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47 Cards in this Set
- Front
- Back
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US diabetes stats
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2012: 29.1 mill with diabetes: 9.3%
by 2050, up to 33% of adults (86.6 mill) will have diabetes |
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types of DM: primary diabetes
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type 1
type 2 geneetic defects of B cellfunction - mature onset diabetes of young: MODY = defect in single autosomal dominant gene = several diff types : each affecting a diff gene - mitochondrial DNA - other genetic defects |
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secondary diabetes types
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infectious: congenital rubella,, CMV
endocrinopathies: cushings, acromegaly drugs: glucocorticoids, nicotinic acid, pentamidine gestational diabetes mellitus pancreatitis CF neoplasia infiltration: hemochromatosis: bronze diabetes pancreatectomy |
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fasting plasma glucose ofprediabetes & diabetes dx
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pre: 100-125 mg/dl
diabetes: >126 mg/dl |
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plasma glucose 2 hours after 75 gram oral glucose tolerance test: OGTT of pre diabetic & diabetic dx
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pre:140-199 mg/dl
diabetic: > 200 mg/dl |
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random plasma glucose with syptoms of diabetes level for dx of diabetes
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> 200 mg/dl
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Hemoglobin A1c for pre diabetic & diabetic dx
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pre: 5.7-6.4%
diabetic: > 6.5% |
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when diagnosing diabetes..
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confirmed by repeat testing
diabetes should ypically not be dx during acute illness |
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55 yo male to ER ater collapsing shows a fib. lab work reveals elevated liver enzymes, blood glucose of 300 mg/dl; recently seen for poor libido and impotence; what further labs will most likel confirm his dx?
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iron saturation, ferritin
thinking hemochromatosis |
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type 1 vs type 2 dm
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type 1 (10%)
- onset < 20 yrs; not obese, absolute insulin def; antibody +; DKA + - 50% concordance int wins; HLA-D linked - autoimmune disease - Islet cells = insulitis early: precides clinical disease; marked atrophy & fibrosis; B cell depletion type 2 (90%) - onset > 30 yrs; obese; normal or increased insulin; antibody - 90-100% concordance in twins; no HLA association - insulin R and relative insulin def - ISlet cells = focal atrophy and amyloid deposits; mild B cell depletion |
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type 1 dm
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characterized by selective destruction of pancreatic islet insulin producing cells : B cells
autoimmune destruction of B cell continues through a long subclinical prodromal phase |
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stages in development of type 1
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1. genetic predisposition
2. triggeringevent - viral infections - dietary exposures: Gliadin, cereal - hygiene hypothesis 3. innate & adaptive immune response 4. islet inflammation 5. beta cell death 6. overt diabetes after loss of about 80% beta cell mass |
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enetics in type 1
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95% of type 1 pts have HLA DR3 and/or HLA DR4
HLA DR2 is negatively associted ris is 50% for monozygotic twins of individuals with type 1 - evidence that clinical disease associated with preciptating event - clearly an envrionmental comopnent |
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auutoantibodies associated with type 1
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ICA: anti islet ceell antibody
IAA: anati insulin antibody GAD: anti lutamic acid decarboxylase ICA 512: anti insulinoma associated protein ZnT8: anti zinc transporter 8 |
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autoimmune disorders associated with type 1
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polyendrcrine def syndrome 1
- addisons: 67% - hypoparathyroidism: 82% - mucocutaneous candidiasis: 73% - type 1 : 5% - pernicious anemia: 15% - vitiligo 8% - hypogonadism: 17% polyendocrine def syndrome 2 - addisons: 100% - hyperthyroidism: 69% - hypothroidism: 69% - type 1: 52% - vitiligo :5% - hypogonadism: 4% |
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group of 20 asymptoatmic individuals with fam history of type 1 undergo screeening tests; all are + for GAD antibody and nearly all have + HLA DR3 or HLA DR4 alleles and glucose levels are normale. what islet abnormaltiies would most likely be found on pancreatic biopsy
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insulitis: WBC's in islet inflamed
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52 yo male with type 2 presents to clinic on oral diabetes meds; blood glucose values high every morning upon awaking; much of this elevation in fasting blood glucoses is related to insulin R in
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liver
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factors responsible for normal glucose tolerance
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insulin secretion
tissue glucose uptake - peripheral : primarily muscle - splanchnic: liver & gut suppression of heptic glucosse production - decreased FFA's - decreased glucagon incretin effect - GLP-1 and GIP secretion with oral glucose load |
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incretin effect
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release of GLP-1 and GIP rom small intestin in response to oral nutrient intake
- no incretin response to IV nutrients GLP-1 & GIP - delay gastric emptying - stimulate insulin secetion and inhibit glucagon release: glucose dependent resonse; asglucose falls so does effect on insulin & glucagon secretion - may promote satiety in type 2, GLP-1 secretion and GIP action are reduced |
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metabolic staging of type 2
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obesity contributtes to insulin resistance
hyperinsulinemia impaired glucose tolerance B- cell defect contributes to decreased insulin secretion early diabetes B cell failure late diabetes |
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pathogenesis of type 2
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genetic predisposition
insulin resistance - muscle, liver & adipocytes insufficient insulin seccreion abnormal splanchnic glucose uptake |
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genetics of type 2
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majority fo pts with type 2 have genetic predisposition
