Action: Facilitates glucose uptake, lowers blood glucose levels.

Efficacy: Most potent glucose-lowering agent.HbA1c: reduce 1.5 – 3.5% w monotherapy

Side Effects: Hypoglycemia, weight gain.

Studies: UKPDS and ORIGIN trials confirm cardiovascular safety and reduced microvascular complications.

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When to Start Insulin Therapy :

• Severe hyperglycaemia at diagnosis (e.g. HbA1c > 10%, BGL > 20 mmol/L)
• Marked weight loss, osmotic symptoms, or ketonuria → consider insulin initiation
• Suspected type 1 diabetes or LADA (e.g., ketonuria, rapid progression) → check autoantibodies/C-peptide
• Failure of oral therapy: HbA1c remains elevated ≥3 months despite dual/triple oral agents
• Acute illness, hospitalisation, or infection where glycaemic control is unstable

Differentiating from Type 1 Diabetes

• Presence of ketonuria or DKA in an adult may suggest type 1 diabetes
• Recommend testing GAD, IA2 antibodies and C-peptide (after stabilisation)
• Endocrinologist referral recommended if:
  • Diagnostic uncertainty
  • Atypical presentation
  • Acutely unwell patients

Underlying Differences

Feature	Type 1 Diabetes (T1DM)	Type 2 Diabetes (T2DM)
Pathophysiology	Absolute insulin deficiency (autoimmune destruction of β-cells)	Insulin resistance ± relative insulin deficiency
Disease Onset	Rapid (days–weeks); often in youth	Gradual (months–years); usually adult onset
Need for Insulin	Mandatory from diagnosis	May be delayed used when oral agents insufficient

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Type 2 Diabetes

key considerations – https://www.racgp.org.au/afp/2015/may/the-introduction-of-insulin-in-type-2-diabetes-mel

💊 Insulin vs. Newer Non-Insulin Agents

• Insulin is no longer a last resort:
  • Consider earlier based on individualised factors
  • Can be used alongside GLP-1 RAs, SGLT2i, DPP-4i as clinically appropriate
• Most effective HbA1c-lowering agent
  • Particularly for HbA1c > 9%
• Endocrinology consult advised when:
  • Complex regimens considered
  • Combining with novel agents
  • Risk of hypoglycaemia is high

⚖️ Benefits of Early Glycaemic Control

• Legacy effect: Early intensive glycaemic control reduces long-term complications and mortality
• Reduces metabolic memory damage
• May limit insulin-associated weight gain when started early
• Avoids therapeutic inertia (delaying needed insulin therapy)

👤 Individualising HbA1c Targets

• Younger patients:
  • Aim for tighter HbA1c (e.g. ≤ 7.0%) → early insulin may be beneficial
• Older/frail patients:
  • Less stringent targets (e.g. ≤ 8.0%) acceptable
  • Emphasis on symptom control, avoiding hypoglycaemia

🚧 Barriers to Optimal Insulin Use

• Fear of hypoglycaemia or needles
• Depression, low health literacy, and psychosocial factors
• Lifestyle issues:
  • High sugar beverage intake
  • Poor dietary adherence
• Inertia: reluctance by patients or providers to escalate therapy

💊 Insulin vs. Newer Non-Insulin Agents

• Insulin is no longer a last resort:
  • Consider earlier based on individualised factors
  • Can be used alongside GLP-1 RAs, SGLT2i, DPP-4i as clinically appropriate
• Most effective HbA1c-lowering agent
  • Particularly for HbA1c > 9%
• Endocrinology consult advised when:
  • Complex regimens considered
  • Combining with novel agents
  • Risk of hypoglycaemia is high

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TYPES of INSULIN

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Schematic representation of insulin time action profile: (Insulin analog therapy: improving the match with physiologic insulin secretion. J Am Osteopath Assoc 2009;109:26–36.)

