Diabetes – Insulin

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.

Types of Short-Acting Insulin

Type	Insulin Name	Brand Name	Onset	Duration
Rapid-Acting Insulin	Insulin Aspart	Novorapid®	1-20 minutes	3-5 hours
	Insulin Lispro	Humalog®	15 minutes	2-4 hours
	Insulin Glulisine	Apidra®	10-20 minutes	3-4 hours
Short-Acting Insulin	Insulin Regular (Neutral)	Actrapid®	30 minutes	6-8 hours
	Insulin Regular (Neutral)	Humulin R®	30 minutes	6-8 hours
Intermediate-Acting	Isophane Insulin (NPH)	Protaphane®	1-2 hours	12-18 hours
	Isophane Insulin (NPH)	Humulin NPH®	1-2 hours	12-18 hours
Long-Acting Insulin	Insulin Glargine	Lantus®, Optisulin®	1-2 hours	Up to 24 hours
	Insulin Detemir	Levemir®	1-2 hours	16-24 hours
	Insulin Glargine U300	Toujeo®	6 hours	Up to 36 hours
	Insulin Degludec	Tresiba®	1 hour	Up to 42 hours
Ultra-Long Acting	Insulin Degludec	Tresiba®	1 hour	Up to 42 hours

When to Start Insulin Therapy in Type 2 Diabetes (T2DM) https://www.racgp.org.au/afp/2015/may/the-introduction-of-insulin-in-type-2-diabetes-mel

Key Considerations for Insulin Initiation:

• Unusual in Newly Diagnosed T2DM: Initiating insulin at diagnosis is rare but should be considered if there is significant weight loss, severe hyperglycaemic symptoms, or marked ketonuria.
• Ketonuria/Ketoacidosis: May indicate Type 1 Diabetes (T1DM); consider testing pancreatic beta cell autoantibodies and C-peptide after stabilisation.
• Consultation with Endocrinologist: Recommended for acutely unwell patients who may require inpatient care.

Benefits of Early Good Glycaemic Control:

• Legacy Effect: Early control of hyperglycaemia can lead to long-term reductions in complications and mortality.
• Early Intervention: Can limit weight gain often seen with insulin therapy; early intervention is crucial to prevent therapeutic inertia.

Individualised Glycaemic Targets:

• Younger Patients: More stringent HbA1c targets are appropriate due to high lifetime risk of complications; early insulin introduction may be beneficial even if HbA1c is just above 7%.
• Elderly Patients: Higher HbA1c thresholds for insulin initiation may be appropriate, especially if the primary concern is macrovascular risk.

Barriers to Good Control:

• Adherence Issues: Consider patient fear of hypoglycaemia, depression, and lifestyle factors such as high intake of sugar-rich beverages.
• Persistent Elevated HbA1c: If elevated for 3 months or more despite non-insulin therapies, further pharmacological intervention is warranted.

Insulin vs. Newer Agents:

• Insulin as a Second-Line Option: Insulin is no longer seen as the last resort; it may be considered alongside newer agents based on clinical context.
• Expected Efficacy: Insulin offers the greatest HbA1c-lowering effect, particularly for HbA1c > 9% on maximal oral therapy.
• Specialist Consultation: Advisable for guidance on combining insulin with newer agents or confirming treatment suitability.

Patient Lifestyle Considerations:

• Lifestyle Alone Often Insufficient: Renewed focus on lifestyle changes may reduce HbA1c by less than 1% on average; should not delay pharmacological intensification.

How to start insulin

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.)

