Diabetes 3 Flashcards
What is insulin?
hormone secreted from pancreatic B-cells to help regulate blood glucose
in the body, proinsulin is cleaved to release insulin + C-peptide
True or false: commercial versions of insulin contain insulin and C-peptide
false
only contain insulin
What is the history of insulin?
originally derived from the pancreases of cows and pigs
-pork insulin still available, uncommonly used
1982/83: Humulin; first human insulin using rDNA
-human insulin produced via rDNA has identical aa sequence
to human insulin
-with rDNA concerns of purity, hypersensitivity, and
lipodystrophy are much less common
What is the structure of insulin?
51 amino acids in 2 chains (A and B) linked by 2 disulfide bonds
Differentiate between basal and bolus insulin.
basal: B cells secrete small amounts of insulin throughout day
bolus: at mealtime, insulin is rapidly released in response to
food
What are the two classes of bolus (prandial or mealtime) insulins?
rapid-acting insulin analogues
short-acting insulins
What are the rapid acting insulin analogues?
aspart (NovoRapid; biosimilars: Trurapi, Kirsty)
glulisine (Apidra)
lispro (Humalog U-100 & U-200 and biosimilar: Admelog U-100)
faster-acting insulin aspart (Fiasp)
What are the short-acting insulins?
insulin regular (Humulin R, Novolin Toronto)
insulin regular U-500 (Entuzity)
When are short acting insulins administered?
30-45 min prior to meals to cover mealtime glucose excursions
What is the appearance of short acting insulins?
clear solutions
What is a special use of short acting insulins?
can be used IV to treat DKA
What is the onset, peak, and duration of action of short acting insulins?
onset: ~30mins
peak: ~2-3hr
duration of action: ~6hr
How does the PK of insulin regular U-500 (Entuzity) differ from the rest of the short acting insulins?
entirely different PK profiles
-onset: 15 mins
-peak: 4-8h
-duration: 17-24h
What do the modifications of RAIAs allow for?
more rapid absorption vs short acting insulins and more closely mimic endogenous insulin release
When are RAIAs administered?
with or just prior to meals (0-15min) to cover mealtime excursions
What is the appearance of RAIAs?
clear solutions
What are the advantages of RAIAs?
more rapid absorption:
-fast onset
-quicker peak
-shorter duration of action
convenience:
-0-15min before a meal or within 15min of eating
-Fiasp: up to 2 min before or 20 min after a meal
-although better before a meal
better PPG control
decreased hypoglycemia
What are the disadvantages of RAIA?
more $ and similar effectiveness
True or false: Fiasp shows better PPG in T2 studies
false
shows better PPG in T1 studies; not T2
What is special about Humalog (lispro) KwikPen 200U/ml?
more concentrated formulation for those who require higher doses
the dose counter window on each of the KwikPen (100U/ml and 200U/ml) indicate the number of units of insulin to be injected. As a result the same number of units of insulin would be chosen for both devices. The Kwikpen automatically delivers the correct volume of insulin so conversion of dose between devices is not needed
Describe Entuzity.
very concentrated form of insulin (500U/ml)
for those who require >200U/d
given 2-3x/d
short-acting: administer 30min before a meal
can dial up in 5U increments
no dose conversion required when using this KwikPen
extreme caution required to avoid inadvertent overdose
What is the onset, peak, and duration of action of RAIA?
onset: 4-20min
peak: 0.5-2h
duration of action: 3-5h
What are the classes of basal insulins?
intermediate-acting
long-acting
What are the intermediate-acting insulins?
insulin neutral protamine Hagedorn
-Humulin N, Novolin NPH
What are the long-acting insulins?
detemir U-100 (Levemir)
glargine U-100 (Lantus; biosimilars: Basaglar, Semglee)
glargine U-300 (Toujeo)
degludec U-100, U-200 (Tresiba)
How frequently are intermediate acting insulins administered?
once or twice daily to provide a background amount of insulin
What is the appearance of intermediate acting insulins?
cloudy (they are a suspension)
-must hand-roll and invert (10x) before use to re-suspend
What is the onset, peak, and duration of action of intermediate acting insulins?
onset: 1-3h
peak: 5-8h
duration of action: ~18h
What do the modifications to long acting insulin allow for?
modifications result in an extended and more flat absorption
What happens to insulin glargine once injected?
has an isoelectric point from pH 5.4-6.8, making it more soluble at acidic pH; buffered to a pH of 4.0 for distribution
once injected, it forms micro precipitates which slowly dissolve