1. The What, When, Where, Who and Why
Insulin
The What, When, Where, Who and Why

2. Disclosures Speaker and Consultant for Jansen and Healthscripts
Speaker and Consultant for Boehringer Ingelheim (BI)

3. Objectives Define background and history of the hormone, insulin
Identify subjective and objective signs and symptoms of hyperglycemia and define glucose toxicity
Guidelines for use of insulin in Diabetes Mellitus
Pharmodynamics and pharmokinetics of current insulins available
Initiation and titration of insulin via multi-dose injection or insulin infusion via insulin pump

4. Background: History of Insulin
During the 19th century, observations of patients who died of DM showed pancreatic damage
In 1869, a German medical student by the name of Paul Langerhans, found that within the pancreatic tissue that produces digestive juices were clusters of cells whose function was unknown
These cluster of pancreatic cells were later revealed to be beta cells which produce insulin. In honor of Paul Langerhans, they were named Islets of Langerhan
In 1889, two German scientists, working with dogs, discovered if the pancreas was removed the dogs developed diabetes. In their research, they also discovered if the pancreatic duct was ligated, the dog developed only minor digestive issues but no diabetes

5. Background: Insulin
Based on this research it was theorized the pancreas had two functions:
To produce digestive enzymes
To produce a substance that regulates blood sugar
It was not until 1921, Charles Banting an unemployed, orthopedic surgeon and Charles Best a medical student performed experiments on dogs and isolated the hormone we know as insulin
In late 1921, a biochemist by the name of Bertram Collip was added to the team to purify the newly discovered insulin so it could be injected into humans
The scientist self injected insulin initially and learned how to diminish the effects by treating with fast acting glucose

6. Photo of Leonard Thompson

7. Background: Insulin
January 1922, the first person received insulin: Leonard Thompson
14 year old Leonard Thompson had been dx with DM three years prior and was near death, drifting in and out of a diabetic coma in Toronto General Hospital. Since the starvation diet was the only treatment for Diabetes at that time, Leonard weighed a mere 65 lbs.
First injection resulted in an allergic reaction. A more pure insulin was extracted and developed by Collip and given again to Leonard. It was after the second injection, his condition improved rapidly
Leonard Thompson lived for 13 more years and passed away from Pneumonia

8. Hyperglycemia Hyperglycemia: elevated blood sugar
Results from body lacking insulin or using insulin inefficiently
Symptoms of hyperglycemia: may be none until blood sugar is consistently above 200
Weakness and fatigue: T1DM ++ T2DM +
Polyuria and thirst: T1DM ++ T2DM +
Polyphagia and weight loss: T1DM ++ T2DM +
Recurrant blurred vision: T1DM + T2DM ++
Vulvovaginitis or pruritus: T1DM + T2DM ++
Peripheral neuropathy: T1DM + T2DM ++
Nocturnal enuresis: T1DM ++ T2DM –
Often asymptomatic: T1DM - T2DM ++
(Gardner and Shoback 2011)

9. Glucose Toxicity: what It is
Definition: pathologic consequence of prolonged hyperglycemia (Campos, 2012)
Some cells are more prone to cellular damage as result of hyperglycemia. These include: pancreatic B cells, neuronal cells, vascular endothelial cells( 2012)
This results in decrease of functioning beta cells and damage to endothelial cells resulting in microvascular and macrovascular complications

11. Insulin
Indication: Individuals with Type 1 DM as well as those with Type 2 whose hyperglycemia does not respond to diet therapy and other diabetes agents
Human insulin is now produced by recombinant SNA techniques. Animal insulins are no longer available in the United States (Gardner and Shobeck, 2011)
Present day insulin is stable and refrigeration is not needed as long as extremes in temperature are avoided (2011)
Available in u100, u200, u300 and u500 concentrations

12. Available insulin preparations Short –acting and Rapid analogs
Rapid acting:
Lispro (Humalog, Lilly)
Aspart (Novolog, NovoNordisk)
Glusisine (Apidra, Sanofi)
Short acting: Regular (Lilly, NovoNordisk)
Clear solutions at neutral PH
Contain small amounts of zinc to improve stability and shelf life
Rapid acting insulin is designed for subcutaneous administration while regular insulin can be given can also be given intravenously
Insulin aspart is also approved for intravenous use but there is no advantage over regular insulin by this route (Gardner and Shoback, 2011)

