Can infection or inflammation worsen the effectiveness of insulin therapy?

Infection and Inflammation Significantly Worsen Insulin Effectiveness

Yes, infection and inflammation significantly worsen insulin effectiveness by inducing insulin resistance, requiring higher insulin doses to maintain glycemic control during acute illness. 1

Pathophysiology of Infection-Induced Insulin Resistance

Inflammatory Mechanisms

• Inflammatory cytokines directly impair insulin sensitivity:
  • TNF-α, IL-1β, and IL-6 released during infection interfere with insulin signaling 2, 1
  • Inflammation down-regulates enzymes involved in fatty acid oxidation and ketone production 2
  • NF-κB activation (triggered by reactive oxygen species) is central to inflammation-induced insulin resistance 1

Metabolic Changes During Infection

• Infections trigger catabolic processes that break down larger molecules to meet increased energy demands 2
• Lipolysis increases dramatically, leading to elevated free fatty acids (FFAs) that can:
  • Accumulate to toxic levels in organs 2
  • Interfere with mitochondrial function 2
  • Directly impair insulin sensitivity through ROS production 1

Severity and Duration of Insulin Resistance

• Acute infections can cause severe insulin resistance - up to 52% reduction in insulin sensitivity 3
• This resistance can persist for 1-3 months after recovery from the infection 3
• The severity of insulin resistance during infection can be equivalent to that of:
  • An 84-year-old person, or
  • Someone with a BMI of 37 kg/m² 3

Clinical Manifestations

Hyperglycemia During Infection

• Hyperglycemia is one of the most established metabolic dysregulations in infection 2
• Results from significant insulin resistance and dysregulation of glycogen metabolism 2
• Glucose is redirected to immune cells to promote aerobic glycolysis and immune function 2

Impact on Diabetic Patients

• Patients with diabetes require increased insulin during infections due to acute metabolic stress 1
• Elevated hemoglobin A1c in people with type 1 diabetes compromises immune function, making them more susceptible to infections 2
• Risk of diabetic ketoacidosis (DKA) increases during infection, particularly in patients taking SGLT2 inhibitors 2

Management Considerations

Insulin Dosing During Infection

• Higher insulin doses are typically needed during infection to overcome resistance 1
• Maintain blood glucose between 90-150 mg/dl (5-8 mM) to minimize glycemic variability 1
• Regular self-monitoring of blood glucose every 2-4 hours is recommended during infection 2

Medication Adjustments

• Consider discontinuing certain medications during severe infections:
  • Metformin (risk of lactic acidosis)
  • SGLT2 inhibitors (risk of euglycemic or moderate hyperglycemic DKA) 2
• Insulin remains the preferred therapy during acute illness 2

Special Considerations

• Critically ill patients require close glucose monitoring and often need insulin infusion 1
• Patients on nutritional support may experience exacerbated stress-related hyperglycemia 1
• Monitor for hypoglycemia, which is the most common adverse reaction of insulin therapy 4

Prevention and Monitoring

• Early detection and treatment of infections in diabetic patients is crucial
• More frequent blood glucose monitoring during illness
• Educate patients about "sick day rules" including:
  • Never stopping insulin during illness
  • Monitoring for ketones (especially in type 1 diabetes)
  • Maintaining hydration
  • When to seek medical attention

Remember that insulin itself has anti-inflammatory properties, inhibiting inflammatory transcription factors and decreasing TNF-α, which may contribute to its therapeutic effects during infection 1, 5.