- up to 40% risk of type 2 in first degress relatives insulin R common in normal, glucose tolerant first degree relatives most cases not explained by single gene model - multiple candidate gnes in combo most likely disproportionately affects minorities no HLA association |
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insulin resistance
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precedes onset of clinical type 2
seen even in lean invidiuals with type 2 present at all concentattion of insulin |
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IR in tpe 2 states
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basal state: liver is major site of IR
- associated with an overproduction of glucosse insulin stimulated state (after meals) - decreased muscle glucose uptake - impared suppression of hepatic glucose production IR involves post Receptor impairment of insulin action |
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post Rimpairment of insulin action
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abnormal insulin R tyrosin kinase activity
- impaired phosphorylation of downstream proteins insulin R substrate (IRS) defects - impaired GLUT4 translocation 7 function : fed state - increased hepatic glucose production: fasting state |
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clinical components of insulin resistnace syndrome
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hyperglycemia
lipid abnormaltiies visceral fat accumulation (around organs) HTN coronary artery disease: overlaps with type 2 |
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lipid abnormalities n IRS
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eleavted TG's
depressed HDL-C small dense LDL |
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insulin secretion & action in DM2
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control: normal glucose, insulin, glucose uptake
obese, glucose intolerant: IGT, elevated insulin, decreased glucose uptake - evidence of IR obese, DM, high insulin: DM level glucoses, elevated insulin, decreased glucose uptake - IR and mild beta cell dysfunction/loss obese, DM, low insulin: DM level glucose, low insulin, low glucose uptake - IR and severe beta cell dysfunction/loss |
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potential mechanisms for insulin def in type 2
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reduced B cel mass
glcuose toxicity islet amyoid genetics lipotoxicity: acute rise in FFA's augments insulin secretion;n chronic elevations in FFA's with type 2 inhibit insulin secretion decreased incerrtin effect cytokines/inflammation |
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pathophys of type 2 insulin secertion
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up regulaion of uncoupling protein 2 (UCP2) - decrease ATP production - decrease insulin secretion
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splanchnic glucose uptake
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most profound uptake issue is in muscle
total splanchnicglucose uptkae in DM2 similar to control BUT, with profound hyperglycemia, splanchnic glucose uptake should increase to counter this - does not happen in DM2 |
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15 yo female presents to ER with 3 days of nausea/vomiting; 2 months of wt loss, polyuria/dipsia; blood glucose 400 and serum bicarb is 8 ; what is most likely expanation fo rpts clniical presentation?
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she has new dx of type 1
DKA: lowbicarb makes acidotic |
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acute complicataions of diabetes
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hyperglycemia
diabetic ketoacidosis hyperosmolar nonketotic states |
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DKA components
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hyperglycemia
ketosis: breakdown of fat ofr energy met acid |
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DKA cause
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relative or absolute insulin def
- infection - omission or inadequate insulin - new onset typee 1 - other severe sress: heart attack, stroe type 2 only rarely associated with DKA |
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DKA pathogenesis
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alterations in met: carb, protein, lipds
lack of effective insulin elevated counter regulatory hormones - glucagon & cats - eleavte glucose & induce lipolysis; lipolysis source of ketones |
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DKA dx
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history
PE labs - hyperglycemia - low bicab (<15) - low pH - ketonemia & ketonuria - increased Anion gap :Na - (Cl + HCO3) |
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diabetic hyperosmolar states
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poorly controled type 2
- glucose impermeable solute - osmotic diuresis from glycosuria = decreases ICF & ECF water = fall in GFR leads to high glucose levels (>1000 mg/dl) = older individuals have higher renale thresholds for glucose |
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is insulin produced in diabetic hyperosmolar states
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yes
- relative nsulin def - insulin resistance high |
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is there ketoacidosis in diabetic hyperosmolar states
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no
- insulin present to inhibit ketosis - counter regulatory hormones less than DKA |
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diabetic hyperosmolar states pt
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age > 55
30-600% with new dx of diabetes women > men precipitating illness uaully present - infection most common - heart attack , stroke |
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diabetic hyperosmolar states presentation
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with concurrent illness
progressive dehyrdation marked volume depletion fever neurologic manifestations |
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neurologic manifestations from diabetic hyperosmolar states
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lethargy & disordered sensorium
coma in 10% psychiatric findings focal neurologic findings seizures in 25% - focal or generalized |
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pathogensis of type 1 related to
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genetic predisposition +triggering event = autoimmune islet destruction
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pathogenic factors in type 2 include
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genetics, insulin resistnace, and abnormal insulin secretion
several forms of secondary diabetes exist |
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DKA most commonly occurs in
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type 1 pts, in insulin def state
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hyperosmlar non ketotic states most common in
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older pts with poorly controled type 2 and inciting factor
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