Diabetes

Question 1

What is an insulin pump?

Answer 1

Small microcomputer which delivers insulin continuously 24 hours a day (may be programmed to deliver increments as small as 0.025 units/hour (pediatrics and insulin sensitive individuals)

Question 2

Insulin pumps use what type of insulin?

Answer 2

One type - rapid acting

Question 3

What are some benefits to using an insulin pump? (8)

Answer 3

1. Insulin delivery that’s customizable, flexible and adjustable
2. Insulin delivery that’s more precise than pen or syringe doses
3. Fewer injections
4. More flexibility with daily routines
5. Feeling healthier, better blood glucose control
6. Improved control during exercise
7. Patient is in control, not the diabetes
8. Opportunity for sensor integration

Question 4

Why is using an insulin pump more effective? (3)

Answer 4

1. Can be programmed to more closely mimic the insulin secretion of a functioning pancreas than injections
2. More predictable insulin absorption
3. More accurate bolus doses

Question 5

What are some of the downsides of using an insulin pump? (3)

Answer 5

1. Can be challenging and more work for the patient, especially initially
2. Expensive
3. Various Complications
   - Empty reservoir, kinked line, set problems, low batteries
   - Higher risk of DKA
   - Body image – always “attached”

Question 6

Who is a good candidate for using an insulin pump? (5)

Answer 6

1. Motivated and willing to check blood sugars
2. Wants to improve glucose control
3. Desire to live a more physiological lifestyle
4. Have family support
5. Realistic Expectations

Question 7

What are some good indications for using an insulin pump? (9)

Answer 7

1. A1C
2. Frequent hypoglycemia
3. Dawn Phenomenon
4. Exercise
5. Pediatrics
6. Pregnancy
7. Gastroparesis
8. Lifestyle
9. Shift work

Question 8

What are some of the available pumps in Canada? (4)

Answer 8

1. Tandem t:slim X2
2. Medtronic 630G, 780G
3. YpsoPump
4. Omnipod DASH

Question 9

What is a pump infusion set? (3)

Answer 9

1. Delivers the insulin from the reservoir in the pump into the body
2. Consists of tubing, an adhesive mount, quick disconnect and a plastic or metal cannula that is inserted into the skin
3. Changed every 2, 3, or 7 days

Question 10

What are the best infusion sites for a pump? (4)

Answer 10

1. Abdomen
2. Hips and Buttocks
3. Outer thigh
4. Back of the arms

Question 11

What is a 90 degree infusion set? (5)

Answer 11

1. Soft, flexible Teflon cannula inserted under the skin at a 90 ̊ angle
2. Cannula lengths can be 6mm or 9mm
3. Various tubing lengths available from 18” to 43”
4. Must be changed every 3 days
5. Extended wear set available for 7 day wear

Question 12

What is a 30 degree infusion set? (4)

Answer 12

1. Soft, flexible Teflon cannula inserted under the skin at a 30 ̊ to 45 ̊ angle
2. Cannula lengths can be 13mm or 17mm
3. Various tubing lengths available from 18” to 43”
4. Must be changed every 3 days

Question 13

What is a steel needle infusion set? (3)

Answer 13

1. Enhanced security: designed with a kink-free steel needle.
2. Combined with an extra disconnection site 10 cm away from the infusion site, this provides extra security against clogging and dislodging.
3. Particularly suited for infants and children, pregnant women or people allergic to Teflon®.

Question 14

Difference between basal and bolus rates in an insulin pump?

Answer 14

1. Basal rate is constantly running – tiny micro-doses delivered as background insulin
   - Different profiles can be programmed to coincide with different physiologic needs
   - Newest insulin pump automatically adjusts basal rates based on sensor glucose readings
2. Bolus amounts are temporary surges in dose, given in response to food intake and as correction

Question 15

What is basal insulin? (4)

Answer 15

1. Rapid-acting insulin delivered around the clock in small pulses preprogrammed to meet metabolic needs when not eating
2. Takes the place of long-acting insulin
3. Typically start on the pump with one basal rate
4. Rate(s) may vary throughout the day and can be increased or decreased according to needs

Question 16

When set correctly, basal insulin will: (2)

Answer 16

1. Keep glucose stable between meals and through the night
2. Allow you to sleep late, eat late, even skip meals

Question 17

There are 2 reasons a bolus of insulin is given. What are they?