Line Colour	Insulin Type	Key Features
🟠 Orange	Endogenous (non-diabetic pattern) Insulin naturally secreted by the pancreas in people without diabetes.	Basal secretion: Continuous low-level insulin release to regulate fasting glucose Bolus secretion: Rapid bursts after meals (post-prandial)
🔵 Blue	Rapid-acting (e.g. aspart, lispro)	Quick onset, short duration — best for bolus/mealtime
🟣 Purple	Analog premixed	Two peaks — covers both meals and some basal
⚫ Black	Short-acting (e.g. regular)	Slower onset than rapid; longer duration
🟡 Yellow	Intermediate (NPH)	Peak at ~6–8h; used for basal or in premix
🟢 Green	Long-acting (e.g. glargine, detemir)	Flat, long-acting profile — ideal for basal insulin needs

Understanding onset, peak, and duration is critical for:

• Choosing the right insulin for the patient’s glucose pattern
• Minimising risk of hypoglycaemia
• Timing injections appropriately with meals and activity

Human vs Analogue Insulin

• historically Extracted from the pancreas of pigs (porcine) or cows (bovine)

• Used before 1980s

Type	Description	Examples
Human insulin – These are recombinant insulins (e.g., made via E. coli or yeast) that replicate the structure of endogenous human insulin.	Bioengineered to mimic natural human insulin	Actrapid® Protaphane® Humulin R® NPH – Neutral Protamine Hagedorn
Analogue insulin – Mid-1990s onwards – These are genetically modified versions of human insulin designed to alter pharmacokinetics (onset, peak, and duration).	Modified to alter absorption and action time	NovoRapid® (aspart) Lantus® (glargine) Humalog® (lispro)

Note: Analogues offer more physiological profiles (faster onset or flatter basal action), and often lower hypoglycaemia risk.

Classification by Action Duration

Class	Onset	Peak	Duration	Use
Rapid-Acting	10–20 min	1–3 hrs	3–5 hrs	Mealtime/bolus
Short-Acting	~30 min	2–4 hrs	6–8 hrs	Pre-meal (esp. with human insulin)
Intermediate-Acting	1–2 hrs	4–12 hrs	12–18 hrs	Basal or in premixed
Long-Acting	1–2 hrs	Flat	Up to 24 hrs	Basal
Ultra-Long Acting	1–6 hrs	Flat	36–42 hrs	Basal with minimal variation

🌙 Basal Insulin

• Covers background insulin needs between meals and overnight
• Types:
  • Long-acting analogues (e.g. glargine, detemir, degludec)
  • Intermediate-acting (NPH – Neutral Protamine Hagedorn)
• Goal: Maintain stable fasting BGL

🍽️ Prandial (Bolus) Insulin

• Taken to cover carbohydrate intake at meals and correct postprandial hyperglycaemia
• Types:
  • Rapid-acting analogues (e.g. aspart, lispro)
  • Short-acting human insulin (e.g. regular/Actrapid®)
• Timing: Inject just before or shortly after meals

🔄 Premixed Insulin

• Fixed combination of basal + prandial insulin in one injection
• Form: Rapid- or short-acting + intermediate-acting (e.g. NovoMix 30, Humulin 30/70)
• Use: Simpler regimens for T2DM with regular meals
• Limitation: Less flexibility for timing or carbohydrate variability

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💉 Insulin – Types, Trade Names, Action Profiles

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🟩 Basal Insulin (Long-Acting & Intermediate-Acting)

Type	Insulin Name	Brand Name	Onset	Duration	PBS Status
Intermediate-Acting	Isophane (NPH)	Protaphane®, Humulin NPH®	1–2 hours	12–18 hours	✅
Long-Acting Analogue	Insulin Glargine	Lantus®, Optisulin®	1–2 hours	Up to 24 hours	✅
	Insulin Detemir	Levemir®	1–2 hours	16–24 hours	❌ Not PBS for T2DM
Ultra-Long Acting	Insulin Glargine U300	Toujeo®	~6 hours	Up to 36 hours	✅
	Insulin Degludec	Tresiba®	~1 hour	Up to 42 hours	✅

