0 evaluări0% au considerat acest document util (0 voturi)
29 vizualizări13 pagini
$174 billion a years is spent on diabetes (this includes lost productivity from diabetes) - 3 / 4 is direct medical costs though. - 9-11 weeks into gestation islets of langerhans in the panacreas develop - 70% beta cells - 20% alpha cells - essentially an endocrine organ embedded in an exocrine organ.
$174 billion a years is spent on diabetes (this includes lost productivity from diabetes) - 3 / 4 is direct medical costs though. - 9-11 weeks into gestation islets of langerhans in the panacreas develop - 70% beta cells - 20% alpha cells - essentially an endocrine organ embedded in an exocrine organ.
Drepturi de autor:
Attribution Non-Commercial (BY-NC)
Formate disponibile
Descărcați ca DOC, PDF, TXT sau citiți online pe Scribd
$174 billion a years is spent on diabetes (this includes lost productivity from diabetes) - 3 / 4 is direct medical costs though. - 9-11 weeks into gestation islets of langerhans in the panacreas develop - 70% beta cells - 20% alpha cells - essentially an endocrine organ embedded in an exocrine organ.
Drepturi de autor:
Attribution Non-Commercial (BY-NC)
Formate disponibile
Descărcați ca DOC, PDF, TXT sau citiți online pe Scribd
← Prevalenc eof diabetes in US is 24 million, 8% of the population
← ¼ of them are not diagnosed ← 233,000 deaths a year are secondary to diabetes, 5th leading cause of death ← $174 billion a years is spent on diabetes (this includes lost productivity from diabetes) – ¾ is direct medical costs though ← 1/10 health care dollars is spent on diabetes ← 1/5 medicare dollars is spent on diabetes ← 9-11 weeks into gestation islets of langerhans in the panacreas develop ← islet hyperplasia is seen in infants of diabetic mothers, but ability of cells to divide is lost after neonatal period ← 1 million islets ← 70% beta cells ← 20% alpha cells ← essentially an endocrine organ embedded in an exocrine organ ← majority of the cells make insulin, the minority make glucagons and tend to be at the periphery of the islets ← insulin is an anabolic hormone ← increases glucose transport into the cells to make glycogen, etc to store it ← it is usually done because the target cells have a transporter for glucose that responds to insulin binding ← this increases glucose phosphorylation (holding it in cells) ← increases glycogen and triglyceride production and storage ← also kind of acts like a growth hormone driving DNA synthesis, cell growth, protein synthesis, etc ← ← hormones that oppose action of insulin are glucagons, cortisol, epinephrine, and growth hormone ← ← originally there was juvenile onset and adult onset diabetes ← (also secondary and latent diabetes, but less important) ← ← this was not an ideal classification system, because it wasn’t that clinically relevant ← ← now there is the insulin-dependent DM (Type I) ← and NIDDM (Type II) • broken down into obese and non-obese types • and maturity onset diabetes of the young ← ← this also wasn’t great, because some Type II people ended up needing insulin ← ← Type I diabetes is due to an auto-immune destruction of the islets ← In Type II, there is insuline resistance and inadequate compensation, leading to relative insulin deficiency ← ← Type I is a more “brittle” diabetes, they are ketoacidosis prone and they don’t make any insulin on their own after awhile, highly genetic ← Type II is more “stable” ← ← Type I is more common among the young, but Type II is by far more common overall ← It is rarer under 20 years old, but it is far far more common in those over 20, especially in the very old ← ← Type I diabetes is an absolute deficiency in insulin secretion ← This means that the diabetics are extremely sensitive to blood glucose levels ← So exogenous insulin, changes in diet, changes in fluid, changes in physical activity, infection, are all problems with them ← They have to adjust insulin they take according to all these things and it is hard ← Fluctuates rapidly as hypoglycemic and hyperglycemic ← ← the thought is that Type I diabetes does not appear clinically until 75- 90% of beta cell function in your islets is gone ← there is some kind of environmental trigger (we think) ← that begins an autoimmune response against your islets ← you have a “latent” period where you are slowly losing beta cells, but you don’t know it yet, because you have a lot of extra capacity ← once you have lost like 80% of your capacity, then you will generally have a stress event that triggers some kind of symptoms that leads to diagnosis of their diabetes ← 1-5 years – “honeymoon” phase follows where patient capacity is usually okay, as the aftermath of the stress event the body recovers ← then they will dip