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87 Cards in this Set
- Front
- Back
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What is definition of Metabolic Syndrome or Syndrome X
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3 or more of factors:
abdominal obesity hyperglycemia dyslipidemia hypertension |
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What secretes insulin, glucagon and amylin?
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Pancreatic Islets (Islets of Langehans)
alpha cells=glucagon beta cells=insulin & amylin |
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What is the primary regulator of insuline and glucagon secretion?
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Glucose.
insulin secretion increases as blood gluose increases moraml glucose is 5mM or 80-90mg/100ml |
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What type of secretion does insulin have?
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biphasic
transient 1st phase sustained 2nd phase |
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What is an early feature regarding insulin secretion in type 2 diabetes?
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a decreased 1st phase
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What does the anabolic hormone insulin prevent?
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hyperglycemia
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What hormone is most important in prevention of acute hypoglycemia
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Glucagon
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what does anabolic mean?
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Insulin promotes synthesis of macro molecules
(makes big things from small things) ie. proteins from amino acid |
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what are some anabolic actions of insulin
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1. gulcose=synthesis & storage of glycogen
2.amino acids=proteins 3.fatty acid=sythesis/storage of fat |
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what is an action of insulin that is not anabolic?
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promotes breakdown of glucose by cells to produce energy
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Insulin acts on what tissues?
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vitually all
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What tissue is glucagon primary target?
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liver
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what is glycolysis?
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"burning" of glucose
glucose-->pyruvate + energy = glycolysis |
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What are the actions of insulin?
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1. stimulates glycolysis
2. stimulates glycogenesis 3. stimulates protein synthesis from amino acids 4. stimulates lipogenesis 5. inhibits gluconeogenesis 6. inhibits lipolysis 7. inhibits ketogenesis |
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Formula for glycogenesis or storage of glucose in cells?
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glucose-->glycogen + insulin = glycogeneis
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Formula for gluconeogenesis or synthesis of new glucose?
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gluconeogenesis= peripheral substrate(amino acids)->-pyruvate + glucagon-->glucose
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Formula for protein sythesis?
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amino acids + inuslin= protein synthesis
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formula for lipogenesis or fat synthesis?
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fatty acids + glycerol-->
triglycerides= lipogenesis |
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formula for lipolysis or fat breakdown?
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triglycerides-->fatty acids + glycerol = lipolysis
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formula for ketogenesis or conversion of fatty acids to ketones?
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fatty acids + glucagon = ketones or keotgenesis
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What is the response to inadequate insulin?
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1. hpyerglycemia
2. hpertriglycerideemia 3. ketonemia |
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What are signs and symptoms of diabetes mellitus?
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1. polyuria
2. polydipsia 3. polyphagia 4. unusal wt loss 5. increased fatigue\ 6. ittiability 7. blurry vision 8. paresthesias 9. chronic skin infections |
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Diagnosis of diabetes entails what?
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sympptoms plus causal plasma glucose of >200mg/dL
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What is "pre-diabetic" states?
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metabolic stages between
normal & diabetes or imparied glucose tolerance (IGT) impaired fasting glucose (IFG) |
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What is type I diabetes?
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IDDM or insulin dependent diabetes mellitus
juvenile onset age 10-14 typically due to cell-mediate autoimmune destruction of beta cells of pancreatic islets |
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What is type II diabetes?
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non-insulin-dependant diabetes mellitus (NIDDM)
maturity-onset diabetes due to functional problems ie. insulin resistance /deficient insulin secretion |
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Type I environmental factors ?
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perinatal factor (preeclampsia)
possible molecular mimicry by coxsackie virus or enterovius early exposure to cereals, nitrate, cow's milk (albumin) |
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Type I genetic factors?
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predisposition is multifactorial inheritence
linked to HLA DR & DQ alleles (DR3/DR4) |
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Which type has a stronger genetic link?
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type II
60-90% monzygotic twins 25% have a first degeree relative affected genes may regulate insulin synthesis, processing, & secretion insulin resistance or regulation of gluconeogenesis |
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What are environmental factors of type II predisposition?
