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Metabolism Lectures Diabetes
Metabolism Lectures Diabetes Dalay Olson Ph.D. Integrative Biology and Physiology Email: [email protected] Office: 3-120 Jackson Hall Learning Objectives 1. Compare and contrast type 1 and type 2 diabetes. Identify the major similarities and differences (insulin level, insulin signaling events, treatment options, glucose tolerance test responses etc.) 2. How is diabetes diagnosed in the clinic? What tests are available and commonly used? What information does a glucose tolerance give you? What information does a hemoglobin A1C tell you? What are the limitations of these tests? 3. Explain how chronic elevation of blood glucose levels can result in AGE formation and AGE receptor (RAGE) activation. Explain the downstream effects of RAGE activation. 4. Identify the role of PKC (Protein Kinase C) in arteriolar vasoconstriction in type 2 diabetics. 5. List the common symptoms you might see in the clinic for a patient suffering from type 2 diabetes. 6. Explain why the plasma becomes acidic in a patient with uncontrolled diabetes. 7. Explain the mechanism of action (what is the point of the drug?) of insulin sensitizers, insulin mimetics, insulin secretagogues and SGLT2 inhibitors. Natural Progression of Type-2-Diabetes Pre-diabetes Lean Obese Henry, Am J Med 1998; 105 (1A):20S-6S Think about what is happening with Type 1 diabetics…how does their response differ from that of a normal person? Glucose Insulin is not present, Insulin binds to receptor therefore the signal transduction pathway is not initiated and glucose Glucose transporters remain in enters cell Exocytosis intracellular vesicles. Signal transduction cascade Plasma glucose remains high! GLUT4 Think about what is happening with Type-2-diabetics…how does their response differ from that of a Type-1- diabetic? Glucose Insulin is present but is not Insulin binds to receptor functional, therefore the signal transduction pathway is not initiated and glucose Glucose transporters remain in Exocytosis enters cell intracellular vesicles. -
Abstracts from the 9Th Biennial Scientific Meeting of The
International Journal of Pediatric Endocrinology 2017, 2017(Suppl 1):15 DOI 10.1186/s13633-017-0054-x MEETING ABSTRACTS Open Access Abstracts from the 9th Biennial Scientific Meeting of the Asia Pacific Paediatric Endocrine Society (APPES) and the 50th Annual Meeting of the Japanese Society for Pediatric Endocrinology (JSPE) Tokyo, Japan. 17-20 November 2016 Published: 28 Dec 2017 PS1 Heritable forms of primary bone fragility in children typically lead to Fat fate and disease - from science to global policy a clinical diagnosis of either osteogenesis imperfecta (OI) or juvenile Peter Gluckman osteoporosis (JO). OI is usually caused by dominant mutations affect- Office of Chief Science Advsor to the Prime Minister ing one of the two genes that code for two collagen type I, but a re- International Journal of Pediatric Endocrinology 2017, 2017(Suppl 1):PS1 cessive form of OI is present in 5-10% of individuals with a clinical diagnosis of OI. Most of the involved genes code for proteins that Attempts to deal with the obesity epidemic based solely on adult be- play a role in the processing of collagen type I protein (BMP1, havioural change have been rather disappointing. Indeed the evidence CREB3L1, CRTAP, LEPRE1, P4HB, PPIB, FKBP10, PLOD2, SERPINF1, that biological, developmental and contextual factors are operating SERPINH1, SEC24D, SPARC, from the earliest stages in development and indeed across generations TMEM38B), or interfere with osteoblast function (SP7, WNT1). Specific is compelling. The marked individual differences in the sensitivity to the phenotypes are caused by mutations in SERPINF1 (recessive OI type obesogenic environment need to be understood at both the individual VI), P4HB (Cole-Carpenter syndrome) and SEC24D (‘Cole-Carpenter and population level. -
