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45 Cards in this Set
- Front
- Back
glucose homeostasis
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-liver-->homeostat
-in well fed state: liver net user of glucose, and converts it to glycogen for future use -in post-absorptive state: liver is the net producer of glucose by breaking down stored glycogen, gluconeogenesis |
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absorptive phase
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-within 3-4h of food ingestion
-source of glucose: exogenous carbs -insulin high, glucagon low time for E storage |
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post absorptive phase
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-5-6 h after start of meal
-source of glucose: liver -initially, glycogen breakdown -later, gluconeogenesis -insulin low, glucagon high: time for E release |
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pancreas and blood sugar regulation
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-islet of langerhans- 2% of pancreas
->80% of pancreas: Exocrine pancreas Alpha cells: glucagon (inc bl sugar)- CATABOLIC Beta cells: insulin (dec blood sugar)- ANABOLIC Delta cells: somatostatin; stops glucagon and growth hormone, dec blood sugar |
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Insulin
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-ANABOLIC HORMONE
-increased synthesis of protein, glycogen and lipogenesis -increased peripheral glucose utilization: inc glucose entry into cells, increased glycolysis, inc glycogen synthesis -decreased hepatic glucose output: dec gluconeogensis, dec glycogen breakdown -polypeptide: 2 chains connect by disulfide bond -C peptide: a measure of endogenous insulin production -half life in circulation: 3-5min -50% removed by 1st pass in liver |
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insulin effects on liver, muscle, adipose tissue
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Liver: promotes anabolism; glycogen, protein, triglyceride synthesis; inhibits catabolism
Muscle: promotes glycogen and prot syntehsis; inhibits glycogenolysis Adipose tissue: promotes triglyceride synthesis and storage and inhibits lipolysis |
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effects of insulin (timing)
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Rapid: inc transport of glucose, aa, and K into insulin sensitive cells
Intermediate: -inc prot synthesis -inc glycogen synthesis -inc glycolysis -dec glycogen breakdown -dec gluconeogenesis Delayed: inc mRNA for lipgenic emzymes |
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insulin secretion
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-basal insulin secretion
-stimulated insulin secretion -GLUCOSE: biphasic response- Early Phase: Release of pre-formed Insulin by B cells Late Phase: Synthesis & release of insulin by B cells |
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regulation of insulin release
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-stimulants of insulin release: glucose, sulfonyureas, vagal stimulation
-amplifiers of glucose dependent insulin release: enteric hormones, B-adrenergic stim -inhibitors of insulin release: somatostatin, a-adrenergic stim, drugs (diazoxide, phenytoin) |
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insulin receptor
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-membrane glycoprotein
-a-subunit: extracellular domain: insulin binding -b-subunit: cytoplasmic domain: tyrosine kinase; autophosphorylates on ligand binding leading to downstream events |
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glucose transporters
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GLUT 1: All Tissues; Basal Glucose Uptake by tissues (esp Blood brain barrier)
GLUT 2: All Tissues (esp Neurons); High affinity for glucose GLUT 3: Liver, Intestine, Kidney;? B-cells GLUT 4: Skeletal muscle & Adipose tissue; sequestered intracellularly; translocates to cell membrane after insulin signalling |
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glucagon
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-A cells of islets
-catabolic hormone -G- protein coupled receptr --> inc cAMP -inc glycogenolysis -inc gluconeogenesis -inc lipolysis -inc ketogenesis |
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counter-regulatory hormones
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-counter insulin effects on glucose metabolism: prevent hypoglycemia, raise blood glucose
1. glucagon 2. cortisol 3. epinephrine 4. GH |
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hypoglycemia causes
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1. inc insulin
2. dec counter-reg homrones: adrenal insufficiency, dec glucagon and Epi, hpothyroidism |
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hypoglycemia sx
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1. palpitations
2. shakiness, jitteriness 3. inc sweating 4. confusion 5. seizures, coma |
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whipples triad
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1. symptoms consistent with hypoglycemia
2. low blood sugar at time of sx 3. sx relieved on correcting hypoglycemia |
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Fasting hypoglycemia
