Does sepsis cause hyperglycemia (high blood sugar) or hypoglycemia (low blood sugar)?

Sepsis Causes Both Hyperglycemia and Hypoglycemia in a Biphasic Pattern

Sepsis initially causes hyperglycemia in the early phase, followed by hypoglycemia in later stages—both are associated with increased mortality and poor outcomes. 1

The Biphasic Glucose Response in Sepsis

Early Phase: Hyperglycemia Predominates

• Hyperglycemia occurs initially in sepsis due to dysregulation of glycogen metabolism, significant insulin resistance, and stress hormone release 1
• This hyperglycemic response is observed in both animal models and human patients at sepsis onset 1
• Glucose is redirected to immune cells to promote aerobic glycolysis and immune function 1
• Severe admission hyperglycemia (≥200 mg/dL) is associated with 66% increased 30-day mortality compared to euglycemia 2
• Hyperglycemia correlates with illness severity and represents one of the most established metabolic dysregulations in sepsis 1

Late Phase: Hypoglycemia Emerges

• In later stages of sepsis, hypoglycemia develops as a result of peripheral glucose consumption, anorexia, and depleted glycogen stores 1
• Hypoglycemia was observed in 16.3% of Ugandan septic patients on hospital admission and was independently associated with in-hospital mortality 1
• Severe hypoglycemia (≤40 mg/dL) in septic patients carries an 8-fold increased risk of 28-day mortality compared to euglycemia 3
• Even mild hypoglycemia (41-70 mg/dL) increases mortality risk 7.5-fold 3

Clinical Implications and Management

Why Both Occur

• The severity of sepsis correlates with risk of sustaining both hyperglycemia and critical hypoglycemia 4
• Sepsis is a predictive marker for hypoglycemia in hospitalized patients, particularly elderly patients 1
• Patients with limited glycogen stores (malnourished, liver disease) are especially vulnerable to hypoglycemia 1

Critical Management Principles

Blood glucose monitoring is mandatory in every septic patient 1:

• Check blood glucose levels as early as possible, especially in patients with altered mental status 1
• If glucose testing is unavailable in a patient with impaired mental state, presume hypoglycemia and administer IV glucose 1

Target glucose levels should avoid both extremes 1:

• Initiate insulin therapy when blood glucose >180 mg/dL with target ≤180 mg/dL 1
• Avoid tight glucose control targeting <150 mg/dL, as this increases hypoglycemic events and mortality 1
• Maintain blood glucose >70 mg/dL (>4 mmol/L) by providing glucose calorie source 1

Common Pitfalls to Avoid

• Intensive insulin therapy increases severe hypoglycemia risk (6-29%) without mortality benefit in septic patients 1
• Continuation of insulin infusions with cessation of nutrition is a major risk factor for hypoglycemia 1
• Point-of-care capillary glucose testing may be inaccurate in shock patients receiving vasopressors; arterial blood gas measurements are more reliable 1
• Both hyperglycemia and hypoglycemia correlate with poor outcomes and organ dysfunction 1

The Bottom Line

Sepsis disrupts glucose homeostasis in both directions—hyperglycemia dominates early while hypoglycemia emerges later, particularly in severe sepsis. The key is avoiding both extremes: treat hyperglycemia >180 mg/dL but never target tight control, and aggressively prevent/treat hypoglycemia <70 mg/dL 1. Both glucose abnormalities signal illness severity and independently predict mortality 1, 2, 3.