How should a patient's insulin regimen be adjusted when starting nighttime prednisone, given they currently take long-acting insulin (e.g. insulin glargine) in the morning and regular insulin (e.g. short-acting insulin) before meals?

Insulin Adjustment for Nighttime Prednisone

When starting nighttime prednisone in a patient on morning long-acting insulin and premeal regular insulin, increase the morning long-acting insulin dose by at least 30-50% and monitor closely for daytime hyperglycemia, as prednisone causes peak hyperglycemia between midday and midnight rather than overnight. 1

Understanding Prednisone's Glycemic Impact

Prednisone causes hyperglycemia predominantly between midday and midnight, not overnight 1. This timing mismatch is critical because:

• Your current regimen (morning long-acting insulin) provides relatively flat 24-hour coverage, which will undertreated the daytime hyperglycemia caused by nighttime prednisone 1
• The hyperglycemic effect peaks during waking hours when prednisone is metabolized, regardless of when the dose is taken 1

Specific Insulin Adjustment Strategy

Initial Dose Increase

Start with 0.5 units/kg total daily insulin if insulin-naive, or increase current total daily insulin by at least 30% (preferably 50% or more) when adding prednisone ≥20 mg daily 1. This is substantially more aggressive than typical adjustments because prednisone-induced hyperglycemia is severe 1.

Distribution of Insulin Doses

• Keep your long-acting insulin in the morning - this timing is appropriate and does not need to change 2, 3
• Increase the morning long-acting insulin dose by 30-50% to provide additional basal coverage during the day when prednisone causes peak hyperglycemia 1
• Increase premeal regular insulin doses by 30-50% as well, since postprandial excursions will be significantly worse 1

Alternative Consideration: NPH vs Long-Acting Analog

Consider switching from once-daily long-acting insulin (glargine) to twice-daily NPH insulin if hyperglycemia remains poorly controlled 1. The research specifically comparing isophane (NPH) to glargine-based regimens for prednisone-induced hyperglycemia found no significant difference in efficacy or safety, but NPH's peaked action profile may better match prednisone's daytime hyperglycemic effect 1.

Monitoring and Titration

Frequency of Adjustments

• Check blood glucose before each meal and at bedtime 1
• Make larger insulin dose adjustments than usual - the study data suggest that typical conservative titration (2 units every 3 days) is insufficient for prednisone-induced hyperglycemia 1
• Adjust every 2-3 days rather than weekly, as prednisone's effect is immediate and profound 1

Hypoglycemia Risk

The risk of nocturnal hypoglycemia is actually lower than expected because prednisone's hyperglycemic effect, while predominantly daytime, still provides some overnight elevation 1. However:

• Monitor for hypoglycemia <80 mg/dL (4.4 mmol/L) 4
• If ≥2 episodes per week occur, reduce the corresponding insulin dose by 10-20% 4

Critical Pitfall to Avoid

Do not use rapid-acting or short-acting insulin at bedtime without food intake 4, 5. Since prednisone causes daytime rather than nighttime hyperglycemia, adding bedtime short-acting insulin would cause nocturnal hypoglycemia without addressing the actual problem 1.

When Prednisone Dose Changes

As prednisone is tapered, reduce insulin doses proportionally 1. The study showed that when prednisone doses decreased over 3 days, insulin requirements changed accordingly (P = 0.02) 1. Plan to decrease total daily insulin by approximately 30-50% as prednisone is discontinued, monitoring closely for hypoglycemia 1.