Insulin

Aka: Insulin, Regular Insulin, NPH Insulin, Lispro, Lente, Ultralente, Novolin, Humulin, Novolog, Humalog, Aspart, Apidra, Glulisine

1. See Also
   1. Insulin Dosing
   2. Insulin Simulation
   3. Glucose Metabolism
2. Technique
   1. Injection sites: Abdomen, outer thigh, back of arm, flank and buttocks
   2. Insert needle at 90 degree angle into skin
   3. Hold needle in place for 5-10 seconds after injection to prevent leakage of Insulin
   4. Rotate injection sites to prevent lipohypertrophy (see adverse effects below)
3. Preparations: Insulin Selection
   1. New Insulin anologues are preferred
      1. More consistent absorption than traditional Insulin
      2. Bolus analogues have more rapid onset
      3. Basal agents release at more constant rate
      4. Only disadvantage is anologues double price
   2. Combination agents are discouraged unless noncompliant
      1. Reduces flexibility in meal and activity timing
4. Drug Interactions: Diabetes Agents
   1. Agents safe to use with Insulin
      1. Metformin
      2. Thiazolidinediones
      3. Alpha-glucosidase Inhibitors
      4. Sitagliptin (Januvia)
   2. Agents safe to use with basal Insulin (Lantus, Levemir); avoid or use caution if used with bolus Insulin (Lispro, Aspart)
      1. Sulfonylureas
      2. Glitinides
5. Agents: Intravenous Regular Insulin
   1. Note that all other Insulins listed on this page are subcutaneous
   2. See Insulin Drip
   3. Onset: Immediate
   4. Half-life: 5-10 minutes
6. Agents: Bolus Insulins (Meal-time Insulin)
   1. Traditional Insulins
      1. Regular Insulin (Novolin R, Humulin R)
         1. Onset: 15 to 30 minutes
         2. Peak: 2.5 to 5 hours
         3. Duration: 6 to 8 hours
   2. Analogue Insulins (Rapid, consistent absorption)
      1. Glulisine (Apidra)
         1. Onset: 5 to 15 minutes
         2. Peak: 1 to 2 hours
         3. Duration: 3 to 5 hours
         4. Similar to other bolus analogues
         5. FDA approved to take after meal
            1. Other analogues expected with same effect
      2. Lispro (Humalog)
         1. Onset: 5 to 15 minutes
         2. Peak: 1 to 2 hours
         3. Duration: 3 to 5 hours
      3. Aspart (Novolog)
         1. Onset: 5 to 15 minutes
         2. Peak: 1 to 2 hours
         3. Duration: 3 to 5 hours
7. Agents: Basal Insulins
   1. Traditional Insulins
      1. NPH Insulin, Novolin N, Humulin N, Humulin L (Lente)
         1. Onset: 1 to 2 hours
         2. Peak: 6 to 8 hours
            1. Peak time is higher risk of hypoglcemia
            2. Consider snack at 6 hours after dose
         3. Duration: 10 to 16 hours (Lente slightly longer)
         4. Humulin L (Lente) discontinued in U.S. in 2006
      2. Ultralente Insulin (extended Insulin zinc suspension)
         1. Discontinued in U.S. in 2006
         2. Significant inconsistent effect even in same person
         3. Onset: 6-10 hours
         4. Peak: No peak
         5. Duration: 18 to 24 hours
   2. Analogue Insulins
      1. Detemir (Levemir)
         1. Onset: 2-4 hours
         2. Peak: 6-8 hours
         3. Duration: 12 to 20 hours (varies by dosage)
      2. Glargine (Lantus)
         1. Onset: 1-2 hours
         2. Duration: 21 to 24 hours
         3. Peak: No peak (flat action curve mimics continuous Insulin Infusion)
8. Combination Agents (Type II Diabetes if poor compliance)
   1. NPH 50/Regular 50
   2. NPH 70/Regular 30 (Humulin 70/30 or Novolin 70/30)
   3. NPL 75/Lispro 25 (Humalog Mix 75/25)
   4. NPH 70/Aspart 30 (Novolog Mix 70/30)
9. Adverse Effects
   1. Hypoglycemia
      1. Increased risk when Hemoglobin A1C <7.4%
      2. Decreased risk with analogue Insulins
      3. Higher risk with severe renal insufficiency
         1. Insulin is excreted by the Kidney (30% of total)
         2. Gluconeogenesis occurs in the Kidney (30% of total)
   2. Weight gain (Excess of 4 kg over 10 years)
      1. Countered with Metformin in type 2 diabetics
      2. Countered with diet and Exercise
      3. Benefits of Glucose control outweigh weight risks
   3. Lipohypertrophy
      1. Localized fat hypertrophy and scar tissue from repeated injections in the same area
      2. Results in variable Insulin absorption as below
      3. Prevent by rotating injection sites (see below)
      4. Medical providers should examine injection sites
   4. Variable Insulin absorption
      1. Insulin absorption varies by body site
         1. Abdomen (best absorption)
         2. Arms
         3. Thigh
         4. Buttocks (least absorption)
      2. Variable absorption at lipohypertrophy sites
         1. Poor absorption causes early postprandial Hyperglycemia
         2. Depot formation causes delayed Hypoglycemia
      3. Site rotation (prevents lipohypertrophy - see above)
         1. Rotate injections within same body region
            1. Avoids Insulin absorption variability
         2. Rotate to widely different sites within region
            1. Example: Abdomen rotate to LUQ, RUQ, LLQ, RLQ
10. References
    1. Lepore (2000) Diabetes 49:2142-8
    2. Mayfield (2004) Am Fam Physician 70(3):489-512