Overview
Definition:
Steroid-induced hyperglycemia in Type 1 Diabetes Mellitus (T1DM) refers to a significant increase in blood glucose levels that occurs when a patient with established T1DM receives corticosteroid therapy
Corticosteroids are potent anti-inflammatory and immunosuppressive agents commonly used for various pediatric conditions, but they have a well-documented diabetogenic effect.
Epidemiology:
While the exact incidence of steroid-induced hyperglycemia in pediatric T1DM patients is not precisely quantified, it is a well-recognized complication
The degree of hyperglycemia is dose-dependent and duration-dependent, and it can vary considerably among individuals due to genetic predispositions and the specific corticosteroid used.
Clinical Significance:
Effective management of steroid-induced hyperglycemia in T1DM is crucial to prevent acute complications such as diabetic ketoacidosis (DKA), to avoid long-term microvascular and macrovascular complications of diabetes, and to maintain overall metabolic stability
Inadequate glycemic control can compromise the efficacy of the corticosteroid therapy itself and lead to increased morbidity.
Pathophysiology
Mechanism Of Action:
Corticosteroids increase glucose production by the liver through gluconeogenesis and glycogenolysis
They also induce insulin resistance in peripheral tissues, particularly muscle and adipose tissue, by interfering with insulin signaling pathways
This dual effect of increased glucose supply and decreased glucose utilization leads to significant hyperglycemia.
Impact On T1dm:
In individuals with T1DM, the pancreatic beta-cells are already destroyed, meaning they have absolute insulin deficiency
Steroid-induced insulin resistance and increased hepatic glucose output place an even greater demand on the limited or absent endogenous insulin production, necessitating substantial increases in exogenous insulin requirements.
Individual Variability:
Factors influencing the severity of steroid-induced hyperglycemia include the dose and type of corticosteroid (e.g., prednisone, dexamethasone), duration of therapy, baseline glycemic control in T1DM, and individual genetic susceptibility.
Clinical Presentation
Symptoms:
New-onset or worsening hyperglycemia symptoms: Increased thirst (polydipsia)
Frequent urination (polyuria)
Unexplained weight loss
Increased hunger (polyphagia)
Fatigue and lethargy
Blurred vision
Irritability
In severe cases, symptoms of diabetic ketoacidosis (DKA) may develop if insulin is insufficient: nausea, vomiting, abdominal pain, rapid breathing, fruity breath odor.
Signs:
Elevated blood glucose levels (>200 mg/dL or >11.1 mmol/L)
Presence of ketones in urine or blood
Dehydration
Rapid heart rate and low blood pressure if DKA is present
Fruity odor on breath if DKA is present.
Diagnostic Criteria:
Diagnosis is made based on persistent elevated blood glucose levels during corticosteroid therapy in a patient with known T1DM, accompanied by characteristic symptoms and signs
The degree of hyperglycemia is often significantly higher than the patient's usual baseline glycemic control
Glycated hemoglobin (HbA1c) may not accurately reflect acute glycemic excursions during short courses of steroids but is important for long-term assessment.
Diagnostic Approach
History Taking:
Detailed history of the corticosteroid therapy: drug, dose, frequency, and duration
History of baseline T1DM control
Previous episodes of hyperglycemia or DKA
Concurrent illnesses or infections
Dietary intake
Adherence to insulin regimen
Symptoms suggestive of hyperglycemia or DKA.
Physical Examination:
General assessment for hydration status and signs of distress
Vital signs (heart rate, blood pressure, respiratory rate)
Abdominal examination for tenderness
Neurological assessment for changes in mental status
Assessment of skin turgor and mucous membranes.
Investigations:
Capillary or venous blood glucose monitoring (frequent measurements are essential)
Urine or serum ketone testing (qualitative or quantitative)
Serum electrolytes and arterial/venous blood gas analysis (if DKA is suspected)
Complete blood count (CBC) and C-reactive protein (CRP) to assess for underlying infection
Liver and kidney function tests.
Differential Diagnosis:
Other causes of hyperglycemia in a patient with T1DM, such as infection, inadequate insulin dosing, missed insulin injections, or dietary indiscretion
Distinguishing steroid-induced hyperglycemia relies on its temporal relationship with corticosteroid initiation and its response to insulin adjustments and steroid withdrawal.