January 2021 Update
PUBLISHED JULY 08, 2021 OCTOBER/DECEMBER 2020; JANUARY 2021 UPDATE CHANGES TO THE HIGHMARK DRUG FORMULARIES Following is the update to the Highmark Drug Formularies and pharmaceutical management procedures for January 2021. The formularies and pharmaceutical management procedures are updated on a bimonthly basis, and the following changes reflect the decisions made in October, December, and January by our Pharmacy and Therapeutics Committee. These updates are effective on the dates noted throughout this document. Please reference the guide below to navigate this communication: Section I. Highmark Commercial and Healthcare Reform Formularies A. Changes to the Highmark Comprehensive Formulary and the Highmark Comprehensive Healthcare Reform Formulary B. Changes to the Highmark Healthcare Reform Essential Formulary C. Changes to the Highmark Core Formulary D. Changes to the Highmark National Select Formulary E. Updates to the Pharmacy Utilization Management Programs 1. Prior Authorization Program 2. Managed Prescription Drug Coverage (MRxC) Program 3. Formulary Program 4. Quantity Level Limit (QLL) Programs As an added convenience, you can also search our drug formularies and view utilization management policies on the Provider Resource Center (accessible via NaviNet® or our website). Click the Pharmacy Program/Formularies link from the menu on the left. Highmark Blue Cross Blue Shield Delaware is an independent licensee of the Blue Cross and Blue Shield Association. NaviNet is a registered trademark of NaviNet, Inc., which is an independent company that provides secure, web-based portal between providers and health insurance companies. IMPORTANT DRUG SAFETY UPDATES 03/31/2021 – Studies show increased risk of heart rhythm problems with seizure and mental health medicine lamotrigine (Lamictal) in patients with heart disease. -
Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products. -
Eflapegrastim-Xnst Submitted by Spectrum Pharmaceuticals
Anton F. Ehrhardt, PhD, VP Medical Affairs Spectrum Pharmaceuticals, Inc One Main St, 11th floor Cambridge, MA 02142 Phone: (617) 477-8091 Email: [email protected] Date of request: 31 August 2020 NCCN Guidelines Panel: Hematopoietic Growth Factors On behalf of Spectrum Pharmaceuticals, Inc., I respectfully request the NCCN Hematopoietic Growth Factors Panel review the enclosed data for inclusion of eflapegrastim-xnst (Rolontis®), a non-biosimilar long-acting G- CSF of noVel structure, as a recommendation for prophylaxis of febrile neutropenia and maintenance of scheduled dose deliVery (MGF-B). Specific Changes: 1. Addition of eflapegrastim-xnst as a recommendation for prophylaxis of febrile neutropenia and maintenance of scheduled dose deliVery (MGF-B) a. Dosing recommendation below listing of eflapegrastim-xnst: One dose of 13.2 mg (MGF-B) 2. Addition of eflapegrastim-xnst to the listing of Filgrastim, Pegfilgrastim and Tbo-filgrastim in table MGF- D (Toxicity Risks for Myeloid Growth Factors) FDA Clearance: Rolontis is undergoing FDA reView based on an original BLA#761148 for a proposed indication of: to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with clinically significant incidence of febrile neutropenia. PDUFA for this reView is October 24th, 2020. Rationale: In support of the proposed change, data were generated in pre-clinical in-Vitro and animal model studies that indicated structure-related enhancement of potency, and increased concentrations in bone marrow compared to pegfilgrastim (Barrett 2020(reference 1)). Eflapegrastim is composed of a recombinant human G- CSF joined to an IgG4 Fc moiety Via a short polyethylene glycol linker. -
62. Deutscher Kongress Für Endokrinologie
