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

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

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

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

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

Photo of Leonard Thompson

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

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)

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

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

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)

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

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 15-20 minutes Duration of action is 3-4 hours irrespective of dosage(2011)

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

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 10-12 hours, rarely may last up to 20 hours Given twice daily: am and bedtime

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

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

Long acting insulin preparations: Degludec Ultralong acting insulin Onset 30-90 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

U500 Insulin Behaves similarly to NPH in peak and duration of action Onset is 30-45 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

Initiation of Insulin Type 1 DM Weight based formula: 0.3-0.4units/kg/day for total day dose OR 0.2units/kg/day of basal and 0.05-0.1units 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

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. 40-50% needs to be basal = 28 units basal dosing. 28 units as mealtime divided by three meals = 9 units with meals.

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

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

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 100-120 IOB: usual is 3-4 hours

Insulin pump(cont) Upload Example of setting page

Insulin pump(cont) upload Example of upload of readings

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

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

References