How to transition a patient with diabetes and possible adrenal insufficiency, taking hydrocortisone (cortisol) and Mixtard (biphasic insulin) 35 units in the morning and 30 units in the evening, to a basal-bolus insulin regimen?

Transitioning from Mixtard to Basal-Bolus Insulin in a Patient with Diabetes and Possible Adrenal Insufficiency

For a patient on Mixtard 35 units morning and 30 units evening with possible adrenal insufficiency on hydrocortisone, transition to a basal-bolus regimen by calculating total daily dose (65 units), giving 50% (approximately 32-33 units) as once-daily basal insulin (glargine or detemir) and dividing the remaining 50% equally among three meals as rapid-acting insulin (approximately 10-11 units per meal), while optimizing hydrocortisone timing to 2/3 of dose in the morning and 1/3 in early afternoon to minimize insulin resistance from glucocorticoid peaks. 1

Calculate Current Total Daily Insulin Dose

• Add the current Mixtard doses: 35 + 30 = 65 units total daily dose 1
• This serves as the foundation for the basal-bolus conversion 1

Split into Basal and Prandial Components

• Give 50% as basal insulin: 32-33 units of insulin glargine (Lantus) or detemir once daily 1, 2
• Give 50% as prandial insulin: Divide remaining 32-33 units equally among three meals = approximately 10-11 units of rapid-acting insulin (lispro, aspart, or glulisine) before each meal 1, 2

Optimize Hydrocortisone Timing to Reduce Insulin Resistance

• Restructure hydrocortisone dosing to mimic physiological cortisol rhythm: give 2/3 of total daily dose in the morning (0730-0800h) and 1/3 in early afternoon (1200-1300h) 1
• If currently on 15-20 mg daily hydrocortisone, consider splitting as 10-13 mg morning and 5-7 mg early afternoon 1
• Avoid evening hydrocortisone doses as they contribute to nocturnal hyperglycemia and increased morning insulin requirements 3, 4
• Patients with adrenal insufficiency and type 1 diabetes require significantly higher insulin-to-carbohydrate ratios at noon (2.0 vs 1.1) and evening (2.1 vs 1.3) compared to those without adrenal insufficiency, reflecting glucocorticoid-induced insulin resistance 5

Initial Dose Adjustments for Glucocorticoid Effect

• Expect 40-60% higher prandial insulin requirements at lunch and dinner due to hydrocortisone-induced insulin resistance 1, 5
• Start with calculated doses but anticipate need to increase afternoon/evening prandial insulin by 2-4 units based on postprandial glucose readings 1
• Morning prandial insulin may require less adjustment as it coincides with peak cortisol replacement 5

Titration Protocol

Basal Insulin Adjustment

• Titrate basal insulin every 3 days based on fasting glucose patterns 1, 2
• Increase by 2 units if fasting glucose 140-179 mg/dL 1
• Increase by 4 units if fasting glucose ≥180 mg/dL 1
• Target fasting glucose: 80-130 mg/dL 1

Prandial Insulin Adjustment

• Adjust each meal's prandial insulin independently based on 2-hour postprandial glucose 1, 2
• Increase by 1-2 units (or 10-15%) every 3 days if postprandial glucose consistently >180 mg/dL 1
• Target postprandial glucose <180 mg/dL 1

Critical Monitoring Requirements

• Check fasting glucose daily during titration phase 1, 2
• Check pre-meal and 2-hour postprandial glucose to guide prandial adjustments 1
• Monitor for hypoglycemia risk, particularly if hydrocortisone dose is reduced or timing changed 6
• Patients with adrenal insufficiency have impaired counter-regulatory mechanisms and are at higher risk for severe hypoglycemia 6

Hypoglycemia Management Considerations

• Educate on stress dosing: Double or triple hydrocortisone dose during illness, which will require proportional insulin dose increases 1
• Provide emergency injectable hydrocortisone and glucagon 1
• If hypoglycemia occurs without clear cause, reduce corresponding insulin dose by 10-20% immediately 1
• Cortisol deficiency impairs gluconeogenesis and increases hypoglycemia risk, particularly overnight and during fasting 6

Common Pitfalls to Avoid

• Do not continue premixed insulin (Mixtard) as it provides inflexible dosing that cannot accommodate variable glucocorticoid effects throughout the day 1
• Do not give rapid-acting insulin at bedtime as this increases nocturnal hypoglycemia risk, especially in patients with impaired counter-regulation from adrenal insufficiency 1, 6
• Do not use long-acting glucocorticoids (prednisone, dexamethasone) as they cause prolonged hyperglycemia and make insulin dosing more difficult; hydrocortisone allows recreation of diurnal rhythm 1
• Do not delay adding prandial insulin if basal insulin alone proves insufficient—the 50:50 split is the starting point, not the endpoint 1

Foundation Therapy Maintenance

• Continue metformin unless contraindicated, as it reduces insulin requirements and provides complementary glucose-lowering effects 1, 2
• Consider discontinuing sulfonylureas when advancing to basal-bolus therapy to prevent hypoglycemia 1

When to Reassess Hydrocortisone Dosing

• If insulin requirements exceed 1.0 units/kg/day despite good adherence, consider whether hydrocortisone dose is excessive (causing iatrogenic Cushing's features: bruising, thin skin, edema, weight gain, hypertension, hyperglycemia) 1
• Reduce hydrocortisone maintenance dosing if these features present 1
• Optimal hydrocortisone replacement is 15-20 mg daily in divided doses, with maximum 30 mg daily for residual symptoms 1