DM - insulin Flashcards
when is insulin indicated?
- pregnant women (drug of choice)
- SYMPTOMATIC hyperglycemia (polyuria, polydipsia, polyphagia, blurring vision, weight loss, dehydration)
- HbA1c >/= 10% (despite optimised oral therapy?)
- BG > 16.7mmol/L
- ongoing catabolism (weight loss)
Therapeutic effect of insulin (on HbA1c)
*most effective in reducing HbA1c
reduces up to 2.5%
MOA of insulin
Regulation of Carbohydrates (CHO), fat, amino acids
Glucose: facilitates uptakes of glucose in muscle & adipose tissue; inhibits hepatic glucose output [glucogenolysis & gluconeogenesis]
Fat: enhances fat storage (lipogenesis); inhibits mobilization of fat for energy in adipose tissues (lipolysis & free fatty acid oxidation)
Protein: increase protein synthesis & inhibit proteolysis in muscle tissue
-> promote uptake of glucose, facilitate use of other sources of energy (fats, protein)
PK/PD of insulin
onset & duration of action
- response to insulin HIGHLY VARIABLE between individuals & within individual
- Route of administration: rapid, shorter for IV>IM>SC
Absorption: Activity after SC administration from injection site is RATE LIMITING STEP (SC depot formation)
Distribution: Blood stream directly after SC administration
Metabolism/ Elimination:
- EXOGENOUS insulin (injected): eliminated mainly via KIDNEYS
- endogenous insulin: eliminated mainly via liver
Range of insulin syringes & needles & which one to use
Needle length:
- Pen length (4mm - 12.7mm)
- Syringe needles (for vials) (6mm - 12.7mm)
Gauge size (thickness of needle): 28/ 29/ 30/ 31/ 32
*higher the gauge = FINER needle -> LESS PAIN (BUT more needle weakness, decreased speed of injection)
*WHICH SYRINGE SIZE TO USE: smallest size for the DOSE involved
*Longer needles NOT NECESSARILY NEEDED for patients with increased body fat (thicker skin(?))
- Average skin thickness at insulin injection sites: 2.4mm
- Difference in skin thickness not clinically different among different BMI, race or age
- “Third Injection Technique Workshop in Athens (TITAN)”: “no medical reason for recommending needles >8mm”
Sites of injection for insulin (& absorption rates + where to inject)
*from fastest to slowest rate of absorption:
- Abdomen (inject 2 inch circle around naval; rotate sites to prevent lipohypertrophy)
- outer upper arms: areas where fatty tissues are present
- top & outer thighs (avoid bony area above knees)
- buttocks
Common insulin vial sizes & stability
Common insulin vial size: U-100 = 100units of insulin per 1mL *usual vial size = 10mL -> each vial contains 1,000 units of insulin
eg. patient who uses 80units per day -> 2,240 to 2,400 units per month -> 3 vials needed each month (round up to 1000 units)
*NEVER ‘break’ vials; even if pt only needs 1.5 vials, give 2
Stability of insulin (rule of thumb):
- Unopened insulin vials; good until expiration date ONLY IF STORED IN REFRIGERATOR
-> if not refrigerated: good for 28 days
- Opened insulin vials: good for 28 days REGARDLESS OF REFRIGERATION
- Other insulin containing devices eg. pen, refill catridge: vary, see package insert
Insulin dose preparation steps
- Check insulin label for insulin type & expiration date
- Visually inspect insulin vial for contamination/ degradation (eg. white clumps, color change)
- FOR ALL CLOUDY INSULINS: roll vial gently back & forth between hands
- wipe top of vial & injection site with alcohol swabs
- remove protective covering over plunger & needle
- DRAW UP AIR EQUAL TO INSULIN DOSE TO BE ADMINISTERED IN THE SYRINGE
- inject the air into the insulin vial
- with the syringe still inserted, INVERT THE VIAL & withdraw the insulin dose
- if bubbles are present, gently tap the syringe & remove syringe from vial
(insulin) Subcutaneous injection technique
- pinch the area to be injected (depends)
**patients using 6-, 8-, 12.7-mm needles NEED to pinch a skinfold (medication can then reach intended absorption site)
-> 4-/ 5-mm needles (only available in insulin pens) CAN BE USED BY ANY PATIENT (lean/ obese children & adults) -> DO NOT NEED TO PINCH A SKINFOLD (unless pts w lesser SC fat + use arms/thighs for injection - still need to pinch) - insert the needle at 90 degree angle