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1. insulinoma
2. drugs 3. liver dz 4. kidney dz 5. sepsis 6. lack of coutner-reg hormones -worrisome! |
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postprandial hypoglycemia
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-post gastric surgery
-reactive hypoglycemia |
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evaluation of hypoglycemia
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-check serum glucose and insulin at time of sx
-If Insulin elevated in face of hypoglycemia, insulin-induced hypoglycemia --> C peptide high: insulinoma, exogenous use of sulfonylurea; Low: exogenous insulin use |
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Insulinoma
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-islet cell tumors
-rare -87% single benign tumor -7% multiple benign tumor, 6% malignant tumor, 8% MEN 1 syndrome -can be lethal -FASTING hypoglycemia -secrete large amts of insuline, pro-insuline, C-peptide -Dx: 48h or 72 h Supervised Fast : ↑ Pro-insulin, C peptide, Insulin, in setting of LOW blood Glucose, AND Negative Sulfonylurea screen -Rx: surgical |
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drug induced hypoglycemia
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-insulin (c-peptide LOW)
-Sulfonylurea (C peptide elevated; blood or urine sulfonylurea screen positive) -Pentamidine -Ethanol -Insulin or Sulfonylurea use may be surreptitious (Factitious Hypoglycemia) -elderly pts, poor PO intake, chronic liver or kidney dz or hear failure -Insulin level would be HIGH or inappropriately in the normal range in setting of hypoglycemia. -Duration of hypoglycemia depends on the duration of action of the drug You can confirm the diagnosis by measuring serum or urine for sulfonylureas |
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hypoglycemia- history
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1. duration: each episode, prior episodes
2. seizure 3. coma 4. accidents due to hypoglycemia 5. fasting or postprandial 6. ? acess to insulin or DM meds |
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reactive hypoglycemia
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1. gastric resection: Rapid absorption of carbs--->Insulin release delayed, and somewhat exuberant--->hypoglycemia
2. defect in 1st phase insulin response: delayed, and exuberant -postprandial sx, esp after high carb mean -in predisposed individuals, inc risk of DM in longterm -often NO HYPOGLYCEMIA demonstatable -often hx of anxiety, depression -Rx: dietary modification; nibble rather than gobble, mixed carbs and protein, eliminated simple/refined carbs from diet |
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Most common caue of hypoglycemia in diabetis is..
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1. insuline to carb mismatch
-too much insulin, too little carbs in the food -gastroparesis OR 2. increased exercise (ie dec insulin requirement) -postpartum also 3. dec counter-reg homones -addrenal insufficiency (schmidts syndrome) |
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Facticious hypoglycemia
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-healthcare workers
-72 hr (or 48 hr fast) -simultaneous C-peptide & pro-insulin along with the serum glucose and insulin -surreptitious insuline intake: inc insulin, LOW c-peptide, LOW pro-insulin -surreptitious sulfonlyurea ingestion |
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hypoglycemia- sick appearing pt (with co-existing diseasE)
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1. starvation
2. anorexia nervosa 3. severe liver dz 4. chronic renal failure 5. isolated growth hormone deficiency 6. isolated corticotropin def 7. primary adrenal insuff 8. hypopituitarism 9. sepsis 10. drugs 11. glycogen storage dz 12. defects in aa and fatty acid metab 13. lage mesenchymal tumors |
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hypoglycemia-healthy appearing pt (with co-exisiting dz)
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1. DM
2. drugs 3. dispensing error 4. ackee-fruit poisoning and undernutrition 5. alcohol 6. insulinoma 7. factitious hypoglycemia 8. intense exercise |
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Classification of DM
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1. Type 1 DM: B cell destruction --> absolute lack of insulin
2. Type 2 DM: dual defect, insulin resistance and impaired insulin secretion -gestational -specific types: genetic defects of B cell function, genetic defect in insulin action, disease of exocrine pancreas, drug induced, rare syndromes |
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Diabetes presentations
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-Asymptomatic: detected onroutine labs
-Acute hyperglycemic crisis: DKA, NKHS -Classic sx: polyuria, nocturia, polydipsia, polyphagia, wt loss |
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Making the diagnosis of DM
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1. symptoms of DX plus random plasma glucose >/= 200 mg/dL
or 2. FPG >/= 126 mg/dL or 3. 2 hr PG during a 75-g OGTT >/= 200 mg/dL |
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measures of hyperglycemia
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Random plasma glucose (RPG)—without regard to time of last meal
