Ndei Beta Cell Slide Kit Insulin Secretion

Slideshow Transcript

1. Slide 1: Section 2 Pancreatic -Cells and Insulin Secretion in Type 2 Diabetes 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: Hypothetical Relationships Determine Categories of Glucose Tolerance 1,500 1,000 AIRglucose (pmol/L) Normal 95th 500 IGT 75th 50th 25th Type 2 Diabetes 5th 0 0 2 4 6 8 10 Insulin sensitivity index (x10 min-1/pmol/L) -5 This slide can be downloaded free of charge from www.ndei.org, the website of the Adapted from Kahn SE et al. Diabetes. 1993;42:1663-1672. National Diabetes Education Initiative
5. Slide 5: Hypothetical Outcomes of Interventions to Treat Type 2 Diabetes 1,500 1,000 AIRglucose (pmol/L) Increased Insulin Secretion IGT 95th 500 Normal 75th Increased Insulin Sensitivity 50th 25th Type 2 Diabetes 5th 0 0 2 4 6 8 10 Insulin sensitivity index (x10 min-1/pmol/L) -5 This slide can be downloaded free of charge from www.ndei.org, the website of the Adapted from Kahn SE et al. Diabetes. 1993;42:1663-1672. National Diabetes Education Initiative
6. Slide 6: Hypothetical Outcomes of Interventions to Prevent Type 2 Diabetes 1,500 1,000 AIRglucose (pmol/L) Increased Insulin Secretion IGT 95th Normal 500 Increased Insulin Sensitivity 75th 50th 25th Type 2 Diabetes 5th 0 0 2 4 6 8 10 Insulin sensitivity index (x10 min-1/pmol/L) -5 This slide can be downloaded free of charge from www.ndei.org, the website of the Adapted from Kahn SE et al. Diabetes. 1993;42:1663-1672. National Diabetes Education Initiative
7. Slide 7: Type 2 Diabetes: Pathogenesis in a Nutshell A failure of the -cell to compensate adequately  for insulin resistance Obesity is the most common cause of  insulin resistance Most obese people have adequate -cell  compensation and therefore do not get diabetes There is a genetic predisposition to -cell failure  Buchanan TA. Clin Ther. 2003;25(suppl B):B32-B46. This slide can be downloaded free of charge DeFronzo RA. Med Clin North Am. 2004;88:787-835. from www.ndei.org, the website of the Kahn SE. J Clin Endocrinol Metab. 2001;86:4047-4058. National Diabetes Education Initiative
8. Slide 8: Type 2 Diabetes: Pathogenesis in a Nutshell (cont.) Type 2 diabetes is a PROGRESSIVE disease   -cell dysfunction first leads to impaired glucose tolerance, which progresses in some individuals to type 2 diabetes  -cell dysfunction starts long before blood glucose rises and worsens after diabetes develops Hyperglycemia may cause additional defects  in insulin secretion and insulin action (glucotoxicity) Buchanan TA. Clin Ther. 2003;25(suppl B):B32-B46. This slide can be downloaded free of charge DeFronzo RA. Med Clin North Am. 2004;88:787-835. from www.ndei.org, the website of the Kahn SE. J Clin Endocrinol Metab. 2001;86:4047-4058. National Diabetes Education Initiative
9. Slide 9: Decreased -Cell Function in Groups With Diabetes and at High Risk 700 600 PCOS Women 500 Relatives of 75th IGT Patients With Former Type 2 Diabetes 400 GDMs AIRglucose 50th (pmol/L) 300 25th Older 200 Subjects 5th 100 Type 2 Diabetes 0 1 2 3 4 5 6 7 0 Insulin sensitivity index (Si; x10-5 min-1/pmol/L) This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative In: Lowe Vidal J, Kahn SE. WL Jr, ed. Genetics of Diabetes Mellitus. 2001:109-131.