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🟦 Premixed Insulin (Biphasic Analogue or Human)

Insulin Type	Brand Name	Components	Onset	Duration
Biphasic Aspart 30/70	NovoMix 30®	Aspart 30% + Aspart protamine 70%	~10–20 mins	Up to 24 hrs (2 peaks)
Biphasic Lispro 25/75	Humalog Mix 25®	Lispro 25% + Lispro protamine 75%	~15 mins	Up to 24 hrs
Biphasic Lispro 50/50	Humalog Mix 50®	Lispro 50% + Lispro protamine 50%	~15 mins	Up to 24 hrs
Neutral/Isophane 30/70	Mixtard 30/70®, Humulin 30/70®	Human regular 30% + NPH 70%	~30 mins	12–18 hrs
Neutral/Isophane 50/50	Mixtard 50/50®	Human regular 50% + NPH 50%	~30 mins	12–18 hrs

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🟥 Short-Acting (Prandial/Bolus) Insulin

Type	Insulin Name	Brand Name	Onset	Duration
Rapid-Acting	Insulin Aspart	NovoRapid®	1–20 mins	3–5 hours
	Insulin Lispro	Humalog®	15 mins	2–4 hours
	Insulin Glulisine	Apidra®	10–20 mins	3–4 hours
Short-Acting (Human)	Insulin Regular	Actrapid®, Humulin R®	30 mins	6–8 hours

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📈 Clinical Matching: Action Profiles with Use Cases

Use	Preferred Insulin Type	Example Products
Fasting hyperglycaemia (T2DM start)	Long-acting	Lantus®, Levemir®, Tresiba®
Basal–bolus regimen (T1DM)	Long-acting + rapid-acting	Lantus® + NovoRapid®
Post-prandial hyperglycaemia	Rapid-acting	NovoRapid®, Humalog®, Apidra®
Fixed meal schedule (T2DM)	Premixed insulin	NovoMix 30®, Humalog Mix 25®
Cost-effective basal	Intermediate-acting (NPH)	Protaphane®, Humulin NPH®

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⚖️ How to start insulin

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Identifying Blood Glucose Patterns to Decide Which Insulin to Use

✅ 1. Identify the Patient and Indication

Condition	Indications for Insulin Initiation
Type 1 Diabetes	Absolute insulin deficiency at diagnosis
Type 2 Diabetes	Inadequate control with – oral therapy – significant hyperglycaemia – pregnancy – intercurrent illness/hospitalisation

✅ 2. Determine Initial Total Daily Dose (TDD)

Patient Group	Typical Starting TDD
Type 1 Diabetes	0.4–1.0 units/kg/day (typically 0.4–0.6)
Type 2 Diabetes (insulin-naïve)	0.2–0.6 units/kg/day Start at 0.1–0.2 units/kg/day or 10 units basal

✅ 3. Select Insulin Regimen

🔹 Type 1 Diabetes – Basal–Bolus or CSII

• Basal–Bolus Regimen:
  • 50% basal insulin (e.g., glargine or detemir)
  • 50% rapid-acting insulin (e.g., aspart/lispro) divided across meals
• CSII (Pump):
  • Continuous basal infusion
  • Bolus before meals and correctional dosing

🔹 Type 2 Diabetes – Basal or Premixed

• Option 1: Basal-Only Start
  • Long-acting insulin once daily (e.g., glargine, detemir, or NPH)
  • Preferred for flexible dosing or if meal pattern is irregular
• Option 2: Premixed Insulin (Biphasic Analogues)
  • Pre-mixed formulations (e.g., NovoMix 30, Humalog Mix 25/50)
  • Given before breakfast and dinner
  • Suitable for consistent daily routines

✅ 4. Dose Calculation – Examples

🔸 Example A: Basal Insulin Start in Type 2 Diabetes

• Weight: 80 kg
• Start Dose: 0.2 units/kg = 16 units once daily

🔸 Example B: Premixed Insulin in Type 2 Diabetes

• Weight: 70 kg
• TDD: 0.3 units/kg = 21 units/day
  • AM: 60% = 12–13 units before breakfast
  • PM: 40% = 8–9 units before dinner