Fasting plasma glucose (FPG)—before breakfast Oral glucose tolerance test (OGTT)—2 hours after a 75-g oral glucose drink Postprandial plasma glucose (PPG)—2 hours after a meal Hemoglobin A1c (A1C)—reflects mean glucose over 2–3 months Fructosamine—reflects mean glucose over 1–2 weeks |
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type 1 DM
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-beta cell destruction
-immune mediated -idiopathic -only 10% of all DM in N. America -higher in whites -absolute lack of insulin -at least 80% of B cells destroyed before DM 1 |
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natural history of type 1 DM
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-genetic predisposision
-putative trigger -insulinitis B-cell injury -"pre" diabetes -diabetes (clinical onset- only 10% of B-cell remain) |
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clinical features of DM 1
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1. lean
2. juvenile onset (<40, often <20) 3. often NO FH 4. positive auto-AB 5. often acute onset: DKA, sometimes after acute viral illness 6. Ketosis prone: insulin dependent DM, need insuline to live, absolute def of insulin (low C-peptide) |
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DM 1 tx
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-Insulin
-basal insulin: NEED BASAL INSULIN EVEN IF NPO; else, DKA----> Death -prandial insulin -best to replace insulin physiologically with basal-bolus insulin replacement with designer insulin analogs |
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Basal insulin
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-control glucose production b/t meals and overnight
-nearly constant levels -50% of daily needs -insuline Glargine -insuline Detemir |
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Bolus insulin
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-limits hyperglycemia after meals
-immediate rise and sharp peak at 1 hr postmeal -50% of total daily insulin requirement |
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rapid acting insulin analogs
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-ideal for mealtime admin: prandial insulin
-quick in, quick out -decreased risk of hypoglycemia later -insulin Lispro, -insulin Aspart -insuline Glulisine |
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insulin transport and storage
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-insulin is a small polypeptide
-very sensitive to temp -must be refrigerated in storage, and preferable for transport -a vial or pen of insulin in use may be left on 'room temp' for up to 4 wks -vial: 1000 units (in 10 mL) -insulin pen: 300 units (in 3 mL) |
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insulin pumps
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-external insulin pumps
-CSII (continuous subcutaneous insulin infusion) -program basal rates -pt takes a bolus at meal times based on pts carb intake!!! -Insulin Pump Management Requires an INTELLIGENT & MOTIVATED patient capable of FULLY PARTICIPATING in the overall plan of care |
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insulin pump cont
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Pt has to:
1. check sugars 6-8 times daily 2. insert the infusion set every 3 days 3. take prandial insulin at EACH mel and DECIDE how much insulin to take at EACH MEAL 4. take correction dose insulin if sugars are elevated -80 yr old pt with dementia: NOT A GOOD IDEA -30 yr old schizophrenic pt: BAD IDEA! |
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insulin pump in hospitals
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-IF intelligent motivated patient, alert, awake, and co-operative, and aware of their Insulin:Carb ratios, and correction factors: CONTINUE the insulin Pump
-let pt manage the pump -Tell the staff to check sugars qac/qhs (If Eating) or q4-6h (as clinically appropriate), and LET the pt give CORRECTION dose insulin via the pump. |
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insulin pump in hospitals cont.
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IF patient
Comatose Sleepy/drowsy/intoxicated Unable to or unwilling to fully co-operate with you Then best to Discontinue the pump Temporarily AFTER giving the patient a dose of BASAL insulin (Glargine or NPH) AFTER close consultation with an Endocrinologist -Do NOT STOP the pump before speaking with an endocrinologist IF type 1 diabetic does not get their basal insulin even for a few hours, they will go into a DKA, and could potentially die |
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inhaled insulin
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Safety issues:
Longterm inhalation of growth factor in the lungs: Need to monitor pulmonary function Absorption: ? Consistent in those with pre-existing lung disease NOT to be used in SMOKERS or those with pre-existing lung disease Prandial Insulin DISCONTINUED by Pfizer in 2008 Novo-Nordisk & Eli Lilly also stopped development of their inhaled insulin products |
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pancreas replacement tranplantation
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-pancreas transplant: PK, PTA
-islet cell transpltan -stem cell transplant |