NonInvasive Cardiac Monitoring in Type 1 Diabetes

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Non-Invasive Cardiac Monitoring in Type 1
Diabetes

• Marian Rewers, MD, PhD
• Professor Clinical Director
• Barbara Davis Center for Childhood
  DiabetesUniversity of Colorado Denver

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Type 1 diabetes affects mostly adultsThe U.S.,
2003 estimates
Number of patients
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Improving survival among T1 DM patients
Allegheny County IDDM Registry 1965-1999
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Declining cumulative incidence of microvascular
complicationsSteno Clinic, Denmark, 600 Patients
with T1 DM onset 1965-84
Diabetic nephropathy
Proliferative diabetic retinopathy
1965-69
1965-69
1961-65
40
1970-74
1966-70
1970-74
30
1975-79
1975-79
1971-75
1971-75
20
1966-70
1980-84
1980-84
10
1976-80
1976-80
Hovind P, et al. Diabetes Care 2003
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Increasing cumulative incidence of Coronary
Artery Disease Epidemiology of Diabetic
Complications Study, Pittsburgh, U.S. 684
Patients with T1 DM diagnosed 1950-1980, followed
up to 2000


Diabetes duration
Orchard T, 2003
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Summary

• The prevalence of T1 DM peaks 50 yrs of age in
  the U.S. The survival has improved, largely due
  to better control of hyperglycemia, hypertension
  and prevention of acute complications and ESRD.
• Coronary artery disease became the leading cause
  of death in people with T1 DM.
• Diabetic women have 10-30 times higher risk of
  CAD, and diabetic men have 4-10 times higher
  risk, compared to the general population.

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Pilot Study Led to NIH Funding N135
Coronary Artery Calcification in Type 1
Pilot Study Participants N109
Baseline examination N1,416

Pilot Study Participants N98
3-yr follow-up examination in progress N1,211
CAC Progression Nested Case-Control
Study Progressors n98, Non-Progressors n173
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Coronary Artery Calcification in Type 1 Diabetes
(CACTI) 1,416 participants, CAD-free, aged 20-55
years Including 652 with T1 DM of at least 10 yrs
duration
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Coronary artery lumen (angiography), plaque
(IVUS) and calcification (EBT) in a young woman
with T1 DM and premature CAD
Coronary Artery Calcification
CACTI 1448, female DM diagnosis age
8 Angioplasty age 26 Deceased age 28
10
Agatston units
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Prevalence of Coronary Artery Calcification
CACTI Study, n1,416
Age
women men age-adjusted OR4.2
(2.4-7.5) OR2.3 (1.5-3.7)
Dabelea D, et al. Diabetes 2003
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Snell-Bergeon et al. Diabetes Care 2003
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Predictors of 3-year Progression of CAC in T1DM
Patients (N500)
Adjusting for age (p0.007), gender (p0.16),
diabetes duration (p0.0004), baseline CAC
(phomocystein

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Hypertension and dyslipidemia remain poorly
controlled in patients with T1D, CACTI,
2000-2002 (n652)
Hypertension
Dyslipidemia Maahs D, Diabetes Care 2005
Wadwa P, Diabetes Care 2005
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Novel Predictors of 3-Year Progression of CAC 98
progressors vs. 173 controls Adjusting for age,
gender, diabetes and baseline CAC
Independent of BMI, hypertension, LDL-ch, HDL-ch,
smoking, AER CRP, fibrinogen, HbA1c,
homocysteine, PAI-1, CD40L
Maahs D, et al. Circulation 2005 Wadwa P, et al.
2005

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Summary of CACTI results

• Coronary calcification is 2-4 x more frequent in
  T1D, compared to non-diabetic controls
• Hyperglycemia, hypertension and low HLD-ch as
  predict progression of coronary calcification
• Inflammatory markers - low adiponectin and
  elevated sIL-2R - are also predictive CRP levels
  are of a limited predictive value
• Hyperglycemia, hypertension and dyslipidemia are
  not yet optimally controlled in many patients

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Myocardial Perfusion Reserve
Basal
Mid
Apical
VLA
Stress
Stress
Rest
RMPR LAD .76 CX .73 RCA 1.1
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PulseMetric
Brachial Artery Distensibility, SVR, CO, LV
dP/dt Uses Oscillometric BP cuff
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Sphygmocor
Pulse Wave Velocity Augmentation Index Uses
Arterial tonometer (radial)
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The Impact of the Early Wave Reflection

• This earlier return to the heart of the reflected
  pressure wave (due to stiffening of the arteries)
  changes the aortic root pressure waveform,
  with 3 key clinical implications
• Central pulse pressure increases ... increasing
  risk of stroke and renal failure
• LV Load increases. increasing LV mass, and
  accelerating progress towards LV hypertrophy and
  heart failure
• Coronary artery perfusion pressure in diastole
  reduces. increasing risk of myocardial ischemia

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Wadwa P al. ADA 2005
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Wadwa P al. ADA 2005
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Wadwa P al. ADA 2005
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Summary

• Arterial stiffness, as measured by pulse wave
  analysis, is related to diastolic blood pressure,
  duration of diabetes and severity of
  hyperglycemia in type 1 diabetes
•  
• Increased arterial stiffness is not associated
  with the presence or extent of coronary
  calcification

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Carotid artery intima-media thickness (IMT)
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Barth JD 2004
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Decreased Progression of Carotid IMT in Intensive
Treatment Group 6 yr after completion of DCCT
6-yr IMT progression mm
p 0.01
DCCT/EDIC Research Group. N Engl J Med.
20033482294
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Conclusions

• Electron beam tomography for coronary artery
  calcification, myocardial perfusion tests,
  carotid IMT, pulse wave analysis of arterial
  stiffness, and MRI to study left ventricular
  dysfunction show promise in patients with
  diabetes mellitus
• For details see Wadwa P. Rewers M. Curr Opin
  Endocrinol Diabetes 200512267-72. Lippincott
  Williams Wilkins.