Ndei Beta Cell Slide Kit Future Therapies

Slideshow Transcript

1. Slide 1: Section 5 What’s on the Horizon: Emerging Therapies This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative
2. Slide 2: -Cell Adaptation and Failure: Opportunities for Prevention and Treatment of Type 2 Diabetes
3. Slide 3: Disclosure This slide kit is intended to provide current  information on issues concerning -cells in patients with type 2 diabetes. Some of the information and agents mentioned may  include discussions of off-label, non–FDA- approved, or investigational uses. Please refer to each manufacturer’s full prescribing information before prescribing any of the agents mentioned in this program. Slides that include discussion of off-label uses are  identified with the symbol . This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative
4. Slide 4: Future Therapies: Incretins GLP-1 agonists   Exendin-4 agonists  DPP-IV inhibitors This slide can be downloaded free of charge from www.ndei.org, the website of the Drucker DJ. Diabetes Care. 2003;26:2929-2940. National Diabetes Education Initiative
5. Slide 5: Glucagon-Like Peptide-1 Secreted from intestinal L-cells with meal ingestion  In humans and animals  – enhances glucose-stimulated insulin release – decreases glucagon release – slows gastric emptying – reduces food intake In animals and in vitro  – increases insulin gene transcription – increases -cell mass and -cell differentiation This slide can be downloaded free of charge Drucker DJ. Curr Pharm Des. 2001;7:1399-1412. from www.ndei.org, the website of the Drucker DJ. Mol Endocrinol. 2003;17:161-171. National Diabetes Education Initiative
6. Slide 6: Insulin and GLP-1 Responses to Meals Meal Meal Meal 400 Insulin (pmol/L) 200 0 40 GLP-1 (pmol/L) 20 0 9 AM 1 PM 7 PM 10 PM 9 AM Hours This slide can be downloaded free of charge from www.ndei.org, the website of the Ørskov C et al. Scand J Gastroenterol. 1996;31:665-670. National Diabetes Education Initiative
7. Slide 7: GLP-1 Release Is Reduced in Type 2 Diabetes Meal 20 * * * * * * 15 * GLP-1 10 (pmol/L) * NGT (n=33) IGT (n=15) 5 Type 2 diabetes (n=54) 0 0 60 120 180 240 *P<0.05 between type 2 diabetes Time (min) and slide can be downloaded free of charge This NGT groups. from www.ndei.org, the website of the Toft-Nielsen MB et al. J Clin Endocrinol Metab. 2001;86:3717-3723. National Diabetes Education Initiative
8. Slide 8: Effect of GLP-1 on the -Cell Stimulation of insulin secretion   Stimulation of insulin gene transcription  Stimulation of insulin synthesis  Increased -cell mass (stimulation of new -cell formation, inhibition of apoptosis) This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative
9. Slide 9: GLP-1 Infusion Improves -Cell Insulin Secretion Saline GLP-1 7,000 0 weeks 1 week 6,000 6 weeks 5,000 4,000 C-peptide (pmol/L) 3,000 2,000 1,000 0 0 10 20 30 40 50 60 70 80 90 Time (min) This slide can be downloaded free of charge from www.ndei.org, the website of the Zander M et al. Lancet. 2002;359:824-830. National Diabetes Education Initiative
10. Slide 10: GLP-1 and First-Phase Insulin Secretion Subjects Without Diabetes Subjects With Diabetes Saline Control GLP-1-Acute (2 minutes) 1,800 750 GLP-1-Prolonged (3 hours) IV Glucose 1,500 IV Glucose 600 Insulin pmol/L 1,200 450 900 300 600 150 300 0 0 -15 0 15 30 45 60 -15 0 15 30 45 60 Time (min) Time (min) This slide can be downloaded free of charge Data are mean  website of the from www.ndei.org, the SEM Quddusi S et al. Diabetes Care. 2003;26:791-798. National Diabetes Education Initiative
11. Slide 11: Exenatide: Effect on the -Cell Synthetic peptide, which mimics actions of glucagon-like protein 1 (GLP-1)  – enhances glucose-dependent insulin secretion – suppresses inappropriately elevated glucagon secretion – delays gastric emptying Effect on -cells  – Animals, cell-line studies • increase expression of key -cell function genes • increase insulin biosynthesis and processing • augment -cell mass (increase neogenesis and proliferation, reduce apoptosis) – Human trials • treated patients demonstrate improved proinsulin:insulin ratio • robust insulin secretion to meal stimulus despite lower fasting and postprandial glucose concentrations Buse JB et al. Diabetes Care. 2004;27:2628-2635. DeFronzo RA et al. Diabetes Care. 2005;28:1092-1100. This slide can be downloaded free of charge Kendall DM et al. Diabetes Care. 2005;28:1083-1091. from www.ndei.org, the website of the Nielsen LL et al. Regul Pept. 2004;117:77-88. National Diabetes Education Initiative
12. Slide 12: Exenatide: Effects on Glycemic Control in Combination With Current Oral Therapies Placebo Change in A1C from baseline (%) 5 g BID 0.40 10 g BID 0.20 0.00 -0.20 -0.40 * -0.60 † † -0.80 * † -1.00 † -1.20 Exenatide + Met Exenatide + SU Exenatide + Met + SU *P<0.001 vs placebo; P<0.0001 vs placebo. † Buse JB et al. Diabetes Care. 2004;27:2628-2635. This slide can be downloaded free of charge Met=metformin; SU=sulfonylurea. DeFronzo RA et al. Diabetes Care. 2005;28:1092-1100. from www.ndei.org, the website of the Kendall DM et al. Diabetes Care. 2005;28:1083-1091. National Diabetes Education Initiative
13. Slide 13: Exenatide: Proportion of Patients Achieving A1C 7% Placebo 50 † 5 g BID Proportion achieving A1C 7% 45 † 10 g BID 40 † † 35 * † 30 25 20 15 10 5 0 Ex + Met Ex + SU Ex + Met + SU *P<0.01 vs placebo; P<0.0001 vs placebo. † Buse JB et al. Diabetes Care. 2004;27:2628-2635. This slide can be downloaded free of charge Ex=exenatide; Met=metformin; DeFronzo RA et al. Diabetes Care. 2005;28:1092-1100. from www.ndei.org, the website of the SU=sulfonylurea. Kendall DM et al. Diabetes Care. 2005;28:1083-1091. National Diabetes Education Initiative
14. Slide 14: Summary Increases in -cell demand result in an  adaptive response with increased -cell function and mass  In individuals susceptible to type 2 diabetes, there is a gradual decrease in -cell function and mass  To prevent loss of -cell function and mass, the -cell work must decrease This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative