Aggressive Hyperglycemia Management.ppt

1、Aggressive Hyperglycemia Management,Significant hospital hyperglycemia requires close follow-up,Previously diagnosed diabetes and elevated A1C,Without previously diagnosed diabetes (with random BG 125 mg/dL),Pre-admission diabetes care plan requires revision,Test (FBG, 2-hr OGTT) to differentiate be

2、tween in-hospital hyperglycemia and T2DM once patient is metabolically stable,Clement S et al. Diabetes Care. 2004;27:553-91. Conaway DLG et al. Am Heart J. 2006;152:1022-7.,Hyperglycemic patients Post-discharge,Glucose control in ACS patients with diabetes often unknown or undertreated at discharge

3、,No,Yes,(n = 235),(n = 162),(n = 58),(n = 39),Conaway DLG et al. Am Heart J. 2006;152:1022-7.,A1C,Diabetes therapy adjusted,Patients (%),N = 235 with diabetes + ACS,(7%),EPIC-Norfolk: CV risk increases with A1C level,A1C (%),Women,Men,Events/ 100 persons,Khaw K-T et al. Ann Intern Med. 2004;141:413-

4、20.,N = 10,232,PTrend 0.001 across A1C categories for all endpoints,CVD events,All deaths,5,55.4,5.55.9,66.4,6.56.9,7,5,55.4,5.55.9,66.4,6.56.9,7,1% A1C associated with: 20% CVD events, 22% mortality,UKPDS 33: Glycemic control declines over time,UKPDS Group. Lancet. 1998;352:837-53.,9876 0,Years fro

5、m randomization,Diet (conventional treatment),Sulfonylurea or insulin (intensive treatment),6.2% (upper limit of normal),0 3 6 9 12 15,ADA target,A1C, median (%),N = 3867 with newly diagnosed T2DM,Need for insulin increases over time,Wright A et al. Diabetes Care. 2002;25:330-6.,Chlorpropamide,UKPDS

6、 57: N = 826 with newly diagnosed T2DM,60,40,20,0,Patients requiring additional insulin (%),1,2,3,4,5,6,Glipizide,Years from randomization,53% of patients required additional insulin therapy by year 6,UKPDS 33: Effect of intensive glucose control on T2DM complications,Relative risk reduction (%),UKP

7、DS Group. Lancet. 1998;352:837-53.,Any T2DM-related endpoint,MI,All deaths,T2DM-related death,Micro-vascular endpoints,P = 0.34,P = 0.029,P = 0.44,P = 0.052,P = 0.0099,Stroke,P = 0.52,A1C 7% vs 7.9% with intensive vs conventional treatment,All P values vs conventional treatment,UKPDS 34: Glucose con

8、trol and CV outcomes,n = 1704 overweight with T2DM; n = 342 metformin group,UKPDS Group. Lancet. 1998;352:854-65.,Favors metformin or intensive,Favors usual care,All-cause mortality Metformin IntensiveMI Metformin IntensiveStroke Metformin Intensive,0.020.120.03,Aggregate endpoint,P*,0,1,2,*Metformi

9、n vs other intensive (sulfonylurea or insulin),Relative risk (95% CI),Limitations of UKPDS,Small difference in A1C between intensive and conventional groups: 7.0% vs 7.9% A1C exceeded current ADA 7% target Delay in adding multiple therapies Insufficient power to assess CV outcomes,UKPDS Group. Lance

10、t. 1998;352:837-53.,Hypothesis-generating study,DCCT/EDIC: Intensive glucose control associated with reduced long-term CV risk,DCCT/EDIC Study Research Group. N Engl J Med. 2005;353:2643-53.,Any initial CV event*,Time (years),N = 1441 with type 1 diabetes, mean baseline age 27,42% Risk (9%63%) P = 0

11、.02,57% Risk (12%79%) P = 0.02,CV death, nonfatal MI, stroke*,52 events,31 events,25 events,11 events,0,0.12,0.08,0.10,0.06,0.04,0.02,0,5,10,15,20,0,0.12,0.08,0.10,0.06,0.04,0.02,0,5,10,15,20,DCCT ends,DCCT ends,A1C 7.4% vs 9.1%,*Cumulative incidence,Conventional,Intensive,EDIC year 11: Patient char

12、acteristics at mean age 45,*BP 140/90 mm Hg; LDL-C 130 mg/dL P 0.01 vs intensive treatment,DCCT/EDIC Study Research Group. N Engl J Med. 2005;353:2643-53.,Glycemic control and vascular disease in T2DM,N = 4472; 6 randomized trials,Stettler C et al. Am Heart J. 2006;152:27-38.,Incidence rate ratio (9

13、5% CI),0,0.5,1,2,Any macrovascular* T2DMCardiac T2DMPeripheral vascular T2DMCerebrovascular T2DM,Favors conventional glycemic control,Favors intense glycemic control,*1587 events; 1197 events; 87 events; 303 events,0.81 (0.730.91),0.91 (0.801.03),0.58 (0.380.89),0.58 (0.460.74),Diabetes management t

14、rials: Clinical trial horizon,UKPDS DCCT/EDIC PROactive DREAM,NAVIGATOR VADT,ORIGIN ACCORD,2007,2010,2008,HEART 2D BARI 2D,1995-2006,RECORD ADVANCE,2009,Look AHEAD,2012,Ongoing trials of glucose lowering and CV outcomes,A1C target (%),*FPG is glycemic target for intervention group,National Institutes of Health (NIH). www.clinicaltrials.gov Buse JB, Rosenstock J. Endocrinol Metab Clin N Am. 2005;34:221-35.,