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Bolus Insulin

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Bolus Insulin, Short-Acting Insulin, Rapid-Acting Insulin, Mealtime Insulin, Regular Insulin, Novolin R, Humulin R, Lispro, Novolog, Fiasp, Humalog, Admelog, Lispro-aabc, Lyumjev, Aspart, Apidra, Glulisine, Insulin Glulisine, Humulin R U-500

  • See Also
  1. Humulin R U-500
  2. Insulin
  3. Insulin Pump
  4. Insulin Dosing
  5. Glucose Metabolism
  6. Type II Diabetes Medications
  7. Type 1 Diabetes Mellitus
  • Definitions
  1. Insulin
    1. Insulin is a polypeptide produced by pancreatic beta cells, with release stimulated by Blood Glucose concentration
    2. Insulin promotes energy utilization via Glycolysis, and energy storage as glycogen, Protein and Triglycerides
    3. First used in Diabetes Mellitus in 1922, by Drs Banting and Best
  2. Bolus Insulin (short-acting)
    1. Similar to physiologic Insulin, with immediate onset (15-30 min) and short duration (2 to 4 hours)
    2. Primarily covers short-term Blood Glucose spikes with meals
  3. Basal insulin (long-acting)
    1. Long-acting coverage to maintain Blood Glucose control throughout the day, between meals
    2. Mimics the low level continuous Insulin release by a normal human Pancreas
    3. Insulin Glargine (Lantus) and similar agents that last approximately 24 hours have largely replaced NPH Insulin (12 hour duration)
  4. Insulin Analog
    1. Historically, short-acting Regular Insulin has been sourced from animal Pancreas (pigs, cows)
    2. As of the 1980s, human Insulins were synthesized in Bacteria
    3. Synthetic Insulins have since been modfied for rapid onset bolus (e.g. Lispro) and longer-acting basal (e.g. Glargine)
  • Indications
  1. Type 1 Diabetes Mellitus
  2. Type 2 Diabetes Mellitus with Insulin Resistance refractory to non-Insulin therapy
  3. Acute Hyperkalemia Management
  4. Acute Pancreatitis due to severe Hypertriglyceridemia (>1000 mg/dl)
  5. Calcium Channel Overdose (or Beta Blocker Overdose)
  • Mechanism
  1. See Insulin
  • Medications
  • Bolus Insulins (Meal-time Insulin)
  1. Precautions: Humulin R U-500 is NOT a Bolus Insulin (NOT equivalent to Bolus Insulins listed below)
    1. Humulin R U-500 is a Regular Insulin that is at 5-fold higher concentration than typical Regular Insulin
    2. At this very high concentration, Humulin R U-500 has Pharmacokinetics that are more like a mixed or Basal insulin
      1. Despite being Regular Insulin, U-500 acts more like NPH or Insulin 70/30
  2. 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
      4. Avoid in Stage IV or Stage V significant Chronic Kidney Disease
      5. Avoid if history of severe Hypoglycemia
      6. Available concentrations
        1. Humulin R U-100 (100 units/ml, orange)
        2. Humulin R U-500 (500 units/ml, green)
          1. High concentration AND basal and Bolus Insulin activity (similar to 70/30)
          2. See Basal insulins below for description
  3. Analog 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 for chilren (age>4 years) and adults, and to take after meal
        1. Other analogs expected with same effect after meal
    2. Lispro (Humalog, Admelog)
      1. Onset: 5 to 15 minutes
      2. Peak: 1 to 2 hours
      3. Duration: 3 to 5 hours
      4. FDA approved for age >3 years
      5. Concentrations
        1. Humalog U-100 (100 units/ml) vial or KwikPen
        2. Humalog U-200 (200 units/ml) KwikPen - for patients using >20 units/day
    3. Lispro-aabc (Lyumjev)
      1. Same manufacturer as Humalog
      2. Four letter designation refers to new FDA labeling of Insulins as biologics
      3. Marketed as 10 minutes faster onset that typical Lispro Insulin
      4. Unlikely to offer any real benefit over other Lispro Insulin
      5. Concentrations
        1. Lyumjev U-100 (100 units/ml) vial or KwikPen
        2. Lyumjev U-200 (200 units/ml) KwikPen - for patients using >20 units/day
    4. Aspart (Novolog, Fiasp)