13. Available insulin preparations Short acting onset, peak effect and duration of action
Regular insulin:
Short acting
Onset 30 minutes after subcutaneous administration
Peaks in two hours
Lasts for 5-7 hours with usual quantities (ie 5-15 units)
Duration is extended prolonged when larger doses are used

14. Available insulin preparations Rapid acting onset, peak, and duration of action
Produced by recombinant technology, that is amino acids are reversed (lispro), substituted (aspart) or replaced (gluisine)
When injected, absorbed rapidly and reach peak values in as soon as 1 hour
Onset is minutes
Duration of action is 3-4 hours irrespective of dosage(2011)

15. Available Insulin preparations Long acting
NPH
Glargine(Toujeo) u100 and u300
Detemir(Levemir)
Degludec (Tresiba)u100 and u200

16. NPH Onset, peak and duration of action
Intermediate insulin
Onset of action is 2-4 hours
Peak action of NPH is 6-8 hours
Duration of action is hours, rarely may last up to 20 hours
Given twice daily: am and bedtime

17. Long Acting insulin preparations Glargine
Two concentrations now available: u100 and u 300
Unit for unit conversion
Onset
No pronounced peak
Cannot be mixed with any other insulin because of its acidic PH
Half life of glargine u100 is 11 hours while half life of u300 glargine is 19.6 hours
Clinical trials comparing glargine u100 with glargine u300 suggest lesser nocturnal hypoglycemia with the u300 concentration (cite trial here)
Once daily dosing for u300 whereas u100 can be split into BID dosing although no real benefit once doses of 20 units achieved

18. Long Acting insulin preparations Determir
Concentration is u100
No pronounced peak
Duration of action is 17 hours
Half life is 11 hours
Inject once or twice daily to achieve stable basal dose since duration of action is 17 hours

19. Long acting insulin preparations: Degludec
Ultralong acting insulin
Onset minutes
No peak
Duration of action is longer than 24 hours
Injected once daily
Approved for use in adults 18 years and older with T1 or T2 DM
Long acting insulin preparations: Degludec

20. U500 Insulin Behaves similarly to NPH in peak and duration of action
Onset is minutes
Peak: 4-8 hours
Duration of action: 12+ hours
Indicated for patients on TDD in excess of 200 units daily
Can be given twice daily or TID dosing
Requires patient education prior to initiating
Consider referral to Diabetes Center or specialist when transitioning patient to u500

21. Initiation of Insulin Type 1 DM
Weight based formula: units/kg/day for total day dose OR
0.2units/kg/day of basal and units f rapid acting insulin/kg administered before meals
Example: 24 yo male recently diagnosed, A1C 13.8%. Current weight is 138 lbs.
67.7 KG X 0.4 = 27 units TDD. 40% of TDD should be basal insulin = 11 units basal. 60% should be given at meals = 16 units divided between three meals = ~5 units rapid acting insulin

22. Initiation of insulin T2DM
0.3 to 0.5 units/kg/day for total daily dose (TDD)
Example: 50 YO female A1C is 10.2%. Weight is 245lbs or 111kg x 0.5u = 56 units TDD % needs to be basal = 28 units basal dosing. 28 units as mealtime divided by three meals = 9 units with meals.

24. 70/30:
75/25:
50/50:
Insulin mixes

25. GLP1a with basal insulin(s)
Description:
Peak:
Onset:
Titration:
GLP1a with basal insulin(s)

26. Insulin administration with insulin pump
Description: insulin infusion with basal/bolus capabilities
Basal
Bolus( based on CHO ratio)
Correction or sensitivity: one unit of insulin will lower BS x points
Target blood sugar: typically range is
IOB: usual is 3-4 hours

27. Insulin pump(cont) Upload
Example of setting page

28. Insulin pump(cont) upload
Example of upload of readings

29. Case presentation(s) T1DM on MDI, newly diagnosed
T1DM on MDI, titration
T2DM A1C of >9%, initiation of insulin: basal
T2DM A1C of 8.9% already on basal, adding mealtime insulin

30. Insulin is growth hormone needed for healthy cell metabolism
Add insulin when blood sugars are elevated : according to guidelines
Insulin “works”!
Explain the benefits of insulin to your patient. Also explain the s/s of hypoglycemia and how to treat
Conclusion

31. References