Answer 17

1. For food or drink that contains carbohydrate at meals or snacks
2. To bring down a glucose level that is above your target range (correction dose)

Question 18

What to know about bolus doses in insulin pumps?

Answer 18

Insulin pumps also track insulin that is still working from previous bolus doses (called Active Insulin or Insulin on Board) and takes this into account when calculation correction doses if blood glucose (BG) is above target

Question 19

Four personal settings are required for bolus dose insulin pump calculation. What are they?

Answer 19

1. Carbohydrate ratio
2. Sensitivity
3. BG target
4. Active insulin time

Question 20

Continuous glucose monitoring (CGM) measures glucose levels in the ____________ _____ in the body

Answer 20

interstitial fluid

Question 21

A higher Time in Range results in a(n) _________ of Glycemic Variability (GV)

Answer 21

reduction

Question 22

What to know about glycemic variability? (4) (mostly why is it bad?)

Answer 22

1. Increasing GV is correlated with more frequent episodes of hypoglycemia
2. GV has been associated with increased is risk of diabetic retinopathy and nephropathy
3. Emerging evidence of the relationship between GV and increased risk of severe hypoglycemia and cardiovascular outcomes
4. Patients experiencing severe hypoglycemia have an increased risk of cardiovascular outcomes and death, therefore reducing hypoglycemia is important

Question 23

What to know about insulin pump coverage in Sask?

Answer 23

1. The Saskatchewan Aids to Independent Living (SAIL) program fully covers insulin pumps for eligible individuals; however supply coverage will vary
2. Coverage is available for one pump every 5 years
3. The selected pump and 3 months of pump supplies are provided at no charge

Question 24

When is A1C of 7.1-8.5 the target? (3)

Answer 24

1. Recurrent severe hypoglycemia and/or hypoglycemia unawareness
2. Limited life expectancy
3. Frail elderly and/or with dementia

Question 25

When is A1C of 7.1-8.0 the target?

Answer 25

Functionally dependent

Question 26

When is A1C of ≤7.0 the target?

Answer 26

Most adults with Type 1 or Type 2 diabetes

Question 27

When is A1C of ≤6.5 the target?

Answer 27

Adults with T2DM to reduce the risk of chronic kidney disease and retinopathy if at low risk of hypoglycemia

Question 28

When is A1C of ≤6.0 the target?

Answer 28

Selected adults with T2DM with potential for remission to normoglycemia

Question 29

What are the 3 currently available biosimilar insulins?

Answer 29

1. Insulin glargine (Lantus; Basaglar, Semglee) 2. Insulin lispro (Humalog U-100; Admelog) - Not Humalog U-200 3. Insulin aspart (NovoRapid; Trurapi, Kirsty)

Question 30

What are 2 classes of drugs with MACE benefits?

Answer 30

1. Injectable GL1 agonists (dulaglutide, liraglutide, semaglutide) - Not oral semaglutide 2. SGLT2i (canagliflozin, empagliflozin) - Dapagliflozin non-inferior to placebo

Question 31

Which diabetes drug class has renal benefits?

Answer 31

1. SGLT2is (all 3) 2. SubQ semaglutide (FLOW trial)

Question 32

Which diabetes drug class has heart failure benefits?

Answer 32

SGLT2is - only dapagliflozin and empagliflozin

Question 33

What was the PICO of the FLOW trial?