      1. FDA approved for age >2 years
      2. Onset: 5 to 15 minutes
      3. Peak: 1 to 2 hours
      4. Duration: 3 to 5 hours
  • Dosing
  1. Precautions
    1. Humulin R U-500 is NOT a Bolus Insulin (see above)
    2. Carefully check Insulin type and concentration before dose
      1. Serious dosing errors due to concentration (100 units/ml or 200 units/ml) may occur
      2. Confirm pen or bottle formulation (Bolus Insulin or Basal insulin)
  2. Subcutaneous
    1. See Insulin Dosing
    2. See Insulin Dosing in Type I Diabetes
    3. See Insulin Dosing in Type II Diabetes
    4. See Carbohydrate Count in Insulin Dosing
    5. See Carbohydrate Counting
    6. Administer analog Insulins (e.g. Lispro) 15 min before meals, and Regular Insulin 30 min before meals
    7. Only NPH Insulin may be mixed in same syringe with bolus/rapid Insulins (draw up Bolus Insulin first)
      1. Do NOT mix other basal/Long-Acting Insulins (e.g. Glargine) with Bolus Insulins
    8. Typical daily dosing
      1. Total daily Insulin
        1. Type 1 Diabetes: 0.3 to 0.5 units/kg (up to 0.5 to 1.0 units/kg in children)
        2. Type 2 Diabetes: 1 to 1.5 units/kg
      2. Bolus Insulin dose
        1. Give 50% of total Insulin daily units as Bolus Insulin divided over 3 meals
        2. Give remaining 50% of total daily dose as Basal insulin (e.g. Insulin Glargine or Lantus)
    9. Initiating Insulin in Type 2 Diabetes
      1. Start 0.1 units/kg OR 4 units OR 10% of basal dose, given before the largest meal
      2. Titrate doses 1-2 units (or 10-15%) every 3 to 7 days
      3. Combine with Basal insulin (roughly 50% of total daily Insulin)
  3. Intravenous Regular Insulin
    1. Intravenous insulin Pharmacokinetics (other listed kinetics above is for subcutaneous dosing)
      1. Onset: Immediate
      2. Half-Life: 5-10 minutes
    2. Insulin Infusion in severe Hyperglycemia
      1. See Insulin Drip
      2. See Diabetic Ketoacidosis Management in Adults
      3. See Diabetic Ketoacidosis Management in Children
      4. See Diabetic Ketoacidosis in Pregnancy
      5. See Hyperosmolar Hyperglycemic State
      6. Do NOT start Insulin replacement until Hypokalemia is corrected
      7. Initial Insulin Bolus (optional): 0.1 units/kg Regular Insulin IV
      8. Insulin IV Infusion: Start at 0.1 units/kg/hour IV using a 1 unit/ml solution (100 units/100 ml NS)
    3. See specific conditions for emergent Insulin use outside of diabetes
      1. Acute Hyperkalemia Management
      2. Acute Pancreatitis due to severe Hypertriglyceridemia (>1000 mg/dl)
      3. Calcium Channel Overdose (or Beta Blocker Overdose)
  4. Insulin Pump
    1. FDA approved Bolus Insulins for Insulin Pump: Humalog, Novolog, Apidra, Admelog
    2. Do NOT mix Insulins in the Insulin Pump
    3. Only use an approved Bolus Insulin at standard concentration (100 units/ml)
  • Adverse Effects
  1. See Insulin
  2. 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)
  3. 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
  4. 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
  5. 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
  • Safety
  1. Considered safe in pregnancy and Lactation
  • Reources
  1. Regular Human Insulin (Humulin R, DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b519bd83-038c-4ec5-a231-a51ec5cc291f
  2. Insulin Lispro (Humalog, DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c8ecbd7a-0e22-4fc7-a503-faa58c1b6f3f
  3. Insulin Aspart (Novolog, DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=3a1e73a2-3009-40d0-876c-b4cb2be56fc5
  4. Insulin Glulisine (Apidra, DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=e7af6a7a-8046-4fb4-9979-4ec4230b23aa
  5. FDA Insulin storage and emergency switching
    1. https://www.fda.gov/Drugs/EmergencyPreparedness/ucm085213.htm
  • References
  1. (2014) Presc Lett 21(12): 69
  2. Lepore (2000) Diabetes 49:2142-8 [PubMed]
  3. Mayfield (2004) Am Fam Physician 70(3):489-512 [PubMed]