Insulin doses, routes MOA and side effects

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Insulin: routes, mechanism, usual doses, adverse effects

Insulin is prescribed individually. Doses must be adjusted for glucose readings, meals, activity, renal/hepatic function, illness, and risk of hypoglycemia. Do not change a prescribed regimen without a clinician.

Mechanism of action

Insulin binds the insulin receptor, a cell-surface receptor tyrosine kinase. This:

Increases glucose uptake into skeletal muscle and adipose tissue via GLUT4
Reduces hepatic glucose production
Promotes glycogen, fat, and protein synthesis
Suppresses lipolysis, ketogenesis, and proteolysis
Drives potassium into cells, which can lower serum K+

Routes

Route	Insulins / use	Key points
Subcutaneous (SC)	Most insulin therapy: pens, syringes, pumps	Usual route for basal and mealtime insulin. Abdomen generally gives most consistent absorption. Rotate sites.
Intravenous (IV)	Regular insulin is standard	Used in DKA, hyperosmolar states, severe hyperkalemia, and perioperative/critical-care glucose control. Requires frequent glucose and potassium monitoring.
Continuous SC infusion	Rapid-acting insulin via pump	Uses lispro, aspart, or glulisine. Provides programmable basal rate plus meal boluses. Interruption can rapidly lead to hyperglycemia and ketosis in type 1 diabetes.
Inhaled	Inhaled human insulin, for meals	Rapid acting. Not for DKA. Avoid in chronic lung disease such as asthma or COPD; spirometry is required.
Intramuscular (IM)	Rarely used	Absorption is less predictable than IV or SC.

Insulin preparations and timing

Class	Examples	Onset	Peak	Approximate duration	Main use
Rapid acting	Lispro, aspart, glulisine	10-20 min	1-3 h	3-5 h	Meal bolus, pump
Short acting	Regular insulin	30-60 min SC	2-4 h	5-8 h	Meals, IV emergencies
Intermediate acting	NPH	1-2 h	4-12 h	12-18 h	Basal coverage, often twice daily
Long acting	Glargine U-100, detemir	1-2 h	Minimal	about 20-24 h	Basal insulin
Ultra-long acting	Degludec, glargine U-300	1-6 h	Minimal	>24 h	Basal insulin
Premixed	70/30 NPH/regular, 75/25 lispro mix, 70/30 aspart mix	Varies	Dual peaks	Varies	Simpler twice-daily regimens

Meal timing

Rapid-acting insulin: inject immediately before eating, or up to 15 minutes before.
Regular insulin: usually inject about 30 minutes before food.
Basal insulins: take consistently at the prescribed time; they are not for meal correction.

Typical starting doses

1. Type 1 diabetes

Usual total daily dose at initiation: 0.4-0.5 units/kg/day SC.

Some newly diagnosed or highly insulin-sensitive people may need 0.2-0.4 units/kg/day
During illness, puberty, obesity, or insulin resistance: 0.6-1 unit/kg/day or more may be required.
Common basal-bolus split: about 40%-50% basal, with the remainder divided as rapid-acting doses before meals.

Example only: 60 kg adult, total daily dose 0.5 units/kg/day = 30 units/day. A possible initial structure is 15 units basal plus 5 units rapid-acting before each of three meals, then titrated to glucose readings and carbohydrate intake.

2. Type 2 diabetes: basal insulin initiation

A common start is:

10 units SC once daily, or
0.1-0.2 units/kg once daily.

Titration is commonly done by increasing about 2 units every 3 days or 10%-15% once or twice weekly until fasting glucose is at the agreed target, provided there is no hypoglycemia.

If basal insulin is insufficient:

Add rapid-acting mealtime insulin, often 4 units, 0.1 units/kg, or 10% of basal dose before the largest meal.
Intensify to doses before two or three meals as needed.
Alternative: use a clinician-directed premixed insulin regimen, often twice daily.

3. Diabetic ketoacidosis

In a monitored hospital setting, a typical regimen is:

Regular insulin IV infusion: 0.1 unit/kg/hour
An initial IV bolus is often not required in modern protocols.
Do not begin insulin if potassium is severely low, usually K+ <3.3 mEq/L, until potassium is replaced.

Rosen's Emergency Medicine describes regular insulin 0.1 units/kg/hour IV, usually up to 5-10 units/hour, with IV preferred in sicker patients because poor perfusion makes SC/IM absorption unreliable.

4. Hyperkalemia

A common emergency regimen is regular insulin 10 units IV with IV dextrose to temporarily shift potassium intracellularly. This must be given under urgent clinical supervision because delayed hypoglycemia can occur.

Important adverse effects

Adverse effect	Notes / prevention
Hypoglycemia	Most common and most serious effect. Symptoms: sweating, tremor, palpitations, hunger, headache, confusion, behavior change, seizures, coma. Treat promptly with carbohydrate if conscious, or glucagon/IV dextrose if severe.
Weight gain	Common, especially with intensive insulin treatment.
Injection-site reactions	Pain, redness, swelling, pruritus.
Lipohypertrophy or lipoatrophy	Repeated injections into one site create fatty lumps or tissue loss, causing erratic absorption. Rotate sites and do not inject into lumps.
Hypokalemia	Especially with IV insulin. Monitor potassium in DKA, hyperkalemia treatment, and high-dose IV infusion.
Edema	Can occur after starting or intensifying insulin, particularly with marked prior hyperglycemia.
Allergy	Uncommon with modern recombinant insulin. May cause local or rarely systemic hypersensitivity reactions.
Hyperglycemia / ketosis from interruption	Especially with pump failure, missed basal insulin, incorrect technique, spoiled insulin, or infusion-set occlusion.
Insulin antibodies / resistance	Rare clinically significant issue with current human insulin analogs.

Hypoglycemia, weight gain, local reactions, and lipodystrophy are the classic adverse effects of insulin therapy. - Lippincott Illustrated Reviews: Pharmacology, p. 1197 and following. Katzung also identifies hypoglycemia as the most frequent complication of insulin therapy. - Katzung's Basic and Clinical Pharmacology, p. 1197.

Safety points

Check the insulin name, concentration, dose, and timing every time. U-100, U-200, U-300, and U-500 products are not interchangeable unit-for-unit by volume.
Never share insulin pens, needles, or pump supplies.
Monitor more closely with renal impairment, reduced food intake, increased exercise, alcohol use, illness, or interacting medicines.
Beta-blockers can reduce awareness of warning symptoms of hypoglycemia.
A recent systematic review of pump-related skin reactions supports recognizing adhesive/contact dermatitis in pump users.

For individualized dose calculation, the key details are diabetes type, body weight, current glucose readings or HbA1c, meal pattern, kidney function, and whether the person has used insulin before.

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