In an adult with type 2 diabetes, weight 95 kg, BMI 28, taking prednisolone 60 mg at 8 am and neutral protamine Hagedorn (NPH) insulin 20 units at the same time with a carbohydrate‑to‑insulin ratio of 1 unit per 10 g, and having capillary glucose 201 mg/dL at noon and 325 mg/dL at 4 pm, how should I adjust his insulin regimen?

Immediate Insulin Regimen Adjustment for Prednisone-Induced Hyperglycemia

Increase the morning NPH dose to 30 units and add 10 units of rapid-acting insulin before lunch to address the severe afternoon hyperglycemia caused by prednisone 60 mg taken at 8 AM. 1, 2

Understanding the Problem

Your patient's glucose pattern—201 mg/dL at noon and 325 mg/dL at 4 PM—reflects the classic circadian pattern of prednisone-induced hyperglycemia, which causes disproportionate afternoon and evening hyperglycemia when the steroid is taken in the morning. 2, 3, 4, 5 The current NPH 20 units at 8 AM is profoundly inadequate for a 95 kg patient on prednisone 60 mg daily. 2, 3

Morning-dosed prednisone peaks 4–6 hours after administration, driving hepatic glucose production and insulin resistance predominantly between midday and midnight. 3, 4, 5 NPH insulin given at breakfast has a pharmacokinetic profile that peaks 4–8 hours post-injection, theoretically matching this hyperglycemic pattern, but your patient's current dose is far too low. 2, 3, 4

Specific Insulin Adjustments Required

Morning NPH Insulin

• Increase NPH from 20 units to 30 units at 8 AM (a 50% increase) to provide adequate basal coverage during the critical afternoon period when prednisone drives maximal hyperglycemia. 2, 3
• For prednisone-induced hyperglycemia, the recommended starting insulin dose is 0.4–0.5 units/kg/day total, which for your 95 kg patient equals 38–48 units daily. 3, 6, 5
• Morning NPH should constitute approximately 60–70% of the total daily dose in a twice-daily NPH regimen, but when prednisone is given in the morning, a single morning NPH dose can be used at 70% of the calculated total. 2, 7

Add Prandial Coverage at Lunch

• Start 10 units of rapid-acting insulin (lispro or aspart) before lunch to directly address the noon glucose of 201 mg/dL and prevent the 4 PM spike to 325 mg/dL. 1, 5
• Patients on high-dose prednisone require 40–60% more prandial insulin than typical basal-bolus regimens because of the marked postprandial insulin resistance induced by glucocorticoids. 8, 5
• Administer the rapid-acting insulin 0–15 minutes before lunch for optimal postprandial control. 1, 8

Correction Insulin Protocol

• Add 2 units of rapid-acting insulin for pre-meal glucose >250 mg/dL and 4 units for glucose >350 mg/dL, in addition to scheduled doses. 1, 8
• Given the 4 PM glucose of 325 mg/dL, implement correction dosing at dinner as well: start with 8–10 units of rapid-acting insulin before dinner plus 2 units correction (total 10–12 units). 1, 5

Titration Protocol Over the Next 3–5 Days

NPH Titration

• Increase morning NPH by 4 units every 3 days if pre-lunch glucose remains ≥180 mg/dL. 1, 2
• Increase by 2 units every 3 days if pre-lunch glucose is 140–179 mg/dL. 1, 2
• Target pre-lunch glucose 80–130 mg/dL. 1, 2

Prandial Insulin Titration

• Increase lunch rapid-acting insulin by 2 units every 3 days based on 4 PM glucose readings until the value falls below 180 mg/dL. 1, 5
• Increase dinner rapid-acting insulin by 2 units every 3 days based on bedtime glucose readings. 1, 5

Expected Insulin Requirements

• Studies show that patients on prednisone ≥20 mg/day require a median final insulin dose of 0.40 units/mg of prednisone (for 60 mg prednisone = 24 units) or 0.15 units/kg bodyweight (for 95 kg = 14 units), though these doses are often insufficient for optimal control. 6
• Your patient will likely require 50–60 units total daily insulin (30 units NPH + 10 units lunch + 10 units dinner + corrections) to achieve adequate control on prednisone 60 mg. 3, 6, 5

Monitoring Requirements

• Check fasting glucose daily to assess overnight control and ensure morning NPH is not causing nocturnal hypoglycemia. 1, 2
• Check pre-lunch glucose daily to guide morning NPH titration. 2, 7
• Check 4 PM glucose daily (or 2 hours post-lunch) to assess lunch prandial insulin adequacy. 1, 5
• Check bedtime glucose to guide dinner insulin dosing. 1, 5

Foundation Therapy Optimization

• Continue metformin at maximum tolerated dose (up to 2000 mg daily) unless contraindicated, as metformin reduces total insulin requirements by 20–30% and provides complementary glucose-lowering effects. 8, 2
• The combination of metformin with insulin provides superior glycemic control compared to insulin alone, even in the setting of glucocorticoid therapy. 8, 2

Critical Safety Considerations

Hypoglycemia Prevention

• Morning NPH peaks 4–8 hours after injection, so the risk of hypoglycemia is highest at lunch and mid-afternoon, not overnight. 2, 3, 9
• Treat any glucose <70 mg/dL immediately with 15 g fast-acting carbohydrate and reduce the implicated insulin dose by 10–20%. 1, 2
• Never give rapid-acting insulin at bedtime as a sole correction dose, as this markedly increases nocturnal hypoglycemia risk. 1, 8

When Prednisone Dose Changes

• If prednisone is tapered or discontinued, reduce total insulin dose by 30–50% immediately to prevent severe hypoglycemia. 2, 3
• Prednisone-induced hyperglycemia resolves within 24–48 hours of stopping the steroid, so aggressive insulin dose reduction is mandatory. 3, 4

Why Not Basal-Bolus with Glargine?

Glargine-based basal-bolus regimens are less effective for prednisone-induced hyperglycemia because glargine provides flat 24-hour coverage, which undertreats daytime hyperglycemia and causes nocturnal hypoglycemia. 3, 4 A randomized trial showed no difference in glycemic control between isophane (NPH) and glargine-based regimens in patients on prednisone ≥20 mg/day, but NPH better matches the circadian pattern of steroid-induced hyperglycemia. 3

Expected Outcomes

• With appropriate insulin intensification (morning NPH + lunch and dinner prandial insulin), 43% of glucose readings should fall within target range by day 3, compared to 23% at baseline. 6
• However, even with aggressive titration, patients on high-dose prednisone often have substantial afternoon and evening hyperglycemia despite protocol-driven insulin therapy, requiring doses higher than standard basal-bolus calculations. 5
• Studies show that mean daily glucose remains elevated at 12.2 mmol/L (220 mg/dL) in hospitalized patients on prednisone despite basal-bolus insulin, compared to 10.0 mmol/L (180 mg/dL) in controls. 5

Common Pitfalls to Avoid

• Do not rely on correction insulin alone—scheduled NPH and prandial insulin must be increased aggressively to match the prednisone effect. 1, 5
• Do not use equal morning and evening NPH doses when prednisone is given in the morning, as this increases nocturnal hypoglycemia risk without addressing daytime hyperglycemia. 2, 7
• Do not delay insulin intensification—glucose values of 201 mg/dL at noon and 325 mg/dL at 4 PM represent complete therapeutic failure and require immediate intervention. 3, 5
• Do not continue the carb ratio 1:10 without adjustment—patients on high-dose prednisone require 40–60% more prandial insulin than standard carb ratios predict. 8, 5