Type 1 Diabetes Therapy - Insulins

What is Brittle T1 DM?

A rare, difficult to control form that presents with frequent hospitalizations related to unpredictable episodes of hypoglycemia

What is Lantidra (Donislecel)?

A suspension of allogeneic pancreatic islets

How is Lantidra (Donislecel) administered? How often?

Infused into hepatic portal vein or transvenous transhepatic or laprascopic open surgical access. Considered a transplant requiring immunosuppressant therapy. Patients could receive up to 3 transplants each separated by one year.

Lantidra (Donislecel) MOA

Purified pancreatic cells from a deceased donor are transplanted into recipients with Brittle DM to supplement endogenous insulin and glucagon production to improve glucose control and may eliminate the need for insulin

What 2 studies are associated with Lantidra (Donislecel)?

UIH 001 Phase 1/2 and UIH 002 Phase 3

- University of Illinois Hospital

What is teplizumab-mzwv. (T-Zeild), what is it for, and who is it for?

A monoclonal antibody that delays onset of diagnosed Stage 3 type 1 DM by 2 years. It is indicated for patients 8 years and older with stage 2 type 1 DM

What is stage 2 type 1 DM?

- Presence of ≥ 2 autoantibodies to insulin producing cells

- Impaired glycemia response to a glucose load, but otherwise normal A1c

- No overt symptoms of DM

What are some common side effects of teplizumab-mzwv. (T-Zeild)?

- Hematological toxicity

- Hypersensitivity and infection risk

- N/V/D

- HA

- Fatigue

How is teplizumab-mzwv. (T-Zeild) given? What is monitored?

- 14 day infusion

- Premedicate with APAP, antihistamine, and antiemetic for first 5 days of infusion

- Infuse within 2 hours over 30 min

- Avoid live vaccines 52 weeks post infusion, inactive for 2 weeks

- Monitor CBC, LFT

Insulin is synthesized as a ____________________, called ___________

single polypeptide chain called pre-proinsulin

How is pre-proinsulin turned into insulin?

It is catalyzed by proteases into insulin and C peptide

________ is a type 2 DM indicator

C peptide, they can still produce insulin, they just can't easily utilize it

How did we used to make insulin and how do we do it now?

Initially manufactured by animal sources (pig/cow) but stopped due to hypersensitivity reactions. Now it is produced by recombinant DNA technology from E. coli, which has an identical structure to that of native human insulin.

How does insulin work in the liver?

Stimulates hepatic glycogen and fatty acid synthesis. Fatty acids are released into the blood as lipoproteins

How does insulin work in the skeletal muscles?

Increased synthesis of protein and glycogen

How does insulin work in adipose tissue?

Stimulates circulating lipoproteins to provide free fatty acids, triglyceride synthesis/storage. Also inhibits the hydrolysis of triglycerides

How does insulin affect electrolyte balance in the body?

Insulin stimulates cellular uptake of amino acids and increased permeability to K+, Mg2+, and PO4. It also activates Na/K/ATPases, causing intracellular shift of K+

What are some side effects of insulin?

1. Peripheral edema

2. Erythemia and pruritus at injection site

3. Hypoglycemia

4. Hypokalemia

5. Weight gain

6. Anaphylaxis can occur

7. Local hypertrophy and lipoatrophy

What causes hyperglycemia?

- too much food

- to little insulin

- illness

- reduced exercise

- medications

How is hyperglycemia managed?

- Check urine for ketones (if T1)

- Check blood glucose and call MD if >3 readings above 250

- Reduce carb intake, continue meds, NO exercise if BS > 250

What are some diabetes product supplies?

- 0.3 mL syringe

- Low dose syringes (0.5)

- U-100 syringes (1.0)

- Pen needles

- Sensors for CGM

- Transmitters/reader for CGM if no smartphone

- Alcohol swabs

- Glucometer, strips, lancets

Who is likely to experience hypoglycemic unawareness?

- Long duration of diabetes

- Central neuropathy

- Older age

- Dementia - unable to recognize or communicate lows

What is the "sick day policy" for someone with T1 DM?

- Evaluate food intake

- May need to reduce insulin dose based on food intake

- Monitor glucose more often

What are 4 problematic medications that can cause glycemic issues?

