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Pathogenesis and Classification of Glycemic Disorders

Pathogenesis and Classification of Glycemic Disorders. Hyperglycemia The Defining Feature of Diabetes. Excessive glucose production. Impaired glucose clearance. Hyperglycemia. Tissue injury. 1. Hyperglycemia Damages Tissues. Effects of hyperglycemia

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Pathogenesis and Classification of Glycemic Disorders

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  1. Pathogenesis and Classification ofGlycemic Disorders

  2. HyperglycemiaThe Defining Feature of Diabetes Excessive glucose production Impaired glucose clearance Hyperglycemia Tissue injury 1

  3. Hyperglycemia Damages Tissues • Effects of hyperglycemia • Glycation of proteins (eg, hemoglobin, collagen) • Accumulation of sorbitol and fructose (eg, in nerves, lens) • Activation of protein kinase C (eg, on vascular cells) • Tissue changes • Altered protein function and turnover, cytokine activation • Osmotic and oxidative stress • Reduced motor and sensory nerve conduction velocity • Increased glomerular filtration rate and renal plasma flow 2

  4. Medical Complications of Hyperglycemia • Retinopathy, nephropathy, neuropathy • Cardiovascular disorders • Infections, cataracts, connective tissue disorders 3

  5. Two Mechanisms of Tissue Injury by Hyperglycemia Hyperglycemia Glycation pathway Sorbitol pathway Advanced glycation end products (AGEs) Glycated proteins (eg, A1C) Sorbitol and fructose Altered function or turnover Receptor-mediated cytokine effects Osmotic effects Oxidative effects 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 4

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