Ndei Beta Cell Slide Kit Clinical Implications

Slideshow Transcript

1. Slide 1: Section 4 Clinical Implications 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: Treatment of Type 2 Diabetes: Getting Back on the Curve Reestablishing Insulin Sensitivity-Secretion Relationships Insulin or Secretagogue Diet+Exercise, Metformin, TZDs Combination Therapy Insulin level Normal curve Diabetes Insulin sensitivity Resistant Sensitive This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative
5. Slide 5: Short-term Methods to Improve - Cell Insulin Secretion Reverse glucotoxicity in severely  decompensated individuals  Add insulin secretagogues  Administer exogenous insulin This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative
6. Slide 6: Lowering Glucose Levels Improves -Cell Function 14 subjects  – age: 50 ± 3 years – diabetes duration: 7.8 ± 2.1 years (new onset to 20 years) – fasting glucose: 286 ± 17 mg/dL – plasma insulin: 15 ± 2 U/mL 22 days of CSII  – euglycemic clamp and hepatic glucose output – insulin secretion over 24 hrs and IV glucose and glucagon This slide can be downloaded free of charge from www.ndei.org, the website of the Garvey WT et al. Diabetes. 1985;34:222-234. National Diabetes Education Initiative
7. Slide 7: Increased Insulin Secretion Following Elimination of Glucotoxicity Meals 450 Glucose (mg/dL) Before 400 350 300 250 200 After 150 100 50 Insulin (U/mL) 40 After 30 20 10 Before 8 am 12 pm 4 pm 8 pm 12 am 4 am 8 am This slide can be downloaded free of charge Time from www.ndei.org, the website of the Garvey WT et al. Diabetes. 1985;34:222-234. National Diabetes Education Initiative
8. Slide 8: Insulin Secretagogues: Sulfonylureas and Glitinides Bind to KATP channels on the -cell and directly  increase insulin secretion – sulfonylureas (longer half-life) • glimepiride • glipizide • glyburide – glitinides (shorter half-life) • nateglinide • repaglinide This slide can be downloaded free of charge from www.ndei.org, the website of the Krentz AJ et al. Drugs. 2005;65:385-411. National Diabetes Education Initiative
9. Slide 9: Effect of Glyburide in Hyperglycemia: Enhanced -Cell Responsiveness Before glyburide Before glyburide After glyburide After glyburide 800 20 700 Insulin secretion (pmol/min) 600 15 Glucose (mmol/L) 500 400 10 300 200 5 Meals Meals 100 0 0 pm m pm 0 pm am am am m m am m m 6 a 10 a 2 p 6a 6p 12 12 6 2 6 6 1 Clock time Clock time Solid red line (left graph) and shaded red area (right graph) represent mean ± SEMfree ofa group of subjects without diabetes. This slide can be downloaded for charge from www.ndei.org, the website of the Shapiro ET et al. J Clin Endocrinol Metab. 1989;69:571-576. National Diabetes Education Initiative
10. Slide 10: Long-term Improvement or Stabilization of Islet Function All therapies for diabetes appear to lose  effectiveness with time, primarily due to a progressive decline in -cell function  Therapies that decrease -cell secretory demand can prevent or possibly reverse islet dysfunction This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative
11. Slide 11: Progressive Hyperglycemia in Type 2 Diabetes Despite Therapy The UKPDS Study 9 Intensive: Chlorpropamide Conventional Glibenclamide (diet) 8 Metformin Insulin A1C (%) 7 Upper Normal 6 0 0 2 4 6 8 10 Years after randomization This slide can be downloaded free of charge from www.ndei.org, the website of the UKPDS Group. Lancet. 1998;352:854-865. National Diabetes Education Initiative
12. Slide 12: Prevention and Early Treatment of Type 2 Diabetes: Changing the Focus 100 Prevention and Early Treatment 80 60 -Cell UKPDS Data 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
13. Slide 13: Prevention and Early Treatment of Type 2 Diabetes: Three Levels of Opportunity Energy Balance Negative Positive 1 Obesity Fat Lifestyle Accumulation Interventions 2 Fatty Acids Insulin Adipose Liver & Resistance Insulin Resistance Tissue Muscle Adipokines 3 Weak -Cells Robust -Cells -Cell Hyperinsulinemia Hyperglycemia Failure This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative
14. Slide 14: Weight Loss Can Improve Diabetic Control and Prevent the Deterioration in -Cell Function Lifestyle interventions (diet and exercise) are  the mainstays of treatment for type 2 diabetes  Exercise and weight loss improve insulin sensitivity, resulting in reduced insulin secretion This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative
15. Slide 15: Effect of Weight Loss on -Cell Function in Obese Patients With Type 2 Diabetes 300 22 Insulin secretion (pmol/min/m²) 20 250 Glucose (mmol/L) 18 200 16 14 150 12 10 100 8 Before (mean BMI 35.5 kg/m2) 50 After (mean BMI 29.5 kg/m2) 6 0 0 0 60 120 180 0 60 120 180 Minutes Minutes This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative Gumbiner B et al. J Clin Endocrinol Metab. 1990;70:1594-1602.
