Insulin Therapy Flashcards
Where is proinsulin normally stored?
Gogli apparatus of Beta cell
Products of proteolytic cleavage of proinsulin
C-peptide + insulin
Regulation of Insulin: Stimulatory (3)
Nutrient load: glucose>fat/protein
Autonomic nervous system: vagal stimulation and cephalic phase
Hormonal: incretins (GLP-1, GIP)
Regulation of Insulin: Inhibitory (3)
Starvation
Hypoglycemia
Hormonal: glucagon, epinephrine, GH, cortisol
Insulin Metabolism: Endogenous
___% Hepatic and ____% Renal
60% immediate hepatic via first pass effect
40% degradation in kidneys
Insulin Metabolism: Exogenous
Subcutaenous tissue–>bloodstream–> renal (60%)–>liver (40%)
Indications for Inuslin (2)
T1DM
Inadequately controlled T2DM
Indications for Temporary use of insulin (5)
Hospitalization/surgery Pregnancy Renal disease Initial glycemic control for T2DM To overcome glucose toxicity and re-regulate decompensated patients
Bolus Insulin: Purpose
Coverage of food intake or correction of hyperglycemia
Types of Bolus Insulin
Short Acting: regular
Rapid Acting: aspart, lispro, glulisine
Pharamcodynamics: Regular insulin vs. short-acting
Onset: 30-60min vs. 5-15min
Peak: 2-4hr vs. 1-2hr
Duration: 6-10hr vs. 4-6hr
Short-Acting insulin structures
Umm
Rapid Analogues vs. Regular: Similarities (4)
Glucose lower effects
Affinity of insulin receptor
Induction of receptor mediated cellular signals
Bioavailability
Rapid Analogues vs. Regular: Differences (4)
Faster absorption
Higher peak concentration
Faster onset of action
Shorter duration of action
Basal insulin: Purpose
Maintain euglycemia in fasting state
Types of Basal Insulin
Intermediate: NPH
Long acting: Glargine, detemir
NPH: Structure and Duration
Suspension of Zn-insulin with positively charged protamine
Intermediate duration of action (10-20hr)–>Must be admin 2x daily
NPH: Pros/Cons
Pros: can be combined with other insulins
Cons: peak in action increases risk of hypoglycemia
Glargine Physical Characteristics: structure/pH
Substitution of glycine on A and addition of two arginines on B
pH=4
Flat peak
Deter Physical Characteristics
Acylation
Neural pH
Flat peak
Insulin Administration Types:
IV, SubQ, inhaled
When do you use IV insulin?
Hospitalized patients or metabolic crisis (due to rapid onset/decay)
Conventional Insulin Administration
Long/intermediate acting only
Twice daily mixed split: 70/30 intermediate-rapid
Issues with Twice-Daily Split-Mixed Regimen
Still have periods of hyperglycemia between doses
Intensive Basal/Bolus Therapy
Injections of rapid-acting insulin before each meal + long acting insulin once daily
Inhaled Insulin Administration
Rapid acting insulin in increments for mealtime coverage
Advantages of Insulin Pump (4)
Uses only regular/rapid insulin
1 Injection site
Eliminates subcutaenous insulin depot
Simulates normal pancreatic function
Exercise & Pump
Must educate people about lowering insulin dose before exercise (since it induces GLUT4)
Insulin Complications (4)
Hypoglycemia (at time of peak insulin)
Insulin Lipodystrophies: lipoatrophy or lipohypertrophy at injection site
Allergy: local or systemic
Insulin resistance
Hypoglycemia: Prevention (3), Treatment (2)
Prevention: awareness, plan for treatment, plan for prevention
Treatment: glucose tablets, glucagon
