Download How does diabetes contribute to peripheral vascular - PBL-J-2015

Diabetes and Vascular Disease
http://circ.ahajournals.org/content/108/12/1527.full.pdf
Vascular diseases are the principal causes of death and disability in people with
diabetes. There is a strong correlation between cardiovascular disease (CVD) and
diabetes.
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Heart disease and stroke are the No. 1 causes of death and disability among
people with type 2 diabetes.
At least 65 % of people of diabetics die from some form of heart disease/stroke.
Adults with diabetes are two to four times more likely to have heart disease or a
stroke than adults without diabetes.
The American Heart Association considers diabetes to be one of the six major
controllable risk factors for cardiovascular disease.
Over time, the excess glucose damages blood vessels throughout the body and vascular
disease may result such as retinopathy and nephropathy which are major causes of
blindness and end-stage renal failure respectively.
Pathophysiology of diabetic vascular disease
Effective endothelial and vascular smooth muscle cell function within vascular walls is
vital and an abnormality may contribute to and exacerbate atherosclerosis and its
complications. In normal endothelial cells, biologically active substances are
synthesised and released to maintain vascular homeostasis to ensure adequate blood
flow and nutrient delivery. One important substance synthesised by the endothelial cell
is nitric oxide (NO). The bioavailability of NO represents a key marker in vascular health
because it; causes vasodilation of smooth muscle cells, protects from endogenous injury.
Also the loss of endothelial-derived NO leads to increased activity of pro-inflammatory
transcription factors that results in greater expression of chemokines and cytokines that
promote formation of macrophage foam cells (initial morphological changes of
atherosclerosis). NO also is a key mediator of molecular signals that prevent platelet
and leukocyte interaction with vascular wall and an inhibitor of vascular smooth muscle
cell proliferation and migration. These abnormalities in endothelial cell function are
mediated by the metabolic derangements which include:
 Hyperglycaemia: studies show hyperglycemia directly decreases endothelium
derived NO and endothelial relaxation is impaired. Leads to a series of events
that produces superoxide anion whilst inactivating NO increased oxidative
stress.
 Excess free fatty acid deposition: impair endothelial function by increased
production of oxygen-derived free radicals, exacerbation of
dyslipidemiaIncrease oxidative stress.
 Insulin resistance: Insulin normally stimulates NO by a complex mechanism
from endothelial cells
Endothelial cell dysfunction also results in not only a decreased NO but also an
increased synthesis of vasoconstrictors prostanoids and endothelin. These promote
inflammation and cause vascular smooth muscle cell contraction and growth.
Figure: The metabolic
abnormalities that
characterize diabetes,
particularly
hyperglycemia, free fatty
acids, and insulin
resistance, provoke
molecular mechanisms
that alter the function
and structure of blood
vessels.
Abnormalities of the cardiovascular system specific to diabetes
What is
it?
Microangiopathy
Autonomic
neuropathy
Damage to small blood
vessels and capillary
circulation
Damage to the nerve
supply of the internal
organs of the body
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Problems with the 
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Retinopathy
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Nephropathy
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Neuropathy
Clinical 
outcome
pulse rate
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Diabetic foot
Other blood vessel damage
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Damage to the inner or outer lining
of blood vessels
Impaired regulation of blood flow
Weakened vessel walls
Postural fall in blood
Aggravated microangiopathy and
pressure
atherosclerosis/macroangiopathy
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Foot ulcers
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Impotence
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Gastro-intestinal
dysfunction