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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