into diabetes for the rest of their life after that ← ← it is believed that it is a rare outcome of exposure to a common environmental factor in genetically susceptibly individual ← risk is directly related to family history/genetics ← ← we think there is an environmental factor because regionally it has differences ← only 20% of type I diabetics have a family history too ← immigrants have risk closer to country that they go to, rather than where they come from ← environmental could be something about our lifestyle ← not necessarily like a specific pollen ← some hypotheses have been chemicals, toxins, and viruses ← ← there is linkage to MHC Class II antigens, indicating it has an autoimmune component ← you can also see inflammatory process in pancreas and you can find autoantibodies ← if you immunosuppress diabetics it can actually slow progression of the disease ← 20% of diabetics have other auto-immune mediated endocrine disorders ← ← histologically you see the insulin-producing cells in particular disappear, glucagon-producing cells also seem to increase, but we aren’t completely sure about that ← islet cell antibodies (ICA) are usually present in 90% of patients at diagnosis and then it decreases over time (but capacity to destroy pancreas remains, i.e. after transplant) ← it is often seen in relatives ← the antibody could be etiologic (the cause) or secondary, we don’t know ← some people think it may be T cell mediated and not antibody mediated ← if you transfer T cells between mice you can transfer diabetes, but not if you transfer the antibodies with the serum ← diabetes has been transferred in humans via bone marrow transplant ← if you transfer a good pancreas into a diabetic, it gets destroyed again ← ← insulin replacement and education are the most important treatment strategies for diabetes ← there is no cure ← you can give a pancreas transplant if you are already giving a kidney transplant and then immunosuppress the patient (bc you will have to for the kidney anyway) and then it will allow the pancreas to stick around ← ← Type II diabetes ← Decreased responsiveness of tissues to insulin ← The receptor number/function doesn’t change, but response to receptor binding decreases ← You also get an impaired compensatory response to this ← The general population prevalence is as high 5% ← Twin of type II diabetes has near 100% chance of developing it ← VERRRY genetic/connected to family history ← ← diabetes type II is increasing worldwide and varies geographically ← native Americans 8% prevalence ← Pima Indians have 50% prevalence ← ← obesity puts you at higher risk ← higher age puts you at higher risk ← hypertension and elevated LDL are also risk factors ← ← lots more obese people these days could account for at least a big part of the increase in Type 2 diabetes ← ← patients present as older and overweight ← the onset is often insidious ← they don’t realize it ← it gets picked up on and a routine urine test ← 25% of Type 2 diabetics have not been diagnosed ← you see a mild depletion of beta cells ← a unique deposition of amyloid (not always there) ← no insulitis ← ← you see hyaline deposits of pink material in islets ← you give them dietary management, life-style changes, oral medications, and possibly eventually insulin supplementation ← ← ← 08/11/2010 10:39:00 ← in prep for lab on Friday, review online cases ← acute complications of diabetes ← ← hyperglycemia ← ketoacidosis ← hypoglycemia ← diabetic coma ← death ← ← Type 1 Diabetes • Increased oxidation of free fatty acids by the liver creates and releases ketones at a greater rate than they are utilized peripherally • Metabolic ketoacidosis results in nausea vomiting, kussmaul breathing ← Type 2 • Presents differently ← ← chronic complications of diabetes are mostly from really high blood sugar, so they are the same in type 1 and 2 ← they are: • susceptibility to infection • microvascular diseases o retinopathy o nephropathy • macrovascular disease o cardiac o cerebral peripheral ← more than half of diabetics die of coronary artery disease ← cerebral vascular disease gets another 15% ← ← non-enzymatic glycosylation ← glucose is covalently bound to the beta chain of hemoglobin A ← so you can measure these levels through hemoglobin A1C ← it is a useful test to assess glucose management over last 120 days ← that is the life of a red blood cell ← AGEs are advanced glycosylation end-products ← The formation of them is reversible ← Attach to collagen in basement membrane of vessel walls where they accumulate over the lifetimes of the vessel ← Binds to receptors on the surface of macrophages and endothelial cells ← ← cellular immunity of diabetics seems to be impaired ← migration of cells is