How to treat diabetes with only Regular insulin, Mixtard (biphasic insulin) and Actrapid (fast-acting insulin) available?

Treatment of Diabetes with Regular Insulin, Mixtard, and Actrapid

When limited to Regular insulin (short-acting), Mixtard (premixed biphasic insulin), and Actrapid (fast-acting regular insulin), start with twice-daily Mixtard 30/70 (30% regular, 70% NPH) before breakfast and dinner, then intensify to a basal-bolus regimen using Actrapid/Regular insulin for prandial coverage if glycemic targets are not met. 1

Initial Insulin Regimen

Starting with Mixtard (Premixed Insulin)

• Begin with Mixtard 30/70 administered twice daily: 2/3 of total daily dose before breakfast and 1/3 before dinner 1
• Initial total daily dose: Start with 10 units per day OR 0.1-0.2 units/kg body weight 1
• Titration approach: Increase by 2 units every 3 days to reach fasting plasma glucose target without hypoglycemia 1
• For hypoglycemia: If no clear cause identified, reduce the corresponding dose by 10-20% 1

When to Start with Insulin Immediately

• Severe hyperglycemia: A1C >10% (>86 mmol/mol) or blood glucose ≥300 mg/dL (≥16.7 mmol/L) 1
• Symptomatic hyperglycemia: Presence of ketosis, unintentional weight loss, or catabolic features 1
• Type 1 diabetes possibility: When diagnosis is uncertain 1

Intensification Strategy When A1C Remains Above Target

Option 1: Add Prandial Regular Insulin/Actrapid

If twice-daily Mixtard fails to achieve glycemic goals, add prandial Regular insulin or Actrapid before meals: 1

• Starting dose: 4 units before the largest meal OR 10% of basal insulin dose 1
• Consider reducing basal dose: Lower by 4 units per day or 10% when adding prandial insulin if A1C <8% 1
• Titration: Increase by 1-2 units or 10-15% twice weekly based on postprandial glucose 1
• Stepwise addition: Start with one injection at the largest meal, then add to additional meals as needed 1

Option 2: Self-Mixed/Split Insulin Regimen

Convert to a self-mixed regimen combining NPH component (from Mixtard concept) with Regular insulin/Actrapid: 1

• Total NPH-equivalent dose: Use 80% of current total Mixtard dose 1
• Distribution: 2/3 before breakfast, 1/3 before dinner 1
• Add Regular insulin/Actrapid: 4 units with each injection OR 10% of the reduced NPH-equivalent dose 1
• Advantage: Allows separate adjustment of short-acting and intermediate-acting components 1

Option 3: Full Basal-Bolus Regimen

Progress to basal insulin coverage with prandial Regular insulin/Actrapid before each meal: 1

• Basal component: Can use the NPH component concept from Mixtard, administered once or twice daily 1
• Prandial component: Regular insulin/Actrapid before breakfast, lunch, and dinner 1
• Titrate each component independently based on fasting and postprandial glucose patterns 1

Practical Considerations with Available Insulins

Understanding Your Available Insulins

• Actrapid and Regular insulin are essentially the same: Both are short-acting human regular insulin with onset in 30 minutes, peak at 2-3 hours, duration 6-8 hours 1, 2
• Mixtard contains both components: Regular insulin (30%) for prandial coverage and NPH (70%) for basal coverage 3
• Mixtard 50/50 alternative: If available, contains 50% regular and 50% NPH, providing more prandial coverage for post-breakfast hyperglycemia 4, 3

Timing of Administration

• Regular insulin/Actrapid: Administer 30 minutes before meals (not immediately before like rapid analogs) 1
• Mixtard: Give immediately before breakfast and dinner 1
• Avoid Regular insulin at bedtime: Risk of nocturnal hypoglycemia due to prolonged action 5

Monitoring and Adjustment

Blood Glucose Targets for Titration

• Fasting plasma glucose: Use to titrate basal component (NPH portion of Mixtard or separate basal insulin) 1
• Postprandial glucose: Use to titrate prandial Regular insulin/Actrapid doses 1
• Target postprandial glucose: <180 mg/dL (10 mmol/L) at 1-2 hours after meals 1

Correction Insulin Scale with Regular Insulin/Actrapid

For hyperglycemia correction between meals (use every 4-6 hours, not more frequently due to Regular insulin's duration): 5

• Blood glucose 5.5-8.3 mmol/L (99-149 mg/dL): 2 units 5
• Blood glucose 8.4-11.1 mmol/L (151-200 mg/dL): 4 units 5
• Blood glucose 11.2-13.9 mmol/L (202-250 mg/dL): 6 units 5
• Blood glucose 14.0-16.7 mmol/L (252-300 mg/dL): 8 units 5
• Blood glucose 16.8-19.4 mmol/L (302-349 mg/dL): 10 units 5
• Blood glucose >19.4 mmol/L (>349 mg/dL): 12 units and contact physician 5

Adjust for insulin sensitivity: Reduce by 50% for insulin-sensitive patients; increase by 50-100% for insulin-resistant patients 5

Critical Pitfalls to Avoid

Hypoglycemia Risk

• Regular insulin has longer duration than rapid analogs: Peak effect at 2-3 hours with duration up to 8 hours increases hypoglycemia risk, especially overnight 1
• Monitor closely: Hypoglycemia is 4-6 times more common with basal-bolus regimens compared to simple insulin scales 5
• Ensure adequate carbohydrate intake: Regular insulin requires consistent meal timing and carbohydrate content 1

Dosing Errors

• Do not use correction doses more frequently than every 4-6 hours: Regular insulin's prolonged action causes insulin stacking 5
• When converting from Mixtard to split regimen: Use only 80% of previous total dose to avoid hypoglycemia 1
• Reduce basal insulin when adding prandial: Prevent excessive total daily insulin dose 1

Overbasalization

• Watch for signs: Basal dose >0.5 units/kg/day, elevated bedtime-to-morning glucose differential, or frequent hypoglycemia 1
• Action needed: Add or increase prandial insulin rather than continuing to increase basal component 1

Algorithm Summary

1. Start: Mixtard 30/70 twice daily (2/3 AM, 1/3 PM) at 10 units total or 0.1-0.2 units/kg 1
2. Titrate: Increase by 2 units every 3 days targeting fasting glucose 1
3. If A1C remains elevated: Add Regular insulin/Actrapid 4 units before largest meal 1
4. If still inadequate: Progress to Regular insulin/Actrapid before each meal with basal coverage 1
5. Alternative: Convert to self-mixed regimen (80% of total dose as NPH-equivalent, split 2/3 AM and 1/3 PM, plus Regular insulin with each) 1