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Diabetes Mellitus A state of premature
cardiovascular death which is associated with
chronic hyperglycemia and may also be associated
with blindness and renal failure.
Fisher BM. Diabetes Mellitus and myocardial
infarction a time to act or a time to wait?
Diabetes Medicine. 1998, 15 275
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Diabetes and CVD

• In people with diabetes
• Heart disease strikes people with diabetes, twice
  as often as people without diabetes.
• CVS complications occur at an earlier age and
  often result in premature death.
• Diabetics are 2-4 times more likely to suffer
  strokes and once having had a stroke, are 2-4
  times as likely to have a recurrence.
• Deaths from heart disease in diabetic women have
  increased 23 over the past 30 years compared to
  a 27 decrease in women without diabetes.
• Deaths from heart disease in men with diabetes
  have decreased by only 13 compared to a 36
  decrease in men without diabetes.

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Glycemia Is a Cardiovascular Risk Factor
Plausible Biochemical Mechanisms
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Haffner Study
1998
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Haffner Study

• Conclusions Our data suggest that diabetic
  patients without previous myocardial infarction
  have as high a risk of myocardial infarction as
  nondiabetic patients with previous myocardial
  infarction. These data provide a rationale for
  treating cardiovascular risk factors in diabetic
  patients as aggressively as in nondiabetic
  patients with prior myocardial infarction.

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CDV Events in Diabetes Patients Framingham Study
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FPG and 2 h Pg Predict Mortality in Persons Not
Known to Have Type 2 Diabetes DECODE Study
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Relation between postprandial blood glucose
levels and cardiovascular mortality
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DECODE IGT Increases Mortality Risk
Diabetes Epidemiology Collaborative analysis Of
Diagnostic criteria in Europe
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Hba1c Predicts MI in Type 2 Diabetes UKPDS 35
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Ticking Clock Hypothesis Glucose Abnormalities
Increase CV Risk
Nurses Health Study, N117.629 women, aged 30- 55
years follow up 20 years (1976 1996)
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Pathogenesis of Increased CVD in Diabetes

• Metabolic Factors
• Hyperglycemia
• Lipids , lipoproteins
• FFA, insulin resistance

• Hypertension

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Role of HYPERGLYCEMIA
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Hyperglycemia and Vascular Disease Pathogenesis

• Many aspects of coagulation impaired
• Platelet behaviour abnormal
• Hypersensitive to stimuli
• Clot lysis inhibited
• Higher Plasminogen activator inhibitor 1 levels
• Fibrinogen levels elevated Disordered kinetics

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Is it only Hyperglycemia?
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Insulin resistance
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Insulin resistance the link between CVD and
type 2 diabetes

• Insulin resistance is an independent predictor of
  CVD2
• Insulin resistance is closely linked to a number
  of CVD risk factors3
• Insulin resistance may develop 20 years before
  onset of type 2 diabetes4 50 of newly
  diagnosed patients show signs of CVD5
• NCEP recognises type 2 diabetes as a coronary
  heart disease risk equivalent6

2Bonora E, et al. Diabetes Care
20022511351141. 3Bonora E, et al. Diabetes
19984716431649. 4Beck-Nielsen H The EGIR.
Drugs 199958(Suppl. 1)710. 5Laakso M. Int J
Clin Pract Suppl 2001121812.6NCEP ATP III.
JAMA 200128524862497.
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Insulin resistance is linked to a range of CVD
risk factors
Insulin resistance
Dyslipidaemia
Endothelial dysfunction
Microalbuminuria
Vascular inflammation
Hypertension
Atherosclerosis
CVD
Adapted from McFarlane SI, et al. J Clin
Endocrinol Metab 200186713718.
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Insulin resistance is an independent predictor of
CVD in type 2 diabetes The Verona Diabetes
Complications Study
2.5


2.0
1.5

Odds ratio (95) for
incident CVD

1.0
0.5
0.0
Insulin
Smoking (yes vs. no)
TCHDL
Age
resistance
(per unit)
(per year)
(per unit)
Error bars 95 CI
P lt 0.001 n 627
Adapted from Bonora E, et al. Diabetes Care
20022511351141.
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Endothelial dysfunction correlates with insulin
resistance
12
Control
Type 2 diabetes
Hypertension
10
8
Whole-body insulin sensitivity (MCR ml/kg/min)
6
4
2
0
20
60
0
20
40
Vasoreactivity (change in forearm blood flow
ratio )
n 27 r 0.46, P lt 0.05
Adapted from Cleland SJ, et al. Hypertens
200035507511.
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Low HDL is associated with hyperinsulinaemia
60
Hyperinsulinaemic Normoinsulinaemic
50


HDL-c (mg/dl)
40
30
20
Non-obese
Obese
Error bars SE
Adapted from Reaven GM. In Diabetes Mellitus.
LeRoith D et al., eds. Philadelphia
Lippincott-Raven 1996509519.
P lt 0.005
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Proportion of small dense LDL is associated with
insulin resistance

(n 52)
(n 29)
(n 19)
Error bars SD
Mean ( SD) LDL diameter (Å) pattern A 268
4 intermediate 261 3 pattern B 250 4P
lt 0.0050.001 compared with pattern A or
intermediate pattern
Adapted from Reaven GM, et al. J Clin Invest
199392141146.
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Proportion of patients with cardiovascular
disease increases with duration of type 2 diabetes
lt2
3-5
6-9
10-14
15
Years T2DM
Harris,S et al. CDA 2003 Type 2 Diabetes and
Associated Complications in Primary Care in
Canada The Impact of Duration of Disease on
Morbidity Load.
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Diabetes and Cardiovascular diseases two sides of
the same coin

• The European Society of Cardiology and the
  European Association for the Study of Diabetes
  (EASD) have together issued new guidelines on the
  management of diabetes, prediabetes, and
  cardiovascular disease, published in the February
  6 issue of the European Heart Journal. (Eur Heart
  J. 20072888-136).

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Key messages are

• 1)Diabetes and CVD are much more common than
  imagined,
• 2) Negative impact of dysglycemia is apparent
  before the onset of diabetes,
• 3) Prognosis is principally amenable to major
  progress, yet still unfavourable,
• 4) Investigational algorithm needs to be employed
  to detect the alternate side of the disease
  starting from diabetes or coronary artery
  disease,
• 5) Oral glucose tolerance test is the best method
  to diagnose previously unknown diabetes or
  pre-diabetes,
• 6) To minimize resources, primary screening for
  the potential of diabetes and /or CVD can be
  effectively done by a non-invasive risk score to
  define high risk,
• 7)Prevention of both diabetes and CVD is
  possible,
• 8) Therapeutic success depends on collaboration
  across speciality borders,
• 9) Treatment comprises multifactorial risk
  intervention and targeted management of CVD,
• 10) The joint ESC/EASD approach provides the
  state-of-the art evidence base. It is time to
  act, it is time to implement the available
  standards for preventing cardiovascular disease
  and diabetes!

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The recommendations suggest

• Patients with coronary artery disease should have
  an oral glucose tolerance test if their diabetic
  status is unknown.
• The treatment targets are much more precise and
  strict than previously outlined (lower blood
  pressure target and lower blood lipid targets for
  example)," and strict glucose control is stressed
  to protect patients from falling ill, or to
  prevent relapses.
• Every patient with diabetes should be screened
  for CAD.

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