insulin Flashcards
insulin MOA
○ Regulation of carbs (CHO), fat, aa
○ Glucose: facilitate uptake of glucose in muscle and adipose tissue
§ Inhibit hepatic glucose output (glycogenolysis, gluconeogenesis)
○ Fat: enhance fat storage (lipogenesis)
§ Inhibit mobilisation of fat for energy in adipose tissue (lipolysis, FFA oxidation)
○ Protein: incr protein synthesis
§ Inhibit proteolysis in muscle tissue
○ Acts on liver, pancreas muscle, adipocytes
benefits of insulin
MOST EFFECTIVE HbA1c: 2.5% lowering
* Indication
○ All types of DM
* Choice of therapy: PREG with DM
PD of insulin
○ Response to insulin is highly variable between individuals and within indiv
○ ROA rapid and shorter for: IV> IM > SC
PK of insulin
○ A: activity after SC admin from inj site rate limiting step
§ SC depot formed
○ D: enter bloodstream after SC depot directly
○ M/E:
§ Exogenous: by kidney
§ Endogenous: by liver
injection factors
needle length
gauge size
syringe size
site
insulin vial size
stability of insulin
Needle length
Pen: 4mm ~ 12.7 mm
Syringes: 6mm ~ 12.7 mm (account for vial stopper)
○ Average skin thickness of 2.4mm (not based on BMI, race, age)
○ No need long needle (may enter IM instead, affect absorption)
○No need > 8mm
Gauge size
- 28,29,30,31,32 guages
○ Higher, more fine needle
○ Less pain
○ More weak needles – break
○Decr speed of inj
Syringe size:
- 1 - 100 units
- 1/2 - 50 units
- 3/10 - 30 units
Med safety: use smallest synringe possible for dose invovled
site of injection
- Absorption speed (fastest is)
○ Abdomen > outer upper arms > top/ outer thighs > buttocks - Reduce lipohypertrophy by rotating sites
insulin vial size, amt
- U100 = 100 units/ 1mL of insulin
- 1 vial = 10mL
○ Each vial contains 1,000 units of insulin
~round up number of vials needed
Stability of insulin (shelf life vs expiration date)
- Shelf life = unopened
○ Fridge = expiration date
○ Not fridge = 28 days - Opened insulin vials
○ Fridge/ no fridge = 28 days
Other devices, pens, refills vary (package insert)
Injection technique
1) Pinch area to be injected
2) Insert needle 90* angle at center of pinched area
1. 45* if small children/ cachexic adults/ frail elderly
3) Release pinch/ continue to pinch
4) Press plunger to inject insulin
5) Hold syringe/ device at area for 5-10s
1. Insulin depot, not leak out
6) Remove syringe/ device
special considerations when inejcting
Angle of injection
* 45* if small children/ cachexic adults/ frail elderly
Pinching
* If use 6,8,12.7 mm
○ Don’t need pinch skinfold for meds to reach intended site
* 4-5mm needle
○ Don’t need pinch skinfold
○ Unless less SC fat (use arm, thighs for inj)
Factors affecting insulin absorption
- Temp = Incr ab with HEAT
- Massage = Incr ab
- Exercise = Incr ab
- Jet injectors
- Incr ab via pressure (not use needles)
- Lipodystrophy
- lipoATROOPHY
- lipoHYPERTROPHY
inj sites
lipoatrophy vs lipohypertrophy
- lipoATROOPHY
○ Incr ab
○ Concavity/ pitting of adipose tissue due to immune resp to porcine/ bovine insulin - lipoHYPERTROPHY
○ Decr ab
○Bulging of adipose tissue, from not rotating
Ultra-short acting
Rapid acting
Aspart
Lispro
Glulisine
——PPG
onset: 5-10min
1-2hr
duration of action: 3-5hr