Identifying Blood Glucose Patterns to Decide Which Insulin to Use

1. Identify Patterns of Hyperglycaemia:
   • Focus on main periods of elevated blood glucose.
   • Aim to start with one insulin injection per day.
   • Self-monitoring of blood glucose (SMBG) is essential.
2. Testing Schedule:
   • Include a 3-day testing schedule with paired pre- and postprandial readings.
   • General targets for glucose levels:
     • Fasting and pre-prandial: 6–8 mmol/L
     • 2-hour postprandial: 6–10 mmol/L
3. Guide Insulin Regimen Based on Glucose Patterns:
   • Fasting Hyperglycaemia Management:
     • Basal/long-acting insulin is appropriate for fasting hyperglycaemia.
     • Pre-bed basal insulin regimen (Figure A) is the simplest approach.
     • Long-acting insulin analogues like glargine(e.g., Lantus) or detemir (e.g., Levemir) are preferred due to their smooth profiles and lower overnight hypoglycaemia risk.
     • Note: Glargine and detemir are not listed on the PBS for T2DM.
   • Postprandial Glucose Management:
     • Postprandial glucose excursions are problematic when readings exceed 10 mmol/L, with a rise of 2.5 mmol/L or more post-prandially (Figure B, C).
     • Basal insulins effectively normalize fasting glucose but do not control postprandial glucose levels.
     • Premixed insulin formulations are suitable for patients needing control of both fasting and postprandial glucose.
     • Premixed insulin analogues are preferred over human insulin due to a lower risk of hypoglycaemia.
4. Decide on Insulin Type:
   • Basal Insulin:
     • Good for normalising fasting glucose; consider analogues like glargine or detemir.
     • If meal patterns are erratic, basal insulin is the safest starting regimen.
   • Premixed Insulin:
     • Useful for fasting and postprandial coverage; appropriate for patients with consistent meal patterns.
     • Clinical trials show premixed analogues improve postprandial glucose compared to glargine but with slightly higher, though infrequent, hypoglycaemia.
     • Insulin preparations with 50% rapid-acting insulin may benefit those on high glycaemic index diets.
     • examples:
       • Insulin Lispro Mix 25/75 (Humalog Mix25®) 25% insulin lispro (rapid-acting) and 75% insulin lispro protamine suspension (intermediate-acting). Typically injected before meals to cover both meal-time and some basal insulin needs.
       • Insulin Lispro Mix 50/50 (Humalog Mix50®) 50% insulin lispro (rapid-acting) and 50% insulin lispro protamine suspension (intermediate-acting). suitable for those needing higher prandial insulin coverage, especially those with high carbohydrate or glycaemic index diets.
       • Insulin Aspart Mix 30/70 (NovoMix 30®) 30% insulin aspart (rapid-acting) and 70% insulin aspart protamine suspension (intermediate-acting).Suitable for most patients as a balanced option for both meal-time and basal insulin needs.
     • Disadvantages:
       • Less flexible in dosing adjustments for meals or activity.
       • Higher risk of hypoglycemia due to the fixed insulin components.
       • Does not allow for individualized bolus adjustments based on carbohydrate intake.
5. Starting Dose and Titration:
   • Basal insulin:
     • Basal insulin typically constitutes about 40-50% of the total daily insulin needs, with the remainder being covered by bolus (mealtime) insulin.
     • Initial Estimation:
       • Type 1 Diabetes: Total daily insulin requirement is usually 0.4 to 0.6 units per kilogram of body weight.
       • Type 2 Diabetes: For insulin-naïve patients, start with 0.1 to 0.2 units per kilogram of body weight. A typical starting basal dose is 10 units once daily
       • Example for Type 2 Diabetes:
         • If a patient weighs 80 kg, start with 0.2 units/kg:Basal dose = 80 kg × 0.2 units/kg = 16 units once daily.
   • Premixed Insulin Analogues:
     • initial total daily insulin dose is generally estimated based on the patient’s weight:
     • Initial Estimation:
       • Type 1 Diabetes: 0.4 to 0.6 units per kilogram of body weight per day.
       • Type 2 Diabetes: 0.3 to 0.5 units per kilogram of body weight per day, often starting at the lower end (0.3 units/kg/day) if the patient is insulin-naïve or overweight.
       • Split the Total Daily Dose into:
         • Morning Dose: 50-60% of the total daily dose, taken before breakfast.
         • Evening Dose: 40-50% of the total daily dose, taken before dinner.
         • Titration mainly focuses on long-acting components, with occasional checks at 2 hours postprandial or pre-bed to minimize hypoglycaemia.
6. Monitoring and Adjustment:
   • Regular testing of fasting and pre-dinner glucose levels for titration.
   • Adjust based on response to achieve target glucose levels without inducing hypoglycaemia.

