Pathogenesis and Classification ofGlycemic Disorders

Hyperglycemia

Excessiveglucose production

Impairedglucose clearance

Tissue injury1

Hyperglycemia Damages Tissues

Effects of hyperglycemiaGlycation of proteins (eg, hemoglobin, collagen) Accumulation of sorbitol and fructose (eg, in nerves, lens)Activation of protein kinase C (eg, on vascular cells)

Tissue changesAltered protein function and turnover, cytokine activationOsmotic and oxidative stress Reduced motor and sensory nerve conduction velocityIncreased glomerular filtration rate and renal plasma flow

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Medical Complications of Hyperglycemia

Retinopathy, nephropathy, neuropathyCardiovascular disorders Infections, cataracts, connective tissue disorders

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Hyperglycemia

Brownlee M. Metabolism. 2000;49(suppl 1):9-13; Greene DA et al. N Engl J Med. 1987;316:599-606; Sheetz MJ, King GL. JAMA. 2002;288:2579-2588

Glycationpathway

Sorbitolpathway

Sorbitol and fructose Glycated proteins(eg, A1C)

Oxidativeeffects

Osmoticeffects

Advanced glycationend products (AGEs)

Altered functionor turnover

Receptor-mediatedcytokine effects

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