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z Epigenetics is also thought to be very important in the development of
T2DM.
z Obesity is the most potent risk factor for developing T2DM.
z The prevalence of T2DM around the world is heavily influenced by race/
ethnicity.
◦ The incidence of T2DM in white Europeans is relatively low compared with
Asian/Pacific Islanders.

z Lack of exercise has a significant impact on the risk of developing T2DM.
z Individuals with impaired glucose tolerance (IGT) or impaired fasting glu-
cose (IFG) are at an increased risk of developing T2DM.
z Regardless of the classification, all complications of T2DM are a conse-
quence of chronic hyperglycaemia and the other metabolic and haemo-
dynamic abnormalities that accompany this disease such as central obes-
ity, dyslipidaemia and hypertension.
z Elevated glucose levels result in the non-enzymatic formation of glycated
proteins and, ultimately, advanced glycosylated end products (AGEs), the
accumulation of sorbitol and fructose, increased hexosamine pathway flux
and the activation of protein kinase C.
◦ This over-abundance of sugars causes oxidative and osmotic stress.
z The cells particularly affected by hyperglycaemia are capillary endothe-
lial cells throughout the body, mesangial cells in the renal glomerulus and
neurons and Schwann cells in the autonomic and peripheral nerves.
◦ These cell types above are unable to reduce their uptake of glucose
when they are exposed to hyperglycaemic conditions.
z The microvascular complications are retinopathy, nephropathy and neuro-
pathy.
z Macrovascular complications include stroke, transient ischaemic attacks,
coronary artery disease, myocardial infarction, hypertension and periph-
eral vascular disease.
◦ As varied as these may seem, they are all a consequence of hypergly-
caemia-induced damage to the endothelium of blood vessels, most no-
tably the arteries.
◦ Data suggest that cardiovascular disease accounts for the largest pro-
portion of all diabetes-related healthcare expenditure.

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