diabetes

Diabetes is synonymous with sugar, but diabetes insipidus, "water diabetes", can't be forgotten. Between 2009 and 2016, 4 people died in hospital in England, when lifesaving treatment for the condition was not given. In this podcast, we hear some practical tips for non-specialists to aid diagnosis, and how patients should be managed during...




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Glucose-Induced Reactive Oxygen Species Cause Apoptosis of Podocytes and Podocyte Depletion at the Onset of Diabetic Nephropathy

Katalin Susztak
Jan 1, 2006; 55:225-233
Complications




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C-Reactive Protein Is an Independent Predictor of Risk for the Development of Diabetes in the West of Scotland Coronary Prevention Study

Dilys J. Freeman
May 1, 2002; 51:1596-1600
Complications




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The Effect of Thiazolidinediones on Plasma Adiponectin Levels in Normal, Obese, and Type 2 Diabetic Subjects

Joseph G. Yu
Oct 1, 2002; 51:2968-2974
Obesity Studies




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Diabetes and Cardiovascular Disease: The "Common Soil" Hypothesis

Michael P Stern
Apr 1, 1995; 44:369-374
Perspectives in Diabetes




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Morbidity and Mortality in Diabetics In the Framingham Population: Sixteen Year Follow-up Study

Mariano J Garcia
Feb 1, 1974; 23:105-111
Original Contribution




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Endothelial Progenitor Cell Dysfunction: A Novel Concept in the Pathogenesis of Vascular Complications of Type 1 Diabetes

Cindy J.M. Loomans
Jan 1, 2004; 53:195-199
Complications




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Thiazolidinediones in the Treatment of Insulin Resistance and Type II Diabetes

Alan R Saltiel
Dec 1, 1996; 45:1661-1669
Perspectives in Diabetes




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Relation Between Antioxidant Enzyme Gene Expression and Antioxidative Defense Status of Insulin-Producing Cells

Markus Tiedge
Nov 1, 1997; 46:1733-1742
Original Article




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Are the {beta}-Cell Signaling Molecules Malonyl-CoA and Cystolic Long-Chain Acyl-CoA Implicated in Multiple Tissue Defects of Obesity and NIDDM?

Marc Prentki
Mar 1, 1996; 45:273-283
Original Article




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Cell-Permeable Peptide Inhibitors of JNK: Novel Blockers of {beta}-Cell Death

Christophe Bonny
Jan 1, 2001; 50:77-82
Islet Studies




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Inflammatory Cytokines and the Risk to Develop Type 2 Diabetes: Results of the Prospective Population-Based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study

Joachim Spranger
Mar 1, 2003; 52:812-817
Pathophysiology




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Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents

G Perseghin
Aug 1, 1999; 48:1600-1606
Articles




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NCEP-Defined Metabolic Syndrome, Diabetes, and Prevalence of Coronary Heart Disease Among NHANES III Participants Age 50 Years and Older

Charles M. Alexander
May 1, 2003; 52:1210-1214
Complications




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Mechanisms of Pancreatic {beta}-Cell Death in Type 1 and Type 2 Diabetes: Many Differences, Few Similarities

Miriam Cnop
Dec 1, 2005; 54:S97-S107
Section III: Inflammation and beta-Cell Death




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Tumor Necrosis Factor {alpha}: A Key Component of the Obesity-Diabetes Link

Gökhan S Hotamisligil
Nov 1, 1994; 43:1271-1278
Perspectives in Diabetes




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Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships

D Dabelea
Dec 1, 2000; 49:2208-2211
Articles




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Insulin Action, Diabetogenes, and the Cause of Type II Diabetes

C. Ronald Kahn
Aug 1, 1994; 43:1066-1085
Banting Lecture




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From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus

Ralph A. DeFronzo
Apr 1, 2009; 58:773-795
Banting Lecture




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Protein kinase C activation and the development of diabetic complications

D Koya
Jun 1, 1998; 47:859-866
Articles