How to transition a patient with diabetes and possible adrenal insufficiency, currently taking Mixtard (mixed insulin) and hydrocortisone (cortisol replacement), to a basal-bolus insulin regimen?

Transitioning from Mixtard to Basal-Bolus Insulin Regimen

For a patient on Mixtard (mixed insulin) with diabetes and possible adrenal insufficiency on hydrocortisone, transition to a basal-bolus regimen by calculating 50% of the total daily Mixtard dose as basal insulin (insulin glargine once daily) and 50% as prandial insulin (rapid-acting insulin divided equally before three meals), while recognizing that glucocorticoid replacement significantly increases insulin requirements, particularly at noon and evening meals. 1, 2, 3

Step 1: Calculate Total Daily Insulin Dose from Mixtard

• Add up all units of Mixtard currently administered per day to determine the total daily dose (TDD) 1, 2
• For example, if the patient takes Mixtard 30/70 at 20 units before breakfast and 15 units before dinner, the TDD = 35 units 2

Step 2: Split the Dose Using 50:50 Basal-Bolus Distribution

Basal Insulin Component:

• Give 50% of TDD as long-acting basal insulin (insulin glargine/Lantus) once daily, typically in the evening 1, 2
• Using the example above: 35 units × 0.5 = 17.5 units (round to 18 units) of insulin glargine at bedtime 2

Prandial Insulin Component:

• Give the remaining 50% of TDD as rapid-acting insulin (insulin aspart, lispro, or glulisine) divided equally among three meals 1, 2
• Using the example: 35 units × 0.5 = 17.5 units total prandial insulin per day 2
• Divide by 3 meals: approximately 6 units before each meal 2
• Administer rapid-acting insulin 0-15 minutes before meals 4, 5

Step 3: Account for Adrenal Insufficiency and Glucocorticoid Effects

Critical Adjustment for Hydrocortisone Replacement:

• Patients with adrenal insufficiency on glucocorticoid replacement require significantly higher insulin-to-carbohydrate ratios at noon and evening meals compared to morning 3
• The insulin/carbohydrate ratio at noon is approximately 1.8 times higher (2.0 vs 1.1 units per 10g carbohydrate) in patients on hydrocortisone replacement 3
• The insulin/carbohydrate ratio in the evening is approximately 1.6 times higher (2.1 vs 1.3 units per 10g carbohydrate) 3

Practical Distribution Adjustment:

• Instead of equal distribution (6-6-6 units), consider a weighted distribution such as 5 units breakfast, 7 units lunch, 7 units dinner to account for glucocorticoid effects 3
• Alternatively, start with equal distribution and rapidly titrate lunch and dinner doses upward based on postprandial glucose readings 3

Step 4: Reduce Initial Dose for Safety

• Reduce the calculated TDD by 20% when transitioning to prevent hypoglycemia during the adjustment period 1
• Using the example: Instead of 18 units basal + 6-6-6 prandial, start with 14 units basal + 5-5-5 prandial 1
• For high-risk patients (elderly >65 years, renal impairment, poor oral intake), reduce to 0.1-0.25 units/kg/day 1

Step 5: Implement Correction Insulin Protocol

• Add correction (sliding scale) insulin using rapid-acting insulin for premeal glucose >180 mg/dL, separate from scheduled prandial doses 4, 1
• Use simplified correction scale: add 2 units for glucose 250-350 mg/dL, add 4 units for glucose >350 mg/dL 1
• Never use correction insulin as monotherapy—it must supplement a scheduled basal-bolus regimen 4, 1

Step 6: Titration Protocol

Basal Insulin Titration (based on fasting glucose):

• Increase basal insulin by 2 units every 3 days if fasting glucose is 140-179 mg/dL 1
• Increase by 4 units every 3 days if fasting glucose ≥180 mg/dL 1
• Target fasting glucose: 80-130 mg/dL 4, 1
• If hypoglycemia occurs, reduce dose by 10-20% immediately 1

Prandial Insulin Titration (based on 2-hour postprandial glucose):

• Increase prandial insulin by 1-2 units or 10-15% every 3 days if 2-hour postprandial glucose consistently >180 mg/dL 1, 2
• Adjust each meal's insulin dose independently based on that meal's postprandial readings 1
• Pay particular attention to lunch and dinner doses in patients on hydrocortisone, as these typically require more aggressive titration 3

Step 7: Monitoring Requirements

• Check fasting blood glucose daily during titration 1
• Check premeal glucose before each meal to calculate correction doses 1
• Check 2-hour postprandial glucose to assess adequacy of prandial insulin 1
• Monitor for hypoglycemia, especially if hydrocortisone dose changes 3, 6

Critical Pitfalls to Avoid

• Never continue Mixtard (premixed insulin) in hospitalized patients—randomized trials show significantly increased hypoglycemia rates compared to basal-bolus regimens 1
• Never give rapid-acting insulin at bedtime—this significantly increases nocturnal hypoglycemia risk 4, 1
• Never use sliding scale insulin as monotherapy—this treats hyperglycemia reactively rather than preventing it 4, 1
• Do not underestimate insulin requirements at lunch and dinner in patients on glucocorticoid replacement—these meals require approximately 60-80% higher insulin doses than morning 3
• Never abruptly discontinue oral medications (especially metformin) when transitioning insulin regimens—continue metformin unless contraindicated 5

Special Considerations for Glucocorticoid-Induced Changes

• If hydrocortisone dose increases (e.g., during illness), increase prandial and correction insulin by 40-60% or more 1
• Glucocorticoid effects are most pronounced on postprandial glucose, requiring aggressive prandial insulin titration 3, 7
• Monitor for changes in insulin sensitivity if glucocorticoid replacement schedule changes 8
• If transitioning to dexamethasone replacement, expect even greater insulin resistance and higher insulin requirements 8