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Elevated levels of glucose are found throughout the body of an in-
dividual with T2DM from the blood in their arteries supplying oxygen
and substrates to the fluid that bathes their cells. If these elevated glu-
cose levels persist for an extended period of time then cellular dam-
age ensues. Exactly how elevated glucose levels damage cells is not
fully understood, but a number of candidate mechanisms have been
identified. Elevated glucose levels result in the non-enzymatic forma-
tion 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. 61-63
One consequence of this over-abundance of sugars is an increase in
oxidative stress, i.e. increased concentrations of free radicals gener-
ated during the metabolism of the overly abundant sugars. 61 62 Similarly,
this excess of sugars causes osmotic stress, i.e. the reduced ability of the
cell to regulate its water and solute levels. 61 62

The damage sustained by cells and tissues accumulates until compen-
satory mechanisms are insufficient to prevent a decline in function and
diabetic complications become symptomatic (Figure 10). The cells
61
particularly affected by hyperglycaemia are capillary endothelial cells
throughout the body, mesangial cells in the renal glomerulus and neu-
rons and Schwann cells in the autonomic and peripheral nerves. Un-
61
like most other cells, the cell types above are unable to reduce their
uptake of glucose when they are exposed to hyperglycaemic condi-
tions. 61

Figure 10. General features of hyperglycaemia-induced tissue damage. 61

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