Answer 33

Population: patients with T2DM and CKD Intervention: subcut semaglutide 1mg once weekly compared to placebo Primary Outcome: Major kidney disease events Results: Risk of primary outcome was 24% lower in semaglutide group

Question 34

Newer diabetes drugs in T1DM. Yay or nay? (That being SGLT2i and GLP1)

Answer 34

1. DEPICT studies: Dapagliflozin - Improved glycemic control and induced weight loss in T1DM - Increased risk of DKA 2. ADJUNCT 1,2: Liraglutide (26 and 52 weeks) - Improved glycemic control, body weight & reduced total insulin dose - Higher rates of hypo and hyperglycemia with ketosis 3. EASE-2,3: Empagliflozin (26 and 52 weeks) - Improved glycemic control and weight without ↑ hypo & reduced total insulin dose - At 2.5mg no increase in DKA; was an ↑ with 10mg and 25mgJAMA review

Question 35

What is the MOA of tirzepatide? (3)

Answer 35

- It is a GIP receptor and GLP-1 receptor agonist - It selectively binds to and activates both GIP and GLP-1 receptors, the targets for endogenous GIP and GLP-1 - It enhances first- and second-phase insulin secretion, and reduces glucagon levels, both in a glucose-dependent manner

Question 36

Who is indicated for tirzepatide use? (3)

Answer 36

1. T2DM adults (not in those <18yo and not in pregnancy/breastfeeding) 2. If a patient wishes to become pregnant, tirzepatide should be discontinued at least 1 month before a planned pregnancy due to the long half-life of tirzepatide 3. Plasma concentrations in people with renal and hepatic impairment do not differ from healthy people (therefore no dose adjustments necessary – although only limited clinical experience so it will depend on prescriber specialty/experience/comfort level)

Question 37

How is tirzepatide administered? (4)

Answer 37

1. A SC injection given once a week 2. Initiate at 2.5mg dose once weekly x 4 weeks (this dose not intended for glucose control) 3. Then increase dose to 5mg once weekly – assess for efficacy 4. If additional glycemic control is needed increase the dosage in 2.5 mg increments after at least 4 weeks on the current dose up to a max dose of 15mg once weekly

Question 38

What if a dose of tirzepatide is missed? (2)

Answer 38

1. Administer as soon as possible within 4 days (96hrs) of missed dose 2. If more than 4 days have passed, the missed dose should be skipped and the next dose should be administered on the regularly scheduled day

Question 39

What sites are appropriate for tirzepatide injection?

Answer 39

1. Stomach 2. Thigh 3. Back of upper arm

Question 40

What are some ADEs of tirzepatide? (4)

Answer 40

1. Nausea: most common. In placebo-controlled trials: 2. Others: diarrhea, vomiting, heartburn, constipation 3. Generally described as mild to moderate but may be severe in some 4. Typically occur during dose escalation and decrease over time

Question 41

What are some practical tips to help manage nausea with tirzepatide use? (8)

Answer 41

1. Tell patients what to expect 2. Appreciate the feeling of fullness: stop eating when full 3. Eat smaller portions and eat slowly 4. Titrate slowly; Stay on low dose until nausea improves 5. Avoid fatty, spicy, and high-fibre foods 6. Consider using on an empty stomach – don’t administer close to a large meal 7. Consider end of day dosing 8. Stay hydrated and drink cold water when nauseous

Question 42

What to know about hypogylcemia use and tirzepatide? (3)

Answer 42

1. Tirzepatide stimulates insulin secretion in a glucose-dependent manner 2. Hypoglycemia is more frequent when tirzepatide is used in combination with a sulfonylurea or basal insulin than when used with non-secretagogues 3. When initiating tirzepatide, consider reducing the dose of concomitantly administered insulin secretagogues (e.g. sulfonylureas) or insulin to reduce the risk of hypoglycemia.

Question 43

What are the CIs of tirzepatide?

Answer 43

- CI in those with a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)

Question 44

Who should be cautioned to use tirzepatide? (2)

Answer 44

1. Retinopathy - caution in those with existing diabetic retinopathy 2. Cholelithiasis - gallbladder

Question 45

Tirzeaptide covered or not?

Answer 45

Not on SK formulary or NIHB

Question 46

What is insulin icodec designed to do?