*if small children/ very thin adults/frail elderly: 45 degree angle to the skin (in the center of pinched area) - release the pinch
- press the plunger to inject the insulin
- HOLD the syringe/ device in the area for 5-10s to ensure FULL DELIVERY OF INSULIN
- Remove device/ syringe
Common misconceptions of needle length required & tips regarding angle of injection + need for pinching skinfold
Needle length required:
- Skin thickness difference is not clinically different among different BMI/ race/ age
- average skin thickness at insulin injection sites: 2.4mm
- longer needles NOT needed for patients with increased body fat (common misconception)
- ‘Third Injection Technique Workshop in Athens (TITAN)’: no medical reason for recommending needles > 8mm
Angle of injection: most needles at 90 degrees angle
- 45 degrees advised for frail elderly/ cachexic adults/ children
Pinching skinfold:
- if using 4/5mm needles (can be used by any patient: lean/ obese children & adults) - DO NOT NEED to pinch a skinfold
*this length only available for insulin pens
**exception: pts with LESSER SC FAT who use ARMS/ THIGHS for injection STILL NEED TO PINCH
Factors altering insulin Absorption:
Temperature (higher temperature: more absorption)
Massage (increases absorption)
Exercise (increases absorption)
Jet injectors (increases absorption)
*via pressure rather than needle
Lipodystrophy:
- LipoAtrophy (concavity/ pitting of adipose tissue due to immune response due to pork/ beef insulin): INCREASES
- LipoHYPERtrophy (bulging of adipose tissue due to not rotating injection sites): DECREASES
Others: increases or decreases
- needle size/gauge, administration technique (IM: INCREASES as compared to SC), insulin preparation, mixtures, concentration, dose, insulin stability
Types of insulin (main classes)
Ultra-short acting
Rapid acting
Short acting
Intermediate-acting
Long-acting
Ultra-long acting
Others: mixed insulin
Rapid-acting insulin details (examples, PK/PD)
Examples: Aspart (novorapid), Glulisine (humalog), Lispro (apidra)
*Target BG: PPG
Onset of insulin: 5-15mins
Peak effects: 1-2h
Duration of action: 3-5h
*Use: one injection per meal (inject 5 mins BEFORE meals)
Short-acting insulin details (examples, PK/PD)
Example: Regular (Actrapid)
*Target BG: PPG
Onset of action: 30-60mins
Peak effects: 2-4h
Duration of action: 6-8h
*Use: one injection per meal (inject 10mins BEFORE meals)
Intermediate acting insulin details (examples, PK/PD)
Example: NPH (insulatard)
*Target BG: FASTING blood glucose
Onset of insulin: 1-2h
Peak effects: 6-12h
Duration of action: 10-16h
*Use: 2 injections for 24h coverage (inject REGARDLESS OF MEAL TIMINGS, AT THE SAME TIME EVERYDAY)
Long-acting insulin details (examples, PK/PD)
Examples: Detemir (Levemir), Glargine U-100 (Lantus)
*Target BG: FBG
Onset of action: 0.8-2h (detemir), 1.5h (glargine)
Peak effects: hill (detemir), peakless (glargine)
Duration of action:
Detemir - 12h for 0.2units/kg; 20-24h for 0.4units/kg
Glargine - ~24h
*Use:
Detemir: 2 injections per 24h for better coverage
Glargine: 1 injection for 24h
**INJECT REGARDLESS OF MEAL TIMINGS, AT THE SAME TIME EVERYDAY
Features of ultra-short acting insulin
- Insulin aspart (Fiasp)
- 2 additional excipients:
1) Vitamin B3 - INCREASES SPEED of inital absorption
2) L-arginine - stabilises formulation - Insulin lispro-aabc (Lyumjev)
- 2 additional excipients:
1) Treprostinil - enchances absorption via VASODILATION
2) Citrate - enhances VASCULAR PERMEABILITY
ultra-long acting insulin details (examples, PK/PD)
- Insulin degludec
- Peakless w duration of action: 42h
- Inject subcutaneously OD at ANY TIME OF DAY - Insulin Glargine U-300
- Peakless w duration of action: 36h
- inject ONCE DAILY AT SAME TIME EVERY DAY
*not the same + NOT bioequivalent to gargline U-100!!!
