0

10

20

30

40

50

60

70

1950 1960 1970 1980 1990 2000

Finland

Sweden

Colorado

Germany

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

Lat

e L

ate

stag

est

age

Ear

ly s

tage

Ear

ly s

tage

BDC HbA1c by Age

7.2

7.4

7.6

7.8

8

8.2

8.4

8.6

8.8

9

9.2

9.4

<6 yr 6-12 yr 13-19 yr

HbA1c

2000200220042006

Mean HbA1c in BDC patients by age diabetes duration > 1 year

n = 150->171 n = 611->850 n = 806 -> 1205

Improvement of glycemic control in Hannover children

0

10

20

30

40

50

60

< 7.5 % 7.5 - 9.0 % > 9.0 %

2000 n = 468

2001 n = 453

2002 n = 469

2003 n = 471

2004 n = 510

2005 n = 530

2006 n = 545

2007 n = 560

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

HbA1c has improved post-DCCT, but the incidence of severe hypoglycemia has

doubled Bulsara et al.Diabetes Care 2004

Risk of Hypoglycemia vs. Complications

Skyler JF. DCCT Endocrinol Metab Clin North Am. 1996;25:243-54

RR

HbA1c %7 8 9 10 11 12

Diabetic retinopathyNephropathyNeuropathyMicroalbuminuria

15

13

11

9

7

5

3

1

Severe hypoglycemia /100 p-yrs

0

20

40

60

80

100

6

ISPAD ‘07

adults ADA kids

<7.5% <7%<8%

Our goal is somewhere there, but it depends on the patient and on a lot of other things

A1c as close to normal as possible

without severe hypoglycemia

0 5 10 150

0,2

0,4

0,6

0,8

1

14.4

HbA1c (3-12mo) < 7.5%(n=112)

12.4

HbA1c (3-12mo) > 7.5%(n=109)

p<0.03

diabetes duration (years)

pro

ba

bili

ty fo

rre

ma

inin

g fr

ee

of r

etin

opa

thy

Metabolic memory from the first year of DM predicts later development of background retinopathy

Berlin Retinopathy Study

Copyright restrictions may apply.

Prevalence of Hypertension at Each Year of the EDIC Study

JAMA 2003;290:2159-2167.

Cumulative Incidence of the First Occurrence of Nonfatal MI, Stroke, or CVD Death

0.00

0.02

0.04

0.06

0.08

0.10

0.12

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21Years since entry

Cu

mu

lati

ve i

nci

den

ce o

f n

on

fata

l M

I,

stro

ke,

or

dea

th f

rom

car

dio

. d

isea

se

Conventional treatment

Intensive treatment

DCCT/EDIC Study Research Group, N Engl J Med 2005; 353:2643-53.

Intensive 705 686 640 118

Conventional 721 694 637 96

No. at Risk

N Engl J Med 2005; 353;2643-2653

0

100

200

300

400

500

600

1960 65 70 75 80 85 90 95 2000 2005

0

5

10

15

20

25

30

T1D cohorts dx: 1950-59 60-64 65-70

CVD incidence in T1D is increasing, despite declining CVD mortality in the

general population

Mort

ality

per

100,0

00 U

.S.

sta

nd

ard

p

op

ula

tion

Cumulative incidence of CAD by 30 yr T1D duration

(%)

CDC/NCHS, National Vital Statistics System, MortalityPabianco G et al. EDC Study , Diabetes 2006 55:1463-9

http://www.cdc.gov/nchs/products/pubs/pubd/hestats/overweight/HealthEstat1206.gif

Think ActivityThink ActivityEncourage daily activity, year-round

0%

50%

100%

150%

200%

M Tu W Th F Sa S

Insulin S

ensit

ivit

y

daily

2-3 x/ wk

never

G Scheiner 2008

Patient characteristics Recommended cutoff points

No other risk factors forcardiovascular disease

LDL-C levels persistently >190 mg/dL despite diet Rx

Other risk factors present,(obesity, hypertension, smokingfamily history of premature CVD)

LDL-C levels persistently >160 mg/dL despite diet Rx

Children with diabetes mellitus

LDL-C levels ≥130 mg/dLLDL-C levels ≥100 mg/dL

Daniels SR et al. Daniels SR et al. PediatricsPediatrics 2008; 2008; 122:198-208122:198-208..

Recommended LDL-Cholesterol Concentrations for Pharmacologic Recommended LDL-Cholesterol Concentrations for Pharmacologic Treatment of Children and Adolescents 10 Years and OlderTreatment of Children and Adolescents 10 Years and Older

Changes in Insulin Therapy 1986 - 2007

T Danne, Hannover, 2008

n= 339 425 521 458 471 510 530 545

0

20

40

60

80

100

1986 90 94 99 03 04 05 06

Proportion of patients (%)

07 589

Two injectionsMDICSII

Insulin Therapy MDI vs. CSIIHbA1c distribution

T Danne, Hannover 2006

MDICSII

Improved Nightime Glucose Excursions with STS Glucose SensorGarg S et al: Diabetes Care: 2006, 29; 44-50

Blinded periodUnblinded period

0.33 0.59 1.89 2.99 2.200.21 0.40 2.15 3.24 2.010

1

2

3

4

<55 55-80 81-140 141-240 241-400

Glucose Range (mg/dl)

Tim

e S

pen

t (h

ou

rs)

38%Reduction*

14%Increase* 9%

Reduction*

33%Reduction*

8%Increase**p < 0.0001

CGM/CSII help those who use it, not those who just wear it!

STAR 1: 138 CSII patients on CGM for 6 months

6

7

8

9

10

100% compliant <60% compliant

Before 6 month on CGM

Hirsh I. et al, STAR 1, ADA 2007, abstract 90

HbA1c (%)

Glucose Levels in CL vs. Hybrid Control

6A Noon 6P MidN 6A Noon 6P0

100

200

300Closed Loop (N=8)

meals

setpoint

Hybrid CL (N=9)

Glu

cose

(mg

/dl)

0 60 120 180 2400

20

40

60

80

100

Closed Loop

Hybrid CL

Time (min)

Pla

sma

Insu

lin

(

U/m

L)

Weinzimer et al. DC 2008;31:934

Nasal Exenatide Serum Glucose and InsulinNasal Exenatide Serum Glucose and Insulin

0 30 60 90 120 150 180 210 24080

100

120

140

160

180

200

220

240 Placebo600 mcg IN

Serum Glucose

Exenatidefollowed bybreakfast

Time (min)

Ser

um G

luco

se (m

g/dL

)

Blase et al. Blase et al. Diabetes Diabetes 2008 57: Suupl 1: Abstract 195-OR.2008 57: Suupl 1: Abstract 195-OR.

0

100,000

200,000

300,000

400,000

Pumps

CG sensors

Patients Using Insulin PumpsPatients Using Insulin Pumps& CG sensors& 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?

Health care reform, perhaps?

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

Electronic Medical Record

30

Therapy Accessibility & Consumer Electronics Integration

Confidential. Not to be circulated outside of Medtronic

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!