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

2. 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

3. 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

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

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

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

7. 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. <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

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

10. 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

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

12. 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:
N Engl J Med 2005; 353; 12

13. 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:
CDC/NCHS, National Vital Statistics System, Mortality
Pabianco G et al. EDC Study , Diabetes :1463-9

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

16. 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: 16

17. 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

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

19. 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 < 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
Glucose Range (mg/dl)

20. 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

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

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

23. Patients Using Insulin Pumps & CG sensors
HSBC Global Research

24. Dow Jones

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

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

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

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

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

31. 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!