What are the next steps for a patient with type 2 diabetes on 80mg of prednisone (corticosteroid), experiencing hyperglycemia despite high doses of NPH (neutral protamine Hagedorn) insulin and regular insulin?

Management of Steroid-Induced Hyperglycemia in Type 2 Diabetes

For this patient with type 2 diabetes on high-dose prednisone with persistent hyperglycemia despite NPH and regular insulin, the most appropriate next step is to convert to a twice-daily NPH regimen while continuing prandial insulin coverage, with 2/3 of the total NPH dose given in the morning and 1/3 at bedtime.

Current Situation Assessment

The patient is experiencing significant hyperglycemia (peaks >400 mg/dL) despite:

• 80 mg prednisone (tapering by 10 mg/week)
• 80 units of NPH insulin administered with prednisone
• Regular insulin before meals (1 unit for every 25 mg/dL above 130 mg/dL)

Recommended Management Strategy

Step 1: Convert to Twice-Daily NPH Regimen

• Total daily NPH dose = 80% of current NPH dose (64 units) 1
• Morning dose = 2/3 of total (approximately 43 units) 1
• Evening dose = 1/3 of total (approximately 21 units) 1

Step 2: Continue Prandial Insulin Coverage

• Maintain the current sliding scale of regular insulin (1 unit per 25 mg/dL above 130 mg/dL)
• Consider increasing the prandial insulin dose if hyperglycemia persists 1

Step 3: Titration Strategy

• Adjust NPH doses based on blood glucose patterns:
  • Morning NPH: Adjust based on afternoon and evening glucose readings
  • Evening NPH: Adjust based on fasting and morning glucose readings
• Increase doses by 10-15% every 2-3 days until target glucose range is achieved 1

Rationale for This Approach

1. Pharmacokinetic Matching: NPH insulin has a peak action at 4-6 hours after administration, which aligns with the hyperglycemic effect of prednisone when given concomitantly 1. This makes NPH particularly suitable for managing steroid-induced hyperglycemia.

2. Timing of Hyperglycemia: Glucocorticoids like prednisone cause disproportionate hyperglycemia during the day, with glucose levels often normalizing overnight 1. The twice-daily NPH regimen addresses this pattern by providing more insulin coverage during daytime hours.

3. Evidence Base: The ADA guidelines specifically recommend twice-daily NPH insulin for patients on glucocorticoid therapy, noting that "NPH is usually administered in addition to daily basal-bolus insulin" 1.

4. Safety Considerations: The split NPH dosing (2/3 morning, 1/3 evening) reduces the risk of overnight hypoglycemia while providing adequate coverage during the day when steroid-induced hyperglycemia is most pronounced 2.

Additional Considerations

• Monitoring: Frequent blood glucose monitoring (before meals and at bedtime) is essential during this transition period 1

• Prednisone Taper: As the prednisone dose decreases (10 mg/week), insulin requirements will also decrease. Plan to reduce insulin doses proportionally with the steroid taper 1

• Alternative Options: If the twice-daily NPH regimen fails to achieve adequate control, consider:

  • Adding a GLP-1 receptor agonist if not contraindicated 1, 3
  • Converting to a full basal-bolus regimen with more aggressive prandial coverage 1
  • Using premixed insulin (e.g., 70/30) before breakfast and dinner 2

• Avoid Long-Acting Analogs: Evidence suggests that glargine may be less effective than NPH for steroid-induced hyperglycemia due to its flat action profile compared to the peaked effect of NPH that better matches steroid-induced glucose excursions 4

By implementing this structured approach with twice-daily NPH insulin plus prandial coverage, you should be able to achieve better glycemic control in this challenging clinical scenario of steroid-induced hyperglycemia.