✅ 5. Monitoring and Titration

Target BGL	Recommended
Fasting	6–8 mmol/L
2-hour postprandial	6–10 mmol/L

🔁 Titration (Basal Insulin)

• Check fasting BGL daily
• Increase by 2 units every 3 days if BGL > 7 mmol/L
• Reduce if BGL < 4 mmol/L or hypoglycaemia occurs

📈 Titration (Premixed Insulin)

• Adjust based on fasting and pre-dinner BGL
• Monitor 2-hour postprandial BGL intermittently

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Interpretation and Insulin Adjustments by Pattern

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Fasting glucose is the main problem: nocte basal insulin would target this:

Key Problem: Elevated fasting BGL = 10.8 mmol/L

Other BGLs (post-meals, bedtime): Within or close to target

Rationale: This pattern suggests inadequate basal insulin overnight

🩺 Adjustment:

• Start or titrate nocte basal insulin
  • E.g., Glargine or Detemir
• Target: Fasting BGL (6–8 mmol/L)
• Titration: ↑ by 2 units every 3 days until fasting BGL is within range

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Fasting glucose is the main problem: nocte basal insulin would target this:

Key Problems:

1. Elevated fasting BGL = 10.1 mmol/L
2. Elevated post-dinner BGL = 13.2 mmol/L

Implication: Basal insulin alone won’t address both issues

🩺 Adjustment:

• Switch to pre-dinner premixed insulin (e.g., NovoMix 30, Humalog Mix25)
  • Covers dinner + overnight period
• Titration target: Fasting BGL
• Monitor: Fasting and 2-hour post-dinner BGL
• Consider split-dose premix if daytime BGLs also elevated

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Daytime hyperglycaemia with morning postprandial excursions: pre-breakfast pre-mixed insulin appropriate; suggested times for SMBG in bold red:

Key Problem:

• Post-breakfast BGL = 12 mmol/L
• Also elevated pre-lunch = 11.4, pre-dinner = 10.0

Implication: Morning insulin insufficient to control post-breakfast and daytime BGLs

🩺 Adjustment:

• Start pre-breakfast premixed insulin
  • Controls breakfast rise + daytime BGL
• Titration target: Pre-dinner BGL (aim <8 mmol/L)
• Monitor: Post-breakfast and pre-dinner BGL
• If needed, may escalate to BID premix or basal-bolus

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✅ Key Information on First Day of Insulin Therapy

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💉 Insulin Administration

• Subcutaneous injection using modern pens/devices is simple and user-friendly.
• Reassure patients—focus on technique, not complex dietary changes initially.
• Use dummy (saline) injections to build confidence and demystify the process.
• Preferred needle length: 6 mm for most adults.

🍽️ Basic Dietary Advice

• Emphasise regular meals and snacks with carbohydrates.
• Delay detailed dietary counselling until follow-up.
• Refer to a dietitian for individualised advice in later visits.

⚠️ Hypoglycaemia Awareness

• Risk is low with proper titration (“start low, go slow”) but not eliminated.
• Teach the “Rule of 15” for mild hypoglycaemia:
  • If BGL <4.0 mmol/L → take 15 g quick-acting carbs:
    • E.g., ½ cup juice, 6 jelly beans, glucose tablets
  • Recheck BGL after 15 min → repeat if still low
  • If meal >15 min away → add long-acting carbohydrate (e.g., sandwich, milk)

📈 Insulin Titration and Follow-Up

Plan follow-up within 7 days to assess BGLs and adjust dose.

• Use lowest BGL from last 3 days to guide titration.
• Titration algorithm example:
  • ↑ by 2–4 units if BGL consistently above target
  • ↓ dose if BGL <4.0 mmol/L or hypoglycaemia occurs
• Patients may self-titrate with instructions and review.

