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79 Cards in this Set
- Front
- Back
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Describe the structure of insulin receptor
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2 identical extracellular a-subunits that bind insulin and transmit the signal through a cell membrane to 2 identical b-subunit
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What happens to the insulin receptor after insulin binds?
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B-subsunit undergoes autophosphorylation -> intrinsic tyrosine kinase activity and promotes phosphorylation of endogenous protein substrates -> cascade leading to insulin action
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What is the rate-limiting step for glucose disposal?
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Glucose transport
GLUT 4 = insulin sensitive transporter expressed in skeletal/cardiac muscle/adipose tissue |
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What happens to Glut 4 levels in type 2 diabetes?
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GLUT 4 is normal but glucose transport is decreased; defect in the action of insulin to translocate GLUT 4 to cell surface - insulin resistance
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What happens to plasma amylin concentrations in diabetes?
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Amylin concentrations are often undectable in patients with type 1 diabetes
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What is GLP 1? Where is it secreted from?
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Glucagon-like peptide 1 which enhances beta-cell function acutely by promoting glucose dependent insulin secretion
It lowers glucose by enhancing pancreatic insulin and amylin secretion when glucose concentrations are high, suppressing glucagon Secreted from L-cells in ileum |
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What is the function of Glucagon?
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Maintaining glucose homeostasis under basal/fasting conditions when endogenous glucose production is necessary
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What is the function of Amylin?
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It is co-secreted with insulin to reduce excess glucagon secretion in postprandial period, leading to suppression of hepatic glucose production
It travels to brain and helps reduce hepatic glucose production, delay gastric emptying, promotes satiety in brain |
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What is the honeymoon period with regards to diabetes?
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Periods of partial remission when beta cells produce insulin but once the period ends, the person will need insulin again to survive
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What is type II diabetes?
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Combination of relative deficiency of insulin and insulin resistance
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What does insulin resistance in liver, muscle and adipose tissue lead to? (3)
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-increased hepatic glucose production
-decreased glucose uptake in peripheral tissue -increased lipolysis |
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What is fasting glucose influenced by? (2)
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-hepatic glucose production
-hepatic sensitivity to insulin |
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What is postprandial glucose influenced by?(4)
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-preprandial glucose
-insulin secretion -glucose load from meal -insulin sensitivity in peripheral tissue |
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Which gives a more accurate picture of an individual's true level of metabolic control? Fasting Glucose, Preprandial Glucose, Postprandial Glucose?
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Postprandial glucose
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Give 4 criteria for Dx of Diabetes.
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A1c >= 6.5%
FPG >= 126 mg/dL, fasting for 8 hours 2Hr PG >= 200mg/dL during a OGTT using 75g glucose load Pt w/ classic Sx: hyperglycemia/hyperglycemic crisis, or random PG >= 200mg/dL |
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What is the criteria for testing diabetes in asymptomatic adults?
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-Should be considered in adults with BMI > 25 and have additional risk factors
-W/o above risk factors, DM testing should begin at 45 -If normal, repeat every 3 years |
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What is the normal HbA1c levels? What is the goal for DM management?
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Normal <6
Goal for ADA, less than 7 For EDPG and AACE, <= 6.5 |
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What is the difference between U-500 insulin and U-100?
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-U500 is 5x more concentrated then U100
-U500 may last up to 24 hrs -Use U500 in pts who have severe insulin resistance |
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What is the basal/bolus insulin concept?
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-Basal Insulin suppresses glucose production between meals and overnight to constant levels
-Bolus Insulin - limits hyperglycemia after meals |
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What are the limitations in giving human regular insulin?
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-Slow onset of action: required administration 20-40 mins prior to meal, mismatch with pp hyperglycemic peak
-Long duration of activity: up to 8 hrs, potential for late pp hypoglycemia |
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What kind of insulin is Lispro, Aspart, Glulisine?
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Rapid acting analog given immediately prior to meals
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How does the activity of Lispro compare with regular human insulin?
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The peak activity of lispro is more rapid than regular human insulin and is disposed of more rapidly.
Lispro more closely mimics normal human response than regular human insulin |
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What are characteristics of the ideal basal insulin?
