How to manage steroid-induced hyperglycemia?

Management of Steroid-Induced Hyperglycemia

For steroid-induced hyperglycemia, initiate NPH insulin at 0.3-0.5 units/kg/day given in the morning (or 3 hours after steroid administration) to match the afternoon peak hyperglycemic effect, with doses adjusted proportionally as steroids are tapered. 1, 2

Understanding the Hyperglycemic Pattern

The timing and pattern of steroid-induced hyperglycemia is critical to effective management:

• Prednisone given in the morning causes peak hyperglycemia 8 hours after administration, corresponding to late morning and afternoon elevations, with glucose often normalizing overnight even without treatment 3
• Dexamethasone peaks at 7-9 hours post-dose, with intravenous dosing triggering greater hyperglycemia than oral administration 3
• The degree of hyperglycemia directly correlates with steroid dose—higher doses cause more significant elevations 3, 2
• Steroids cause hyperglycemia through impaired beta cell insulin secretion, increased total body insulin resistance, and enhanced hepatic gluconeogenesis 3, 2

Diagnosis

Make the diagnosis with two abnormal tests: random blood glucose ≥11.1 mmol/L on different occasions and/or newly elevated HbA1c ≥6.5%, in the context of corticosteroid use. 3

Monitoring Protocol

Critical pitfall: Do NOT rely on fasting glucose alone—this will miss the peak hyperglycemic effect and underestimate severity. 1, 2

• Implement four-times-daily glucose monitoring: fasting and 2 hours after each meal 1, 2
• Target glucose range: 5-10 mmol/L (90-180 mg/dL) 1, 2
• Focus monitoring on afternoon/evening readings when steroids peak 1, 2
• For glucose levels persistently >10 mmol/L, continue daily monitoring at minimum 3

Treatment Algorithm

First-Line: NPH Insulin

NPH insulin is the preferred agent because its 4-6 hour peak action aligns perfectly with the peak hyperglycemic effect of morning glucocorticoid doses. 1, 2

• Starting dose: 0.3-0.5 units/kg/day given in the morning (or 3 hours after steroid administration) 3, 1, 2
• For patients on high-dose glucocorticoids (prednisone ≥50 mg), those with higher baseline HbA1c, or pre-existing diabetes, increase starting doses by 40-60% 3, 1, 2
• For elderly patients or those with renal impairment, start with lower doses (0.2-0.3 units/kg/day) 2

Dose Titration Strategy

As steroids are tapered, insulin doses MUST be proportionally decreased to prevent hypoglycemia—this is a common and dangerous pitfall. 3, 1, 2

• Adjust insulin based on blood glucose patterns, focusing on afternoon/evening readings 1, 2
• Increase NPH by 2 units every 3 days if target not achieved 2
• Review and adjust the diabetes treatment regimen with every steroid dose change 3

Severe Hyperglycemia: Basal-Bolus Regimen

For more severe cases requiring prandial control:

• Initiate basal-bolus insulin at 0.3-0.5 units/kg/day, split 50/50 between long-acting basal insulin (glargine) and rapid-acting insulin (e.g., Novorapid) with each meal 3
• Alternative for patients struggling with four injections daily: mixed insulin such as Novomix 30 (30% rapid-acting/70% intermediate protamine insulin) 3
• For high-dose glucocorticoids (e.g., prednisone 80 mg), extraordinary amounts of prandial and correctional insulin may be needed in addition to basal insulin 2

Adjunctive Oral Agents

Critical limitation: Oral antidiabetic agents alone are insufficient for high-dose steroid therapy. 2

• Metformin can be added as adjunct therapy in patients with preserved renal and hepatic function, with evidence it alleviates some metabolic effects of steroids 3
• Sulfonylureas may be considered for isolated daytime hyperglycemia, but patients must be warned about hypoglycemia risk 3
• Long-acting basal insulin (glargine) is useful for patients with prolonged glucose elevation 3

Special Situations

Nighttime Steroid Dosing

When prednisone is taken at night, the pattern shifts:

• Switch from NPH to long-acting basal insulin (glargine or detemir) given at bedtime, as the hyperglycemic pattern peaks overnight and into the following day 2
• Starting dose remains 0.3-0.5 units/kg/day 2

Long-Acting Glucocorticoids (Dexamethasone)

• Long-acting basal insulin may be required to control fasting blood glucose 2
• For continuous steroid use or multiple daily doses, long-acting basal insulin becomes more important 2

Patient Education

All patients with steroid-induced hyperglycemia must receive comprehensive education—this is non-negotiable. 3

• Glucose monitoring technique and frequency 3
• Symptoms of severe hyperglycemia and when to seek emergency care 3
• For patients on glucose-lowering therapy: hypoglycemia management and warning signs 3
• Emphasize that steroid adjustments necessitate diabetes treatment regimen review 3

Life-Threatening Complications

Hyperosmolar hyperglycemic state can develop in very severe cases of steroid-induced hyperglycemia. 3, 1, 2

• Patients should present to hospital immediately if capillary blood glucose persistently >20 mmol/L despite treatment or glucose meter reads "HI" 3
• This is a life-threatening condition driven by persistent hyperglycemia leading to profound dehydration and severe hyperosmolality 3

Perioperative Management

For surgical patients on steroids:

• Target glucose: 100-180 mg/dL (5.6-10.0 mmol/L) 1, 2
• Hold oral glucose-lowering agents on day of surgery 1, 2
• Give half of NPH dose or 75-80% of long-acting insulin dose 2
• Monitor blood glucose at least every 2-4 hours while NPO and dose with short- or rapid-acting insulin as needed 2

Common Pitfalls to Avoid

These errors lead to poor outcomes and must be actively prevented:

• Using only fasting glucose for monitoring—this misses the peak hyperglycemic effect and underestimates severity 1, 2
• Relying solely on sliding-scale correction insulin—this is associated with poor glycemic control and has been discouraged in guidelines 1, 2
• Waiting for fasting hyperglycemia before treating—this leads to delayed intervention and prolonged exposure to hyperglycemia 1, 2
• Failing to anticipate the diurnal pattern with peak effects in afternoon/evening 1, 2
• Not reducing insulin doses proportionally when steroids are tapered—this causes hypoglycemia 1, 2

Multidisciplinary Care Coordination

• Share ongoing management with primary care physician for all patients with hyperglycemia 3
• Refer to endocrinology when insulin is expected to be required 3
• Early communication between oncology, primary care, and endocrinology optimizes outcomes 3