💊 Oral Hypoglycaemic Agents

✅ Continue initially:

• Metformin: Continue indefinitely (insulin-sparing, weight neutral)
• Other agents: Help stabilise glucose and reduce insulin requirement

⚠️ Avoid stopping abruptly:

• Discontinuation → ↑ BGL → misinterpreted as insulin “failure”
• May need 20–30 unit increase in insulin to compensate

🚫 Consider ceasing:

• Pioglitazone: Discontinue if oedema worsens
• Sulfonylureas: Consider stopping with pre-mixed insulin (reduces hypoglycaemia risk)

💡 Other agents:

• GLP-1 RAs: Useful for weight gain from insulin
• DPP-4 inhibitors: Modest insulin-sparing, low hypoglycaemia risk
• SGLT-2 inhibitors: Continue if PBS-eligible and renal function permits

⏳ When to Consider More Complex Regimens

When fasting/pre-prandial glucose is at target, but HbA1c remains elevated:

• Twice-daily pre-mixed insulin
• Basal-plus regimen (add short-acting insulin before main meal)
• Prandial dosing for large meals—not carb counting but range-based (e.g., 4, 6, 8 units based on portion size)

📝 Overcoming Clinical Inertia

• Introduce insulin early in discussions—even before it is needed
• Use dummy pens for comfort
• Provide written titration plan or visual chart
• Enlist support from:
  • Credentialled diabetes educators
  • Practice nurses
  • Dietitians

🚗 Special Considerations

• Driving and work safety:
  • Discuss hypoglycaemia risks
  • Patients must comply with licensing requirements for insulin users (e.g., notify transport authority, avoid driving if BGL <5 mmol/L)
  • Occupations involving heavy machinery, working at heights, or night shifts may require modification or additional monitoring

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🍞 Carbohydrate Counting for Insulin Adjustment

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🔍 Identify Carbohydrate-Containing Foods

• Found in:
  • Grains: Bread, pasta, rice
  • Fruits: Apples, bananas, oranges
  • Vegetables: Starchy types like potatoes, carrots
  • Dairy: Milk, yoghurt
  • Sweets: Honey, jam, desserts
• Focus on total carbohydrate grams, not sugar content alone.

🧮 Calculate Carbohydrate Content

• Use food labels for packaged foods.
• Refer to carbohydrate reference books, mobile apps, or online tools for unpackaged items.
• Weigh or estimate portion sizes to improve accuracy.

⚖️ Estimate Standard 10g Carbohydrate Portions

Food Item	Approx. 10g Carbohydrate Serving
1 slice of bread	10 g
½ medium apple	10 g
⅔ cup raw carrots	10 g
½ banana	10–12 g
1 small potato (60 g)	10 g
⅓ cup cooked rice/pasta	10 g
1 small orange (100 g)	10 g
¾ cup air-popped popcorn	10 g
1 tbsp honey or jam	10 g
½ cup (125 mL) milk	10 g

💉 Determine the Insulin-to-Carbohydrate Ratio (ICR)

• Defines units of insulin per grams of carbs
• Example:
  • ICR = 1:10 → 1 unit of insulin for every 10 g of carbohydrates
• Often personalised:
  • May vary by time of day
  • May be adjusted based on insulin sensitivity

📊 Adjust Rapid-Acting Insulin Dose Based on Carb Intake

• Total Carbohydrate Intake ÷ ICR = Insulin Dose
• Example:
  • Meal contains 50 g carbs
  • ICR = 1:10
  • → 5 units of rapid-acting insulin required

✅ Additional Tips

• Encourage consistency in meal timing and carb content for basal-bolus regimens.
• Teach pattern recognition using SMBG or CGM data to refine ICRs.
• Consider individual insulin sensitivity, physical activity, stress, and illness when adjusting doses.

