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Diabetes II - Diabetes II Learning Objectives...

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Diabetes II Learning Objectives Define IR and pancrea-c beta cell dysfunc-on Describe the stages of diabetes progression Discuss the molecular mechanisms by which hyperglycemia can contribute to diabetes related pathologies: ‐Glutathione (GSH) deple-on ‐Advanced Glyca-on End‐products (AGEs) ‐Protein Kinase C (PKC) ac-va-on β β
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Atherosclerosis Re-nopathy Neuropathy Nephropathy Matthaei, S. et al. Endocr Rev 2000;21:585-618 T2DM: Represents the “tip of the iceberg” of long existing disturbances with deleterious effects on the vascular system, tissues and organs
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• The risk of diabetes is 93 and 42 -mes higher at a BMI > 35 in women and men respec-vely. 93 Risk of Diabetes Obesity dramatically increases risk for T2DM
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Insulin resistance Genetic susceptibility, obesity, Western lifestyle Type 2 diabetes IR β -cell dysfunction β Rhodes CJ & White MF. Eur J Clin Invest 2002; 32 (Suppl. 3):3–13. Insulin resistance (IR) and β -cell dysfunction are underlying causes of T2DM
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•IR contributes to hyperglycemia and dyslipidemia •Increases in gluconeogenesis and lipolysis •Reduc-ons in glucose uptake •People who are IR may have the ability to overcome the resistance by producing more insulin •If the body cannot produce sufficient amounts, blood glucose increases and T2 diabetes ensues. IR occurs when the body fails to respond to the insulin it already produces
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β β β β DeFronzo RA, et al. Diabetes Care 1992; 15:318–354. •May be a consequence of IR but also occurs in insulin sensi-ve people •When β ‐cells are unable to maintain increased insulin secre-on in IR individuals, impaired glucose tolerance and T2 diabetes ensues β -cell dysfunction is the reduced ability to secrete insulin in response to hyperglycemia
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Diabetes 53:S16-S21, 2004 Fasting Blood Glucose, mg/dL Stage 1: Compensa-on •Insulin secre-on increases to maintain
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