Insulin preparations and kinetics

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Insulin Synthesis - The Body's Sugar Boss

Insulin synthesis and secretion in pancreatic beta cell

  • Origin: Synthesized in pancreatic β-cells, encoded by the INS gene on chromosome 11.
  • Process: Follows the secretory pathway from preproinsulin (RER) to proinsulin (Golgi), finally cleaved into active insulin and C-peptide.
  • Storage: Held in secretory granules with zinc, awaiting a glucose signal for release.

⭐ C-peptide is the most accurate measure of endogenous insulin production. It has a longer half-life (30 min) than insulin (5 min), making it a more stable clinical marker.

Insulin Kinetics - The Insulin Lineup

Insulin kinetics: onset, peak, and duration by type

  • Rapid-Acting: Lispro, Aspart, Glulisine. 📌 Mnemonic: No LAG.
    • Onset: 15 min
    • Peak: 1-2 hr
    • Duration: 3-5 hr
  • Short-Acting: Regular (Humulin R, Novolin R).
    • Onset: 30-60 min
    • Peak: 2-4 hr
    • Duration: 6-8 hr
  • Intermediate-Acting: NPH (Humulin N, Novolin N).
    • Onset: 1-2 hr
    • Peak: 4-12 hr
    • Duration: 12-18 hr
  • Long-Acting: Detemir, Glargine, Degludec.
    • Onset: 1-2 hr
    • Peak: Flat (no true peak)
    • Duration: >24 hr (Glargine, Degludec), 16-24 hr (Detemir)

⭐ IV regular insulin is standard for hyperglycemic emergencies like DKA, while rapid-acting (Lispro/Aspart) can also be used IV.

Clinical Use & Complications - The Balancing Act

  • Therapeutic Uses:

    • Type 1 & advanced Type 2 DM
    • Gestational Diabetes
    • DKA/HHS emergencies
    • Hyperkalemia (with glucose to prevent hypoglycemia)
  • Major Complications:

    • Hypoglycemia: Most common/dangerous.
      • Autonomic symptoms (tachycardia, sweating) precede neuroglycopenic ones (confusion, coma).
      • Treat: Glucose (oral/IV), glucagon (IM).
    • Weight Gain: Due to anabolic effects.
    • Lipodystrophy: Atrophy/hypertrophy at injection sites; prevented by site rotation.
    • Hypokalemia: Especially with IV insulin; drives K⁺ into cells.

Exam Favorite: Differentiating morning hyperglycemia. Check glucose at 3 AM.

  • Somogyi Effect: Low 3 AM glucose. Caused by nocturnal hypoglycemia → counter-regulatory surge. Fix: Decrease evening insulin.
  • Dawn Phenomenon: Normal/High 3 AM glucose. Caused by morning cortisol/GH surge. Fix: Increase evening insulin.

Somogyi Effect vs. Dawn Phenomenon vs. Underbasalization

High‑Yield Points - ⚡ Biggest Takeaways

  • Rapid-acting insulins (Lispro, Aspart, Glulisine) are crucial for postprandial glucose control.
  • Regular insulin is the only preparation for IV use, making it essential in Diabetic Ketoacidosis (DKA).
  • NPH, an intermediate-acting insulin, has a cloudy appearance and exhibits more variable absorption.
  • Long-acting, peakless insulins (Glargine, Detemir, Degludec) provide basal glycemic control.
  • The most common and dangerous adverse effect across all insulin types is hypoglycemia.
  • When mixing, always draw up clear (Regular/Rapid) before cloudy (NPH).

Practice Questions: Insulin preparations and kinetics

Test your understanding with these related questions

A 62-year-old man presents to the emergency department with confusion. The patient’s wife states that her husband has become more somnolent over the past several days and now is very confused. The patient has no complaints himself, but is answering questions inappropriately. The patient has a past medical history of diabetes and hypertension. His temperature is 98.3°F (36.8°C), blood pressure is 127/85 mmHg, pulse is 138/min, respirations are 14/min, and oxygen saturation is 99% on room air. Physical exam is notable for a confused man with dry mucous membranes. Initial laboratory studies are ordered as seen below. Serum: Na+: 135 mEq/L Cl-: 100 mEq/L K+: 3.0 mEq/L HCO3-: 23 mEq/L BUN: 30 mg/dL Glucose: 1,299 mg/dL Creatinine: 1.5 mg/dL Ca2+: 10.2 mg/dL Which of the following is the most appropriate initial treatment for this patient?

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Flashcards: Insulin preparations and kinetics

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A metabolic adverse effect of mecasermin, a recombinant IGF-1, is _____

TAP TO REVEAL ANSWER

A metabolic adverse effect of mecasermin, a recombinant IGF-1, is _____

hypoglycemia

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