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-Mimics normal pancreatic basal insulin secretion
-Long-lasting effect ~ 24hrs -Smooth, peakless profile -Reproducible and predictable -Reduced risk of noctural hypoglycemia -Once daily administration |
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What are limitations of Human NPH?
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-Doesn't mimic basal insulin profile
-Cause unpredictable hypoglycemia |
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What kind of insulin is Glargine?
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Long-acting insulin analog
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What is the MOA of Glargine?
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Glargline is an acidic solution that precipitates when injected into subcutaneous tissue and then dissociates to be absorbed across capillary membrane; slow dissolution ->extended time action profile
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Who has more hypoglycemic episodes? NPH or Glargine?
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NPH has about 70% more
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What compartments must insulin pass through to get to receptor?
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Subcutaneous - insulin self associates and binds to albumin
Plasma - insulin monomers are albumin bound delaying distribution to tissues Interstitial Fluids - Monomers bind to cellular insulin receptors |
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Which gives more of a 24 hr duration? Which is more reproducible? Glargine or Detemir?
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24 hr - Glargine
Reproducible - Detemir |
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Sole Sliding scale insulin in inpatient setting leads to? (2)
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-increased hyper and hypoglycemic episodes
-increased length of stay |
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What is the starting insulin dose for an insulin naive patient? bolus dose? basal dose?
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Starting = .2x wt in lb or .45 X wt in kg
Bolus = 20% of starting dose at each meal Basal Dose = 40% of starting dose once or twice daily |
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How do you estimate the correction bolus?
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1800 rule.
CF = 1800/total daily dose Correction dose = (Current BG- ideal BG)/CF |
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How do you estimate the carbohydrate to insulin ration (CIR)?
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CIR = (2.8 x wt in lbs)/TDD
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What is Pramlintide?
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Synthetic Amylin Analog that overcomes amylin's tendency to aggregate and adhere to surfaces
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What is the main side effect of Pramlintide?
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Nausea - dose dependent
DM1 gets more nausea |
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How should pramlintide acetate be administered?
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Subcutaneously and not mixed with insulin
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Insulin absorption is affected by... (4)
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injection site - abdomen provides most rapid absorption
massage at injection site exercise of injected limb body temperature |
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What conditions slow absorption of insulin at site?
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low site temperature
smoking anxiety stress |
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What should you remember about the storage of insulin products?
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Avoid heat, light and freezing,
Check for expiration date |
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What is a sensor-augmented insulin pump?
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Patients are expected to make immediate therapy adjustments based off of continuous glucose readings
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Improper administration of insulin can lead to? (2)
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Lipoatrophy
Lipohyperatrophy |
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What is "starlings law of the pancreas"?
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As a person becomes more insulin resistant, the more insulin they need to stay on the curve
If a person falls off the curve, you get them back on by increasing insulin level or making them more sensitive |
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What is the MOA of sulfonylureas?
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They close the ATP dependent K channels of the B-cell via binding protein. The cell depolarizes and gives voltage-dependent Ca2+ channels a signal to open and allow Ca to flow in. The rise of intracellular calcium ->insulin secretion
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Which Meglitinide does not release insulin from B-cell in absence of glucose?
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Repaglinide
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What is the main risk of insulin secretagogues: sulfonylureas and meglitinides?
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Hypoglycemia because sulfonylureas release insulin independent of glucose presence
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List 4 first generation sulfonylureas
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Tolbutamide
Chlorpropamide Acetohexamide Tolazamide *Note: not really used anymore bc of side effects and drug interactions |
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List 3 second generation sulfonylureas
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Glyburide
Glipizide Glimiperide |
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Name 2 Meglitinides
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Repaglinide
Nateglinide |
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What are biguanides? What's available on the market?
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Oral antihyperglycemic agent - insulin sensitizing hormones
Metformin is available |
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What is the MOA of metformin?
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Not well understood but may activate AMP-activated kinase (required for inhibitory effect on hepatic glucose production); enhances hepatic response to glucose
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What is the main risk of Metformin?
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Lactic acidosis?
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What are the advantages of Metformin?
