胰岛素治疗22493ppt课件

Therapeutic Options Insulins,Insulin Preparations,Class Agents Human insulins Regular, NPH, lente, ultralente Insulin analogues Aspart, glulisine, lispro, glargine Premixed insulins Human 70/30, 50/50 Humalog mix 75/25 Novolog mix 70/30,Human Insulin,A-chain,B-chain,Zn+,Zn+,Self-aggregation in solution,Monomers,Dimers,Hexamers,21 amino acids,30 amino acids,Modified Human Insulin,Regular Insulin Short acting Hexamers in Zn2+ buffer Neutral Protamine Hagedorn (NPH) Insulin Intermediate acting Medium-sized crystals in protamine-Zn2+ buffer Lente and Ultralente Insulin Intermediate and Large crystals in acetate-Zn2+ buffer long acting,Profiles of Human Insulins,Plasma insulin levels,Regular 68 hours,NPH 1220 hours,Ultralente 1824 hours,Hours,Insulin Analogues,Human Insulin Dimers and hexamers in solution,A-chain,B-chain,Lys Pro,Gly,Arg Arg,Asp,Lispro Limited self-aggregation Monomers in solution,Aspart Limited self-aggregation Monomers in solution,Glargine Soluble at low pH Precipitates at neutral (subcutaneous) pH,Glu,Glulisine Limited self-aggregation Monomers in solution,Lys,500 400 300 200 100 0,Insulin Aspart A Rapid-Acting Insulin Analogue,Plasma Insulin,Mudaliar SR et al. Diabetes Care. 1999;22:1501-1506,Insulin Action,pmol/L,700 600 500 400 300 200 100 0,Minutes,0,100,200,300,400,500,600,0,100,200,300,400,500,600,Glusose infusion rate (mg/min),Insulin aspart,Regular insulin,20 Healthy Subjects, 10-h Euglycemic Clamp,Insulin Lispro A Rapid-Acting Insulin Analogue,Heinemann L et al. Diabet Med. 1996;13:625-629,Insulin lispro,Regular insulin,-60 -30 0 30 60 90 120 150 180 210 240,Minutes,mg/dL,pmol/L,400,-60 -30 0 30 60 90 120 150 180 210 240,Meal and insulin,Meal and insulin,Plasma Insulin,Plasma Glucose,10 Patients With Type 1 Diabetes Following a Meal,300,200,100,0,200,150,0,100,0,4,8,12,16,20,24,Insulin Action Profiles in Type 1 Diabetes,Lepore M et al. Diabetes. 2000;49:2142-2148,Glucose infusion (mg/kg/min),20 Patients,4 3 2 1 0,Glargine,NPH,Ultralente,Hours,Action Profiles of Insulin Analogues,Plasma insulin levels,Regular 68 hours,NPH 1220 hours,Ultralente 1824 hours,Hours,Glargine 24 hours,Aspart, glulisine, lispro 46 hours,Human Insulins and Analogues Typical Times of Action,Polonsky KS et al. N Engl J Med. 1988;318:1231-1239,0600,0600,Time of day,20,40,60,80,100,B,L,D,Normal Daily Plasma Insulin Profile,B=breakfast; L=lunch; D=dinner,0800,1800,1200,2400,U/mL,Time of day,20,40,60,80,100,B,L,D,Evening Basal Insulin Bedtime NPH,B=breakfast; L=lunch; D=dinner,NPH,Normal pattern,U/mL,Starting Basal Insulin for Type 2 Diabetes Bedtime NPH Added to Diet,Cusi K et al. Diabetes Care. 1995;18:843-851,300,200,0,0800,1200,1600,Time of day,2000,2400,0400,0800,400,100,Diet only,Bedtime NPH,Plasma glucose (mg/dL),NPH,12 Patients Treated for 16 Weeks,Starting Basal Insulin for Type 2 Diabetes Suppertime 70/30 Added to Glimepiride,Riddle MC et al. Diabetes Care. 1998;21:1052-1057,0,100,150,200,250,300,*,*,12,16,8,4,20,24,Weeks,Fasting Glucose,0,0,25,50,75,100,12,16,8,4,20,24,*P0.001,Insulin Dosage,*,*,*,*,*,*,Placebo + insulin (N=73),Glimepiride + insulin titrated to FPG 140 mg/dL (N=72),mg/dL,Units / day,*P0.001,FPG=fasting plasma glucose,Time of day,20,40,60,80,100,B,L,D,Split-Mixed Regimen Human Insulins,B=breakfast; L=lunch; D=dinner,NPH Regular,NPH Regular,Normal pattern,U/mL,Split-Mixed Regimen NPH + Regular for Type 2 Diabetes,Henry RR et al. Diabetes Care. 1993;16:21-31,200,400,100,300,0,0,200,600,1000,400,800,0600,0600,1800,2400,1200,Time of day,0600,0600,1800,2400,1200,Diet only,Insulin 6 months,Plasma Glucose,Serum Insulin,B,L,D,N + R,N + R,mg/dL,pmol/L,B,L,D,N + R,N + R,B=breakfast; L=lunch; D=dinner,Time of day,20,40,60,80,100,B,L,D,Multiple Daily Injections Human Insulins,B=breakfast; L=lunch; D=dinner,Regular,NPH,NPH Regular,Normal pattern,U/mL,Regular,Multiple Daily Injections NPH + Regular for Type 2 Diabetes,0,300,250,200,150,100,50,0800,1200,1600,2000,2400,0400,0800,Time of day,0800,1200,1600,2000,2400,0400,0800,Plasma Glucose,Serum Insulin,R,N,R,R,0,300,200,100,Baseline oral agents,Insulin 8 weeks,Normal,mg/dL,pmol/L,B,L,D,B,L,D,R,N,R,R,Sn,Sn,Sn,Sn,Sn,Sn,Lindstrm TH et al. Diabetes Care. 1992;15:27-34,B=breakfast; Sn=snack; L=lunch; D=dinner,10 Patients With Diabetes, 10 Normal Controls,Multiple Daily Injections NPH + Regular or Aspart for Type 1 Diabetes,Home