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1. diet
2. obesity BMI (apple shape) 3. peripheral insulin resistance - decreased receptor function or defect in cellular pahtways 2. insulin resistance (60-80%) 3. impaired insulin secretion decrease beta cell mass & loss of 1st phase secretion |
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In type II diabetes (altered function) what is primary insulin resistance or Beta cell failure?
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insulin resistance is a primary factor.
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What occurs with Beta cell failure?
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1. glucotoxicity=apoptosis
2. glucolipotoxicity=apoptosis 3. unfolded protein response (UPR)=apoptosis 4. islet amyloid oligomers=membrane channels that triggers UPR or apoptosis |
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What are complications of acute insulin deficit?
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1. infections (pneumonia or
UTI) 2. inadequate insulin therapy 3. hyperglycemia 4. osmotic diuresis 5. hypovolemia due to diruesis 6. increased hyperglycemia due to less glucose eliminated 7. release of "stress" hormones which suppresses insulin secretion |
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Describe Hyperosmolar Syndrome
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It is fluid loss due to glucose osmotic diuresis with electrolyte loss Na+ & K+
1. severe dehydration due to polyuria 2. polydipsia 3. lethargy, obtudation, coma hyperglycemia, hyperosmoality, hypovolemia, metabolic acidiosis, K depletion |
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what is the treatment for Hyperosmolar Syndrome?
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Goals: rapidly expand intravascular volume, stablize B/P,
improve circulation & urine flow administer insulin and correct fluid & electrolyte imbalances 1. 0.9% NS 1L/h 2. 0.1 U/kg wt of regular insulin 3. plasma glucose monitored q 1-2 hours glucose = 300 mg/dL reduce insulin to 0.5-1 U/kg/h 4. K+ replacement 20-30mEq/L for serum level 3.3-5.3 |
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What are signs and symptoms of ketoacidosis?
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1.lethargy,
2.vomiting, 3.kussmaul breathing 4. increased heart rate 5. stupor 6. cerebral edema 7. coma |
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What are long term complications due to diabetes?
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1. cardiovascular disease
2. neuropathies 3. diabetic foo 4. retinopathies 5. nephropathies |
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What interconnected pathways does hyperglycemia trigger?
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1. produces reactive oxygen
species (ROA) & superoxides causing oxidizing environment =apoptosis due to increased cytokines & growth factor 2. glycation of proteins & (AGEs) advanced glycosylation end products 3. increases proten kinase C (PKC) |
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What do AGEs (advanced glycosylation end products) cause?
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1. increased basement
membrane permeability 2. decrease cell matrix interaction 3. increase secretion of cytokines & growth factor 4. increase ROS production |
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"What does PKC (protein kinase C) cause?
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1. decreased blood flow
2. procoagulatory actions 3. proinflammatory actions 4. increased ROS production 5. increased vascular permeability |
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What characteristics of CHD is increased 3-4X in Diabetes?
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1. hypertension
2. obesity 3. dyslipidemia 4. hyperglycemia 5. macrovascular dx 6. microvascular dx 7. autonomic nerve dysfunction (tachycardia) 8. renal dysfunction |
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What is macrovascular dx?
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disease of the large blood vessels, including the coronary arteries & involves atherosclerosis
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What is the common pattern of dyslipidemia in Type 2 Diabetes?
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increased triglycerides
decreased HDL-C increased VLDL increased small, dense LDL-C level LDL-C |
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what are Atherogenic risk factors for diabetics?
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1. hypertension
2. obesity 3. increased total-to-HDL- cholesterol ratio 4. oxidized LDL 5. hyperglycemia (ROS, AGEs, PKC) 6. hypertriglyceridemia 7. elevated plasma fibrinogen |
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What is micovascular Disease?
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changes in basement membrane
-thinkcening -increased permeability AGEs, ROS, inceased growth factors & cytokines, PKC, changes in cell adhesion |
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what are nonpharmocological interventions for hypertension related to diabetes?
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weight reduction
exercise Na+ restriction avoid smoking & alcohol |
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What drugs are used to treat hypertension?