16. Slide 16: Weight Loss Improves Insulin Secretion in Obese Patients With Type 2 Diabetes Before (mean BMI 35.5 kg/m2) After (mean BMI 29.5 kg/m2) 25 300 250 20 Glucose (mmol/L) Insulin secretion (pmol/min/m2) 200 15 150 10 100 5 50 0 0 0 60 120 180 240 300 360 0 60 120 180 240 300 360 Minutes Minutes This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative Gumbiner B et al. J Clin Endocrinol Metab. 1990;70:1594-1602.
17. Slide 17: Prevention of Type 2 Diabetes Results of Recent Randomized Trials Relative Risk Study Subjects Intervention Reduction Behavior Finnish DPS IGT Lifestyle 58% US DPP IGT Lifestyle 58% US DPP IGT Metformin 31% Medication Stop-NIDDM IGT Acarbose 25% TRIPOD Prior GDM Troglitazone 55% XENDOS IGT Orlistat 45% Buchanan TA et al. Diabetes. 2002;51:2796-2803. Chiasson JL et al. Lancet. 2002;359:2072-2077. Knowler WC et al. N Engl J Med. 2002;346:393-403. This slide can be downloaded free of charge Torgerson JS et al. Diabetes Care. 2004;27:155-161. from www.ndei.org, the website of the Toumilehto J et al. N Engl J Med. 2001;344:1343-1350. National Diabetes Education Initiative
18. Slide 18: Finnish Diabetes Prevention Study: Effect of Lifestyle Intervention 1.0 0.9 Cumulative 0.8 probability of remaining free 58% Relative 0.7 of diabetes Risk Reduction Control (23%) 0.6 Intensive Lifestyle (11%) 0.5 0 1 2 3 4 5 6 Years on trial This slide can be downloaded free of charge from www.ndei.org, the website of the Toumilehto J et al. N Engl J Med. 2001;344:1343-1350. National Diabetes Education Initiative
19. Slide 19: US Diabetes Prevention Program: Effect of Lifestyle Intervention 40 30 Placebo 58% Relative Cumulative Risk Reduction incidence 20 of diabetes (%) 10 Lifestyle 0 0 1 2 3 4 Years from randomization This slide can be downloaded free of charge from www.ndei.org, the website of the Adapted from Knowler WC et al. N Engl J Med. 2002;346:393-403. National Diabetes Education Initiative
20. Slide 20: US Diabetes Prevention Program: Effect of Metformin 40 30 Placebo Cumulative incidence 20 31% Relative of diabetes Risk (%) Metformin Reduction 10 0 0 1 2 3 4 Years from randomization This slide can be downloaded free of charge from www.ndei.org, the website of the Adapted from Knowler WC et al. N Engl J Med. 2002;346:393-403. National Diabetes Education Initiative
21. Slide 21: Metformin and Islet Function Metformin directly reduces glucose production  by the liver, resulting in lower insulin levels Metformin has a minimal peripheral insulin-  sensitizing effect Metformin does not directly affect insulin  secretion Metformin usually results in modest weight loss  This slide can be downloaded free of charge from www.ndei.org, the website of the Krentz AJ et al. Drugs. 2005;65:385-411. National Diabetes Education Initiative
22. Slide 22: Metformin in Type 2 Diabetes: Improved Glucose Without Changes in Insulin Secretion Before After 60 300 Plasma insulin (U/mL) Plasma glucose (mg/dL) 250 40 200 150 20 100 50 0 8 9 10 11 12 1 2 3 4 8 9 10 11 12 1 2 3 4 Time of day Time of day This slide can be downloaded free of charge from www.ndei.org, the website of the Wu MS et al. Diabetes Care. 1990;13:1-8. National Diabetes Education Initiative
23. Slide 23: -Glucosidase Inhibitors Decrease the rate of digestion of complex carbohydrates  in the small intestine Delay glucose absorption and attenuate postprandial  rises in blood glucose and insulin Efficacious as first-line therapy and in combination with  sulfonylureas, metformin, and insulin Beneficial effects on hyperglycemia and  hyperinsulinemia Do not cause weight gain  May lower triglyceride levels  This slide can be downloaded free of charge from www.ndei.org, the website of the Krentz AJ, Bailey CJ. Drugs. 2005;65:385-411. National Diabetes Education Initiative
24. Slide 24: The STOP-NIDDM Study: Effect of Acarbose 1.00 0.95 Acarbose 0.90 0.85 Cumulative 0.80 probability 0.75 of remaining Placebo 0.70 free of 0.65 diabetes 0.60 0.55 25% Relative Risk 0.50 Reduction 0.45 0.40 0 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 Days after randomization This slide can be downloaded free of charge from www.ndei.org, the website of the Chiasson JL et al. Lancet. 2002;359:2072-2077. National Diabetes Education Initiative
