T1D incidence is rising 3-5% per year Incidence /100,000/ yr in children aged 0-14

Ongoing Prevention Trials TRIGR - cow’s milk elimination NIP - omega-3 nutritional supplementation PrePoint Study – oral insulin in high risk subjects TrialNet – oral insulin TrialNet – oral GAD – in development TrialNet – anti-CD3, anti CD20, anti CTLA-4 Early stage Late stage

Mean HbA1c in BDC patients by age diabetes duration > 1 year 12% increase in those <6, but a 50% increase in teens - the most labor intense group 37% overall increase in patient volume n = 150->171 n = 611->850 n = 806 -> 1205

Improvement of glycemic control in Hannover children Proportion of patients (%) Individual yearly median HbA1c T Danne 2008

Glycemic Control Is Improving in US Adults with T2D & T1D NHANES Diabetes Care 2008; 31:81-86 5

HbA1c has improved post-DCCT, but the incidence of severe hypoglycemia has doubled Bulsara et al. Diabetes Care 2004

Risk of Hypoglycemia vs. Complications Severe hypoglycemia /100 p-yrs Diabetic retinopathy Nephropathy Neuropathy Microalbuminuria RR 15 13 11 9 7 5 3 1 100 ISPAD ‘07 80 60 Risk of Progression of Diabetic Complications DCCT in Type 1 Diabetes The impact of aggressive control of hyperglycemia was first demonstrated in a large, long-term study of patients with type 1 diabetes. In the DCCT, a 50% to 75% reduction in microvascular complications was achieved with a mean HbA1c of 7.2% in the intensive insulin-treated group. (ADA, 1995; ADA, 1999) The DCCT also demonstrated that, at 6 to 10 years, there is a 10% to 50% reduction in complications for every 1% decline in HbA1c. (The Diabetes Control and Complications Trial Research Group, 1993; Klein R, 1995) 40 20 6 7 8 9 10 11 12 adults ADA kids HbA1c % Skyler JF. DCCT Endocrinol Metab Clin North Am. 1996;25:243-54

<8% Our goal is somewhere there, but it depends on the patient and on a lot of other things <8% <7.5% <7% I guess you would like me to be a bit more specific

A1c as close to normal as possible without severe hypoglycemia The easiest topic that we will discuss today All experts agree

Metabolic memory from the first year of DM predicts later development of background retinopathy 1 14.4 HbA1c (3-12mo) < 7.5% (n=112) 12.4 HbA1c (3-12mo) > 7.5% (n=109) p<0.03 0,8 0,6 remaining free of retinopathy probability for 0,4 0,2 5 10 15 diabetes duration (years) Berlin Retinopathy Study

Prevalence of Hypertension at Each Year of the EDIC Study JAMA 2003;290:2159-2167. Copyright restrictions may apply.

Conventional treatment Cumulative Incidence of the First Occurrence of Nonfatal MI, Stroke, or CVD Death Conventional treatment Cumulative incidence of nonfatal MI, stroke, or death from cardio. disease Intensive treatment Years since entry No. at Risk Intensive 705 686 640 118 Conventional 721 694 637 96 DCCT/EDIC Study Research Group, N Engl J Med 2005; 353:2643-53. N Engl J Med 2005; 353;2643-2653 12

CVD incidence in T1D is increasing, despite declining CVD mortality in the general population (%) Cumulative incidence of CAD by 30 yr T1D duration Mortality per 100,000 U.S. standard population T1D cohorts dx: 1950-59 60-64 65-70 CDC/NCHS, National Vital Statistics System, Mortality Pabianco G et al. EDC Study , Diabetes 2006 55:1463-9

Think Activity Encourage daily activity, year-round G Scheiner 2008

Recommended LDL-Cholesterol Concentrations for Pharmacologic Treatment of Children and Adolescents 10 Years and Older Patient characteristics Recommended cutoff points No other risk factors for cardiovascular disease LDL-C levels persistently >190 mg/dL despite diet Rx Other risk factors present, (obesity, hypertension, smoking family history of premature CVD) LDL-C levels persistently >160 mg/dL despite diet Rx Children with diabetes mellitus LDL-C levels ≥130 mg/dL LDL-C levels ≥100 mg/dL Daniels SR et al. Pediatrics 2008; 122:198-208. 16

Changes in Insulin Therapy 1986 - 2007 Proportion of patients (%) 100 Two injections MDI CSII 80 60 40 20 1986 90 94 99 03 04 05 06 07 n= 339 425 521 458 471 510 530 545 589 T Danne, Hannover, 2008

Insulin Therapy MDI vs. CSII HbA1c distribution MDI CSII T Danne, Hannover 2006

Improved Nightime Glucose Excursions with STS Glucose Sensor Garg S et al: Diabetes Care: 2006, 29; 44-50 4 Blinded period Unblinded period 8% Increase* *p < 0.0001 3 14% Increase* 9% Reduction* Time Spent (hours) 2 A true goal of intensified insulin therapy should be reduction of the time that patients are exposed to extremely low or high BG levels, like in this study where unblinded use of dexcom STS CGM results helped the patients to reduce overnight time spent < 80 mg/dl by over 33% and time while exposed to hyperglycemia (>240 mg/dl) by ~10%. 33% Reduction* 38% 1 Reduction* 0.33 0.21 0.59 0.40 1.89 2.15 2.99 3.24 2.20 2.01 <55 55-80 81-140 141-240 241-400 Glucose Range (mg/dl)

CGM/CSII help those who use it, not those who just wear it CGM/CSII help those who use it, not those who just wear it! STAR 1: 138 CSII patients on CGM for 6 months HbA1c (%) Hirsh I. et al, STAR 1, ADA 2007, abstract 90

Glucose Levels in CL vs. Hybrid Control PP = postprandial Weinzimer et al. DC 2008;31:934 21

Nasal Exenatide Serum Glucose and Insulin Enhanced glucose-dependent insulin secretion As glucose approached euglycemia insulin secretion was attenuated Blase et al. Diabetes 2008 57: Suupl 1: Abstract 195-OR. 22

Patients Using Insulin Pumps & CG sensors HSBC Global Research

Dow Jones

Cost Estimates of Intensive Treatment Annual Cost Estimates* DCCT 1995 BDC 2003 2008 Pumps $5,800 $9,400 $11,000 MDI $4,000 $4,900 $ 7,000 * cost of DKA, hypoglycemia not included

Between 2000 and 2006, Colorado had a 73 percent increase in the number Of children living in poverty

Two tracks of diabetes care: For Haves and Have Nots Two tracks of diabetes care: For Haves and Have Nots? Health care reform, perhaps?

Electronic Medical Record Patient web portal - replace ‘log-book’ - empower patient interface with provider 3rd party reimbursement

Therapy Accessibility & Consumer Electronics Integration Confidential. Not to be circulated outside of Medtronic 30 30

Thank you for coming and for active participation! Safe travels! Final versions of slides next week on www. BarbaraDavisCenter.org Many thanks to the Speakers, Sponsors and Staff! See you back in July 2010!