Therapy For Diabetes Michigan Association of Osteopathic Family Physicians Mid-Winter Family Medicine Update Shanty Creek Resort, MI January 19-22nd 2017 Michael R. Brennan D.O., M.S., F.A.C.E Director Beaumont Endocrine Center Chief of Endocrine Beaumont Grosse Pointe Disclosure I m married to a drug representative and she works for Novo Nordisk Makers of liraglutide (Victoza/Saxsenda), aspart (NovoLog), determir (levemir), 70/30 mix insulin (NovoLog and Novolin 70/30), degludec (Tresiba), repaglinide (Prandin), glucagon (GlucaGen HypoKit), estradiol vaginal tablets (Vagifem), estradiol/norethindrone (Activella), somatropin (Norditropin), coagulation factor VIIIa (NovoSeven) I m a consultant on insulin pumps and lead groups for the Insulet Corporation They make an insulin delivery system (pod/pump) called the Omni Pod 1/16/2017 2 1/16/2017 3 1
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Resources 2017 ADA 1/16/2017 7 Resources - https://www.aace.com/publications/algorithm 1/16/2017 8 Objectives To understand the general types of insulin Be able to start and dose a patient on a reasonable amount of insulin therapy in a physiologic replacement pattern Be aware of all continuous insulin infusion devices (insulin pumps, pods and patches) Understand the device settings of a continuous insulin infusion device (pump) 9 3
Background/Physiology The physiologic range of insulin produced by the body in a normal individual 0.3 to 0.5 units/kg per day Half a person s daily pancreatic insulin secretion is basal (chronic relatively constant secretion) and half is bolus (secreted in bursts with hyperglycemia) Most people you see have insulin resistance and will be slightly beyond the physiologic range 10 All Diabetes Classes of Medication Bigunides Alpha-Glucosidase Inhibitors Amylin Mimetic Bile Acid Sequestrants Dipeptidyl Peptidase-4 inhibitor Dopamine-2 Agonist Glucagon-Like Peptide-1 Inhaled insulin Meglitinides Thiazolidinedione Sodium-glucose transporter 2 Sulfonylurea Subcutaneous/IV 11 Four Generalized Classes: Basal Rapid Acting Regular Mix 12 4
Basal insulin: administered to cover endogenous glucose production (glucose made by the liver/body). Doses can be administered subcutaneously one, two, or three shots per day Glargine (Lantus/Toujeo/Basaglar) Detemir (Levemir) Degludec U-100 and U-200 (Tresiba) Neutral Protamine Hagedorn (NPH, Humulin N or Novolin N) 13 Rapid acting insulin Covers the glucose created by stress, consumption of glucose or infusion of glucose. It is used in subcutaneous bolus method to correct or prevent hyperglycemia Lispro and Lispro U-200 (Humalog) Glulisine (Apidra) Aspart (Novolog) 14 Regular insulin Conceptually can be considered the first insulin (just the human insulin molecule). No substitutions in molecule configurations, amino acids. Now relatively slow compared to rapid insulin, and not long acting compared to basal for subcutaneous use. Great for IV use as it is inexpensive and extremely effective. Regular insulin has a short IV half-life, which can be a problem in a patient that requires insulin. Regular insulin (Humulin R, Novolin R) 15 5
Mix insulin An attempt to cover both meal and endogenous glucose in one shot. This is not an ideal insulin with fluctuating PO intake (e.g. the hospital). Dosed generally before breakfast and dinner or before all meals: 30% Aspart, 70% Prot-aspart (NovoLog 70/30) 30% Novolin-R, 70% NPH (Novolin 70/30) 25% Lispro, 75% Prot-Lispro (Humalog 75/25) 30% Humulin-R, 70% NPH (Humulin 70/30) 50% Lispro, 50% Prot-Lispro (Humalog 50/50) 16 Concentrated resistance can be so severe that the volume of the insulin injection can be overwhelming. Therefore, the units of insulin can be manufactured in a smaller volume. U-500 Regular U-300 Glargine (Toujeo) U-200 Lispro (U-200 Humalog) U-200 Degludec (U-200 Tresiba) 17 Normal secretion of insulin Basic Slide Header Theoretical insulin secretion (always normal glucose levels) secretion duration over 24 hours 18 6
Starting Basal Basal insulin covers endogenous glucose production (glucose made by body) Basal insulin Dose can be one or two shots per day: Start patient on 0.25 units per kg/d Glargine (Lantus/Toujeo/Basaglar) Indicated for once a day dosing Detemir (Levemir) Indicated for once or twice a day dosing Degludec (Tresiba) Indicated for once a day 1/16/2017 19 Basic Basal Slide Header Theoretical insulin secretion and duration with one basal shot secretion duration over 24 hours 1/16/2017 20 Basic Basal Slide Header Theoretical insulin secretion and duration with two basal shot regimen secretion duration over 24 hours 1/16/2017 21 7