Answer 46

Designed to achieve a long half-life by changes to the human insulin molecule

Question 47

Insulin icodec creates 3 amino acid substitutions which does what? (3)

Answer 47

1. Molecular stability 2. Reduced enzymatic degradation 3. Slow receptor-mediated clearance

Question 48

What to know about the first injection MOA of insulin icodec? (4)

Answer 48

1. The formulation (700 U/mL) ensures the injection volume is similar to once-daily insulin 2. After injection, hexamers slowly dissociate into monomers and bind to albumin 3. Although a week’s worth of insulin is administered, almost all icodec is albumin-bound to form an inactive depot 4. Slowly, a small fraction of icodec reaches the insulin receptors at target tissues to stimulate glucose lowering

Question 49

What to know about the second/third injection MOA of insulin icodec? (3)

Answer 49

1. With the second injection, more icodec is added to the inactive icodec albumin-bound depot 2. Slow clearance of icodec via the insulin receptor further contributes to the build-up of albumin-bound icodec 3. Over time, the glucose-lowering effect slowly increases as more icodec interact with insulin receptors

Question 50

Once insulin icodec is at steady state, what is the steady state MOA? (3)

Answer 50

1. After 3–4 injections, steady state* is achieved, giving the full effect of the icodec dose 2. The icodec-albumin-bound depot is sufficiently large enough to provide slow and continuous release of active icodec to achieve effective glucose lowering throughout the week 3. At steady state, any variations in dosing time and amount lead to minimal changes in immediate glucose-lowering effects due to the slow release of icodec

Question 51

For an insulin naive person, what is the starting dose of insulin icodec?

Answer 51

70 units once weekly

Question 52

For someone currently using basal insulin, what is the dosing of insulin icodec? (2)

Answer 52

1. Current daily dose x 7 = new weekly insulin dose - If current daily dose = 10 units - New weekly dose = 70 units 2. OR loading dose (1st dose only) – current daily dose x 7 x1.5 - If current daily dose = 10 units - 1st dose – 105 ~ 110 units (round to nearest 10 units) - Subsequent doses = 70 units weekly

Question 53

When switching daily to a weekly insulin it is common to give a higher initial dose. What to know about this when it comes to insulin icodec? (4)

Answer 53

1. Shortens time to reach efficacious insulin level 2. Only one higher starting dose then back to 7x daily basal dose (rounded to nearest 10) for subsequent week 3. Further dose increases and reductions may be required 4. For a patient taking 20 units of daily basal insulin: - Week 1 dose is 20U x 10.5 = 210 units - Week 2 dose is 20U x 7 = 140 units - Week 3 adjust based on fasting glucose levels

Question 54

Weekly dosing adjustment of insulin icodec is based on what?

Answer 54

The average of the three pre-breakfast CBG values, measured 2 days prior to and on the day of titration or CGM fasting reading average

Question 55

How many U of insulin icodec is adjusted when titrating to target dose?

Answer 55

20U + or -

Question 56

What are some side effects of insulin icodec? (4)

Answer 56

Same concerns as with all insulins 1. Hypoglycemia 2. Injection site reactions 3. Lipohypertrophy (rotate injection sites) 4. Weight gain

Question 57

Insulin icodec covered or not?

Answer 57

Not on SK formulary or NIHB formulary

Question 58

What is cool about the InsuJet?

Answer 58

The first needleless insulin administration device

Question 59

What are 2 ways to calculate starting doses for insulin?

Answer 59

1. Of the total daily dose (TDD) of insulin: - 40-50% should be basal insulin - 50-60% should be prandial insulin 2. Calculating a baseline dose can be based on either: - Body weight - Current TDD (sum of basal and bolus) - if already using insulin and we want to change their regimen

Question 60

How to calculate starting dose of insulin by weight? (3)

Answer 60

1. TDD of insulin for adults with T1DM range from 0.3 to 1 unit per kg 2. TDD of insulin for adult with T2DM range from 0.3 to 0.5 units per kg (on initiation) 3. Most often, we initiate at 0.5mg/kg/day

Question 61

How to calculate starting dose of insulin by TDD?

Answer 61

For patient currently using insulin, and we want to change their insulin regimen (change the types of insulin used and/or the number of daily injections) - Start by calculating their total daily dose - Reduce the dose by ~10% to determine the new starting dose

Question 62

What to know about basal-bolus insulin regimen adjustments? (4)

Answer 62

1. Adjustments to insulin doses will be guided by blood glucose readings 2. Only change one dose at a time 3. Treat the lows first! 4. Treat the first problem of the day