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💉 Continuous Subcutaneous Insulin Infusion (CSII)

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📌 Description

• Insulin pump delivers:
  • Continuous basal infusion of rapid-acting insulin (e.g. insulin aspart, lispro, glulisine)
  • Bolus doses before meals and for correction of hyperglycaemia
• Mimics physiological insulin delivery more closely than injections

⚙️ Insulin Delivery Components

🔹 Basal Insulin

• Delivered 24/7 at programmed rates
• Can have variable rates during the day to match circadian insulin needs

🔹 Bolus Insulin

• Given at mealtimes and for corrections
• Doses calculated using:
  • Insulin-to-Carbohydrate Ratio (ICR)
  • Insulin Sensitivity Factor (ISF) or correction factor

✅ Requirements for CSII Use

• High patient motivation and adherence
• Comprehensive training in:
  • Carbohydrate counting
  • Insulin dose calculation
  • Pump troubleshooting
• Close follow-up by a specialist diabetes team (e.g. endocrinologist, diabetes educator)

🔧 Logistics & Operation

• Uses a disposable infusion set with a subcutaneous cannula:
  • Changed every 2–3 days
• Pump worn externally (waistband, pocket, or clipped to clothing)

⚠️ Complications & Risks

• Site infections or abscesses
• Catheter kinking or blockage → insulin interruption → risk of DKA
• Pump failure → requires immediate access to backup (usually basal-bolus injections)

🚀 Advanced Pump Features

• Integration with CGM:
  • Real-time glucose data
  • Alarms for hypo/hyperglycaemia
• Automated insulin suspension for predicted low glucose
• Hybrid closed-loop systems (artificial pancreas):
  • Automatically adjust basal insulin based on CGM readings

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📊 Monitoring and Education Requirements

Monitoring and Education Requirements – CSII (Insulin Pump Therapy)

Aspect	Details	Applicability
Self-Monitoring of Blood Glucose (SMBG) / Continuous Glucose Monitoring (CGM)	– Essential for safe insulin pump use due to reliance on rapid-acting insulin only – SMBG: At least 4–6 times/day if not using CGM (pre-meal, post-meal, bedtime, and overnight if needed) – CGM: Strongly recommended; allows real-time data and alerts for hypoglycaemia/hyperglycaemia – Integrated CGM + CSII systems (e.g. hybrid closed-loop) improve control and reduce variability	T1DM: 🔴 Essential T2DM (on CSII): 🔴 Strongly recommended
Hypoglycaemia Education	– Critical due to increased risk of severe hypoglycaemia without long-acting insulin “buffer” – Patients and carers must know: – Symptoms of hypoglycaemia – Treatment (e.g., Rule of 15) – When to seek help – Consider glucagon emergency kit training	Both T1DM & T2DM
Sick Day Rules	– Illness increases insulin requirements even if appetite is reduced – Continue basal insulin at all times – Increase monitoring to every 2–4 hours – Watch for ketosis and dehydration – Have clear guidance on ketone testing and insulin dose adjustments	Both T1DM & T2DM (especially insulin-dependent)
Injection Technique	– Must still be taught despite pump use: – For emergency use if pump fails – For temporary insulin delivery if pump is removed (e.g. surgery, infection at site) – Include training on subcutaneous site rotation and injection devices	Both T1DM & T2DM
Regular Review	– At least 3-monthly review with diabetes team – Review includes: – SMBG/CGM data, HbA1c, time-in-range – Pump data download – Insulin settings: basal rates, insulin:carb ratios, correction factors – Lifestyle, activity, dietary adherence – Infusion site health	Both T1DM & T2DM
Emergency Plan / Backup Plan	– Always have a backup basal-bolus regimen ready: – Short-acting insulin for meals and correction – Long-acting insulin for basal needs if pump stops – Supply emergency contact numbers (educator, endocrinologist) – Carry extra cannulas, insulin pens, batteries	Both T1DM & T2DM

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🧠 Additional Educational Components to Reinforce:

• Understanding of insulin pharmacodynamics (especially for CSII users)
• Management of infusion site rotation to avoid lipohypertrophy or infections
• Data interpretation training (SMBG logs or CGM trend arrows)
• Use of pump features: temporary basal rates, dual/square boluses, and alarms
• Travel planning: crossing time zones, carrying supplies