1. Glycemic Control in Type 2 Diabetes: How Tight is Too Tight? Frederick L. Brancati, MD, MHS Professor of Medicine & Epidemiology Director, Division of General Internal Medicine Visit Hopkins GIM at www.hopkinsmedicine.org/gim NCH Healthcare System, Naples, FL 21 January 2010

2. Objectives Identify controversy in diabetes care Establish framework for decision-making Compare/contrast results from recent trials

3. Why Treat A1c to 7% Target ? Hyperglycemia predicts micro & macrovascular disease epidemiologically The link with micro & macrovascular disease is biologically plausible Hyperglycemia poses non-vascular risks –Infection, Hypovolemia, Urinary Frequency Improved glycemic control reduces risk of microvascular disease

4. Why Treat A1c to 7% Target ? Improved glycemic control reduces CVD in –Type 1 diabetes (DCCT) –Recently diagnosed type 2 diabetes (UKPDS) Black box warnings require context –Lactic acidosis with metformin is very rare –CHF with TZDs is relatively mild/reversible –Black box MI warning for rosiglitazone only

5. Cumulative Risk of Infectious Disease Death by Diabetes Status in US Adults, NHANESII Mortality Study AG Bertoni et al. Diabetes Care 2001 24:1044-9.

6. Selvin, E. et al. Arch Intern Med 2005;165:1910-1916. Age, Sex, Race- Adjusted Relative Hazard of CHD by HbA1c in 1321 Adults without Diabetes (A) and 1626 Adults with Diabetes (B)

7. Cumulative Incidence of First Episode of Falling in 139 Elderly Nursing Home Residents by Diabetes Status In multivariate analysis, only diabetes (adjusted hazard ratio 4.03; 95% confidence interval, 1.96–8.28) and gait and balance (adjusted hazard ratio 5.26; 95% confidence interval, 1.26–22.02) were significantly and independently associated with an increased risk of falls. MS Maurer et al. J Gerontol A Biol Sci Med Sci (2005) 60:1157–62