NPH Insulin Dose Adjustment with Prednisone Increase
When increasing prednisone from 10 mg to 25 mg daily, increase NPH insulin from 5 units to approximately 12-13 units, administered in the morning to match the peak hyperglycemic effect of prednisone. 1
Rationale for Dose Calculation
The dose adjustment is based on the principle that insulin requirements increase proportionally with glucocorticoid dose escalation:
For steroid-induced hyperglycemia, insulin requirements typically increase by 40-60% above baseline when glucocorticoid doses are elevated. 1, 2
The 2.5-fold increase in prednisone (from 10 mg to 25 mg) necessitates approximately a 2.5-fold increase in NPH insulin (from 5 units to 12-13 units), though this should be adjusted based on glucose monitoring. 1
NPH insulin is specifically recommended for once-daily prednisone because its intermediate-acting profile peaks at 4-6 hours, aligning with prednisone's peak hyperglycemic effect. 3, 1
Algorithmic Approach to NPH Adjustment
Step 1: Calculate Initial Dose Increase
- Start with a proportional increase based on the steroid dose change: 5 units × (25 mg/10 mg) = 12.5 units 1
- Round to practical dosing: 12-13 units NPH in the morning 1
Step 2: Timing of Administration
- Administer NPH insulin in the morning (between 0600-0800 hours) to coincide with prednisone administration. 1, 4
- This timing is critical because prednisone causes disproportionate hyperglycemia during the day, with blood glucose often normalizing overnight. 3, 1
Step 3: Add Prandial Coverage if Needed
- For higher doses of glucocorticoids like 25 mg prednisone, increasing doses of prandial and correctional insulin are often needed in addition to NPH. 3, 1
- Consider adding rapid-acting insulin at meals using a 1:10 carbohydrate ratio (1 unit per 10g carbohydrate). 1
- Use correction insulin at 1 unit for every 40-50 mg/dL above target (150 mg/dL), with more aggressive correction in afternoon/evening when steroid effect peaks. 1
Monitoring Protocol
Monitor blood glucose every 2-4 hours initially, with special attention to afternoon and evening values when steroid effect peaks: 1
- Target blood glucose range: 80-180 mg/dL 3, 1
- If afternoon/evening glucose remains >180 mg/dL despite NPH adjustment, increase the NPH dose by 2 units every 1-3 days. 1, 2
- If fasting glucose is <80 mg/dL, reduce NPH by 10-20% to prevent nocturnal hypoglycemia. 1
Evidence Supporting This Approach
A randomized controlled trial demonstrated that an NPH insulin-based protocol significantly improved glycemic control in hospitalized patients receiving corticosteroids, with mean blood glucose 226 mg/dL in the NPH protocol group versus 269 mg/dL in usual care. 4
The study used 0.15 U/kg NPH for low-dose corticosteroids (10-40 mg prednisone equivalent), which would translate to approximately 10-15 units for an average 70-80 kg patient. 4
Critical Pitfalls to Avoid
Do not rely solely on fasting glucose to guide NPH dosing in steroid-induced hyperglycemia, as this will lead to under-treatment of daytime hyperglycemia and potential nocturnal hypoglycemia. 1
Do not use only long-acting basal insulin (like glargine) without adding NPH, as this may lead to inadequate coverage of daytime hyperglycemia caused by prednisone. 1, 5
Insulin requirements typically decrease rapidly after steroid discontinuation or dose reduction, requiring prompt dose adjustments to avoid hypoglycemia. 1, 2
Adjustments based on anticipated changes in glucocorticoid dosing and point-of-care glucose test results are critical. 3
Alternative Dosing Consideration
If the patient is insulin-naive, an initial NPH dose of 0.1-0.2 units/kg per day is recommended, which for a 70 kg patient would be 7-14 units. 1 However, since this patient is already on 5 units with 10 mg prednisone, the proportional increase to 12-13 units is more appropriate.