Does diabetes affect the risk and outcome of sepsis?

Diabetes and Sepsis: Impact on Risk and Outcomes

Diabetes significantly affects sepsis by increasing susceptibility to infections and altering metabolic responses during sepsis, though paradoxically, diabetic patients may not experience worse mortality outcomes compared to non-diabetic patients with sepsis. 1

Effect of Diabetes on Sepsis Risk

Diabetes increases the risk of developing sepsis through several mechanisms:

• Immune dysfunction: Diabetes causes abnormalities in host immune response, particularly affecting neutrophil chemotaxis, adhesion, and intracellular killing 2
• Humoral immunity defects: Evidence suggests impairments in antibody-mediated immunity play a larger role than previously recognized 2
• Hyperglycemia effects: Chronic hyperglycemia contributes to immune dysfunction, making patients more susceptible to infections that can progress to sepsis 1

Metabolic Alterations in Sepsis

During sepsis, significant metabolic alterations occur that can be further complicated by diabetes:

• Hyperglycemia: Common in sepsis due to dysregulation in glycogen metabolism and significant insulin resistance 3
• Lipolysis: Infection triggers lipolysis of lipid stores mediated by inflammatory cytokines, adrenalin, glucocorticoids, and glucagon 3
• Free fatty acid accumulation: In severe systemic inflammation, plasma triglycerides and free fatty acids can increase up to four-fold, potentially causing organ damage 3

Impact on Mortality and Outcomes

Interestingly, diabetes may not worsen mortality in sepsis patients:

• Similar or lower mortality: Multiple studies show that diabetes does not significantly increase mortality in sepsis patients, with some evidence suggesting slightly lower mortality rates (RR=0.97,95% CI: 0.96-0.98) 4
• Admission glucose levels: In diabetic patients with sepsis, blood glucose levels between 110-240 mg/dL were associated with better outcomes compared to levels <110 mg/dL 5
• Hyperglycemia effects differ: While admission hyperglycemia (>11.1 mmol/L; 200 mg/dL) in non-diabetic septic patients is associated with increased mortality (43.0% vs. 27.2%), this relationship doesn't hold for diabetic patients 6

Organ-Specific Effects

Diabetes affects organ dysfunction in sepsis differently:

• Increased kidney injury risk: Septic patients with diabetes have a significantly higher incidence of acute kidney injury (RR=1.56,95% CI: 1.25-1.95) 4
• Similar respiratory dysfunction: No significant difference in respiratory dysfunction between diabetic and non-diabetic septic patients (RR=0.86,95% CI: 0.71-1.04) 4

Glycemic Management in Sepsis

Guidelines for glycemic control in septic patients recommend:

• Moderate glycemic targets: Maintain blood glucose ≤180 mg/dL (10 mmol/L) while avoiding hypoglycemia 3
• Avoid tight glycemic control: Intensive insulin therapy aiming at strictly normal blood glucose levels (80-120 mg/dL) is not recommended as it increases mortality and hypoglycemia risk 3
• Hypoglycemia prevention: Hypoglycemia (<70 mg/dL) should be avoided as it's associated with increased mortality in sepsis 7
• Monitoring frequency: Check blood glucose every 1-2 hours until glucose values and insulin infusion rates stabilize, then every 4 hours 7

Clinical Implications

For clinicians managing diabetic patients with sepsis:

• Blood glucose monitoring: Immediate blood glucose assessment is essential in all septic patients 7
• Glycemic targets: Aim for blood glucose levels between 140-180 mg/dL rather than strict normoglycemia 3
• Measurement accuracy: Use arterial blood rather than capillary blood for point-of-care testing when arterial catheters are available 7
• Hypoglycemia management: Treat hypoglycemia urgently with 30-50g of glucose and maintain levels above 70 mg/dL 7

Pitfalls and Caveats

• Capillary blood glucose testing: May be inaccurate in critically ill patients, especially those in shock receiving vasopressors 3
• Glycemic variability: Wide swings in glucose levels are associated with increased mortality and should be avoided 3
• Insulin infusion risks: Continuing insulin infusions when nutrition is stopped increases hypoglycemia risk 3
• Diabetic vs. non-diabetic hyperglycemia: The prognostic significance of hyperglycemia differs between diabetic and non-diabetic patients 6, 5

Understanding these complex interactions between diabetes and sepsis is crucial for optimizing patient care and improving outcomes in this high-risk population.