**BOTH appears to have LOWER RATES OF HYPOGLYCEMIA than glargine (U-100)
Compatibility of insulin mixes (self-mixed)
Stable mixes:
1. NPH + regular
2. NPH + rapid-acting
UNSTABLE mixes:
1. Glargine + ANY other insulin
*incompatible pH
2. Glulisine (rapid) + other insulins (other than NPH)
3. Detemir + ANY OTHER INSULIN
(not recommended by manufacture)
-> LONG-ACTING INSULINS NOT COMPATIBLE WITH ANY OTHER INSULINS
-> when self-mixing, draw up CLEAR insulin first, then CLOUDY (NPH)
Examples of pre-mixed insulin products
- Novomix 30: 30% insulin aspart, 70% insulin aspart protamine (long-acting)
- Humalog Mix 75/25: 25% insulin lispro, 75% lispro protatmine (long-acting)
- Humalog Mix 50/50: 50% insulin lispro, 50% insulin lispro protamine
*1-3: give within 30mins of a meal
- Mixtard 70/30: 70% NPH, 30% regular
*give 30mins before meals
**NPH/ NPH-like component -> give 2x a day
Use of pre-mixed insulin products
*for meal/snack AND basal coverage
Benefits:
- Beneficial for pts who have difficulty measuring & mixing insulins
- Retains individual PD profile
- Less injections
- multiple peaks expected
Limitations:
Challenging to titrate & adjust dose
-> BOTH basal & prandial coverage adjusted TOGETHER
*not impossible if know pts & their lifestyle
**Easier to optimise if pts perform self monitored blood glucose (SMBG) at home
Considerations for oral therapies when injectables are started
Metformin - CONTINUE
TZDs - DISCONTINUE when initiating insulin OR REDUCE TZD dose
SUs
-> DISCONTINUE or REDUCE dose by 50% when BASAL insulin is initiated (if PT AT RISK OF HYPOGLYCEMIA)
->IF MEALTIME INSULIN INITIATIED/ ON PREMIX REGIMEN: DISCONTINUE SU
**effectiveness will gradually wear off; might have to completely rely on insulin
SGLT-2i: CONTINUE
DPP-4i: IF GLP-1 agonist initiated: DISCONTINUE
Insulin Dosing Conversion principles
General: most insulin conversions at 1:1 units
eg. Mixtard 30 (70% NPH, 30% regular)/ Insulatard (NPH) 16 units AM, 8 units PM <-> Novomix 30 (30% insulin aspart, 70% insulin aspart protamine) 16 units AM, 8 units PM
- REDUCE DOSE BY 10-20% if pt is at HIGH RISK OF HYPOGLYCEMIA
Exceptions (MUST DECREASE DOSE)
1. Switching from 2x daily NPH (alone/ in pre-mixed) to 1x daily GLARGINE/ DETEMIR: DECREASE BY 20%
eg. 20u NPH twice daily (total 40u daily) -> 32u glargine once daily
2. Switching from Glargine U-300 to OTHER ALTERNATIVE BASAL INSULIN ANALOG: DECREASE BY 20%
eg. 40units of U-300 glargine -> 32 units of U-100 glargine/ detemir
Insulin adverse effects
- HYPOGLYCEMIA (BG < 4.0mmol/L (70mg/dL)
- S/Sx: blurry vision, sweating, tremor, hunger, confusion, anxiety, shaking, rapid heart beat, dizziness, headache, weakness & fatigue, irritability etc.
*nocturnal: nightmares, restless sleep, profuse sweating, morning headache
-> MANAGEMENT: 15-15-15 -> 15g of fast-acting carbs (1/2 cup fruit juice/ soft drinks *not sugar-free, 3cubes/1tbsp sugar, 5-6pc hard candy, 1 tbsp honey // glucose tablets/gel), then wait 15 mins, then check BG - if still <4.0mmol/L then another 15g of fast-acting carbs - Weight gain (> SU) [~4kg more than conventional treatment @ 5y (T1DM) or 10y (T2DM)]
*benefits of glycemic control > weight gain -> remind pts on diet, exercise & losing weight - Lipodistrophy
- Lipoatrophy: concavity/ pitting of adipose tissue due to immune response due to pork/beef insulin (less common due to phasing out)
- LipoHYPERtrophy: bulging of adipose tissue due to not rotating injection sites - Local allergic reaction: redness, swelling, itching at injection site (more common with beef/pork insulin)
- *RARE: Systemic allergic reaction
- *RARE: Insulin resistance (immune phenomenon)
Insulin Dosing (initial initiation, titration, MAX )
Normally: initial with BASAL control (FBG) ** higher HbA1c levels -> major contributor is FBG
Intiation: NPH 10 units/ 0.1-0.2units/kg/day
(glargine, detemir possible BUT costly)
If A1c UNCONTROLLed (target FBG range: 5-7mmol/L), continue to act on FBG
-> INCREASE insulin 2 units EVERY 3 DAYS until FBG at goal
(may increase by 4 units every 3 days if FBG consistently >10mmol/L)
-> may decrease by 10-20% if no clear reason for HYPOglycemia
MAX: 0.5units/kg/day
When to adjust insulin dosing (from 1 dose -> add prandial coverage etc)?
*when A1c still ABOVE goal, DESPITE
1. basal dose >0.5units/kg
OR
2. FBG at goal
-> Add Prandial coverage (rapid/ regular insulin)
- start with 1 dose with LARGEST meal
- 4 units OR 10% of basal
*if A1c <8%: ALSO DECREASE basal dose by 4units/ 10%
OR
-> if on BEDTIME NPH: consider splitting doses into 2: 2/3 in AM, 1/3 in evening
Insulin regimens & populations suitable for each regimen
- Full basal-bolus regimen (total: 4 injections)
- one basal (detemir/ glargine) + THRE injections of rapid/ regular for each meal
-> T1DM w SEVERE insulin deficiency
-> LONG duration of T2DM (insulin deficiency)
-> Specific situations that require TIGHT control (pts undergoing Coronary Artery Bypass Grafting CABG// Gestational Diabetes with inadequate glycemic control on medical nutritional therapy) - Twice daily pre-mixed regimen (total: 2 injections)
- NPH + rapid (Novomix)/ regular (Mixtard)
*2/3 in AM, 1/3 in PM
*BASAL DOSE: 50% OR MORE of total daily dose
