1 / 13

Therapy of Type 2 Diabetes Mellitus: UPDATE

Therapy of Type 2 Diabetes Mellitus: UPDATE. Glycemic Goals in the Care of Patients with Type 2 Diabetes- 2013 ADA and AACE Guidelines: Room For Improvement (Be HAPPY/ Avoid Burnout, While Caring for Patients with DM). Stan Schwartz MD, FACP, FACE Affiliate, Main Line Health System

leslieperez
Download Presentation

Therapy of Type 2 Diabetes Mellitus: UPDATE

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Therapy of Type 2 Diabetes Mellitus: UPDATE Glycemic Goals in the Care of Patients with Type 2 Diabetes- 2013 ADA and AACE Guidelines: Room For Improvement (Be HAPPY/ Avoid Burnout, While Caring for Patients with DM) Stan Schwartz MD, FACP, FACE Affiliate, Main Line Health System Clinical Associate Professor of Medicine, Emeritus, U of Pa. Part 4

  2. Metformin Advantages Improves insulin resistance in liver High initial response rate Effective, 2% HbA1c (1% with extended-release metformin) No initial weight gain or modest weight loss (UKPDS) Advantageous lipid profile No hypoglycemia when used alone or with TZD, incretins Potential to delay or prevent DM and progression, but secondary failure is = SU Decreases MIs (39% UKPDS obese subgroup,retrospective analysis) Decreases AGEs, improved endothelial dysfunction Potential decrease in some cancer risk Cheap

  3. Metformin Disadvantages GI side effects on initiation Hold after radiologic studies using intravascular iodinated contrast media until Cr stable Risk of lactic acidosis: Don’t use if… Cr >1.4 female, >1.5 male Cr Clearance <70 (age >70), blood levels increase Cr Clearance <40, lactic acidosis cases seen Impaired hepatic function (CHF not a contr-indication any more) Rarely order metformin as admit to hospital

  4. Pioglitazone • ADVANTAGES- • Improves insulin resistance (fat/muscle), decreases insulin conc., improves endothelial dysfunction , dysfibrinolysis, BP, decreased microalbumin, improved beta-cell function, treats PCOS and steatohepatitis Lipids (GLIA study) • Advantage to pio - decrease TG, decreased # of buoyant LDL particles, decrease non-HDL chol. May use in renal insufficiency • No hypoglycemia used alone or with metformin , incretin mimetics • Potential to delay or prevent DM and progression; lower secondary failure rate than SU/met • Pio decreased prospective composite endpoint (MI,CVA, death) 16% in PROactive trial (Can’t assume class effect) , dec. risk second MI/ ACS, decreased risk second stroke 47%

  5. Pioglitazone in Dysmetabolic Syndrome, Prediabetes, Type 2 Diabetes Safety No liver toxicity Increased distal fractures in women Edema-renal sodium and total body water retention - can be prevented/minimized (patient selection, NAS diet) - treated with spironolactone, amilioride, triamterene Weight gain not an obligatory side effect- studies- portion control/ education freq. Bone loss in women = risk/benefit evaluation for each patient CHF not a cardiac issue except more susceptible with diastolic dysfunction –function of renal sodium and total body water retention -Can be prevented/reduced- low salt diet/ patient selection; ranolazine

  6. No !!! Increased Risk Bladdder Cancer at 8 years in K-P Prospective Study All Analyses Cross 1.0 line Independent of duration of use, total dose

  7. Natural History of Type 2 DiabetesInsulin Secretion Age 0-15 15-40+ 15-50+ 25-70+ Envir.+ Other Disease Genes Macrovascular Complications Obesity (visceral) Poor Diet Inactivity IR phenotypeAtherosclerosisobesityhypertensionHDL,TG, HYPERINSULINEMIA Endothelial dysfunctionPCO,ED Disability Insulin Resistance MICVAAmp pp>7.8 DEATH IGT – OMINOUS OCTET Type II DM 8 mechanisms of hyperglycemia  Beta Cell Secretion EyeNerveKidney BlindnessAmputationCRF Disability Risk of Dev. Complications ETOHBPSmoking Microvascular Complications

  8. Incretins • Gut-derived hormones, secreted in response to nutrient ingestion, that potentiate insulin secretion from islet b-cells • Stimulation of insulin secretion is glucose-dependent. Incretins only work when glucose levels are above basal levels- THUS , NO HYPOGLYCEMIA if not on secreatogogue or insulin • Two predominant incretins • glucagon-like peptide-1 (GLP-1) • glucose-dependent insulinotropic peptide ([GIP] also known as gastric inhibitory peptide) Holst JJ et al. Diabetes. 2004;53(suppl 3):s197-s204;Meier JJ et al. Diabetes Metab Res Rev. 2005;21:91-117.

