21 - *Diabetes *BCH3120 *Lecture21 *March30,2011...

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* BCH3120 * Lecture 21 * March 30, 2011 * Diabetes
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* Outline * Different types of diabetes * Clinical features * History * Type 1 * Type 2 * Alterations in metabolism * Glucose tolerance * Untreated type 1 * Type 2 * Treatment of diabetes mellitus * Type 1 * Type 2 * Longer term complications * Micro- and macro- vascular disease * Non-enzymatic glycation of proteins * The polyol pathway * The hexosamine pathway Protein kinase c activation
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* Different types of diabetes mellitus * Most common forms are type 1 and type 2 * All forms characterized by abnormally high blood glucose * Overt symptoms: intense thirst and frequent urination  * Diabetes (greek – syphon) mellitus (greek - honey; due to sticky  sugary urine)  * Type 1 used to be  called “juvenile” and “insulin-dependent  diabetes mellitus (IDDM)”  * Type 2 used to be  called “mature-onset” and “non-insulin- dependent diabetes mellitus (NIDDM)”
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* Type 1:  * Occurs due to autoimmune destruction of the beta cells in the  pancreas * Age of onset is typically 6 mo to 25 y * Population prevalence: ~0.5% * Body phenotype: lean (weight loss at diagnosis) * Treatment: insulin injections * Type 2:  * Occurs due to defective insulin sensitivity in ‘target’ tissues and  insulin secretion  * Age of onset is usually >40 y (but recently younger) * Population prevalence: ~4% * Body phenotype:  usually  obese and inactive  * Treatment: diet, drugs, later insulin injections
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Other (more rare) forms of diabetes mellitus * Gestational:  Diabetes in pregnancy, disappears after pregnancy.  Due to metabolic stress during pregnancy. Women who develop it  are at increased risk of developing T2DM later in life.  * Mature onset diabetes of the young (MODY) :  a group of  conditions each inherited in a Mendelian fashion (MODY 1 – 7).  E.g., MODY 2 caused by mutation in glucokinase affecting insulin  secretion; others can include mutated transcription factors in beta  cells.   * Latent autoimmune diabetes in adults (LADA) : usually  incorrectly diagnosed as T2DM; in fact estimated that 10% of all  T2DM are actually patients with LADA. 
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* Clinical features History * Earliest known record: Egyptian papyrus dating from 1500BC * Greek physician Aretaeus of Cappadocia named the disease  in ~100AD “… the patients are tortured with an unquenchable  thirst; the whole body wastes away” * 19th C: discovery of the islets of Langerhans; and that the  removal of the pancreas in dogs led to diabetes * 1921 Toronto: Dr Frederick Banting and  Charles Best made extract of pancreas that  when injected restored health to diabetic dogs,  and then human patients
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Type 1 * Autoimmune destruction of the insulin secreting cells of the islets 
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21 - *Diabetes *BCH3120 *Lecture21 *March30,2011...

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