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
What gives insulin detemir its prolonged duration of action?
its hexamer stability
What are the advantages of LAIAs compared to intermediate acting insulins?
peakless
more consistent/less variable BG
less hypoglycemia (mainly nocturnal)
What are the disadvantages of LAIAs compared to intermediate acting insulins?
cost more $ and they all have similar efficacy
What is the onset and duration of action of LAIAs?
onset: 90 mins
duration of action:
-glargine U-100: 24H
-detemir: 16-24h
-U-300 glargine: >30h
-degludec: 42h
True or false: use of intermediate acting insulin is declining
true
due to the LAIAs
How frequently is insulin NPH dosed?
usually BID
What is the duration of action of detemir based on?
dose dependent:
-0.2U/kg ~12hrs
-0.4U/kg ~20hrs
administered OD or BID
How frequently is insulin glargine U-100 dosed?
usually OD but some use BID
How is Toujeo dosed?
SoloSTAR: 1.5ml disposable pen, can dose between 1-80U per injection
DoubeSTAR: 3ml disposable pen, can dose between 2-160U per injection
How is insulin degludec dosed?
prefilled pens: 100U/ml & 200U/ml
dosed OD at any time of day, if miss dose inject when realize the omission
ensure at least 8hrs between injections
What are the forms of insulin delivery?
syringes and vials
insulin pens
insulin pumps
Describe syringes and vials as a form of insulin delivery.
the traditional method of insulin delivery, some still prefer:
-least expensive
-used to it
-prefer less injections and want to combine insulins
syringes available in differing volumes (3/10, 1/2, 1cc) and differing lengths (BD 6mm and 8mm) and differing thickness (30 and 31 gauge)
What volume of syringe is needed for the following:
<30 units of insulin
31-50 units of insulin
51-100 units of insulin
<30U: 3/10 cc/ml
31-50U: 1/2 cc/ml
51-100U: 1 cc/ml
Describe insulin pens as a form of insulin delivery.
largely supplanted vials/syringes because:
-portable/convenient/easier to use
-advantageous id dexterity/visually impaired
-allows for precision dosing
a new needle tip must be attached each time, they are available in different lengths
-BD 4, 5, 8mm
-31 and 32 gauge
Describe insulin pumps as a form of insulin delivery.
small computerized device that delivers insulin continuously 24hrs a day
worn on outside of body, and delivers insulin via a tube, which is attached to a cannula placed under the skin
-changed every 3d
only uses RAIA and delivers it continuously, as well as increased amounts when a bolus dose is required
When should insulin pumps be considered?
poorly controlled with optimized injections
significant glucose variability
frequent severe hypoglycemia
pregnacny
How do insulin pumps and CGM work in tandem?
a closed loop system-the pump and CGM automatically communicate to one another via a computer program to create somewhat of an artificial pancreas
What are the adverse effects of insulin?
hypoglycemia
-most common AE and more frequent in those trying to
achieve tight control
weight gain
-insulin is anabolic
-varies (2-7kg); depends on amount taken and often a result of
over correcting
localized fat hypertrophy (minimize by rotating sites)
blurry vision
-not really an AE, can occur when initiate for a few weeks
allergic reactions: rare
What are the factors affecting insulin absorption?
site of injection
-abdomen>arm>thigh>buttock (not as much of an issue for
R/LAIA)
exercise of injected area
-strenuous exercise of a limb within 1hr will speed absorption
massage
-vigorous massage will speed absorption
temperature
-heat can increase absorption rate
lipohypertrophy
-delays absorption
dose
-larger doses delay absorption and prolong action
renal function
-renal failure decreases insulin clearance
depth of injection
-IV>IM>SQ
What are some good practices for injection technique of insulin?
wash your hands
alcohol swabs to clean cartridge/vial
rotate injections systematically within the same anatomical region
avoid moles, scars, etc
use quick, smooth movement
What are the preferred injection sites of insulin?
abdomen
thigh
buttock
under arm
How do we systematically rotate injection site within the same anatomical region?
split selected injection area into four large sections
select one section and split it into four smaller sections
rotate clockwise through these four small sections for a week
in the following week select the next large section (clockwise) and divide into four smaller sections
What are the steps for injecting insulin via syringes?
