Insulin Therapy
Insulin is the most effective glucose-lowering therapy available.
It replaces or supplements endogenous insulin when pancreatic beta-cell function is inadequate or absent.
Used in:
- Type 1 Diabetes (required)
- Advanced Type 2 Diabetes
- DKA / HHS
- Severe hyperglycemia
- Hospital settings
Mechanism of Action
Insulin binds to the insulin receptor (a tyrosine kinase receptor).
This activates:
- IRS signaling pathways
- PI3K/Akt cascade
- GLUT4 translocation (muscle & adipose)
Effects:
Liver:
- ↓ Gluconeogenesis
- ↑ Glycogen synthesis
- ↑ Lipogenesis
Muscle:
- ↑ Glucose uptake
- ↑ Glycogen storage
Adipose:
- ↑ Glucose uptake
- ↓ Lipolysis
Insulin is anabolic.
Insulin Comparison Table
| Type | Agent | Onset | Peak | Duration | Dosing Role | Key Features |
|---|---|---|---|---|---|---|
| Rapid-Acting | Lispro | 10–15 min | ~1 hr | 3–5 hr | Mealtime | Rapid absorption, less stacking |
| Rapid-Acting | Aspart | 10–20 min | 1–3 hr | 3–5 hr | Mealtime | Structurally modified, rapid profile |
| Rapid-Acting | Glulisine | 10–20 min | ~1 hr | 3–5 hr | Mealtime | Rapid analog, comparable to lispro/aspart |
| Short-Acting | Regular | 30–60 min | 2–4 hr | 6–8 hr | Mealtime / IV use | Only insulin used IV (DKA, HHS) |
| Intermediate | NPH | 1–2 hr | 4–8 hr | 12–18 hr | Basal (older regimens) | Protamine-bound, clear peak |
| Long-Acting | Glargine | 1–2 hr | Minimal | ~24 hr | Basal | pH-dependent precipitation |
| Long-Acting | Detemir | 1–2 hr | Minimal | 12–24 hr | Basal | Albumin binding, may require BID |
| Ultra-Long | Degludec | ~1 hr | None | >42 hr | Basal | Multi-hexamer depot, very stable |
Types of Insulin
Insulins are categorized by onset and duration.
Rapid-Acting (Mealtime)
Onset: 10–30 minutes Duration: 3–5 hours
Used for:
- Mealtime glucose control
- Correction dosing
Short-Acting
Onset: 30–60 minutes Duration: 6–8 hours
Used in:
- IV infusion (DKA)
- Some prandial regimens
Intermediate-Acting
Long-Acting (Basal)
Ultra-Long Acting
Basal-Bolus Concept
Physiologic insulin secretion includes:
- Basal insulin (background suppression of hepatic glucose production)
- Bolus insulin (mealtime glucose control)
Modern therapy mimics this:
Basal insulin:
- Once daily (glargine, degludec)
Bolus insulin:
- Rapid-acting insulin before meals
This is the most physiologic regimen.
Initiating Insulin (Type 2)
Step 1:
- Start basal insulin
- Titrate based on fasting glucose
Step 2:
- Add prandial insulin if needed
Continue:
- Metformin when possible
- Consider combination with:
Adverse Effects
Common:
- Hypoglycemia
- Weight gain
Serious:
- Severe hypoglycemia
- Hypokalemia (high-dose therapy)
Hypoglycemia symptoms:
- Sweating
- Tremor
- Confusion
- Seizures (severe)
DKA & HHS
Insulin deficiency leads to:
- Unchecked lipolysis
- Ketone production
- Metabolic acidosis (DKA)
Treatment requires:
- Fluid resuscitation
- Electrolyte management
Insulin vs Other Therapies
Compared to:
- Sulfonylureas → direct replacement vs stimulation
- Metformin → more potent glucose lowering
- GLP-1 Receptor Agonists → more hypoglycemia, more weight gain
- SGLT2 Inhibitors → no intrinsic CV benefit
Insulin is unmatched in glucose-lowering potency.
Clinical Pearls
- Most potent antihyperglycemic therapy
- Required in Type 1 Diabetes
- Basal suppresses hepatic glucose output
- Bolus controls meals
- Causes weight gain
- Hypoglycemia is primary risk
- Continue metformin when possible