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1. thiazide diuretics
(chlorthalidone) 2. angiotensien converting enzyme (ACE) inhibitors (lisnopril) *decrease formation of angiotensin II a vasoconstrictor & stimulator of aldosterone secretion 3. ARB angiotensin II receptor blockers (losartan) 4. Beta Blockers (atenolol) *blocks beta aderneric receptors 5. Ca+ Channel blockers (verapamil)-decreases heart contraction & vasoconstriction |
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What are clinical manifestations of diabetic autonomic neuropathy of cardiovascular system?
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1. postural hypotension
(loss of vasoconstriction by sympathetic nervous system) 2. Fixed tachycardia 80-90/min (loss of parasympathetic inhibitory input to heart) 3. Exercise Intolerance (due to impaired augmentationof cardiac output resulting from inadequate sympatheic activity) |
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What is glycation or Glycosylation?
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glucose attaches to amino groups in proteins such as
proteoglycans, collagen, elastin, and LDL. |
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How are AGEs implicated in pathogenesis of diabetic retinopayth, nephropathy,& microvascular dx?
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there is binding of AGEs by receptors (RAGEs) on the endothelial cells, smooth muscle cells, & renal mesangial cells
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What is the gold standard for determining the amount of glycation?
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HbA1c it correlates with mean blood glucose ovr the previous 8-12 wks
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What is the HbA1c target?
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fasting glucose of <110mg/dl
and HbA1c <6.5% |
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What is the mean glucose for an HbA1c at 6?
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135 mean plasma gulocose
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What is the most common diabetic neuropahty?
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distal symetric sensorimotor polyneuropathy
Stocking and glove neuropathy it is the loss of cutaneous sensation, including temp., touch, pain. |
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What are the autonomic neuropathies?
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abnormal function of sympathetic & parasympatheic nerous system
Includes: reduced sweating of feet postural hypotension fixed heart rate gastroparesis bladder dysfunction retrograde ejaculation erectile dysfunction |
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What causes neuropathies?
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nerve ischemia
decreased conduction velocity demyelinization loss of nerve fibers metabolic factors such as -sorbitol -AGEs -increased PKC -increased oxidative stress ROS |
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What happens to glucose in the cells when hyperglycemic?
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1.the glucose is metabolized with the enzyme Aldose Reductase into sorbitol
2.the sorbitol accumulates in the cells that leads to increased oxidative stress & increased intacellular osmolality with a decrease in intracellular myoinositol 3. cataract formation due to sorbitol causing cell swelling resulting in rupture of lens fiber cells |
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How does Diabetes promote ulcer formation of the diabetic foot?
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1. decreased pain sensation
2. decreased pressure sensation 3. decreased sweating of foot 4. poor proprioception (muscle imbalance)that leads to anatomical defects 5. impaired microcirculation 6. impaired integirity of skin |
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what is the most common cause of blindness in the middle aged subjects?
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diabetic retinopathy
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What is the primary cause of retinopathy?
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hyperglycemia
causes: impaired autoregulation of retinal blood flow promotes accumulationof sorbitol in retinal cells promotes accumulation AGEs in extracellular fluid may cross-link with collagen & initiate microvascular complications |
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What is the cause of retinopathies?
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1.death of retinal pericytes
2.death of microvascular endothelial cells 3. impairment of basement membrane |
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What is NPDR or nonproliferative diabetic retinopathy?
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1. microaneurysms due to loss
of pericyte causes outpouchings in capillaries 2. leakage of "hard" exudates (lipids & proteinaceous material) 3. macula edema (loss of visual acuity) 4. hemorrhages due to vascular occulsions |
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What is proliferative retinopathy?
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New formation of vessels that spread out within the retinal layers. Forms a lace-like pattern with a fine mesh of fibrous tissue
vessels prone to rupture contraction of fibrous tissue can cause distrortion of retina or detachment |
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What is the 1st clinical sign of diabetic nephropathy?
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microalbuminauria
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What are the 3 hitological changes in glomeruli with nephropathy?
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1. glomerular basement membrane thickening
2. mesangial expansion 3. glomerulosclerosis |
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What are the pathogenic factors involved with diabetic nephropathies?
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1. intraglomerular
hypertension 2. hyperglycemia increased glyosylation of matrix proteins increases VEGF expression 3. AGEs increased matrix production or mesangial expansion & injury 4. Cytokines inflammation & VEGF |
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What are the stages of Nephropathy?
