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nomic impacts, diabetic neuropathy is a typically overlooked compli-
cation of T2DM.

Macrovascular complications

People with T2DM are at increased risk of macrovascular complica-
tions, such as stroke, transient ischaemic attacks, coronary artery dis-
ease, myocardial infarction, hypertension and peripheral vascular dis-
ease. As varied as these may seem, they are all a consequence of
hyperglycaemia-induced damage to the endothelium of blood ves-
sels, most notably the arteries. This injury to the endothelium triggers a
cascade of events, collectively known as atherogenesis (Figure 11).
60
This process also involves an inflammatory response within the vessel
wall, which ultimately results in the formation of atherosclerotic lesions
that effectively narrow the lumen of arteries throughout the body, as
well as hardening the arterial walls (Figure 11). This narrowing impedes
blood flow and can increase the chances of clot formation. However,
the most catastrophic consequence of this inflammatory process is the
potential for the lesion to rupture with debris and associated clots oc-
cluding a downstream portion of a blood vessel, which in some cases,
can be fatal. 60

The atherogenic cascade begins with the oxidation of lipids from LDL
particles, which accumulate in the endothelial wall of arteries. An-
60
giotensin II is thought to promote the oxidation and accumulation of
lipids. Following this initial step, monocytes infiltrate the arterial wall
60
and differentiate into macrophages, which accumulate oxidised lipids
to form foam cells. Once formed, these foam cells stimulate macro-
60
phage proliferation as well as attracting T-lymphocytes. In turn, the
60
T-lymphocytes induce smooth muscle proliferation and the accumula-
tion of collagen in the arterial walls. The net result of this inflammatory
60
cascade is the formation of a lipid-rich atherosclerotic lesion with a
fibrous cap. 60
In addition to the inflammatory mechanisms outlined above, there is
also evidence of increased platelet adhesion and hypercoagulability
in people with T2DM. These phenomena may be as a result of impaired
nitric oxide generation, increased free radical formation and altered
calcium regulation in the platelets, all of which promote platelet ag-
gregation. Not only is platelet aggregation often increased in people
with T2DM, but there is also evidence that the process of fibrinolysis may
be impaired due to elevated levels of plasminogen activator inhibitor
type 1. It is very likely this combination of increased coagulability and
60
impaired fibrinolysis further increases the risk of vascular occlusion and
cardiovascular (CV) events in T2DM. 81

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