📚 Diabetes & Metabolism — L7: Insulin Therapy

📚 Lecture Overview

This lecture covers the historical background, indications, preparations, and clinical regimens of insulin therapy for both Type 1 and Type 2 diabetes. Understanding these concepts is essential for managing glycemic control, preventing acute complications, and appropriately escalating treatment in clinical practice.

🎯 Key Concepts & Definitions

• Basal Insulin: Long-acting or intermediate-acting insulin that controls blood glucose levels between meals and overnight (e.g., Glargine, Detemir, Degludec, NPH).
• Prandial Insulin: Rapid-acting or short-acting insulin injected immediately before or during meals to control postprandial glucose spikes (e.g., Aspart, Lyspro, Glulisine, Regular).
• Basal-Bolus Regimen: An intensive insulin regimen combining one or more daily injections of basal insulin with rapid-acting prandial insulin before each meal.
• Premixed Insulin: Fixed combinations of intermediate-acting (NPH) and short/rapid-acting insulin in a single vial or pen, offering fewer injections but less lifestyle flexibility.
• Total Daily Dose (TDD): The total amount of insulin required in 24 hours, calculated in Type 1 diabetes as $Weight (kg) × 0.5 U/kg$.
• Beta-cell Function: Progressive decline of insulin-producing pancreatic cells in Type 2 diabetes, measured by HOMA, making insulin therapy eventually necessary for most patients.

📖 Main Content

1. Historical Background & Indications

• Insulin was discovered in Toronto 1921 by Fred Banting, Charles Best, James Collip, and John Macleod, transforming diabetes from a fatal disease into a manageable condition.
• Indications for insulin therapy include:
• Type 1 Diabetes (absolute requirement).
• Type 2 Diabetes with failure of Oral Antidiabetic Drugs (OADs).
• Contraindications to OADs.
• Acute illness or surgery.
• Pregnancy.

2. Insulin Preparations & Pharmacokinetics

• Prandial (Meal-time) Insulins:
• Human Insulin (Regular): Slower onset; injected 30 minutes before meals.
• Rapid-Acting Analogs (Aspart, Lyspro, Glulisine): Quicker onset; injected immediately before meals.
• Basal Insulins:
• Human Insulin (NPH): Shorter duration of action (~12 hours); must be taken twice a day.
• Long-Acting Analogs (Glargine, Detemir, Degludec): Longer duration (~24 hours); taken once a day.

3. Insulin Regimens

• Premixed Regimen: Fewer injections, fixed daily routine, but inflexible meal times; suits less-motivated patients.
• Basal-Bolus Regimen: More injections, high meal flexibility, variable routine; suits motivated patients.
• Basal Plus Regimen: Basal insulin combined with a single rapid-acting dose before the largest meal.
• Starting T1D Regimen (Basal-Bolus):
• $TDD = Weight (kg) × 0.5 U/kg$
• Basal = $\frac{1}{2} TDD$, Bolus = $\frac{1}{2} TDD$ split equally across 3 meals ($\frac{1}{6} TDD$ each).

4. Dose Adjustment & Patient Education

• Fix Fasting First: Always titrate basal insulin based on Fasting Blood Glucose (FBG) with a target of $<130 mg/dl$:
• FBG 130–150 mg/dl: Increase by 2 Units.
• FBG 150–170 mg/dl: Increase by 4 Units.
• FBG 170–200 mg/dl: Increase by 6 Units.
• FBG $>200 mg/dl$: Increase by 8 Units.
• Prandial Adjustment: Target postprandial BG of $180 mg/dl$; increase corresponding meal dose by 2–4 units every 3–4 days.
• Patient Education Rules:
• Store insulin in the refrigerator; never freeze.
• Roll suspension insulins gently; avoid vigorous shaking which damages the molecule.
• Inject strictly into subcutaneous tissue at a 90° angle with skin gently pinched (avoid intradermal or intramuscular).
• Rotate injection sites to prevent lipodystrophy.
• In Type 2 diabetes starting insulin, continue Metformin to reduce required insulin dose and limit weight gain.
• Never use insulin as a threat, as it causes patient fear and depression.

📊 Visual Learning

💡 Important Points to Remember

• Calculation Formula: TDD for Type 1 diabetes is $Weight (kg) × 0.5 U/kg$.
• Basal/Bolus Split: Exactly 50% basal and 50% prandial for starting T1D regimens.
• Timing Rule: Regular human insulin requires a 30-minute pre-meal interval, whereas rapid-acting analogs are taken immediately before meals.
• Injection Depth: Insulin must go into subcutaneous tissue via a 90° angle using a pinched fold of skin.
• Storage: Refrigerated, never frozen. Roll gently, do not shake vigorously.
• Rule of Titration: Always fix fasting blood glucose first before aggressively chasing postprandial spikes.
• Metformin Retention: Always keep Metformin when initiating insulin in Type 2 diabetes to mitigate weight gain and lower total insulin requirements.
• Beta-cell Decline: Beta-cell function declines progressively over time in Type 2 diabetes; insulin is a natural progression, not a personal failure or punishment.

⚠️ Common Exam Questions

• Calculation Traps: Examiners will test if you can calculate the exact TDD and divide it into basal and prandial components for a given patient weight. Watch out for unit conversion or incorrect fractional allocation (e.g., forgetting to split the bolus evenly across three meals).
• Timing Traps: Multiple-choice questions often swap the injection timing of Regular insulin (30 minutes before) with rapid-acting analogs (immediately before).
• Titration Order Traps: Examiners may ask which dose to adjust first when a patient has both high fasting and high postprandial blood glucose. The correct protocol is always to fix fasting first by adjusting the basal insulin before modifying prandial doses.
• Management Traps: Questions testing whether to stop Metformin when starting insulin in T2D—remember, do not stop Metformin.

📝 Quick Review Checklist

I can explain the discovery of insulin and its primary clinical indications
I understand the difference between basal and prandial insulin preparations
I can define and calculate Total Daily Dose (TDD) for Type 1 diabetes
I know how to titrate basal insulin based on fasting blood glucose targets
I understand the proper storage, mixing, and subcutaneous injection techniques
I know why Metformin should be continued when initiating insulin in Type 2 diabetes