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

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

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

Key Information to Provide on the First Day of Insulin Therapy

1. Insulin Administration:
   • Subcutaneous insulin injections using modern devices are generally easy for patients to manage.
   • Provide reassurance and focus on practical aspects of insulin delivery rather than detailed dietary changes at this stage.
2. Dietary Advice:
   • Emphasize the importance of regular meals and snacks containing carbohydrates.
   • Detailed dietary advice can be deferred to future consultations.
3. Hypoglycaemia Awareness:
   • Reinforce the “start low and go slow” approach to minimize the risk of hypoglycaemia, although it cannot be entirely eliminated.
   • Discuss symptoms and treatment of hypoglycaemia, including the “Rule of 15” for managing mild hypoglycaemia:
     • If blood glucose level (BGL) is <4.0 mmol/L, provide 15 grams of quick-acting carbohydrates (e.g., non-diet soft drink, fruit juice, glucose tablets).
     • Wait 15 minutes, recheck glucose, and repeat if necessary.
     • If the next meal is more than 15 minutes away, provide longer-acting carbohydrates (e.g., sandwich, fruit).
4. Titration of Insulin:
   • Plan for a follow-up review within 7 days to assess response and adjust insulin dose as needed.
   • Use a titration algorithm to adjust insulin based on the lowest BGL over the last 3 days:
     • Increase by 2–4 units if BGL remains above target.
     • Decrease insulin dose if BGL is consistently low (<4.0 mmol/L) or after a hypoglycaemic event.
   • Patients may be taught to self-titrate insulin with regular clinical reviews.
5. When to Stop Other Medications with Insulin Therapy:
   • Continue Metformin and Other Agents Initially: At insulin commencement, continuing these agents improves glucose levels from baseline.
   • Avoid Discontinuation of Oral Therapy Initially: Stopping oral agents can cause glucose rises, often misinterpreted as insulin failure.
   • Dose Adjustment: Discontinuation of oral agents may require a 20–30 unit increase in insulin dosage.
   • Oral Agents as Insulin-Sparing: Oral agents continue to provide an insulin-sparing effect.
   • Discontinuing Pioglitazone: May worsen edema when combined with insulin; consider discontinuation if no glycemic benefit.
   • Long-Term Practice: Continue at least metformin with insulin.
   • Sulphonylurea Withdrawal: Consider withdrawing when using pre-mixed insulin.
   • Newer Agents (DPP-4, SGLT-2, GLP-1RA): Usage depends on PBS guidelines and patient preference; beneficial in combination with insulin but consider hypoglycemia risks.
   • GLP-1RAs: Useful for weight-sparing effects, especially in insulin-induced weight gain.
   • DPP-4 Inhibitors: Insulin-sparing effect, less hypoglycemia but still possible; may prompt cessation if needed.
6. When to Consider More Complex Insulin Regimens:
   • Current Therapy: Patients typically use 20–30 units of insulin with oral agents when fasting/pre-prandial glucose is at target, but HbA1c remains high.
   • Twice Daily Insulin: Consider if HbA1c remains elevated.
   • Basal Plus Regimen: Add short-acting insulin before the main meal if post-prandial glucose control is needed.
   • Prandial Insulin Dosing: Detailed insulin-to-carbohydrate ratios usually unnecessary in T2DM; a prandial dose range for different meal sizes can be helpful.
7. Overcoming Inertia and Clinical Notes:
   • Early Introduction of Insulin Concept: Discuss insulin early, and administer a dummy saline injection to demystify the process.
   • First Injection Experience: Let the patient perform a dummy injection before explaining the device’s technicalities.
   • Needle Size: 6 mm needles are suitable for most patients.
   • Support: Diabetes nurse educators and dietitians provide valuable assistance.
   • Driving and Occupational Hazards: Review patient obligations related to insulin use.