10. Slide 10: Short-term -Cell Adaptation: Response to Pregnancy 1,000 Nonpregnant postpartum 800 3rd trimester Insulin Normal 600 secretion rate 400 (pmol/min) Gestational Diabetes 200 0 0 0.1 0.2 0.3 0.4 Insulin sensitivity index (mol/kg/min per pmol/L) This slide can be downloaded free of charge from www.ndei.org, the website of the Buchanan TA. J Clin Endocrinol Metab. 2001;86:989-993. National Diabetes Education Initiative
11. Slide 11: Pathogenesis of Type 2 Diabetes: -Cell Dysfunction vs Insulin Resistance 48 Pima Indians were studied  – 17 progressed from NGT to type 2 diabetes (over 5.1 ± 1.4 years) – 31 subjects maintained NGT (4.8 ± 2.3 years) This slide can be downloaded free of charge from www.ndei.org, the website of the Weyer C et al. J Clin Invest. 1999;104:787-794. National Diabetes Education Initiative
12. Slide 12: Declining -Cell Function: Best Correlation of Progression 500 400 Nonprogressors NGT 300 NGT Acute insulin NGT response NGT 200 (U/mL) IGT Progressors 100 DIA 0 0 1 2 3 4 5 Measure of insulin resistance (mg/kg EMBS/min) This slide can be downloaded free of charge from www.ndei.org, the website of the body EMBS=estimated metabolic size Weyer C et al. J Clin Invest. 1999;104:787-794. National Diabetes Education Initiative
13. Slide 13: Loss of -Cell Function in People Who Develop Type 2 Diabetes: Longitudinal Data 4 * EMBS/min) 3 (mg/kg M-low 2 Insulin Action 1 0 NGT IGT Diabetes * † 300 AIR (U/mL) 250 200 Insulin Secretion 150 100 50 0 NGT IGT Diabetes *P<0.05; P<0.01 † EMBS=estimated metabolic body size This slide can be downloaded free of charge from www.ndei.org, the website of the Adapted from Weyer C et al. J Clin Invest. 1999;104:787-794. National Diabetes Education Initiative
14. Slide 14: Changing Glucose: Different Rates at Different Clinical Stages NGTNGT  NGT IGT  D  D NGT  D  D IGT  IGT  D NGT  NGT  D 10 9 8 Fasting plasma 7 glucose 6 (mmol/L) 5 4 3 Baseline 3.25 years 7 years This slide can be downloaded free of charge from www.ndei.org, the website of the Ferrannini E et al. Diabetes. 2004;53:160-165. National Diabetes Education Initiative
15. Slide 15: Functional Defects in -Cells in the Development of Diabetes Progressive decrease in -cell insulin secretion  in response to nutrients – first manifested as a decrease in early or acute insulin secretion (decreased first phase insulin secretion) Loss of normal minute-by-minute pulsatile  insulin secretion and daily ultradian rhythm of secretion Decreases in insulin processing with increased  proinsulin:insulin ratio This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative
16. Slide 16: UKPDS: Progressive Deterioration in Glycemic Control Over Time A1C 9 100 Median A1C (%) -Cell function (%) 80 8 60 7 40 Conventional Intensive 20 6 0 0 -12 -10 -8 -6 -4 -2 0 2 46 0 3 6 9 12 15 Time from randomization (y) Years from diagnosis This slide can be downloaded free of charge from www.ndei.org, the website of the1998;352:837-853. UKPDS Group. Lancet. Holman RR. Diabetes Res Clin Pract. 1998;40(suppl):S21-S25. National Diabetes Education Initiative
17. Slide 17: UKPDS: Progressive Deterioration in -Cell Function Over Time 100 80 60 -Cell function (%) 40 20 0 -12 -10 -8 -6 -4 -2 0 2 4 6 Years from diagnosis This slide can be downloaded free of charge from www.ndei.org, the website of the Holman RR. Diabetes Res Clin Pract. 1998;40(suppl):S21-S25. National Diabetes Education Initiative
18. Slide 18: Insulin and Glucose Patterns: Normal and Type 2 Diabetes Normal Type 2 diabetes 400 120 Glucose (mg/dL) Insulin (U/mL) 100 300 80 200 60 40 100 20 0600 1000 1400 1800 2200 0200 0600 0600 1000 1400 1800 2200 0200 0600 B L S (meals) B L S (meals) Time of day Time of day This slide can be downloaded free of charge from www.ndei.org, the website of the Polonsky KS et al. N Engl J Med. 1988;318:1231-1239. National Diabetes Education Initiative
19. Slide 19: Early Nutrient-Induced Insulin Secretion A crucial factor of postmeal glucose tolerance  Loss of first-phase insulin release can result in  glucose intolerance In type 2 diabetes, restoring first-phase  response improves postmeal glycemia and FFA levels Intensive blood glucose control can partially  restore first-phase insulin secretion This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative
20. Slide 20: Fasting Plasma Glucose and the Acute Insulin Response 800 FPG (mg/dL) n 79–89 24 600 90–99 20 100–114 7 Relative acute 400 115–149 3 insulin response 150–349 (% increase) 12 200 0 -100 0 15 30 60 90 120 Time (min) This slide can be downloaded free of charge from www.ndei.org, the website of the Brunzell JD et al. J Clin Endocrinol Metab. 1976;42:222-229. National Diabetes Education Initiative
21. Slide 21: Acute Insulin Response to Glucose Control (n=9) Type 2 Diabetes (n=9) 120 120 100 100 80 80 Plasma Plasma 60 60 IRI (U/mL) IRI (U/mL) 40 40 20 20 0 0 -30 0 30 -30 0 30 Time (min) =20g IV glucose This slide can be downloaded free of charge from www.ndei.org, the website of the IRI=immunoreactive Initiative National Diabetes Education insulin Pfeifer MA et al. Am J Med. 1981;70:579-588.
