What is the optimal evening insulin dose for a patient on hydrocortisone (cortisol) therapy, with a history of hypoglycemia after increasing their morning Mixtard (insulin) dose from 35 to 37 units, to prevent both hypoglycemia and hyperglycemia?

Evening Insulin Dose for Hydrocortisone-Treated Patient with Hypoglycemia History

For a patient on hydrocortisone therapy who experienced hypoglycemia after increasing morning Mixtard from 35 to 37 units, reduce the morning dose back to 35 units and increase the evening Mixtard dose by 2-4 units to address afternoon/evening hyperglycemia caused by hydrocortisone's peak effect. 1

Understanding Glucocorticoid-Induced Hyperglycemia Patterns

Hydrocortisone causes disproportionate hyperglycemia during daytime hours, with peak effects 4-6 hours after morning administration, while patients frequently reach normal glucose levels overnight regardless of treatment. 1 This creates a specific pattern where:

• Morning cortisol levels are physiologically low (early morning is the time of highest insulin sensitivity), placing patients at risk for nocturnal hypoglycemia 2
• Afternoon and evening hyperglycemia predominate due to hydrocortisone's pharmacologic action lasting through the day 1
• The hyperglycemic effect peaks between midday and midnight 3

Specific Insulin Adjustment Strategy

Immediate Dose Modifications

Reduce the morning Mixtard dose back to 35 units to prevent recurrent morning/nocturnal hypoglycemia. 1 The hypoglycemia you experienced indicates the 37-unit morning dose exceeded your basal insulin needs during the period of highest insulin sensitivity. 2

Increase the evening Mixtard dose by 2-4 units to address the afternoon/evening hyperglycemia caused by hydrocortisone. 1, 4 For patients on morning steroid regimens, NPH insulin (the intermediate-acting component of Mixtard) administered in the evening provides appropriate coverage for daytime hyperglycemia. 1

Rationale for NPH/Mixtard Timing

Because NPH action peaks 4-6 hours after administration, evening dosing provides maximal insulin effect during the afternoon and evening when hydrocortisone-induced hyperglycemia is most pronounced. 1 This approach has been validated in randomized trials showing that isophane (NPH)-based regimens effectively manage steroid-induced hyperglycemia without increasing hypoglycemia risk. 3

Monitoring and Titration Protocol

• Check fasting glucose daily to ensure the reduced morning dose prevents nocturnal hypoglycemia 4
• Monitor pre-dinner and bedtime glucose to assess adequacy of the increased evening dose 4
• Adjust the evening dose by 2 units every 3 days based on afternoon/evening glucose patterns, targeting pre-dinner glucose of 80-130 mg/dL 4
• If hypoglycemia recurs, reduce the relevant dose by 10-20% immediately 5

Critical Threshold Considerations

When total daily insulin exceeds 0.5 units/kg/day and glucose control remains inadequate, adding rapid-acting prandial insulin before the largest meal becomes more appropriate than continuing to escalate Mixtard doses alone. 5 However, given your recent hypoglycemia, focus first on optimizing the twice-daily Mixtard regimen before considering intensification.

Hydrocortisone-Specific Adjustments

For patients with diabetes on steroids, adding 0.1-0.3 units/kg/day of intermediate-acting insulin (like the NPH component in Mixtard) to the usual insulin regimen is recommended, with doses determined by steroid dose and oral intake. 1, 5 Insulin requirements can decline rapidly after hydrocortisone is stopped, so doses must be adjusted accordingly. 1

Common Pitfalls to Avoid

• Do not increase the morning dose further despite afternoon hyperglycemia—this will worsen nocturnal hypoglycemia risk 1, 2
• Do not use sulfonylureas in combination with steroids and insulin, as this increases hypoglycemia risk 1
• Do not rely on correction insulin alone—scheduled basal-bolus or twice-daily premixed regimens are superior to sliding scale monotherapy 1, 5
• Anticipate changing insulin needs as hydrocortisone doses are tapered, requiring frequent dose adjustments 1

Alternative Consideration

If twice-daily Mixtard proves insufficient despite optimization, consider switching to a basal-bolus regimen with long-acting basal insulin plus rapid-acting prandial insulin at meals. 1, 5 For higher doses of glucocorticoids, increasing doses of prandial and correctional insulin are often needed in addition to basal insulin. 1