- pull air in syringe (to roughly 5U)
- push air into the bottle
- pull in and push out a little insulin to remove air bubbles
- pull your exact dose of insulin into the syringe
What are the recommendations regarding syringes and vials for injecting insulin?
6mm syringe:
-recommended
-with or without skin lift
-preferentially a 90 angle (45 angle if lean)
8mm syringe:
-do a skin lift and inject at 90 angle
-if lean at 45 angle
12mm syringe: not recommended
hold needle in place for 10 seconds, when needle is removed skin should look normal
What are the steps in using an insulin pen?
- wash hands, remove pen cap
- wipe pen tip with alcohol swab, attach needle (new needle)
- prime (2U) with needle pointing up, watch for stream
- dial up amount of insulin
- inject at 90 angle with no skin lift for most, count to 10
- remove needle, dose window should say 0
Where should unopened insulin be kept? What if in-use?
unopened: fridge
closed: room temperature
How long is in-use good for?
depending on the insulin, recommended to discard after 28 days up to 56 days (degludec)
What is a sign of unstable insulin?
cloudy or with particles (NPH is suspension so its cloudy)
avoid freezing, extreme heat, direct sunlight
Which insulins can be mixed?
R + NPH: may be pre-mixed and stored together
RAIA + NPH: may mix together with immediate administer
LAIA: cannot mix with any other insulins
What are the average daily insulin requirements for T1DM?
initial dose: 0.5-0.6 U
honeymoon: 0.1-0.4 U
ketosis or acute illness: 0.5-1.0 U
What are the average daily insulin requirements for T2DM?
initial dose: 0.1U/kg (or more commonly 10U of basal insulin hs)
with insulin resistance: up to 2.5U/kg (or greater)
What is the usual split of insulin for T1DM or those who are on MDI with T2DM?
bolus: 50-60% (<60%)
basal: 40-60% (>40%)
True or false: the insulin regimen and dose is usually the same for life for Type 1 diabetics
false
changes over time, rarely ever the same
What are insulin changes in Type 1 diabetics based on?
age
goals
general health
glucose levels
physical activity
What is the carbohydrate to insulin ratio?
ratio used to estimate how many grams of CHO each unit of meal-time insulin will cover
typical ratio is 15:1 but may be higher or lower
How is C:I ratio calculated?
initial C:I ratio can be estimated by 500 or 550 by the total daily dose of insulin
What is the use of the correction factor?
for someone who is counting carbs, utilizing a correction factor can help bring down BG detected before meals
What is the correction factor?
expected amount that 1 unit of insulin will normally decrease BG by
-typically 1U of insulin will decrease BG by 2-3mmol over the
next 2-4hrs
How do we estimate CF? What about how many units must be given to correct a high reading?
100/TDD
current glucose-target glucose/CF
What are general rules when interpreting BG/adjusting doses?
fix the lows first
-generally adjust by 1-2 units at a time
only adjust 1 dose at a time, begin with correcting the 1st problem BG of the day
make dose adjustments every few days based on glucose trends
How do we evaluate morning hyperglycemia?
try to determine the cause before adjusting therapy
do this by checking blood glucose levels while one is sleeping x several nights
-3am CBG or via CGM
-glucose <4mmol suggest Somogyi effect
-glucose >4mmol suggests the dawn phenomenon
What are tell tale signs of nocturnal hypoglycemia?
nightmares
restless sleep
sweating (wet pillow/sheets)
headache in am
hunger
What is the Somogyi Effect?
unrecognized nocturnal hypoglycemia that patient sleeps through; as a result the body increases production of counter-regulatory hormones & see rebound hyperglycemia
What are possible ways to rectify the Somogyi Effect?
fix the excess/ill-timed insulin
-decrease dose of insulin
-shift predinner basal (NPH) to hs
-consider a LAIA if on NPH
consider a bedtime snack, evaluate meals/alcohol/exercise
the key is to prevent overnight lows
What is the Dawn Phenomenon?
fasting hyperglycemia that is the result of growth hormones, cortisol, glucagon being released in early am before waking (usually between 3-8am)
What are possible ways to rectify Dawn Phenomenon?
avoid eating CHO after dinner/eat earlier
be active after dinner
adjust basal insulin/dose time
consider an insulin pump
