Page 319 - fbkCardioDiabetes_2017

CVD in Diabetes- Is It Only Macrovascular? 295

accumulate Diabetes also disturbs vascular function
through nonenzymatic glycation of macromolecules.

In states of hyperglycemia and increased oxida-
tive stress, many proteins and even lipids undergo
nonenzymatic glycation. Glycated proteins can form
structures known as AGEs that cause the macromol-
ecule to take on a brown hue, similar to burnt sugar.
AGEs accumulate in the vessel wall and appear to
contribute to the pathobiology of complications of
diabetes, notably the accelerated vascular disease
characteristic of this conditionduring atherosclerotic
lesion formation.Phospholipids and apolipoproteins
can form AGEs and AGE-modified proteins can ac-
cumulate in diabetic subjects. The presence of gly-
cated forms of low-density lipoproteins (LDLs) can
engender an immune response and contribute to
macrovascular disease. AGE-modified LDL apopro-
tein and LDL lipid levels increase in diabetic subjects
compared with nondiabetics.Increased AGE produc-
tion is associated with reduced nitric oxide bioavail-
ability through impairment of eNOS transcription and
activity, production of oxygen-derived free radicals,
and activation of NF-kBDiabetes impairs vascular
smooth muscle function and augments the produc-
tion of vasoconstrictor mediators, angiotensin II and
vasoconstrictor prostanoids, including endothelin-1,
which causes vascular smooth muscle growth and
inflammation. However, most diabetics have periph-
eral autonomic impairment at the time of diagnosis,
and vascular beds regulated by these nerves have
decreased arterial resistance. Similar to endotheli-
al cells, diabetes activates atherogenicmechanisms
within vascular smooth muscle cells, including pro-
tein kinase C, RAGE, NF-kB and the production of
oxidative stress.Diabetes heightens vascular smooth
muscle cell migration in atherosclerotic lesions.
Advanced atherosclerotic lesions have fewer vas-
cular smooth muscle cells in diabetic patients than
nondiabetic patients, possibly resulting in decreased
resiliency of the fibrous cap and thereby increasing
the risk of rupture and luminal thrombi.

To sum up the interconnection between Type 2 DM
and CVD, various genetic and environmental play up
ending in Macrovascular complication namely ath-
erosclerosis through various steps namely endothe-
lial dysfunction. It gives room for the plaque rupture
and then activation of clotting system resulting in
thrombus formation. So we can conclude that CVD
is only a macrovascular complication of Type 2 DM

Cardio Diabetes Medicine