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1. renal hypertrophy
(increased GFR) 2. microalbuminuria (30-299mg protein/day) 3. proteinuria (>300mg protein/day) 4. end stage renal dx (glomerulosclerosis) |
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What occurs with renal hypertrophy?
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1. dilatation of afferent
arterioles=increased glomerular pressure & renal blood flow or GFR 2. accumulation of sorbitol 3. accumulation of AGE & micro vascular problems 4. sodium-glucose transport due to enhanced tubular Na+ reabsorption = extracellular fluid volume expansion 5. IGFI insulin-like growth factor & other hormones |
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What occurs with microalbuminuria?
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1. increased number of large
pores in filtration membrane 2. decrease in negative charge of basement membrane 3. AGEs increase vascular premeability 4. hyperglycemia activates protein kinase C (PKC) 5. up-regulates heparanase expression |
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Nephropathy treatments?
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1. glycemic control
2. anti-hypertensive therapy 3. dietary protein restriction 4. dialysis 5. peritoneal dialysis 6. kidney transplant |
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What is the gylcemic control goal of diabetic with nephropathy?
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lower HbA1c to less than 6.5%
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What is the recommended anti-hypertensive therapy goal for diabetic with nephropathy?
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lower B/P to 120/75
treat with ACE inhibitors or ARBs |
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What is the recommended dietary protein restriction for diabetic with nephropathy?
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lowre intake to 0.6-0.8 g/kg/day
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How does the hemodialyzer in dialysis work?
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restores acid-base blance with electrolytes similar to plasma
no urea, creatinine, uric acid or other uremic toxins raises pressure to force out some water |
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What are some problems with the hemodialyzer?
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vascular access may be difficult due to atherosclerotic plaques
half-time survival rate for diabetic is 3 years |
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what is CAPD?
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Continuous ambulatory peritoneal dialysis
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How does CAPD work?
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indewelling cath into peritoneal space
pt exchanges 2-3L of sterile dialysate 3-5X daoily exchange is slow to decrease rapid swings in volume or chemistry No better survival rate than dialysis |
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what is the treatment of choice for the uremic diabetic patients?
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kidney transplant
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what is the treatment & goals for diabetes mellitus?
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Goals:normalize glycemia &
minimize cardiovascular risk factors 1. diet 2. exercise 3. control B/P 4. control dyslipidemia 5. control glycemia |
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what are different types of insulin?
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1. rapid acting 5-10min onset
(lispro, aspart, glulisine) 2. short-acting 30min onset (regular) 3. intermediate to long acting 2hour onset (NPH, detemir, glargine) |
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What type of insulin provides basal insulin levels that suppress hepatic glucose produciton & maintain near normoglycemia in the FASTING STATE?
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Intermediate to long-acting preparations
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What type of insulin is used as a PREMEAL bolus to cover extra requirements after food is absorbed?
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short acting or rapid acting preparations
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what are 3 ways insulin can be administered?
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injections
pump inhaled |
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What is drugs are used for glycemic control for the type II diabetic?
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1. sulfonylureas (diabenese)&
meglitinides (Prandin) (stimulates insulin secretion from beta cells of pancrease) 2. Biguanides(glucophage) & thiazolidenediones (insulin resistance decreased by improving insulin action) 3. alpha-glucosidase inhibitors (precose) (carbohydrate absorption) slows glucose absorption by inhibiting enzymes that convert carbs to monosaccharides |
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How does GLP-1 analog (glucagon-like peptide -1) work?
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Byetta is an example.
GLP-1 analog stimulates glucose-dependent inulsin release from the pancreatic islets. restores 1st phase & 2nd phase insulin response to glucose slows gastric emptying inhibits post-meal glucagon release reduces food intake modestly decreases HbA1c causes wt. loss |
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What is the action of dipeptidyl pepidase-4 inhibitor (DPP-4)?
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extends the half-life of GLP-1 because GLP-1 is normally degraded by a dipeptidyl peptidase
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What does Amylin analog (pramlintide)work?
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decreases post-meal blood glucose levels by slowing gastric emptying & suppressing postproandial rise of glucagon
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