One inj per meal (15min before)
Short acting
regular — PPG
30-60ming
2-4 hr
6-8hr
One inj per meal (30min before)
intermediate
NPH –FPG
onset: 1-2hr //6-12hr
duration of action: 10-16hr
2 inj for 24hcoverage
Long acting
Detemir —- FPG
Onset: 0.8-2hr
DOA:
12hrs for 0.2units/kg
20-24hrs for 0.4units/kg
2inj for 24hr coverage
Glargine U-100
1.5h
Peakless
24hr
1 inj for 24hr
Ultra long acting
Degludec —— FPG
Peakless
Duration of 42hr
Anytime of the day OD, sc inj
Glargine (U-300) ——FPG
36hr
OD, same time daily
stable mixed
- Regular + NPH
- Rapid + NPH
- Rapid + degludec
- Prior to admin
unstable mixes to avoid
- Glargine + other
○ Incompatible pH - Glulisine + (not NPH)
○ Incompatible - Detemir + other
○ Not recc
EG OF MIXED (cover FPG + PPG)
- Novomix 30
- 30% aspart
- 70% aspart protamine
- Humalog mix 75/25
- 25% lispro
- 75% lispro protamine
- Mixtard 70/30
- 30% regular
- 70% NPH
- Mixtard 50/50
- 50% regular
- 50% NPH
benefits of pre-mixed products
- Covers for meal/snack & BASAL
- Beneficial for pt difficulty measuring and mixing insulin
○ Retains indiv PD profile - Less inj
- Expect multiple peaks (rapid + intermediate)
- Challenging to titrate, adjust dose
- Basal + prandial adjusted tgt
○ Need pt to SMBG: optimise drug therapy
continue PO metformin?
YES
continue TZD?
discontinue when initiate insulin
OR
reduce TZD dose
TZDL insulin sensitiser, incr risk of hypoglycemia
continue SU
discontinue. reduce SU dose by 50% when BASAl insulin (pt risk of hypogly)
discontinue is mealtime insulin (PPG added)
- effectiveness of SU will wear off over time
SU: targets PPG
continue SGLT2i?
YES
insulin dosing conversions
Most insulin conversion 1: 1unit
□ Reduce dose 10-20% if pt high risk of hypoglycemia
Exceptions
□ BD NPH –> OD glargine/ detemir
* Reduce dose by 20%
□ U300 glargine --> basal insulin (U-100 glargine/ detemir) * Decr dose by 20%
mixtard 30 (BD) —> glargine +aspart
Mixtard (70% NPH, 30% regular)
30units BD = 60 units
NPH = 0.70 x 60 = 42.0 —- FBG
42 x 0.80 = 33.6 (34) decr dose
Regular = 0.3 x 60 = 18.0 —- PPG
same
= 34units of glargine OD + 18/3 =6units aspart TDS during meals
ADR of insulin
hypoglycemia (<4mmol/L)
Weight gain
Lipodystrophy (lipoatrophy, lipohypertrophy)
local allergic rxn
systemic allergic rxn (rare)
insulin resistance (rate)
Management: 15-15-15 rule
15g fast acting carb
wait 15mins
check BG, still <4.0mmol/L, add another 15f of fasting cards
Individual therapeutic interventions
- First line = metformin
a. Continued as long as possible, start early also
b. Combi can be considered if HbA1c really quite elevatedc. If history of: 1) ASCVD: GLP1 agonist/ SGLT2i 2) HF: SGLT2i 3) CKD: SGLT2i
after adding metformin still above target…
a. Need minimise hypoglycemia (elderly) = AVOID: SU, Insulin
b. Need promote weight loss = GLP1, SGLT2i
c. Financial difficulties = SU > TZDs > DPP4
If need greater glucose lowering (despite PO drugs)
a. GLP1 agonist INJ
b. Insulin
□ Only first line INJ if:
Catabolism (weight loss)/ symp of Hypergly, A1c > 10%, BGL > 16.7 mmol/L
how start insulin
a. Initiate with BASAL, FPG
□ Contributes most to HbA1c readings
□ 10 units or 0.1IU/Kg
□BEDTIME NPH
□ Or glargine/ determir/ degludec ($$$$$)