62. Deutscher Kongress für Endokrinologie dge2019.de TAGUNGS- FÜHRER 20.–22. März 2019 © Conny Blaack M.A., kunst & mediendesign, 37130 Gleichen/Bremke GÖTTINGEN Kongresspräsidentin: HAUPTTHEMEN Prof. Dr. Heide Siggelkow Knochen als hormonelles Organ Wissenschaftliche Kongresssekretärin: Vitamin D, das endokrine und Dr. Katja Gollisch metabolische System Kongressorganisation: Individualisierte Osteoporosetherapie EndoScience Endokrinologie Service GmbH Update Andrologie nach Berthold Endokrine Onkologie Mittwoch, 20.03.2019 Programmübersicht Raum Lichtenberg Raum Gauss Raum Heisenberg Raum Gebrüder Grimm Raum Göttinger Sieben 09:00 – 10:30 Vorstandssitzung 09:00 – 12:00 S. 18 Sektionstreffen YARE / MuSkITYRS 10:30 – 11:30 Pressekonferenz S. 18 S. 18 11:30 – 12:30 Eröffung der Industrieausstellung S. 19 12:30 – 13:00 Kongresseröffnung S. 19 13:00 – 13:45 Aktuelles zur Mikrobiom-Hor- mon-Achse: Prof. Dr. Bar- bara Obermayer- Pietsch, Graz, Österreich S. 19 13:45 – 14:15 Lunch 13:45 – 14:45 Akromegalieregister 14:00 – 15:00 Neugründung 14:15 – 15:15 14:00 – 16:00 S. 19 der AG Labor Satelliten Symposium 1: 14:15 – 15:45 S1: Vom Tiermodell zum UCB Pharma GmbH S. 20 Satelliten Symposium 2: Menschen – Aktuelles S. 22 Merck Serono GmbH zur Reproduktions- endokrinologie S. 22 15:45 – 16:15 Kaffeepause S. 20 16:00 – 17:30 16:15 – 17:15 16:00 – 17:30 S2: Hypophysen- Sektionstreffen MTE 1 16:15 – 17:45 15:00 – 19:15 erkrankungen Reproduktions- MTE 2 S3 Hauptthema: Endokrinologie in der Schwangerschaft biologie und -medizin Cortisol und Knochen: für die Praxis S. 24 Freunde oder Feinde? update 2019 S. 23 S. 23/24 (kostenpflichtig) separate Anmeldung S. -
Insulin Tolerance Test (ITT)
Insulin Tolerance Test (ITT) Indications: • This test is less frequently performed now but it is regarded as being the gold standard for the assessment of ACTH / Cortisol and Growth Hormone (GH) reserve in patients with pituitary/hypothalamic disease. • It is also sometimes used in the diagnosis of Cushing’s Syndrome. • The test may be combined with the GnRH or TRH tests although this is also rarely indicated. Contraindications: Ischaemic Heart Disease, Epilepsy or unexplained blackouts, severe long-standing; Hypoadrenalism and Glycogen Storage Disease. Precautions: ECG must be normal. Serum cortisol (09:00) must be > 100mmol/l. T4 must be normal - if abnormal or in doubt perform a Glucagon Test. Prior to test: • Give Lab. require prior warning (one weeks notice preferred) • Obtain accurate weight of patient. • Check patient has had recent ECG. • Give or send patient information letter at time of booking. • Arrange test for around 08:30am. • Ensure that the registrar on call is given prior warning of test date and time. Registrar should complete the prescription chart with the calculated Insulin dose. Registrar should remain in unit throughout test. • Insulin dose = 0.15u/kg body weight. Actrapid Insulin used. • Trolley prepared with : Dextrose 50% - 50ml syringe ; Hydrocortisone 100mg & syringes. • One Touch Glucose Meter. Minute minder required to time sample collection Procedure: • One nurse dedicated to test. • Patient fasting. • Patient supine throughout test. • Observation sheet to be completed (see example attached) Observations to include BP, pulse, sweating, cognitive function.. • IV cannula sited (green preferred) • Blood samples are collected at time 0 , IV bolus dose of insulin given and cannula flushed with 5mls 0.9% Normal Saline. -
Insulin Tolerance Test
ENDOCRINE TESTING UNIT Patient Information Sheet – Insulin Tolerance Test Your doctor has referred you to the Endocrine Testing Unit (ETU) for an Insulin Tolerance Test. What is an insulin tolerance test (ITT)? The insulin tolerance test or insulin stress test is designed to see how your pituitary gland (a small gland that lies just under the brain) functions under stress. Your pituitary gland normally produces several hormones, two of these are: ACTH (adreno-cortico-trophic hormone) which stimulates the adrenal glands (above the kidneys) to make the hormone cortisol. Cortisol is a