Management
Initial Management:
Immediate assessment of glycemic status and hydration
Aggressive insulin therapy is the cornerstone
Frequent blood glucose monitoring (e.g., every 1-2 hours initially)
Correction of dehydration and electrolyte imbalances if present
Treatment of any precipitating infection.
Insulin Adjustments:
Increased insulin requirements are almost universal
Basal insulin (long-acting) doses often need to be increased by 20-50% or more
Bolus (rapid-acting) insulin doses for meals and corrections may also need significant increases
A common approach is to increase basal insulin by 20-30% and bolus insulin by 25-50%
Continuous glucose monitoring (CGM) is highly beneficial for real-time feedback and trend analysis
Sliding scale insulin regimens may be necessary for temporary management, but they should be used judiciously as they do not address the underlying basal need.
Pharmacological Treatment:
Exogenous insulin is the primary treatment
Rapid-acting insulin analogs (lispro, aspart, glulisine) for mealtime and corrections
long-acting insulin analogs (glargine, detemir, degludec) or NPH insulin for basal coverage
The total daily insulin dose will likely need to be significantly increased
In severe cases, intravenous insulin infusion might be required
Oral antidiabetic agents are generally not effective or appropriate in T1DM and should not be used.
Supportive Care:
Close monitoring for signs of hyperglycemia, hypoglycemia (especially as steroids are reduced or withdrawn), and DKA
Patient and family education on recognizing and managing hyperglycemia, insulin dose adjustments, and sick day rules
Nutritional counseling to ensure adequate carbohydrate intake while managing hyperglycemia
Regular communication with the pediatric endocrinology team is vital.
Steroid Discontinuation
Managing Hypoglycemia:
As corticosteroid doses are reduced or tapered, insulin requirements will decrease
Failure to adjust insulin doses downwards can lead to severe hypoglycemia
Gradual reduction of insulin doses, mirroring the steroid taper, is essential
Close monitoring for hypoglycemia symptoms is paramount.
Tapering Strategy:
The insulin adjustment strategy should be closely coordinated with the corticosteroid tapering schedule
It is often prudent to reduce insulin doses incrementally as steroid doses are reduced, anticipating the rebound in insulin sensitivity
Continuous glucose monitoring is invaluable during this phase.
Reassessment:
Once corticosteroid therapy is completed, the patient's insulin regimen should be reassessed and adjusted back to their pre-steroid baseline, or as dictated by their ongoing glycemic control and growth needs
This often requires close follow-up with the endocrinology team for several weeks.
Complications
Early Complications:
Diabetic ketoacidosis (DKA) due to insufficient insulin management
Severe hyperglycemia leading to dehydration
Electrolyte disturbances
Increased risk of infections due to immunosuppression and hyperglycemia.
Late Complications:
Accelerated development of long-term diabetes complications (retinopathy, nephropathy, neuropathy) if hyperglycemia is poorly controlled over prolonged periods
Impact on growth and development in pediatric patients.
Prevention Strategies:
Proactive and aggressive insulin management tailored to steroid therapy
Frequent and diligent glucose monitoring
Patient and family education
Close collaboration between pediatric endocrinology, the treating specialist initiating steroids, and the patient/family
Utilizing CGM for early detection of glycemic trends.
Key Points
Exam Focus:
Corticosteroids increase glucose by gluconeogenesis and insulin resistance
T1DM patients require significant insulin dose increases during steroid therapy
Monitor closely for hyperglycemia and DKA, but also for hypoglycemia when steroids are tapered/stopped
Insulin needs correlate with steroid dose and type.
Clinical Pearls:
Always anticipate increased insulin needs when a T1DM patient starts steroids
Use CGM if available
it is a game-changer
Educate families thoroughly about sick day rules and insulin adjustments
Start by increasing basal insulin, then adjust bolus and correction factors
Do NOT use oral agents for T1DM
Dexamethasone is generally more potent in inducing hyperglycemia than prednisone.
Common Mistakes:
Underestimating the magnitude of insulin dose increase needed
Failing to adjust insulin downwards when steroids are tapered or stopped, leading to hypoglycemia
Not monitoring ketones promptly when hyperglycemia is severe
Delaying consultation with pediatric endocrinology.