Basic Rapid Slide acting Header insulin Theoretical insulin secretion and duration with three rapid acting shots secretion duration over 24 hours 1/16/2017 22 Basic Mixed Slide Header An attempt to cover both meal and endogenous glucose in one shot Mix insulin Dose generally before breakfast and dinner or before all meals: Start patient on 0.5 units per kilogram per day and divide the dose by 2-3 to determine the doses for the day 30% Aspart, 70% Prot-Aspart (NovoLog Mix 70/30) 30% Novolin-R, 70% NPH (Novolin 70/30) 25% Lispro, 75% Prot-Lispro (Humalog 75/25) 30% Humalin-R, 70% NPH (Humulin 70/30) 50% Lispro, 50% Prot-Lispro (Humalog 50/50) 1/16/2017 23 Basic Mixed Slide Header Theoretical insulin secretion and duration with two mix injections secretion duration over 24 hours 1/16/2017 24 8
Basic Basal Slide Plus Header Bolus Theoretical insulin secretion and duration with one basal shot and three bolus shots secretion duration over 24 hours 1/16/2017 25 Basic Basal Plus Slide Two Header Bolus Theoretical insulin secretion and duration with two basal shot and three bolus shots secretion duration over 24 hours 1/16/2017 26 Normal Basic secretion Slide Header of insulin Theoretical insulin secretion (always normal glucose levels) secretion duration over 24 hours 1/16/2017 27 9
Basal-Bolus Versus Mix To Simplify: Hypoglycemia is less, and meal flexibility is greater in a four to five shot a day regimen using rapid acting and long acting insulin On the other hand, frequency of injection is less using a two to three shots per day mixed insulin regimen. In this scenario, hypoglycemia is greater and flexibility is less 1/16/2017 28 The physiologic range of insulin produced by the body in a normal individual 0.3 to 0.5 units/kg per day 1/16/2017 29 Basic Slide Case #1 Header Example #1: a 72kg T1DM admitted and treated for DKA, is now ready to transition to sub Q insulin using basal bolus (4 shots): 0.5units/kg/day * 72 kg = 36 units per day Choose 18 units of basal The (18/3) 6 units of rapid acting with meals Patient is 72 kg and the total daily dose of insulin is 36 units 1/16/2017 30 10
Basic Slide Case #2 Header Example #2: A 100kg T2DM admitted and treated for DKA, is now ready to go home (hates shots, but needs them) on sub Q insulin using mix insulin (2 shots): 0.5units/kg/day * 100 kg = 50 units per day 25 units of mix insulin for breakfast 25 units of mix insulin for dinner Total daily dose is 50 units of insulin and the patient weighs 100kg 1/16/2017 31 Transition Out of the Hospital Talk to care management and write scripts before discharge (maybe 2 days before) Try to fill the insulin to determine what is available via their insurance (basal, rapid, and mix insulin) within the same class (basal, rapid acting, and mix) can be used similarly KEY: Instruct the nurse to give the insulin used at the bedside in the hospital to the patient at discharge 1/16/2017 32 Outpatient Basic Slide Transition Header How do you transition the basal only patient to basal bolus? Remember goal of basal is to titrate the fasting am glucose to 80-130mg/dlNOT to hemoglobin A1C of 7% Once goal a.m. glucose (70-120mg/dl) is attained, then you can consider taking that basal dose, dividing it by 3, and administering that number of units 3 times a day with meals 1/16/2017 33 11
Basic Slide Case #3 Header Example #3: a 120kg T2DM takes 30 units of basal insulin every evening. The a.m. fasting glucoses are 70-150 mg/dl but the HbA1c is 8.9%. Starting dose of meal time insulin could be? 1/16/2017 34 Basic Transition Slide Case Header #3 Example #3 a 120kg T2DM takes 30 units of basal insulin every evening. a.m. glucoses are 70-150 mg/dl but the HbA1c is 8.9% Starting dose of meal time could be: 30 units/3 = 10 units rapid acting insulin before meals three times a day That s a total daily dose of 60 units, which in this individual equals 0.5 units/kg/day 1/16/2017 35 Delivery delivery can generally be done via three methods of subcutaneous delivery: Vial and syringe Pens Pump/Pods/Patch 36 12
Vial and Syringe 37 Pens and Pen Needles 38 Pens and Pen Needles 39 13
Continuous Delivery Systems Pumps Company/Pump 1/16/2017 40 Continuous Delivery Systems Pumps 1/16/2017 41 Continuous Delivery Systems Pods Company/Pod 1/16/2017 42 14
