What adjustments should be made to a patient's 75/25 Humalog Mix (insulin lispro protamine/insulin lispro) regimen, taking 60 units twice daily, to mitigate nocturnal hypoglycemia?

Adjustment for Nocturnal Hypoglycemia on 75/25 Humalog Mix

Reduce the evening dose of 75/25 Humalog Mix by 10-20% (6-12 units from the current 60 units) to address the nocturnal hypoglycemia, as the 75% protamine component provides overnight basal coverage that is causing the middle-of-night blood sugar drops. 1

Understanding the Problem

The 75/25 Humalog Mix contains 75% insulin lispro protamine suspension (intermediate-acting) and 25% rapid-acting lispro 2. When taken at dinner:

• The 25% rapid-acting component covers the evening meal
• The 75% protamine component provides basal insulin coverage through the night 2
• Nocturnal hypoglycemia indicates excessive overnight insulin effect from the evening dose 1

Nocturnal hypoglycemia is common with premixed insulins, with reported incidence of 14-47%, and may be asymptomatic or present with nightmares, restless sleep, or morning headaches 1.

Specific Dose Adjustment Algorithm

Step 1: Immediate dose reduction

• Decrease the evening (dinner) dose by 10-20% initially 1
• This means reducing from 60 units to 48-54 units at the evening meal
• Keep the morning dose at 60 units initially, as this is not contributing to nocturnal hypoglycemia 1

Step 2: Monitor and titrate

• Check fasting blood glucose daily to guide further adjustments 3
• If nocturnal hypoglycemia persists, reduce the evening dose by an additional 2-4 units every 3-4 days 3
• If fasting glucose becomes elevated (>130 mg/dL), consider smaller reductions or alternative strategies 3

Alternative Strategies if Simple Reduction Fails

Consider switching the evening insulin formulation:

• Replace evening 75/25 with 50/50 Humalog Mix (50% rapid-acting, 50% protamine) 4, 5
• The 50/50 formulation has less protamine component, reducing overnight insulin effect and showing fewer nocturnal hypoglycemia episodes 5
• Studies demonstrate that 50/50 mix achieves better glycemic control with reduced nocturnal hypoglycemia compared to 75/25 5

Timing adjustment:

• Move the evening injection earlier (before dinner rather than at bedtime) if not already doing so 6
• This allows the protamine peak to occur earlier in the night 6

Critical Monitoring Requirements

• Check blood glucose at 2-3 AM for several nights to confirm resolution of nocturnal hypoglycemia 1
• Monitor fasting glucose daily to ensure it remains <130 mg/dL 3
• Assess for hypoglycemia symptoms at every visit 1
• Check for hypoglycemia unawareness, which increases risk of severe episodes 1

Common Pitfalls to Avoid

Do not reduce both doses simultaneously - The morning dose is not causing nocturnal hypoglycemia; only adjust the evening dose 1

Do not skip the evening dose entirely - This will cause uncontrolled fasting hyperglycemia and increase risk of DKA 1

Do not ignore asymptomatic nocturnal hypoglycemia - It may present only as morning headaches or elevated fasting glucose (rebound hyperglycemia) 1

Ensure consistent meal timing - Premixed insulins require relatively consistent mealtimes and carbohydrate intake 1

Treatment of Hypoglycemic Episodes

If nocturnal hypoglycemia occurs before adjustment:

• Treat with 15-20g of fast-acting carbohydrates 3
• Recheck blood glucose after 15 minutes 3
• For severe hypoglycemia with altered consciousness, administer glucagon 1 mg subcutaneously 1