  9. Insulin Glucose-Stimulated Secretion of Insulin Glucose Independent Triggering Glucose Pancreatic Beta Cell GLUT2 SUR Glucose Potassium channel Glucose metabolism K+ GK Pyruvate GLP-1 ATP + ATP 1 TCA Cycle* GIP AC + Calcium channel 3 cAMP [Ca2+] 2 Amplifying- Glucose Dependent Calmodulin inhibitors (Transplant meds) PKA corticosteroids AC = adenylyl cyclase ATP = adenosine triphosphate cAMP = cyclic adenosine monophosphate GK = glucokinase GLUT2 = glucose transporters SUR = sulfonylurea receptor *TCA = Tricarboxylic acid (Kreb’s cycle) Hinke SA et al. J Physiol. 2004;558:369–380. Henquin JC. Diabetes. 2000;49:1751–1760. Henquin JC. Diabetes. 2004;53:S48–S58. Gillison, Tranplantation 1991;52:890

  10. Insulin synthesis INC. PDX-1 b-cell proliferation b-cell apoptosis Insulin sensitivity Gastric emptying Production of glucose Insulin secretion: glucose-Dependent Glucagon secretion Neuroprotection Appetite Cardio-protection Cardiac output GLP-1 Actions Extend Beyond the Pancreas: Address 6 of 8 Aspects of the Ominous Octet + Improves Cardiac Function Stomach Heart 5 6 Brain Pancreas GLP-1 4 Liver 1,2 3 Muscle 9-37, dec. ox. stress Adapted from Drucker DJ. Cell Metab. 2006;3:153-165., Brownlee EASD,2007

  11. Location and Impact of GLP-1/Receptors in the Cardiovascular System • Cardiomyocytes • Endocardium • Endothelium • Smooth Muscle Cells • T Lymphocytes/Macrophages • GLP-1 agonists improve endothelial function and reduce BP • Reduce inflammation • Improve function in post-MI LV dysfunction and CHF • Reduces Apo 48 synthesis and non-HDL fraction Koska J, et al. Diabetes Care. 2010;33(5):1028-30. Basu A, et al. Am J Physiol Endocrinol Metab 2007;293(5);1289-1296. Zhao T, et al. J Pharmacol Exp Ther. 2006;317(3):1106–1113. Nikolaidis, et al. Circulation. 2004;110(8):955–961. Nikolaidis LA, et al. Am J Physiol Heart CircPhysiol. 2005;289(6):H2401–H2408. Nikolaidis LA, et al. Circulation. 2004;109(8):962–965. Sokos GG, et al.J Card Fail. 2006;12(9):694–699. Watts GF, Chan DC. Diabetes 2013;62(2);336-338.

  12. S e c t i o n 12, 12.2 Mechanism of Incretins Incretin Mimetic Glucose dependent Insulin (GLP-1andGIP) Glucose uptake by peripheral tissue Ingestion of food Pancreas Release of active incretins GLP-1 and GIP Beta cells Alpha cells GI tract  Blood glucose in fasting and postprandial states Glucose- dependent X DPP-4 inhibitor DPP-4 enzyme Hepatic glucose production Glucagon (GLP-1) Inactive GLP-1 Inactive GIP • Incretin hormones GLP-1 and GIP are released by the intestine throughout the day, and their levels  in response to a meal. • Incretin Mimetics are resistant to DPP-4 inactivation Concentrations of the active intact hormones are increased by DPP-4 inhibition, thereby increasing and prolonging the actions of these hormones. GLP-1=glucagon-like peptide-1; GIP=glucose-dependent insulinotropic polypeptide.

More Related