A1c still uncontrolled with basal = STRAT TITRATE
Act on FPG (TITRATION)
- Incr insulin 2 units every 3 days (until FPG goal)
- Incr 4 units every 3 days (if FPG consistently >10 mmol/L)
◊ Must be out of control for 3 days then u titrate
*Decr insulin by 10-20% if hypogly with no reason
Target FPG 5-7mmol/L
- Higher end if pt needs
Start prandial insulin when:
A1c still high, but
1) basal>0.5 IU/kg
2) FPG alr at goal
- Change to pre-mixed insulin/ self-mixed to decr number of injections (Prandial + NPH)
why cannot just keep incr basal
- OVER-BASALISATION
◊ Basal insulin at ceiling effective dose
◊ Incr dose, less proportional decr FBG
=Lead to weight gain, hypogly, Postpradial hypergly
start prandial insulin by (2 methods)
- Add Prandial coverage (rapid / regular insulin)
- Initiate 1 dose with largest meal
- 4IU/ 10% of basal dose
◊ STOP SU (glipizide)
-Decr BASAL by 4IU/ 10%
◊ If A1c <8%
- (or) Split dose of bedtime NPH
- 2/3 for morning
- 1/3 for evening
- 2/3 for morning
insulin dosing when pt have multiple inj dose
1) full basal-bolus regimen
* 1 inj (basal, glargine)
+ 3 inj (regular/ rapid for each meal)
=4inj
2) or twice daily pre-mix regimen
*BD NPH+regular/ rapid insulin = 2inj
(basal consist >50% of total daily dose) – premix
Diabetic emergencies;
Ketones are byproducts of fat metabolism
Type1 > type2
- Absolute insulin deficiency
Lipolysis + metabolism of FFA
□ Form ketones (beta-hydroxybutyrate, acetoacetic acid, acetone) in liver - Stress
Stimulates insulin counter regulatory hormones
(glucagon, catecholamines, glucocorticoids, growth hormone)
□ Excess glucagon: incr gluconeogenesis, decr peripheral ketone ultilisation
Diabetic ketoacidosis (DKA)
- Ketones formed
○ Found in blood, urine
○ Fruity breath odor
○ Acidosis - Still alert
- BG > 14mmol/L
DKA labs
Glucose
pH low Bicar low
Acetoacetate (ketones) high
Osmolarity (conc with blood) not too high
Anion gap (acidosis) HIGH
Sensorium = alert
T2DM emergency = Hyperglycemic hyperosmolar state
- Still residual insulin, usually no ketones
○ No acidosis - Extremely dehydrated BGL >33 mmol/L
- Stupor
T2DM hypergly labs
Glucose HIGH
pH neutral Bicar high
Acetoacetate (ketones) ABSENT
Osmolarity (conc with blood) HIGH
Anion gap (acidosis) NO <12
Sensorium = COMA
Somogyi effect
- BG drop at night
- Too much insulin/ no snack
- Body respond by release glucagon
- Incr BGL
= SMBG at 3am
at night is high or LOW
Dawn phenomenon
Release of cortisol in waking hrs causes BGL rise sharply
=SMBG at 3am
at night is normal
Prevention and management of comorbidities
Aspirin admin// clopidogrel (if allergic to aspirin)
2nd prevention strategy if DM, ASCVD
1st prevention strategy if DM + incr risk of CV
risk of CV (for aspirin therapy)
□ LDL cholesterol >2.6mmol/L
□ High BP
□ Smoke
□ CKD
□ Albuminuria
□ Fam hist/ premature ASCVD
no need aspirin in
Not needed — Incr risk for bleeding events
□ Low/ no risk of ASCVD
□ Young <40 yrs
□ Old > 70 yrs
limitations of HbA1c
- fail to correlate with macro complications
- pop A1c diff among race, ethnic grps
- fail to reflect harms of hypogly
- fails tp reflect glycemic variability
- represent a target without providing guidance as to how to achieve