slower ← there is decreased chemotaxis ← and sometimes you don’t get the right T cell response ← ← there are certain organisms you tend to become susceptible to as a diabetic ← ← poor blood supply further impedes inflammatory response ← ← mucormycosis is pretty much confined to diabetes ← TB, staph, and candida all show increased rates in diabetics ← ← nephropathy ← microalbuminuria ← glomerulosclerosis, etc ← ← you get basement membrane thickening, this is particularly damaging to kidney function ← 30% increase in thickness in 5 years ← greater than 5 times thicker eventually perhaps ← ← arteriolonephrosclerosis – kidneys get granular appearance ← gives kidney granular appearance ← nephrons die and contract creating microscopic dimples, leading to granular appearance ← same thing can happen from chronic hypertension ← ← many diabetic patients get to end stage renal disease ← more common in Type 1 diabetics, but more prevalent in type 2 ← genetic predisposition to ESRD in diabetes ← African Americas, Hispanic Americans, native Americans at particularly high risk ← Hypertension accelerates progression to ESRD ← ← retinal capillary microaneurysms occur, when endothelial cells get killed off by high glucose levels ← you can also get cotton-wool spots – nerve fiber layer infarcts due to microvascular injury ← neovascularization is the worst thing that can happen to a retina ← ← you can lose your vision through diabetes in a number of ways ← basement membrane thickening can lead to macular edema ← arteriolar hyalinization, neovascularization ← there is a whole big slide of it ← ischemic retina releases angiogenic factor ← now we have some medical therapies that inhibit this that are intravitreol injections ← there is also pan-retinal photocoagulation – where you destroy ischemic retina with a lazer ← you will see these as blanched spots that are now there from lost photoreceptors and RPE ← ← diabetic neuropathy ← sensory neuropathy that affects longer and smaller nerves of hands and feet ← motor neuropathy, you start having muscle wasting of intrinsic muscles of hands and feet ← you also have an autonomic neuropathy ← you lose sweating and get drying of the skin ← ← macrovascular disease – you get bad atherosclerosis ← this leads to occlusive problems, MI, stroke, etc ← ← feet are a major problem with diabetics ← they get lower extremity gangrene ← 100x more common in diabetics than nondiabetics ← ← 08/11/2010 10:39:00 ← macrovascular disease kills people ← microvascular disease causes lots of morbidity ← foot amputations, blindness/retinopathy, nephropathy ← the number of people with diabetes is expected to double by 2025 ← it is already a worldwide epidemic of almost 200 million people ← fasting hyperglycemia – criteria of diabetes ← glucose test, give a drink of something sugary, see a huge jump in blood sugar ← measure plasma insulin (not normal) ← normal is like 10, in diabetics you will see insulin levels of 100 ← lack of insulin is not the problem ← there is plenty of insulin but blood sugar levels are still high ← ← can deal with this by losing weight ← will go away if person loses weight ← but they will probably gain the weight back ← at first they will be okay on glucose, but insulin levels will start to rise ← eventually the system breaks down and the beta cells stop overproducing insulin, and you just have straight hyperglycemia and diabetes ← ← insulin resistance leads to hyperinsulinemia ← you have compensation by beta cells and normal glucose tolerance ← eventually beta cell “failure” ← ← most glucose in fasting state comes from liver, a little from kidney ← 30% of glucose at fast will come from glycogen breakdown, 70% from gluconeogenesis ← the reason glucose comes from those 2 organs is because those are the only organs that have G6P enzyme for gluconeogenesis ← ← impaired insulin secretion from pancreas, increased glucose production in liver, and insulin resistance in muscle – triangle of type 2 diabetes ← in pancreas there is alpha and beta cell dysfunction ← glucose is maintained in a narrow window in the blood ← ← insulin resistance in muscle ← the GLUT4 receptor binds glucose and a pathway follows ← we don’t know where the resistance comes from in this pathway for sure ← bottom line though is that we think that it has directly to do with transport ← GLUT4 is not transporting glucose into the cell ← ← increasing free fatty acid levels in blood of healthy people can inhibit glucose transport in the same way ← how does fat cause this block ← it is possible that intracellular lipids are blocking trafficking of GLUT4 to the surface ← it is also possible that they are interfering with the insulin signaling cascade that also activates GLUT4 ←