Insulin

Insulin is an anabolic peptide hormone that is produced and secreted from beta cells located in the islets of Langerhans of the pancreas. It has important metabolic functions, which include promoting the storage of carbohydrates, amino acids, and fat in the liver, skeletal muscle, and adipose tissues. By modulating glucose absorption from the blood, insulin lowers blood glucose levels. Insulin therapy is an important part of treatment for individuals with insufficient or absent insulin production (e.g., diabetes mellitus, gestational diabetes). Several insulin analogs (e.g., insulin glargine) are available that are related to human insulin but have a different molecular structure and differ in onset, peak, and duration compared to human insulin. It is crucial that patients receiving insulin therapy undergo in-depth training to prevent potentially life-threatening conditions such as hypoglycemia as a result of an insulin overdose or drug interactions.

For further information, see also insulin therapy and inpatient management of hyperglycemia.

Overview of the different types of insulin
Types of insulin	Pharmacokinetics [1]	Application [2][3]	Additional considerations [1]
Rapid-acting insulin
Insulin lispro	Onset: 5–15 minutes Peak: ∼ 1 hour Duration: 3–4 hours	Basal-bolus insulin regimen Sliding scale insulin regimen	Insulin analogs Rapid absorption due to immediate dissociation into individual insulin molecules No time interval between injection and meal necessary Usually combined with long-acting insulin
Insulin aspart
Insulin glulisine
Short-acting insulin
Regular insulin	Onset: ∼ 30 minutes Peak: 2–3 hours Duration: 4–6 hours	Standard insulin for lowering blood glucose levels in an acute setting (see hyperglycemic crises) Sliding scale insulin regimen Basal supported oral therapy (BOT)	Recommended interval between injections and meals: 15–30 minutes Often used in combination with long-acting insulin The only insulin available for intravenous use
Intermediate-acting insulin
NPH insulin	Onset: 1–2 hours Peak: 6–10 hours Duration: 10–16 hours	Glucocorticoid-induced hyperglycemia (see weight-based NPH insulin regimen for glucocorticoid-induced hyperglycemia) Insulin regimens for enteral and parenteral nutrition Basal-bolus insulin regimen for treatment-resistant type 2 diabetes mellitus	Crystalline suspension Recommended interval between injections and meal, if it is the only antidiabetic drug used: 30–60 minutes Often used in combination with rapid-acting or short-acting insulin Usually administered twice daily
Long-acting insulin
Insulin glargine	Onset: 1–4 hours Peak: flat; not defined Duration: ∼ 24 hours	Basal-bolus insulin regimen Basal supported oral therapy (BOT)	Insulin analogs More consistent effect and longer duration of action compared to NPH insulin Often used in combination with rapid or short-acting insulin Administered once or twice daily
Insulin detemir
Insulin degludec
Mixed insulin
Mixed insulin	Biphasic effect Short-term effect similar to that of regular insulin/lispro/aspart Long-term effect similar to that of NPH insulin	Basal-bolus insulin regimen	Typically a mixture of NPH insulin and either rapid-acting insulin or regular insulin, mixed in a predefined ratio Administered 2–3 times daily Only requires one injection per application without the need to mix fast- and intermediate-acting insulin

Rapid acting insulins leave no LAG - to remember Lispro, Aspart, Glulisine

Basal-bolus insulin regimen ^[2][3]

1. Calculate the total daily dose of insulin (TDD) needed.
   • If the patient is already on a correction scale: Increase or decrease total daily dose by 10–20% as needed.
   • If the patient is lean, has T1DM, age ≥ 70 years, and/or GFR < 60 mL/min: 0.2–0.3 units/kg
   • If none of the above criteria applies, use the blood glucose level:
     • BG 140–200 mg/dL: 0.4 units/kg
     • BG > 200 mg/dL: 0.5 units/kg
2. Divide the total daily dose of insulin into basal insulin (50%) and nutritional insulin (50%).
   • Basal insulin: Administer as long-acting insulin (e.g., glargine) at bedtime.
   • Nutritional insulin: Administer as rapid-acting insulin (e.g., lispro) in equally divided doses before meals.
3. Add sliding scale insulin as supplemental insulin.
   • Take 5% of the TDD (e.g., 50 → 2.5).
   • Round down to the safest whole number (e.g., 2.5 → 2).
   • For every 40 mg/dL (2.2 mmol/L) above the goal serum glucose of 140 mg/dL, increase the nutritional insulin scale by this increment.
4. Adjust as needed.
   • If glucose persistently > 140 mg/dL and no episodes of hypoglycemia: Increase basal insulin by 20% and/or increase sliding scale insulin by 2 units.
   • In cases of hypoglycemia < 70 mg/dL: Reduce basal insulin by 20% and/or sliding scale insulin by 2 units.