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Low risk of hypoglycemia
No weight gain, 5-10 lb loss LDL and triglycerides reduced Protection from heart attacks and death |
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Metformin is not recommended for what group of people?
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Elevated serum creatinine
>1.5 mg/dL in men >1.4 mg/dL in women CHF, liver disease |
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Name 2 Alpha-glucosidase inhibitors
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Acarbose
Miglitol |
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What is the function of alpha-glucoside inhibitors?
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delay the digestion of ingested carbs leading to a smaller rise in blood glucose concentration following meals
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What is the main side effect of alpha-glucoside inhibitorys
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Flatulences
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Who are the best candidates for Acarbose and Miglitol? Who is it not recommended for?
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Candidates - Marked postprandial hyperglycemia
Not recommended - intestinal/liver disease |
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What are thiazolidinediones/Glitazones?
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Not insulin secretagogues but lower blood glucose by improving target cell response to insulin if circulating insulin is present
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WName 3 thiazolidinediones.
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Rosiglitazone
Pioglitazone troglitazone |
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What is the MOA of thiazolidinedione?
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Thiazolidinediones bind to PPAR-gamma receptors in the nucleus causing increased insulin signal to increase number of Glut 2 transporters and entry of glucose into cells
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What are the main side effects of thiazolidinediones?
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Peripheral edema
Pulmonary edema/CHF risk Weight gain |
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When is Pioglitazone and Rosiglitazone contraindicated?
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If ALT>2.5x upper limit of normal
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How is diabetic dyslipidemia characterized by?
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low HDL-c, high triglycerides and predominance of small, dense LDL-c
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What has GLP1 been shown to do in animals?
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Increase beta cell mass and maintain beta cell function
Improve insulin sensitivity reduce food intake |
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What is GLP limited in managing diabetes?
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It is rapidly and extensively inactivated. The N-terminus is quickly cleaved by dipeptidyl-peptidase 4, an enzymes that circulates freely in plasma
T1/2 = 1-2 mins |
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What is Exenatide?
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It is a gene product that has similar binding affinity to the GLP-1 receptor and may have antidiabetic effect
A 30 week study showed to reduce fasting plasma glucose and postprandial glucose in people who took exenatide BID |
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What is the most common adverse effect for exenatide?
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Nausea
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What is Liraglutide?
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Long-acting GLP-1 analogue
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Wha are the clinical effects of Liraglutide?
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Glucose lowering
Weight reduction B-cell preservation |
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Compare and contrast Liraglutide and Extendin4
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Liraglutide - once daily, peakless, good effect on HbA1c and FBG, weight loss, no antibodies, no injection site reactions
Extendin 4 - 2x daily, peak, good effect on A1c, weight loss, antibodies, injection site reactions with prolonged use |
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What is the purpose of DPP inhibitor?
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Inhibiting DPP4 blocks endongenous GLP1 inactivation ->improve metabolic control
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What is the MOA of sitagliptin?
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Blocks DPP4 to enhance the level of active incretins for 24 hours
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What are the results of sitaglipin when used as a monotherapy
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-A reduction of A1c of about 1.4 in people great than 9
-significant reduction in FP PPG |
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What is the indication for saxagliptin?
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Adjunct to Diet and exercise for glycemic control in type II DM
Monotherapy or combo therapy |
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What drugs requires you to adjust the dose of saxagliptin?(5)
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rifamin
Atazanavir/indinavir/ritonavir/saquinavir ketoconazole/itraconazole clarithromycin/telithromycin nefazodone |
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What does research say about Vildagliptin?
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-Postential to increase B-cell neogenesis and decrease islet cell apoptosis
-Lower HbA1c over 1 year |
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What drugs do you give fasting?
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-Metformin
-TZDs: Pioglitazone, Rosiglitazone -Sulfonylureas -Repaglinide -Basal Insulin glargine, detemir, NPH |
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What drugs do you give for postprandial control?
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-Exenatide
-DPP4 inhibitors - sitagliptin, saxagliptin -Nateglinide -alpha-glucosidase inhibitors - acarbose, miglitol -Prandial insuline - aspart, lispro, glulisine, regluar |
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What is the current treatment paradigm for DMII?
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Diet and exercise -> monotherapy -> combo -> insulin
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