- Glucocorticoids *

- Anti-psychotics

- Niacin

- Phenytoin

What is the dawn (natural) phenomenon?

Natural rise in glucose in the morning with rise in cortisol. Test blood glucose in the mornings to detect highs

What is the Somogyi phenomenon?

A recound effect caused by too much insulin at night (high evening/bedtime dose or treating lows in the early morning). While there might have been a low at night, BG will rebound high in the morning. Best treatment is a decreased dose at bedtime or bedtime snack. Symptoms include trouble sleeping and nightmares

Rapid acting insulin onset, peak, duration

Onset: 2.5-15 min

Peak: 1-2 hr

Duration: 3-5 hr

Short acting insulin onset, peak, duration

Onset: 30 min

Peak: 2-3 hr

Duration: 6-10 hr

Intermediate (NPH) acting insulin onset, peak, duration

Onset: 1-2 hr

Peak: 4-12 hr

Duration: 14-24 hr

Long acting insulin onset, peak, duration

Onset: 1-4 hr

Peak: 3-12 hr

Duration: 6-42 hr

If glucose is abnormal before breakfast or overnight, what dose of insulin might need to be changed?

Evening LA

If glucose is abnormal before morning snack or lunch, what dose of insulin might need to be changed?

Morning RA or morning LA

If glucose is abnormal before dinner, what dose of insulin might need to be changed?

Morning LA or afternoon RA

If glucose is abnormal before bedtime, what dose of insulin might need to be changed?

Evening RA

What is Afrezza?

Inhaled rapid acting insulin

For Afrezza, what are the strengths of the cartridges?

Blue = 4 units

Green = 8 units

Yellow = 12 units

Who is Humulin R U-500 indicated for?

Patients on > 200 units of insulin per day (significant insulin resistance). It is a concentrated form of regular insulin that uses special green needles

Which type of insulin does not have a peak?

Insulin Glargine, Basaglar (long acting)

Which long acting insulin lasts the longest?

Insulin Degludec (42 hour duration)

How does Novolin 70/30 differ from Novolog Mix 70/30?

Novolin 70/30 = 70% NPH, 30% Regular

Novolog Mix 70/30 = 70% Aspart Protamine, 30% Aspart

What is Soliqua?

Insulin Glargine + Lixisenatide

What is Xultophy?

Insulin Degludec + Liraglutide

What is the 300 u/mL insulin product called?

Toujeo Max

How many mL are in 1 insulin pen?

3 mL

How many mL are typically in a vial of insulin?

10 mL

What is the starting dose of insulin for T2 DM?

0.1-0.2 u/kg/day, 70% of which is given in the morning and 30% at night, if BID

Drip rates have what units?

mL/min

Why do we use a standard bag of insulin in a hospital?

For better control, it is a high alert medication

Describe insulin pumps

- most intensive regimen mimics physiological insulin release

- more common in type 1

- patients must know/understand insulin basics and carb counting

- algorithms calculate the basal and bolus dose based on the linked continuous glucose monitor

- some require patient confirmation prior to dose administration

What are the top 4 common insulin pumps?

1. T-slim x2

2. Omnipod

3. Cequr Simplicity

4. Minimed 780G

5. Ilet Bionic Pancreas (Beta Bionics)

Describe the T-Slim x2 insulin pump. What kind of insulin does it use?

Hardware or actual insulin pump that uses rapid acting insulin through a looped tube system.

Describe the Omnipod insulin pump. How often does it need to be charged and how much can it hold/inject?

Simplified, automated, tubeless system that is integrated with Dexcom G6. Has an app on the phone to help with dosing and does not have any contracts or fees attached to it.

- Changed every 72 hours

- Holds 85-200 units

- Bolus dose = 0.05-30 u

- Basal can be as low as 0.001 u/hr

Describe the Cequr Simplicity.

A 3-day insulin patch for bolus dosing (with meals). You need to purchase a reusable inserter. It has a canula and is NOT a pen or pump.