Continuous Delivery Systems Patch Company/Patch 1/16/2017 43 Continuous Delivery Systems Pods and a patch 1/16/2017 44 Delivery with Syringe/Pen Vial and syringe or insulin pens: Mealtime dose/carbohydrate Ratio Basal dose Sliding Scale/Correction Factor and Target 1/16/2017 45 15
Delivery with Syringe/Pen Mealtime Dose: Usually aspart (NovoLog), lispro (Humalog), or glulisine (Apidra) Example: I take 10 units before breakfast, lunch and dinner, and like 5 units with snacks. 1/16/2017 46 Delivery with Syringe/Pen Basal Dose - Covers endogenous glucose production (glucose made by body). It will be either glargine (Lantus/Toujeo/Basaglar), detemir (Levemir), or degludec (Tresiba) Example: I give myself 24 units of Lantus every night 1/16/2017 47 Delivery with Syringe/Pen Sliding Scale: Usually aspart (NovoLog), lispro (Humalog), or glulisine (Apidra) Patient uses this scale to correct high glucoses (generally Q 4 or AC TID and QHS) Example: Glucose (mg/dl) (units) 150-199 2 200-249 4 250-299 6 300-349 8 >350 10 1/16/2017 48 16
Delivery with a Pump/Pod Background: Based on informal observations by Paul Davidson in 1982, he attempted to calculate a correction factor (sliding scale) and a carbohydrate to insulin ratio (meal time insulin) for patients with type 1 diabetes (but it applies to anyone with insulin requiring diabetes) 1/16/2017 49 Delivery with a Pump/Pod for Pump/Pod: Any insulin can be placed in a pump/pod 99% of the time it is a rapid acting analog insulin: Aspart (NovoLog) Lispro (Humalog) Glulisine (Apidra) Other pump insulin includes: Regular (Humulin R and Novolin R) Used for years prior to rapid acting insulin analogs U-500 Regular U-200 Lispro 1/16/2017 50 Delivery with a Pump/Pod Pump/Pod: to carbohydrate ratio (Mealtime dose) Basal Rate (Basal dose) Target glucose and correction factor (Sliding scale) 1/16/2017 51 17
Delivery with a Pump/Pod Background: The carbohydrate to insulin ratio is the insulin required to maintain a static blood sugar per the amount of carbohydrates (in grams) consumed Basal Rate is a continuous amount of insulin being infused subcutaneously to keep the patient euglycemic The correction factor is the estimated change in blood glucose from one unit of insulin 1/16/2017 52 Delivery with a Pump/Pod Carbohydrate Ratio: The carbohydrate ratio is the insulin required to maintain a static blood sugar per the amount of carbohydrates (in grams) consumed Example: 1 unit of insulin for every 10 grams of carbohydrate If patient is about to eat 80 grams of carbohydrates, then they get 8 units of insulin at meal time Carbs in grams are entered in the pump 1/16/2017 53 Delivery with a Pump/Pod Carbohydrate Ratio: Advantage: Patient can change the amount and the types of food per meals as long as carbohydrates are counted Patient can eat at whatever time they like, or however frequently they like Both within reason Disadvantage If the Pump/pod fails or gets removed, then there would be no more insulin on board (set up for DKA) 1/16/2017 54 18
Delivery with a Pump/Pod Basal Rate: Instead of Degludec (Tresiba), glargine (Lantus/Toujeo/Basaglar) or detemir (Levemir), a continuous subcutaneous infusion is given with rapid acting insulin (either aspart(novolog), lispro(humalog), or glulisine(apidra) 1/16/2017 55 Delivery with a Pump/Pod Basal Rate: Advantage: Rates can be given at various amounts (1/100 th of a unit per hour) Varying times the basal rate can be adjusted in half hour increments based on various levels of need Disadvantage If the Pump/pod fails or gets removed, then there would be no more insulin on board (set up for DKA) 1/16/2017 56 Delivery with a Pump/Pod Basal Rate: Example: Basal Rate Midnight 5a.m. = 1.2 units/hr (5 hours, 6 units) 5a.m. 2p.m. = 1 units/hr (9 hours, 9 units) 2p.m. 7p.m. = 1.75 units/hr (5 hours, 10.5 units) 7p.m. Midnight = 0.9 unit/hr (5 hours, 4.5 units) Total basal in this case is 30 units of insulin over 24 hours (6 + 9 + 10.5 + 4.5 = 30) 1/16/2017 57 19