PD et al. Diabetes Care. 1998;21:1904-1909,100,80,60,40,20,0,mU/L,0600,1200,1800,2400,0600,Plasma Glucose,Serum Insulin,A,A,A,N,NPH + regular insulin,B=breakfast; L=lunch; D=dinner,B,L,D,250,200,150,mg/dL,14,12,10,8,6,mmol/L,16,Time of day,Insulin aspart,The Basal-Bolus Insulin Concept,Basal insulin Controls glucose production between meals and overnight Nearly constant levels 50% of daily needs Bolus insulin (mealtime or prandial) Limits hyperglycemia after meals Immediate rise and sharp peak at 1 hour postmeal 10% to 20% of total daily insulin requirement at each meal For ideal insulin replacement therapy, each component should come from a different insulin with a specific profile,Time of day,20,40,60,80,100,B,L,D,Basal-Bolus Insulin Treatment With Insulin Analogues,B=breakfast; L=lunch; D=dinner,Glargine,Lispro, glulisine, or aspart,Normal pattern,U/mL,Barriers to Using Insulin,Patient resistance Perceived significance of needing insulin Fear of injections Complexity of regimens Pain, lipohypertrophy Physician resistance Perceived cardiovascular risks Lack of time and resources to supervise treatment Medical limitations of insulin treatment Hypoglycemia Weight gain,Barriers to Using Insulin Attitudes of Patients With Type 1 and Type 2 Diabetes,0,20,40,60,80,100,% of patients,High anxiety about injections,Troubled by idea of more injections,Avoid injections because of anxiety,Troubled by idea of more injections,Avoid injections because of anxiety,All Patients,Patients With High Anxiety,Zambanini A et al. Diabetes Res Clin Pract. 1999;46:239-246,14%,42%,28%,45%,70%,Barriers to Insulin Therapy Cardiovascular Risk Is Not Supported by Trials,6-14,Type 2 Diabetes in the UKPDS Risk of myocardial infarction Conventional treatment 17.4 events/1000 pt-yr Intensive insulin 14.7 events/1000 pt-yr (P=0.052) Type 1 and 2 Diabetes in the DIGAMI Study Long-term survival after acute myocardial infarction Conventional treatment 44% mortality Intensive insulin 33% mortality (P=0.011),UKPDS Group. Lancet. 1998;352:837-853; Malmberg K. BMJ. 1997;314:1512-1515,Barriers to Insulin Therapy Severe Hypoglycemia,DCCT Research Group. Diabetes. 1997;46:271-286; UKPDS Group. Lancet. 1998;352:837-853,6-14,Type 1 Diabetes in the DCCT Conventional insulin 35% of pts 19 events/100 pt-yr A1C 9%, 6.5 yr Intensive insulin 65% of pts 61 events/100 pt-yr A1C 7.2%, 6.5 yr Type 2 Diabetes in the UKPDS Intensive policy insulin 37% of pts 2.3% pts/yr A1C 7.0%, 10 yr,Barriers to Insulin Therapy Weight Gain,DCCT Research Group. Diabetes. 1997;46:271-286; DCCT Research Group. N Engl J Med. 1993;329:977-986; UKPDS Group. Lancet. 1998;352:837-853,Type 1 Diabetes in the DCCT Intensive insulin + 10.1 lb more A1C 7.2%, 6.5 yr than conventional insulin Type 2 Diabetes in the UKPDS Intensive insulin + 8.8 lb more A1C 7.0%, 10 yr than diet treatment,Insulin Injection Devices,Insulin pens Faster and easier than syringes Improve patient attitude and adherence Have accurate dosing mechanisms, but inadequate mixing may be a problem,Insulin Pumps,Continuous subcutaneous insulin infusion (CSII) External, programmable pump connected to an indwelling subcutaneous catheter to deliver rapid-acting insulin Intraperitoneal insulin infusion Implanted, programmable pump with intraperitoneal catheter. Not available in the United States,New Insulins in Clinical Development,Long-acting insulin analogue Insulin detemir Acylated insulin analogue Soluble, binds to albumin Rapid-acting insulin analogue Insulin 1964 Limited aggregation, like lispro and aspart Rapid absorption from injection site Inhaled insulins Aerodose, AERx, Exubera Liquid aerosol or particulate cloud Delivered by portable devices Buccally absorbed insulin Oralin Liquid aerosol Delivered by portable device,Subcutaneous insulin: 16 U regular + 31 U long-acting,Inhaled insulin: 12 mg inhaled + 25 U ultralente,Inhaled Insulin in Type 1 Diabetes,Skyler JS et al. Lancet. 2001;357:331-335,10,Weeks,A1C (%),0,4,8,12,73 Patients Taking Inhaled Insulin tid in Addition to Injected Long-Acting Insulin,9,8,7,6, A1C (%) (mean baseline, 8.7%),2,Baseline,Week 8,Week 12,Week 4,Inhaled Insulin in Type 2 Diabetes,Cefalu WT et al. Ann Intern Med. 2001;134:203-207,26 Patients With Subcutaneous Regular Replaced by Inhaled Insulin tid, in Addition to Long-Acting Insulin Baseline mean dose: 19 U regular + 51 U