steroid hormone that is vital for health. Its functions include: o Helping to regulate blood pressure o Helping to regulate the immune system o Helping to balance the effect of insulin and blood sugar levels o Helping the body respond to stress GH (growth hormone) effects childhood growth and adult body composition as well as the functioning of several body systems. The insulin tolerance test will assess how much ACTH, cortisol and growth hormone is produced when your body is under stress. This ‘stress’ will be induced by injecting a small amount of insulin to cause a lowering of your blood glucose (hypoglycaemia), under very controlled conditions. Your Endocrinologist will use the results of this test to determine if these hormones are being produced in sufficient quantities naturally or if they need to be replaced by medication. You should not have this test if you have epilepsy, ischaemic heart disease such as angina or previous heart attack or stroke. How do I prepare for this test? You must have nothing to eat or drink (except water) from midnight the night before the test If you are taking steroid medication, such as prednisone or cortisone, you should omit your dose 24 hours prior to the test. -
WO 2018/102397 Al 07 June 2018 (07.06.2018) W !P O PCT
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/102397 Al 07 June 2018 (07.06.2018) W !P O PCT (51) International Patent Classification: John; 64 Gray Street, Arlington, Massachusetts 02476 A61K 9/133 (2006.01) A61K 9/10 (2006.01) (US). MUTAMBA, James Tendai; 70 Longfellow Road, A61K 9/127 {2006.01) Newton, Massachusetts 02462 (US). SHYAM, Rishab R.; 995 Massachusetts Avenue, Arlington, Massachusetts (21) International Application Number: 02476 (US). PCT/US2017/063681 (74) Agent: RED), Andrea L.C. et al; One International (22) International Filing Date: Place, 40th Floor, 100 Oliver Street, Boston, Massachusetts 29 November 201 7 (29. 11.201 7) 021 10-2605 (US). (25) Filing Language: English (81) Designated States (unless otherwise indicated, for every (26) Publication Langi English kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (30) Priority Data: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, 62/427,53 1 29 November 2016 (29. 11.2016) US DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, 62/559,921 18 September 2017 (18.09.2017) US HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, 62/559,967 18 September 2017 (18.09.2017) US KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (71) Applicant: PURETECH HEALTH LLC [US/US]; 501 MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, Boylston Street, Suite 6102, Boston, Massachusetts 021 16 OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (US). -
Pipeline Report November 2020
Pipeline Report November 2020 Pipeline Report November 2020 © 2020 Envolve. All rights reserved. Page 1 This quarterly at-a-glance publication is developed by our Clinical Pharmacy Drug Information team to increase your understanding of the drug pipeline, Table of Contents ensuring you’re equipped with insights to prepare for shifts in pharmacy benefit management. In this issue, you’ll learn more about key themes and notable drugs: Recent Specialty Drug Approvals1 1 > On COVID-19, the FDA granted full approval to Veklury (remdesivir) for the treatment of COVID-19. Veklury is approved for use in hospitalized adults and pediatric patients (≥ 12 years of age and weighing ≥ 40 Recent Non-Specialty Drug Approvals 6 kg), and represents the very first therapy to garner full FDA approval for COVID-19. Other therapies will follow, gaining market access through EUA (LLY’s Bamlanivimab and Olumiant, and <likely> Regeneron’s Upcoming Specialty Products 7 REGN-COV2). With the US crossing the 11 million total coronavirus infection mark, demand for these agents will be high while supply of the antibody treatment will be especially tight. The vaccine race accelerates as there are now two m-RNA based candidates both showing greater than 94% Upcoming Non-Specialty Products 15 efficacy in study populations. Both vaccines require 2 doses. Neither has FDA approval, and EUA reviews are pending. Supplies will be limited for months to come. Pfizer has stated it could produce 50 million doses by the end of 2020, and Moderna has promised up to 20 million doses in the same time frame. During 2021 Pfizer Biosimilars 18 forecasts 1.3 billion doses while Moderna states between 500 million and 1 billion. -