Carbohydrate counting

Identify Carbohydrate Foods:

• Carbohydrates are found in foods such as bread, pasta, rice, fruits, vegetables, dairy, and sweets.
• Focus is on counting total carbohydrates, typically measured in grams.

Calculate Carbohydrate Content:

• Read food labels to determine the amount of carbohydrates per serving.
• Use carbohydrate counting books, apps, or online resources for foods without labels (e.g., fresh produce).
• Measure or estimate portion sizes to ensure accurate counting.

Determine Insulin-to-Carbohydrate Ratio (ICR):

• The insulin-to-carb ratio helps calculate how much insulin is needed to cover a specific amount of carbohydrates.
• Example: An ICR of 1:10 means 1 unit of insulin is needed for every 10 grams of carbohydrates consumed.
• 10 grams of carbohydrates
  • 1 Slice of Bread: A typical slice of white, whole wheat, or multigrain bread usually contains about 10 grams of carbohydrates.
  • Half a Medium Apple: A medium-sized apple (about 150 grams) contains around 20 grams of carbs, so half of it will be approximately 10 grams.
  • 2/3 Cup of Raw Carrots: This amount of raw carrots provides about 10 grams of carbohydrates.
  • Half a Banana: A medium banana typically has about 20-25 grams of carbs, so half of it will be close to 10 grams.
  • 1 Small Potato (about 60 grams): A small boiled or baked potato contains roughly 10 grams of carbohydrates.
  • 1/3 Cup of Cooked Rice or Pasta: This portion of cooked rice or pasta contains about 10 grams of carbs.
  • 1 Small Orange (about 100 grams): A small orange provides around 10 grams of carbohydrates.
  • 3/4 Cup of Popcorn (Air-Popped, Unsweetened): This amount of plain, air-popped popcorn has about 10 grams of carbohydrates.
  • 1 Tablespoon of Honey or Jam: Each tablespoon contains approximately 10 grams of carbohydrates.
  • Half a Cup of Milk (125 mL): Whether it’s whole, skim, or low-fat milk, this amount has about 10 grams of carbs.

Adjust Insulin Dose Based on Carb Intake:

• Once the total carbohydrate intake for a meal is calculated, adjust the rapid-acting insulin dose accordingly using the ICR.
• Example: If a meal contains 50 grams of carbohydrates and the ICR is 1:10, then 5 units of insulin are needed.

Continuous Subcutaneous Insulin Infusion (CSII)

• Description: Utilizes an insulin pump to deliver a continuous basal rate of short-acting insulin with bolus doses administered based on carbohydrate intake and blood glucose readings.
• Basal Insulin:
  • Delivered continuously throughout the day and night to mimic natural insulin release.
• Bolus Insulin:
  • Administered during meals and for correction of high blood glucose levels. Doses are calculated based on carbohydrate intake and insulin sensitivity factors.
• Requirements:
  • High motivation and commitment from the patient.
  • Ongoing education and support from a specialist diabetes team.
  • Close monitoring of glucose levels, accurate carbohydrate counting, and careful bolus dose adjustments.
• Logistics:
  • Uses disposable catheters that need to be replaced every 2-3 days.
• Complications:
  • Risks include injection site infections, abscesses, and catheter blockages.
  • Requires a backup plan (usually switching to a basal-bolus regimen) in case of pump failure.
• Advanced Features:
  • Modern pumps often integrate with continuous glucose monitors (CGMs) for real-time glucose monitoring and alarms for hypoglycemia or hyperglycemia.
  • Some pumps have automatic insulin delivery adjustments, such as suspending insulin in response to low glucose levels.