Delivery with a Pump/Pod Basal Rate: EXTEREMLY helpful BASAL RATE for 24 hours is a great approximation of the basal dose! In the previous slide, the patient s basal rate - Indicates the patient s basal insulin dose is approximately 30 units of detemir (Levemir), glargine (Lantus/Toujeo/Basaglar) or degludec (Tresiba) 1/16/2017 58 Delivery with a Pump/Pod Target glucose and correction factor: Target is chosen by the practitioner It is ideally where we would like the individual s glucose to always be People generally choose between 80-150 mg/dl I generally choose 90 or 100 mg/dl Correction Factor: the estimated amount of blood glucose (mg/dl) that will change with one unit of insulin 1/16/2017 59 Delivery with a Pump/Pod Correction Factor: The correction factor in mg/dl can be estimated using 1500 divided by the total daily dose of insulin: Example: Our 100kg gentleman takes 30 units of long acting and 10 units 3 times a day before meals Therefore he generally takes 60 units total daily dose (or 0.6units/kg/day) 1500 divided by 60 = 25 Correction factor is 1 unit for every 25mg/dl greater than the target 1/16/2017 60 20
Pump/Pod vs Sub Q Correction Factor (CF): If the CF is 1 unit for 25mg/dL, and If the target is 150 mg/dl Then every 25 mg/dl greater than the target, the patient gets one unit from the pump Example: The patient s glucose is 225mg/dL, then when the patient tells this info to the pump, the pump suggests 3 units of insulin be administered Sliding Scale: Glucose (mg/dl) (units) 151-200 2 201-250 4 251-300 6 301-350 8 >350 10 IN THIS CASE: SAME EXACT THING!!! (Just sliding scale has less precision with delivery) 1/16/2017 61 Delivery with a Pump/Pod Correction Factor Advantage Correction intervals can be in 1mg/dL units (doesn t have to be every 50 mg/dl) The correction insulin dose can be less than 1 unit increments The pump can use the known ½ life of the insulin in the pump to prevent insulin stacking Disadvantage If the Pump/pod fails or gets removed, then there would be no more insulin on board (set up for DKA) 1/16/2017 62 Delivery with a Pump/Pod Correction Factor: Extremely useful Use this to determine how much insulin it takes to lower a patient s glucose This is helpful if you want to try to lower a person s glucose by 50mg/dl 1/16/2017 63 21
Delivery with a Pump/Pod Correction Factor: Example #1: Patient reports My correction factor is 1 unit for 25 mg/dl above my target Then you have a clue that in order to lower the blood glucose by 50 mg/dl, it would take approximately 2 units of insulin subcutaneously 1/16/2017 64 Delivery with a Pump/Pod Correction Factor: Example #2: Patient reports My correction factor is 1 unit for 40 mg/dl above my target Then you have a clue that in order to lower the blood glucose by 50 mg/dl, it would take approximately 1.25 units of insulin subcutaneously 1/16/2017 65 Delivery with a Pump/Pod Correction Factor: Example #3: Patient reports My correction factor is 1 unit for 10 mg/dl above my target Then you have a clue that in order to lower the blood glucose by 50 mg/dl, it would take approximately 5 units of insulin subcutaneously 1/16/2017 66 22
Delivery with a Pump/Pod For an insulin pump patient try to know the following: The sum of the basal rate, because then you know the basal dose if needed The correction factor, to help estimate how much rapid acting insulin is required to correct the glucose Extremely useful if the pump delivery is stopped 1/16/2017 67 Delivery with a Pump/Pod What should a doctor do when the pump fails or is removed? Give a basal dose of insulin!!! With basal insulin, give at least 0.25 units/kg or the summation of the basal rates In Hospital setting: Make sure the attending, team or consultant is aware, takes responsibility, and has an immediate plan of insulin management now that the pump failed 1/16/2017 68 1/16/2017 69 23
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1/16/2017 76 Conclusion is a great medication and frequently required to manage diabetes Classify different insulin as either basal, rapid, mix, or regular The use of pumps/patches/pods and subcutaneous insulin pens is now common Be familiar with knowing: Basal dose or rate Meal time/carb ratio doses Sliding scales/correction factors and targets The physiologic range of insulin produced by the body in a normal individual 0.3 to 0.5 Units/kg per day When in doubt poke the finger and check the blood glucose, then give insulin when the glucose is too high and glucose if the glucose is too low 1/16/2017 77 Thanks 1/16/2017 78 26
Questions? 1/16/2017 79 Thank you! Questions? To Contact Dr. Michael R. Brennan Contact the Beaumont Endocrine Center 25631 Little Mack, Suite 204 St. Clair Shores, MI 48084 Phone: 586-443-2380 Fax: 586-443-2381 Call Beaumont Health system and ask to have him paged 248-898-5000 1/16/2017 80 27