How is dexamethasone-induced hyperglycemia treated?

Treatment of Dexamethasone-Induced Hyperglycemia

For dexamethasone-induced hyperglycemia, initiate basal-bolus insulin therapy with a starting dose of 0.3-0.5 units/kg split 50/50 between long-acting basal insulin (glargine) and rapid-acting prandial insulin (aspart or lispro), with dose adjustments based on the severity of hyperglycemia and steroid dosing schedule. 1

Understanding the Glycemic Pattern

Dexamethasone causes a predictable hyperglycemic pattern that peaks 7-9 hours after administration, with intravenous dosing triggering greater elevations than oral administration. 1 The degree of hyperglycemia directly correlates with the steroid dose. 1 This results in disproportionate afternoon and evening hyperglycemia that can persist for 24 hours or longer after administration. 2, 3

Diagnosis

Diagnose steroid-induced diabetes when you document persistent hyperglycemia with two abnormal tests (random blood glucose ≥11.1 mmol/L or ≥200 mg/dL on different occasions and/or newly elevated HbA1c ≥6.5%) in the context of corticosteroid use. 1

Treatment Algorithm by Severity

Mild to Moderate Hyperglycemia

For isolated daytime hyperglycemia with preserved renal and hepatic function:

• Start with NPH insulin given once daily in the morning, as this intermediate-acting insulin matches the pharmacokinetic profile of once-daily morning dexamethasone. 1
• Add metformin as an adjunctive agent, which has evidence for alleviating some metabolic effects of steroids. 1
• Consider sulfonylureas for isolated daytime hyperglycemia, though patients must be warned about hypoglycemia risk. 1

Moderate to Severe Hyperglycemia

Initiate basal-bolus insulin regimen:

• Starting dose: 0.3-0.5 units/kg total daily dose, split 50/50 between once-daily glargine (Optisulin) and rapid-acting insulin (Novorapid/aspart) with each meal. 1
• Higher starting doses may be warranted based on weight, baseline HbA1c, pre-existing diabetes status, and current diabetes therapy, as these independently influence insulin requirements. 1
• Lower initial doses in elderly patients and those with renal impairment. 1

Research evidence supports this approach: a retrospective study of 40 patients with hematologic malignancies receiving dexamethasone demonstrated that basal-bolus insulin (detemir and aspart) achieved mean blood glucose of 219 ± 51 mg/dL compared to 301 ± 57 mg/dL with sliding scale regular insulin (P <0.001). 4 The basal-bolus regimen reduced average blood glucose by 52 ± 82 mg/dL, while sliding scale increased it by 128 ± 77 mg/dL. 4

Alternative for Patients Unable to Manage Multiple Injections

Use mixed insulin such as Novomix 30 (30% rapid-acting aspart/70% intermediate protamine insulin aspart) for patients who struggle with four injections daily. 1

Specific Dosing for Intermittent Dexamethasone

For patients already on basal insulin who receive intermittent dexamethasone:

• Increase basal insulin to 150% of baseline on the evening of dexamethasone administration. 2
• Maintain this increased dose for at least 24 hours after dexamethasone administration. 2
• Gradually taper back to baseline as blood glucose normalizes. 2, 3
• If on mealtime insulin, increase the carbohydrate ratio from 1:10 to 1:7 (approximately 30% increase) for 24-48 hours after dexamethasone. 2

Monitoring Requirements

• Check blood glucose every 4-6 hours while affected by dexamethasone. 1, 2
• Focus on afternoon and evening readings, as steroid-induced hyperglycemia is most pronounced during these times. 2, 3
• For self-management at home, monitor four times daily (fasting and 2 hours post-meals). 1
• Add correctional insulin before each feeding or meal as needed. 1, 2

Critical Dose Adjustments

As steroids are reduced, insulin doses must be down-titrated to prevent hypoglycemia, since steroids are the primary driver of hyperglycemia. 1 This is a common pitfall—failure to reduce insulin as steroids taper can lead to severe hypoglycemia.

Emergency Situations

Warn patients to present to hospital immediately if:

• Capillary blood glucose persistently above 20 mmol/L (360 mg/dL) despite treatment. 1
• Glucose meter reads "HI." 1
• These scenarios indicate risk for hyperosmolar hyperglycemic state, a life-threatening condition requiring intravenous insulin and fluid resuscitation. 1

Three patients in one study developed diabetic ketoacidosis or hyperosmolar hyperglycemia during steroid therapy when managed with sliding scale insulin alone. 4

Patient Education

All patients require education on:

• Glucose monitoring techniques. 1
• Symptoms of severe hyperglycemia. 1
• Safety thresholds for hospital presentation. 1
• Hypoglycemia management for those on glucose-lowering therapy. 1
• The critical understanding that steroid dose adjustments necessitate diabetes treatment regimen review. 1

Special Populations

For patients with pancreagenic diabetes:

• Expect more unpredictable insulin requirements due to variable beta-cell function. 2, 3
• Implement more frequent glucose monitoring. 2, 3
• Consider nutritional status and oral intake when adjusting doses. 2, 3

Comparative Evidence Limitations

While one retrospective study compared NPH insulin, insulin glargine, and combination therapy in 96 COVID-19 patients receiving 6 mg daily dexamethasone, no significant difference in mean blood glucose control was found among groups (254 ± 60 vs 234 ± 39 vs 250 ± 51 mg/dL, P = 0.548). 5 However, all groups had poor glycemic control, suggesting inadequate dosing rather than insulin type being the issue. 5 Standard long-acting basal insulin glargine was non-inferior to intermediate insulin in clinical trials. 1