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Aggressive Hyperglycemia Management

Aggressive Hyperglycemia Management. Significant hospital hyperglycemia requires close follow-up. Hyperglycemic patients Post-discharge. Previously diagnosed diabetes and elevated A1C. Without previously diagnosed diabetes (with random BG >125 mg/dL).

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Aggressive Hyperglycemia Management

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  1. Aggressive Hyperglycemia Management

  2. Significant hospital hyperglycemia requires close follow-up Hyperglycemic patients Post-discharge 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 between 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.

  3. Glucose control in ACS patients with diabetes often unknown or undertreated at discharge N = 235 with diabetes + ACS Diabetes therapy adjusted A1C Patients (%) (<7%) (n = 235) (n = 39) (n = 58) (n = 162) Yes No Conaway DLG et al. Am Heart J. 2006;152:1022-7.

  4. EPIC-Norfolk: CV risk increases with A1C level N = 10,232 Women Men Events/ 100 persons <5 5–5.4 5.5–5.9 6–6.4 6.5–6.9 ≥7 <5 5–5.4 5.5–5.9 6–6.4 6.5–6.9 ≥7 A1C (%) CVD events All deaths 1% A1C associated with: 20% CVD events, 22% mortality PTrend < 0.001 across A1C categories for all endpoints Khaw K-T et al. Ann Intern Med. 2004;141:413-20.

  5. UKPDS 33: Glycemic control declines over time N = 3867 with newly diagnosed T2DM 9 8 7 6 0 A1C, median (%) ADA target 6.2% (upper limit of normal) 0 3 6 9 12 15 Years from randomization Diet (conventional treatment) Sulfonylurea or insulin (intensive treatment) UKPDS Group. Lancet.1998;352:837-53.

  6. Need for insulin increases over time UKPDS 57: N = 826 with newly diagnosed T2DM 60 40 Patients requiring additional insulin (%) 20 0 1 2 3 4 5 6 Years from randomization Chlorpropamide Glipizide ~53% of patients required additional insulin therapy by year 6 Wright A et al. Diabetes Care. 2002;25:330-6.

  7. UKPDS 33: Effect of intensive glucose control on T2DM complications P = 0.029 P = 0.34 P = 0.44 P = 0.052 P = 0.0099 Relative risk reduction (%) P = 0.52 AnyT2DM-related endpoint T2DM-related death All deaths MI Stroke Micro-vascular endpoints A1C 7% vs 7.9% with intensive vs conventional treatment All P values vs conventional treatment UKPDS Group. Lancet. 1998;352:837-53.

  8. UKPDS 34: Glucose control and CV outcomes n = 1704 overweight with T2DM; n = 342 metformin group Favors metforminor intensive Favors usual care Aggregate endpoint P* All-cause mortality Metformin Intensive MI Metformin Intensive Stroke Metformin Intensive 0.02 0.12 0.03 0 1 2 Relative risk(95% CI) *Metformin vs other intensive (sulfonylurea or insulin) UKPDS Group. Lancet. 1998;352:854-65.

  9. 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 Hypothesis-generating study UKPDS Group. Lancet. 1998;352:837-53.

  10. DCCT/EDIC: Intensive glucose control associated with reduced long-term CV risk N = 1441 with type 1 diabetes, mean baseline age 27 52 events 0.12 0.12 57% Risk (12%–79%) P = 0.02 42% Risk (9%–63%) P = 0.02 0.10 0.10 0.08 0.08 CV death, nonfatal MI, stroke* Any initial CV event* 25 events 0.06 0.06 0.04 0.04 31 events 11 events 0.02 0.02 0 0 0 5 10 15 20 0 5 10 15 20 Time (years) DCCT ends DCCT ends A1C 7.4% vs 9.1% Conventional Intensive DCCT/EDIC Study Research Group.N Engl J Med. 2005;353:2643-53. *Cumulative incidence

  11. EDIC year 11: Patient characteristics 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.

  12. Glycemic control and vascular disease in T2DM N = 4472; 6 randomized trials Favors intense glycemic control Favors conventional glycemic control Any macrovascular*T2DM Cardiac† T2DM Peripheral vascular‡ T2DM Cerebrovascular§ T2DM 0.81 (0.73–0.91) 0.91 (0.80–1.03) 0.58 (0.38–0.89) 0.58 (0.46–0.74) 2 0 0.5 1 Incidence rate ratio(95% CI) *1587 events; †1197 events; ‡87 events; §303 events Stettler C et al. Am Heart J. 2006;152:27-38.

  13. Diabetes management trials: Clinical trial horizon UKPDSDCCT/EDIC PROactive DREAM Look AHEAD NAVIGATORVADT HEART 2D BARI 2D RECORD ADVANCE ORIGINACCORD 2012 1995-2006 2007 2008 2009 2010

  14. Ongoing trials of glucose lowering and CV outcomes A1C target (%) National Institutes of Health (NIH). www.clinicaltrials.gov Buse JB, Rosenstock J. Endocrinol Metab Clin N Am. 2005;34:221-35. *FPG is glycemic target for intervention group

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