T1DM: Insulin Initiation Recommended to start conservatively at approximately 0.5 units/kg/day (Range: 0.4-1.0 units/kg/day) Calculate TDD Total Basal Insulin Dose Total Prandial/Basal Dose Breakfast Lunch Dinner ~50% TDD: Total Daily Dose (insulin) American Diabetes Association. Medical Management of Type 1 Diabetes, 6th Ed 2012. Walsh J et al. Using Insulin. 2003.

T1DM: Insulin Initiation Example What would be a reasonable initial regimen for a patient newly diagnosed with T1DM that weighs 80 Kg? Calculate TDD based on weight in Kg: 80 Kg x 0.5 units/kg/day = 40 units/day (TDD) Determine the amount of insulin to be given as basal and prandial insulin, respectively: 40 units/day / 2 = 20 units basal insulin 20 units prandial insulin Counsel patient to monitor blood glucose (BG) levels and titrate insulin products per individual needs. Once the insulin is started we aren’t done! The insulin will need to be actively titrated to meet fasting and postprandial targets/goals.

T1DM: Insulin Initiation Example Applying Dosing Instructions The patient’s insulin has been titrated per individualized needs. His insulin prescription is now as follows: Insulin glargine U-100 (Lantus) 24 units SubQ QHS Insulin lispro U-100 (Humalog) 1:10 + 1/50 > 100 Let’s break this down: Insulin glargine = 24 units at bedtime in a single injection Insulin lispro = 1 unit per 10 grams of carbohydrate (Insulin:Carb Ratio) 1 additional unit added for every 50 mg/dL the patients pre-meal blood glucose is above 100 mg/dL (Sensitivity/Correction Factor) We will practice use and application of Insulin:Carb Ratios and Correction Factors in Class

Pharmacokinetic Profile of Currently Available Single Insulin Products Plasma Insulin Levels 12 16 20 24 8 4 2 14 18 22 10 6 Intermediate (NPH) Long (detemir) Long (U-100 glargine) Time (hr) 26 28 30 32 34 36 Ultra-long Rapid (aspart, lispro, glulisine, inhaled human insulin) Short (regular U-100) (glargine U-300) Mixed short/intermediate (regular U-500) Ultra-long (degludec) Hirsch IB. N Engl J Med. 2005; 352:174-83. Flood TM. J Fam Pract. 2007; 56(suppl 1):S1-S12. Becker RH et al. Diabetes Care. 2015; 38:637-43.

Insulin PK/PD Comparison* Time to Onset of Action (hr) Time to Peak Action (hr) Duration of Action (hr) Rapid Acting Insulin Lispro (U-100 , U-200) within 0.25 0.5-1.5 4-6 Aspart† Glulisine 0.5-2 Insulin human (inhaled) 1 3 Short Acting Human Insulin Insulin human regular (U-100) 0.5 8 U-500 Human Insulin Insulin human regular (U-500) 0.25 4-8 13-24 Intermediate Acting Insulin Neutral Protamine Hagedorn (NPH) 2-4 4-10 12-18 Long Acting Insulin Detemir 3-4 6-8 (though relatively flat)  Up to 24  Glargine (U-100) flat Up to 24 Ultra-Long Acting Insulin Glargine (U-300) 6 up to 36 Degludec (U-100, U-200) ~42 *Patient-specific onset, peak, and duration may vary from times listed in table. †Insulin aspart is available in 2 formulations: Novolog and Fiasp. Fiasp has a faster relative onset of action. Hirsch IB. N Engl J Med. 2005; 352:174-83; Individual product prescribing information.

Premixed insulin analogs Aspart 70/30 Insulin Effect B L S HS 6 6

Select Premixed Insulin Products Trade Name Description Humulin 70/30 Novolin 70/30 70% NPH insulin/30% regular insulin Humulin 50/50 50% NPH insulin/50% regular insulin NovoLog Mix 70/30 70% insulin aspart protamine/30% insulin aspart Humalog Mix 75/25 75% insulin lispro protamine/25% insulin lispro Humalog Mix 50/50 50% insulin lispro protamine/50% insulin lispro The first number in the mix designation (70/30, 75/25, etc.) is the basal fraction & the second number is the prandial fraction.