Health Plan Insights
Health Plan Insights September 2020 Updates from August 2020 Confidential – Do not copy or distribute. 800-361-4542 | elixirsolutions.com 1 Recent FDA Approvals New Medications TRADE NAME DOSAGE FORM APPROVAL MANUFACTURER INDICATION(S) (generic name) STRENGTH DATE Blenrep GlaxoSmithKline Injection, For the treatment of adult patients with August 5, 2020 (belantamab 2.5 mg/kg relapsed or refractory multiple myeloma who mafodotin-blmf) have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. Lampit Bayer Healthcare Tablets, For use in pediatric patients (birth to less than August 6, 2020 (nifurtimox) 30 mg and 120 18 years of age and weighing at least 2.5 kg) mg for the treatment of Chagas disease (American Trypanosomiasis), caused by Trypanosoma cruzi. Olinvyk Trevena, Inc. Injection, For use in adults for the management of August 7, 2020 (oliceridine) 1 mg/mL acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. Evrysdi Genentech, Inc. Oral Solution, For the treatment of spinal muscular atrophy August 7, 2020 (risdiplam) 0.75 mg/mL (SMA) in patients 2 months of age and older. Viltepso NS Pharma, Inc. Injection, For the treatment of Duchenne muscular August 12, 2020 (viltolarsen) 50 mg/mL dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with VILTEPSO. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. -
Endocrine Emergencies M W Savage, P M Mah, a P Weetman, J Newell-Price
506 Postgrad Med J: first published as 10.1136/pgmj.2004.018853 on 8 September 2004. Downloaded from REVIEW Endocrine emergencies M W Savage, P M Mah, A P Weetman, J Newell-Price ............................................................................................................................... Postgrad Med J 2004;80:506–515. doi: 10.1136/pgmj.2003.013474 Diabetic and endocrine emergencies are traditionally Endocrinology: adrenal (acute adrenocortical insufficiency, phaeochromocytoma crisis); treated by the acute medical admitting team or accident hypercalcaemia; thyroid (myxoedema coma, and emergency department staff. Most will see diabetic thyroid storm); and pituitary (pituitary apo- emergencies on a regular basis, as they are common and plexy). both type 1 and type 2 disease are increasing in DIABETES prevalence. Diabetic emergencies are usually easily treated Diabetic ketoacidosis (DKA) and the patients discharged. However, it is vital not to This is a condition characterised by hyperglycae- become complacent as these disorders can lead to death. It mia, ketosis, and acidosis. Hyperglycaemia is a result of severe insulin deficiency, either absolute is particularly important to follow local guidance and to or relative, which impairs peripheral glucose involve the diabetes team both during and after each uptake and promotes fat breakdown; relative episode. Recently it has become clear that about 30% of glucagon excess promotes hepatic gluconeogen- esis. Ketosis is caused by a switch to fat patients admitted with acute coronary syndrome (including metabolism, leading to free fatty acid oxidation infarction) have either diabetes or ‘‘stress in the liver forming the ketone bodies acetoacetic hyperglycaemia’’; evidence suggests that these patients acid and 3-hydroxybutyric acid. The dissociation of the ketone bodies (weak acids) results in should be treated not only as a cardiac emergency but also acidosis.