In a 48‑year‑old female, weight 75 kg (BMI 26), with normal renal function (serum creatinine 0.88 mg/dL), near‑normal hemoglobin A1c 5.7 %, anemia (hemoglobin 8.2 g/dL), liver cirrhosis, left adrenal adenoma, status post liver transplant, and on prednisone 25 mg daily, what initial neutral protamine Hagedorn (NPH) basal insulin dose, carbohydrate‑to‑insulin ratio, and correction factor should be used?

Initial NPH Insulin Dosing for Steroid-Induced Hyperglycemia Post-Liver Transplant

Start NPH insulin at 15 units administered in the morning (at the same time as prednisone 25 mg), use a carbohydrate ratio of 1:10 (1 unit per 10 grams of carbohydrate), and implement a correction scale of 1 unit for every 40-50 mg/dL above 150 mg/dL, with more aggressive correction in the afternoon and evening. 1

Rationale for NPH Insulin Dosing

Calculating the Initial NPH Dose

• For steroid-induced hyperglycemia, the American Diabetes Association recommends NPH insulin at 0.1-0.2 units/kg per day, administered in the morning to coincide with prednisone administration. 1
• At 75 kg body weight, this translates to 7.5-15 units daily; given the moderate prednisone dose (25 mg) and near-normal baseline A1c (5.7%), starting at 15 units is appropriate. 1
• NPH insulin peaks at 4-6 hours after administration, which aligns perfectly with the peak hyperglycemic effect of morning prednisone that occurs 4-6 hours post-dose. 2, 1

Why NPH Over Long-Acting Basal Insulin

• Morning-administered prednisone causes disproportionate hyperglycemia during the day (particularly afternoon and evening), with blood glucose often normalizing overnight regardless of treatment. 2, 1
• Long-acting basal insulin would provide excessive overnight coverage when the steroid effect has waned, increasing nocturnal hypoglycemia risk. 3
• NPH is specifically recommended because its intermediate-acting profile matches the pharmacokinetics of daily prednisone therapy. 1, 4

Carbohydrate Ratio and Correction Scale

Carbohydrate-to-Insulin Ratio

• Start with a ratio of 1:10 (1 unit of rapid-acting insulin per 10 grams of carbohydrate) for meal coverage. 1
• This ratio should be applied at lunch and dinner when steroid-induced hyperglycemia is most pronounced. 1
• For high-dose glucocorticoids, insulin requirements typically increase by 40-60% above standard dosing, but at 25 mg prednisone, the 1:10 ratio is a reasonable starting point. 2, 1

Correction Factor (Sensitivity Factor)

• Use an initial correction scale of 1 unit of rapid-acting insulin for every 40-50 mg/dL above target (150 mg/dL). 1
• More aggressive correction may be needed in the afternoon and evening when steroid effect peaks (approximately 6-9 hours after morning prednisone). 1, 4
• Avoid correction insulin overnight, as glucose typically normalizes during sleep with prednisone-induced hyperglycemia. 2, 1

Monitoring Protocol

Blood Glucose Monitoring Schedule

• Monitor blood glucose every 2-4 hours initially, with special attention to afternoon and evening values when steroid effect peaks. 1, 4
• The most important reading is 2 hours after lunch (approximately 2-3 PM), which captures the peak steroid-induced hyperglycemia. 4
• Target blood glucose range should be 100-180 mg/dL (5.6-10.0 mmol/L) throughout the day. 2, 1, 4

Dose Titration Strategy

• Increase NPH insulin by 2 units every 3 days until target blood glucose is achieved. 4, 3
• If overnight hypoglycemia occurs, reduce the NPH dose by 10-20%. 4
• Daily insulin adjustments should be guided by point-of-care glucose values and any anticipated changes in steroid dosing. 2, 4

Special Considerations for This Patient

Post-Liver Transplant Factors

• Liver transplant recipients maintained on prolonged corticosteroid immunosuppressive treatment commonly develop functional adrenal gland atrophy, with prevalence around 26%. 5
• The patient's normal creatinine (0.88 mg/dL) indicates adequate renal function for insulin clearance, requiring no dose reduction. 2
• Hemoglobin 8.2 g/dL suggests anemia, which may affect A1c reliability; actual glycemic control may be slightly worse than the 5.7% A1c suggests. 2

Cirrhosis and Prednisone Metabolism

• Patients with liver cirrhosis have impaired conversion of prednisone to prednisolone (the active form), which may reduce the hyperglycemic effect compared to patients with normal liver function. 6
• However, post-transplant patients have restored liver function, so normal prednisone-to-prednisolone conversion should be expected. 7
• Most hemodynamic and humoral abnormalities of cirrhosis are reversed within 2 weeks after liver transplant. 7

BMI and Weight Considerations

• At BMI 26 (slightly overweight), this patient has mild insulin resistance independent of steroid effects. 5
• Weight gain after liver transplant is associated with increased risk of functional adrenal gland atrophy and may increase insulin requirements. 5

Critical Pitfalls to Avoid

Common Errors in Steroid-Induced Hyperglycemia Management

• Do NOT rely solely on fasting glucose to guide NPH dosing, as this will miss the peak hyperglycemic effect of steroids and lead to undertreatment of daytime hyperglycemia. 1, 4
• Avoid using only sliding-scale correction insulin without scheduled insulin, as this approach is associated with poor glycemic control and is discouraged in guidelines. 4
• Do NOT continue the same insulin doses when prednisone is tapered; insulin requirements decrease rapidly after steroid dose reduction, and failure to adjust causes severe hypoglycemia. 1, 4

Monitoring for Hypoglycemia

• Relying solely on long-acting insulin without adding NPH may lead to inadequate coverage of daytime hyperglycemia while causing nocturnal hypoglycemia. 1
• Monitor for overnight hypoglycemia, especially if the patient experiences unexplained morning hyperglycemia (Somogyi effect). 4

Anticipated Dose Adjustments

When Prednisone is Tapered

• Insulin requirements typically decrease rapidly after steroid discontinuation, requiring prompt dose adjustments to avoid hypoglycemia. 1, 4
• Reduce NPH insulin by 10-20% when tapering glucocorticoids to prevent hypoglycemia. 1
• Many liver transplant recipients can be successfully withdrawn from corticosteroids 6 months or more post-transplant, at which point insulin may be discontinued entirely if baseline diabetes control was good. 8

If Hyperglycemia Persists

• If afternoon/evening glucose remains >180 mg/dL despite initial NPH dosing, increase NPH by 2 units every 3 days. 4, 3
• Consider adding prandial rapid-acting insulin at lunch and dinner if post-prandial glucose exceeds 180 mg/dL. 4
• For persistent glucose >270 mg/dL (>15 mmol/L), seek endocrinology consultation. 4