Describe Minimed 780 G

It is a hybrid with a closed loop pump that uses SmartGuard technology to allow users to choose from increasing levels of automation that best fits their diabetes management needs. - - Max capacity is up to 300 units per fill

- waterproof for 12 ft up to 24 hrs

- Works with medtronic Guardian 4

Describe Ilet Bionic Pancreas (Beta Bionics) AID

- AID = automatic insulin delivery system

- Interprets CGM (Dexcom and Libre 3 plus)

- Closed loop system that does it all

- app for adjustments

What are the steps to insulin dosing?

1. Start with the basal dose. Reduce to less than total daily, divide the total # of LA units by 24 to get units/hour.

2. Add regular bolus with meals based on carb counting

Where is insulins place in therapy for T2DM?

- Last line after dual/triple oral medication failures and/or GLP-1 for type 2

- May be considered when hyperglycemia is severe, symptomatic or catabolic (weight loss, ketosis)

- A1c > 11%

Does insulin have a ceiling effect?

No, it will work if you tirate it up to the right dose

What is the first step to initiating insulin in someone with T2DM?

Select the basal insulin type (IA or LA). May continue oral therapies with glucose monitoring but in older adults avoid those with significant hypoglycemia risk such as glyburide

What is the second step to initiating insulin in someone with T2DM?

Intensification of therapy options such as adding a mealtime insulin (SA or RA), adding a GLP-1 receptor agonist (liraglutide, dulaglutide, semaglutide), or transitioning to a premixed insulin

After starting the initial insulin dose for T2DM (0.1-0.2 u/kg/day) how should it be titrated?

Increase by 2 units (or 10%) every 3 days Ho

After a basal insulin dose has been added for someone with T2DM, what is the next step?

Check A1c in 3 months, if not at goal, add RA insulin at largest meal, GLP-1, or change to premixed insulin BID

What is the starting insulin dose range for T1 DM?

0.5-0.6 u/kg/day, 50% of which is basal and 50% is bolus

What is a typical bolus dose breakdown for someone with T2DM?

20% breakfast, 15% lunch, 15% supper (adjusted based on patient's eating habits)

Insulin resistance can be encountered by T2DM and typcially requires doses of _______ u/kg/day

1.0-1.5

How often should someone on insulin monitor their glucose level?

At least 4 times daily

When taking BG measurements and glucose is high prior to eating, correct this high using...

Correction factor calculation.

For regular insulin: 1,500 / total daily insulin = # of units of insulin for correction

For rapid-acting insulin: 1,600 / total daily insulin = # of units of insulin for correction

How do we interpret the correction factor calculation for a high glucose reading prior to eating?

Ex: 1,600 / TDD = 21 mg/dL

- this means 1 unit of insulin will lower glucose 21 mg/dL, rounding is acceptable

- give however many units will get patient back to goal (<180)

1 serving of carbohydrates is how many g of carbs?

15 g

How do you calculate how many units of insulin to give for a certain number of carbs eaten?

Insulin to carb ratio

- Rapid acting: 500 / TDD insulin

- Regulat insulin: 450 / TDD insulin

How is an insulin to carb ratio interpreted?

Ex: 500 / TDD insulin = 7

- 1 unit of insulin will cover 7 g carbs

How do you determine the total amount of insulin needed with a meal?

Add the correction factor for high glucose prior to eating plus the insulin-carb ratio amount to get the total bolus to be administered

What is MNT?

Medical nutrition therapy

- can reduce A1c and reduce amount of insulin required

- Typical % of calories from - carbohydrates (45-60%), protein (35-45%), fat (<10%)

- individualized meal plans for each patient is important with consideration of cultural preferences

Describe the recommendations for non-starchy vegetables

- 3-5 servings per day

- 45-75 g carb per meal

- 15 g per serving (1/2 cup cooked veg or veg juice, 1 cup raw veg)

- fresh or frozen prefered, canned acceptable (low sodium, drain and rinse)

Describe the recommendations for protein

- 3 oz at least

- plant based like beans, nuts, soy, tofu

- eggs, fish, seafood, poultry, white meat over red meat

Describe the recommendations for carbohydrates

- non-starchy

- fruits with skins for added fiber

- whole grains like steel cut oats, brown rice

- avoid or eat less of starchy fruits/veggies like bannanas, potato, peas, squash, corn, white bread

What type of sweetener is best for DM patients?

Artificial sweeteners