How to manage hyperglycemia (high blood sugar) caused by chemotherapy and steroid use?

Management of Hyperglycemia Due to Chemotherapy and Steroids

Start NPH insulin at 0.3-0.5 units/kg/day given in the morning to match the afternoon peak hyperglycemic effect of glucocorticoids, with dose adjustments proportional to steroid tapering. 1, 2

Understanding the Hyperglycemic Pattern

The timing of hyperglycemia is critical to understand:

• Peak hyperglycemia occurs 6-9 hours after morning steroid administration, typically in the afternoon and evening, with glucose levels often normalizing overnight even without treatment 1, 2
• Prednisolone causes hyperglycemia predominantly between midday and midnight, with peak effects approximately 8 hours after morning administration 3
• The degree of hyperglycemia directly correlates with the steroid dose—higher doses cause more significant elevations 1, 3
• Chemotherapy-related hyperglycemia occurs in approximately 10-30% of patients, with glucocorticoids being the primary driver 4

Immediate Monitoring Protocol

Implement four-times-daily glucose monitoring (fasting and 2 hours after each meal) rather than relying on fasting glucose alone, which will miss the peak hyperglycemic effect 1, 2:

• Target glucose range: 5-10 mmol/L (90-180 mg/dL) 1, 2, 3
• Monitor glucose 2 hours after lunch (around 2-3 PM) as this captures the peak steroid effect 1
• For hospitalized patients, monitor every 2-4 hours initially 1

Insulin Therapy Algorithm

First-Line Treatment: NPH Insulin

NPH insulin is the preferred agent because its 4-6 hour peak action aligns 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) 1, 2, 3
• Higher doses (40-60% increase) may be needed for patients on high-dose glucocorticoids (e.g., prednisone ≥50 mg), those with higher baseline HbA1c, or pre-existing diabetes 1, 2
• For elderly patients or those with renal impairment, start with lower doses (0.2-0.3 units/kg/day) 1, 3

Severe Hyperglycemia Management

For more severe cases requiring additional control 5:

• Basal-bolus insulin regimen: Once daily long-acting insulin (glargine) and rapid-acting insulin (e.g., Novorapid) with each meal at 0.3-0.5 units/kg, split 50/50 between basal and bolus 5
• For patients struggling with multiple injections, consider mixed insulin (e.g., Novomix 30) 5
• For very high-dose glucocorticoids (e.g., 80 mg), increasing doses of prandial and correctional insulin in extraordinary amounts may be needed in addition to basal insulin 1

Long-Acting Glucocorticoids

For long-acting glucocorticoids like dexamethasone 1:

• A combination of long-acting basal insulin AND NPH may be required
• Long-acting basal insulin becomes more important for controlling fasting glucose with continuous steroid use

Dose Adjustment Strategy

As steroids are tapered, insulin doses must be proportionally decreased to prevent hypoglycemia 1, 2, 3:

• 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 1
• Review diabetes treatment regimen whenever steroid adjustments are made 5

Role of Oral Antidiabetic Agents

Oral agents alone are insufficient for high-dose steroid therapy 2, 3:

• Metformin can be added as an adjunct in patients with preserved renal and hepatic function, with some evidence it alleviates metabolic effects of steroids 5, 2
• Sulfonylureas can be considered for isolated daytime hyperglycemia, though patients must be warned of hypoglycemia risk 5
• For patients on prednisolone 50 mg already taking oral agents, intensify to insulin therapy as oral agents are likely insufficient 3

Chemotherapy-Specific Considerations

For targeted oncologic agents causing hyperglycemia 6, 4:

• Highest incidence occurs with mTOR inhibitors (13-50%) and IGF-1R inhibitors 6, 4
• Immunotherapy (anti-PD-1 antibodies) induces hyperglycemia in 0.1% through autoimmune insulitis 4
• Screen patients before initiating mTOR or PD-1 inhibitor therapy and monitor glucose levels periodically 4

Critical Warning Signs

Hyperosmolar hyperglycemic state can develop in very severe cases 1, 2, 3:

• Warn patients that capillary blood glucose persistently above 20 mmol/L despite treatment, or glucose meter reading "HI," requires immediate hospital presentation 5
• This is a life-threatening condition driven by persistent hyperglycemia leading to profound dehydration and severe hyperosmolality 5

Common Pitfalls to Avoid

• Using only fasting glucose for monitoring (misses peak hyperglycemic effect) 1, 2
• Relying solely on sliding-scale correction insulin (associated with poor glycemic control and discouraged in guidelines) 1, 7
• Waiting for fasting hyperglycemia before treating (leads to delayed intervention) 1, 2
• Not anticipating the diurnal pattern with peak effects in afternoon/evening 1, 2
• Failing to reduce insulin doses proportionally when steroids are tapered (leads to hypoglycemia) 1, 2, 3

Patient Education Requirements

Provide comprehensive education on 2, 3:

• Glucose monitoring technique and frequency (four times daily)
• Symptoms of severe hyperglycemia and emergency thresholds
• Symptoms of hypoglycemia as insulin is initiated
• When to seek medical attention (persistent glucose >20 mmol/L)