How to adjust insulin for a patient on morning Mixtard (NPH insulin and regular insulin) and hydrocortisone, experiencing afternoon hypoglycemia?

Adjusting Insulin for Afternoon Hypoglycemia on Morning Mixtard and Hydrocortisone

Reduce the morning NPH component of Mixtard by 10-20% to address the afternoon hypoglycemia, as the NPH peaks 4-6 hours after administration and is causing excessive insulin action when steroid effect is waning. 1, 2

Understanding the Problem

• Morning-administered NPH insulin peaks at 4-6 hours after injection, which corresponds to afternoon timing 2
• Hydrocortisone administered in the morning creates a characteristic glycemic pattern with normal/mild fasting hyperglycemia, increasing hyperglycemia during the afternoon, and peaking in the evening 1
• The mismatch occurs because NPH peaks in the afternoon while the steroid's hyperglycemic effect is still building, creating a window of relative insulin excess 1, 2

Specific Adjustment Protocol

Immediate action:

• Reduce the NPH component of the morning Mixtard dose by 10-20% 1, 2
• If hypoglycemia recurs without clear cause, reduce by an additional 10-20% 1, 2
• Keep the regular insulin component unchanged initially, as it addresses breakfast coverage 1

Monitoring strategy:

• Check blood glucose every 2-4 hours for the first 24-48 hours after adjustment to identify patterns 2
• Target afternoon glucose of 140-180 mg/dL 2
• Watch specifically for the 2-6 PM window when NPH peaks 2

Alternative Regimen Considerations

If hypoglycemia persists despite dose reduction:

• Consider splitting to a twice-daily NPH regimen (2/3 morning, 1/3 evening) rather than using Mixtard 1, 2
• This allows independent adjustment of morning and evening NPH doses 1
• The conversion would use 80% of current total NPH dose, distributed as 2/3 before breakfast and 1/3 before dinner 1, 3

For steroid-induced hyperglycemia management:

• The morning NPH dose specifically targets the afternoon-to-evening hyperglycemic peak caused by hydrocortisone 2, 4
• However, if the steroid dose is being tapered, NPH requirements decrease proportionally (typically 10-20% reduction per significant steroid decrease) 2, 4

Common Pitfalls to Avoid

• Do not reduce the regular insulin component first - afternoon hypoglycemia indicates NPH excess, not prandial insulin excess 1, 2
• Do not wait to adjust - prior hypoglycemia blunts counterregulatory responses to subsequent episodes, increasing risk of severe hypoglycemia 1, 5
• Do not assume the problem is dietary - the pharmacokinetic mismatch between NPH peak and steroid effect is the primary issue 1, 2
• Avoid unit-for-unit conversions if switching insulin types - always use the 80% rule when converting from long-acting to NPH 1, 3

Coordination with Hydrocortisone Timing

• Ensure hydrocortisone is administered in the morning to match the NPH timing 2, 4
• If hydrocortisone is given in divided doses, the larger portion should be in the morning 2
• As hydrocortisone dose changes, reassess NPH requirements every 3 days 2

Special Considerations for Mixtard Users

• Mixtard combines NPH and regular insulin in fixed ratios (typically 70/30 or 50/50) 1
• Reducing the total Mixtard dose affects both components proportionally 1
• If independent adjustment of basal and prandial components is needed, transition to separate insulin formulations 1
• Some patients may benefit from switching to a self-mixed regimen where NPH and short-acting insulins can be adjusted separately 1