22. Slide 22: Acute Insulin Response to Arginine 400 300 Acute Controls (n=8) insulin 200 response Type 2 diabetes (n=8) to arginine (U/mL) 100 0 0 200 400 600 Plasma glucose (mg/dL) This slide can be downloaded free of charge from www.ndei.org, the website of the Ward WK et al. J Clin Invest. 1984;74:1318-1328. National Diabetes Education Initiative
23. Slide 23: Decreases in Insulin Response 1,000 800 600 AIRmax (pmol/L) 400 Type 2 diabetes=9 200 Healthy subjects=10 0 0 4 8 12 16 20 Fasting glucose (mmol/L) This slide can be downloaded free of charge r=-0.58; P=0.07 from www.ndei.org, the website of the Røder ME et al. J Clin Endocrinol Metab. 1998;83:604-608. National Diabetes Education Initiative
24. Slide 24: Disproportionate Increase in Proinsulin in Patients With Type 2 Diabetes 70 60 50 40 Basal PI (%) IRI 30 20 10 0 Controls Type 2 diabetes (n=28) (n=22) P<0.001 This slide can be downloaded free of charge from www.ndei.org, the website of the Ward WK et al. Diabetologia. 1987;30:698-702. National Diabetes Education Initiative
25. Slide 25: Mechanisms Responsible for Changes in -Cell Function Normal -cell adaptation to insulin resistance  – increased secretion from each cell – increased -cell mass  Impaired -cell adaptation in type 2 diabetes result of – decreased secretion from each cell – reduced -cell mass This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative
26. Slide 26: -Cell Mass in Normal Patients and Patients With Diabetes: Autopsy Study 4 3 * -Cell - 40% volume (%) 2 * † - 41% -63% 1 0 Lean Obese Normal Diabetes Normal Impaired Diabetes *P<0.05;can be downloaded free of charge This slide P<0.01 † from www.ndei.org, the website of the Butler AE et al. Diabetes. 2003;52:102-110. National Diabetes Education Initiative
27. Slide 27: Altered -Cell Mass and Function in Islets From Subjects With Type 2 Diabetes -Cell Mass -Cell Function Islet mass (IEq/g pancreas) 9,000 4.0 GSIR (ng/min/100 islets) 8,000 3.5 7,000 3.0 6,000 2.5 5,000 * 2.0 4,000 † 1.5 3,000 1.0 2,000 0.5 1,000 0 0 Control Type 2 Control Type 2 (n=14) diabetes (n=14) diabetes (n=14) (n=14) GSIR=glucose-stimulated insulin release This slide can be downloaded free of charge *P<0.001; †P<0.05 from www.ndei.org, the website of the Deng S et al. Diabetes. 2004;53:624-632. National Diabetes Education Initiative
28. Slide 28: Potential Causes for Falling Insulin Secretion: Glucolipotoxicity Increased flux of FFAs into a genetically susceptible  -cell is thought to result in multiple deleterious effects – inhibition of proper glucose utilization – disruption of normal cell signaling cascades – mitochondrial damage from reactive oxygen species – activation of cellular stress responses, which cause impairment in multiple metabolic pathways – nitric oxide generation, which can also alter multiple metabolic pathways This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative
29. Slide 29: Potential Causes for Falling Insulin Secretion: Glucolipotoxicity (cont.) Additional deleterious effects are  – altered secretion of cytokines that can affect islet response to nutrients – decreased -cell neogenesis or ability of -cells to proliferate in response to increased metabolic demand As a consequence of decreasing -cell function  and loss of -cell mass, remaining -cells work harder, increasing their potential for damage This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative
30. Slide 30: Role of Islet Amyloid in -Cell Dysfunction IAPP/amylin cosecreted with insulin   Islet amyloid present in up to 90% of patients with type 2 diabetes at autopsy  Extent of deposits related to disease severity  Early deposition of fibrils seen in many individuals  Similar to amyloid deposits in Alzheimer’s disease, rheumatoid arthritis, and multiple myeloma This slide can be downloaded free of charge from www.ndei.org, the website of the Kahn SE et al. Diabetes. 1999;48:241-253. National Diabetes Education Initiative
31. Slide 31: Amyloid Deposits in Pancreatic Islets in Type 2 Diabetes 50m This slide can be downloaded free of charge pancreatic Amyloid deposits in islets of human with type 2 diabetes from www.ndei.org, the website of the National Diabetes Education Initiative Verchere CB et al. Proc Natl Acad Sci USA. 1996;93:3492-3496.