Decrease or hold nutritional insulin if the patient is NPO.

Sliding scale insulin regimen ^[3]

• If the patient is eating all or most of each meal: administer as short-acting insulin (or rapid-acting insulin) before each meal and at bedtime
• If the patient is not eating: administer as short-acting insulin every 6 hours

Blood glucose (mg/dL)	Insulin units
	Insulin sensitive	Usual insulin	Insulin resistant
71–140	0	0	0
141–180	2	4	6
181–220	4	6	8
221–260	6	8	10
261–300	8	10	12
301-350	10	12	14
351-400	12	14	16

If the blood glucose is < 70 mg/dL, hold all insulin and administer hypoglycemia measures.

Weight-based NPH insulin regimen for glucocorticoid-induced hyperglycemia ^[6]

1. Convert glucocorticoid to equivalent prednisone dose (see glucocorticoids).
2. Calculate daily NPH dose based on prednisone dose equivalent and patient weight.
3. Administer glucocorticoid with NPH as a single dose in the morning.

Prednisone dose equivalent (mg/day)	NPH (units/kg/day)
10	0.1
20	0.2
30	0.3
≥ 40	0.4

NPH doses should be administered in addition to usual basal insulin in patients who are already receiving insulin.

Consider using glargine or detemir in patients receiving dexamethasone. Dexamethasone has a longer hyperglycemic effect than prednisone and most other commonly used systemic glucocorticoids.

Insulin regimens for enteral and parenteral nutrition

Enteral nutrition ^[7][8]

1. Determine basal insulin needs.
   • For patients already on insulin: Continue prior dose or administer 30–50% of the total daily dose as long-acting insulin (e.g., glargine) daily.
   • For patients not already on insulin, consider:
     • 5 units of NPH every 12 hours
     • or 10 units of glargine (or equivalent) daily
2. Add nutritional insulin
   • For patients receiving continuous tube feedings
     1. Calculate the total daily nutritional insulin dose:
        • 1 unit of insulin per 10–15 g of carbohydrates per day
        • or 50–70% of the total daily dose
     2. Administer as rapid-acting insulin (e.g., lispro) in divided doses every 4–6 hours.
   • For patients receiving bolus feeding
     1. Calculate the nutritional insulin dose to cover each meal: 1 unit of insulin per 10–15 g of carbohydrates per meal
     2. Administer as rapid-acting insulin (e.g., lispro) before each feeding.
3. Add sliding scale insulin as supplemental insulin.
   • For patients on continuous tube feedings: Administer rapid-acting insulin (e.g., lispro) every 4 hours or regular insulin every 6 hours.
   • For patients receiving bolus feedings: Administer rapid-acting insulin before every meal.
4. Adjust as needed to glycemic targets, changes in medication, and changes in nutrition.

Patients with type 1 diabetes mellitus require basal insulin even if (enteral) feeding is discontinued.

Total parenteral nutrition (TPN) ^[7][9]

• Add short-acting insulin to IV parenteral nutrition solution.
  • Diabetic patient: 1 unit per 10–15 g dextrose
  • Nondiabetic patient: 0.5 units per 10 g dextrose
• Add sliding scale insulin as supplemental insulin: Administer as short-acting insulin (e.g., regular insulin) every 6 hours or rapid-acting insulin (e.g., lispro) every 4 hours.
• Adapt protocol to glycemic targets, changes in medication, and changes in nutrition.