25. Slide 25: Lipase Inhibitor: Orlistat Inhibits intestinal lipase, decreasing the  absorption of fat in the small intestine  In clinical trials, orlistat-treated patients lost 5% to 10% of body weight vs 2% to 7% in placebo-treated patients following 6 to 48 months of treatment  Reduces LDL cholesterol and insulin levels This slide can be downloaded free of charge from www.ndei.org, the website of the Curran MP, Scott LJ. Drugs. 2004;64:2845-2864. National Diabetes Education Initiative
26. Slide 26: The XENDOS Study: Effect of Orlistat Placebo + lifestyle - IGT patients Orlistat + lifestyle - IGT patients Placebo + lifestyle - all patients Orlistat + lifestyle - all patients 45% Relative Risk 30 Reduction 25 20 Cumulative P=0.0024 incidence of 15 diabetes (%) 37% Relative Risk 10 Reduction 5 P=0.0032 0 0 26 52 78 104 130 156 182 208 Week This slide can be downloaded free of charge from www.ndei.org, the website of the Torgerson JS et al. Diabetes Care. 2004;27:155-161. National Diabetes Education Initiative
27. Slide 27: PPAR Activators and Islet Function The thiazolidinediones and other PPAR  activators – improve insulin sensitivity in muscle and liver primarily by redirecting FFAs to adipose tissue, reducing TG levels – improve insulin sensitivity by reducing insulin concentrations – improve -cell secretion patterns – prevent diabetes in high-risk populations This slide can be downloaded free of charge from www.ndei.org, the website of the Krentz AJ et al. Drugs. 2005;65:385-411. National Diabetes Education Initiative
28. Slide 28: TRIPOD Study: Effect of Troglitazone 12.1% Annual 50 Incidence Rate 40 55% Relative 30 Patients Risk Reduction Placebo with diabetes 5.4% Annual 20 (%) Incidence Rate Troglitazone 10 0 0 36 48 12 24 60 Months on study This slide can be downloaded free of charge from www.ndei.org, the website of the Buchanan TA et al. Diabetes. 2002;51:2796-2803. National Diabetes Education Initiative
29. Slide 29: Stabilization of -Cell Function at IGT Stage: Evidence From the TRIPOD Study Baseline 8 Months post-trial Placebo (n=40) Troglitazone (n=44) Acute insulin response 1,000 1,000 (U/mL x min) 800 800 600 600 400 400 Stable 200 200 39% decrease in -cell compensation 0 0 0 2 4 6 0 2 4 6 MINMOD Si MINMOD Si This slide can be downloaded free of charge from www.ndei.org, the groups the P=0.01 between website of Buchanan TA et al. Diabetes. 2002;51:2796-2803. National Diabetes Education Initiative
30. Slide 30: Stabilization of -Cell Function at Early Diabetes: Evidence From the TRIPOD Study 800 On Trial Off Trial Placebo Troglitazone 600 Disposition index 400 (Si x AIRg) -35% -3% 200 P=0.02 P=0.82 0 0 1 2 3 4 5 Years This slide can be downloaded free of charge from www.ndei.org, the website of the Xiang AH et al. J Clin Endocrinol Metab. 2004;89:2846-2851. National Diabetes Education Initiative
31. Slide 31: Effect of Troglitazone on -Cell Function in PCOS Before treatment After treatment P<0.005 NS P<0.005 1.25 1,500 900 800 1,250 1.00 AIR glucose (pmol/L) Si (10-5 min-1/pmol/L) 700 Disposition index 1,000 600 0.75 500 750 400 0.50 500 300 200 0.25 250 100 0 0 0 Data slide can be downloaded free of charge This are the mean±SEM. from www.ndei.org, the website of the National Diabetes Education Initiative Ehrmann DA et al. J Clin Endocrinol Metab. 1997;82:2108-2116.
32. Slide 32: Prevention of Type 2 Diabetes Tools for identification of high-risk people  Step 1: Find Insulin Resistance – Overweight by BMI (ethnicity-specific) – Increased waist circumference – Components of the metabolic syndrome – Family history of type 2 diabetes and/or metabolic syndrome  Step 2: Find -Cell Dysfunction – Impaired fasting glucose (100-125 mg/dL) – Impaired 2-hour postprandial glucose (140-199 mg/dL) – Rising glucose levels over time This slide can be downloaded free of charge from www.ndei.org, the website of the National Diabetes Education Initiative
33. Slide 33: Prevention of Type 2 Diabetes: One Clinical Strategy At-Risk Clinical Characteristics Measure Glucose Impaired Diabetic Normal Lower Risk Diabetes Higher Risk Lifestyle Treat to Lifestyle Intervention Achieve Advice an A1C <6.5%-7% Rising Glycemia Stable Glycemia Follow-up Glucose Testing Consider Pharmacologic Continue Lifestyle This slide can be downloaded free of charge Treatment Intervention from www.ndei.org, the website of the National Diabetes Education Initiative