2. Angiopathy
Disease of the blood vessels
Classified by caliber into:
Microangiopathy
Macroangiopathy
3. Diabetic macroangiopathy
Hyperglycemia has a direct toxic
influence on the arterial wall by increased
accumulation of irreversible glycosylation
end products, and secondly, it provokes
endothelial dysfunction.
Manifestation:
Coronary heart disease
Cerebrovascular disease
Peripheral vascular disease
Hypertension
Arteriolar nephrosclerosis
5. In diabetic patients, collateralization and
angiogenesis are insufficient to overcome
the loss of blood flow through narrowed or
occluded arteries leading to ischemia and
often nontraumatic limb amputation.
Increased glucose levels in the body end up
in uncontrolled covalent bonding of aldose
sugars to a protein or lipid without any
normal glycosylation enzymes. These stable
products then accumulate over the surface
of cell membranes, structural proteins and
circulating proteins. These products are
called advanced glycation endproducts
(AGEs)
6. AGEs are prevalent and contribute to the
development of atherosclerosis.
AGEs contribute to a variety of microvascular and
macrovascular complications through the
formation of cross-links between molecules in the
basement membrane of the extracellular matrix
and by engaging the receptor for advanced
glycation end products (RAGE).
Activation of RAGE by AGEs causes;
Upregulation of the transcription factor nuclear
factor-κB and its target genes.
Soluble AGEs activate monocytes, and AGEs in the
basement membrane inhibit monocyte migration.
AGE-bound RAGE increases endothelial
permeability to macromolecules.
AGEs block nitric oxide activity in the endothelium
and cause the production of reactive oxygen
species.
7. Ischemic Injury Leading to Gangrenous Foot
Ischemic injury is the result of progressive occlusion
of the capillaries of the skin (atrophy) and skeletal
muscles (intermittent claudication) due to
thickening of capillary basement membranes.
Diabetes hinders wound healing and causes
peripheral sensory neuropathy further exaberating
ischemic injury to the lower extremitiy. Diabetes is
the most frequent cause of non-traumatic lower
limb amputations.
9. Reference
Alison Goldin, Joshua A. Beckman, Ann Marie
Schmidt, Mark A. Creager. Advanced Glycation
End Products: Sparking the Development of
Diabetic Vascular Injury. Circulation. 2006; 114:
597-605
Jean-Sébastien Silvestre, Bernard I. Lévy.
Molecular Basis of Angiopathy in Diabetes
Mellitus. Circulation.2006;98:4-6
University of California School of Medicine. 2012.
Pathological Condition of Diabetes Mellitus.
Accessed at:
http://missinglink.ucsf.edu/lm/IDS_106_DM_Com
plications/default.htm
Editor's Notes
The presence and accumulation of AGEs in many different cell types affect extracellular and intracellular structure and function.
