Can an infection cause hyperglycaemia in patients with or without diabetes, and how should blood glucose be monitored and treated during the illness?

Infection-Induced Hyperglycemia: Mechanisms, Monitoring, and Management

Yes, infection causes elevated blood sugars in both diabetic and non-diabetic patients through stress hormone release and inflammatory mediators that increase insulin resistance and hepatic glucose production. 1, 2, 3

Pathophysiology of Infection-Related Hyperglycemia

Acute infection triggers a cascade of metabolic derangements that directly elevate blood glucose through multiple mechanisms:

• Counterregulatory hormone surge: Physical stress from infection causes elevations in cortisol, epinephrine, glucagon, and growth hormone, which increase insulin resistance and stimulate gluconeogenesis 1, 2, 4
• Hepatic glucose overproduction: The liver increases glucose production through both gluconeogenesis and glycogenolysis, even in the presence of high insulin levels, indicating profound insulin resistance 2, 3
• Peripheral insulin resistance: Inflammatory cytokines and stress hormones impair insulin-mediated glucose uptake in peripheral tissues 2, 3, 5
• Immune cell glucose demands: Hyperglycemia redirects glucose to immune cells promoting aerobic glycolysis during early infection stages 2

Critical distinction: Stress-induced hyperglycemia in previously non-diabetic patients carries a worse prognosis than comparable glucose elevations in known diabetics at the same glucose level 2, 6

Clinical Impact and Prevalence

The magnitude of this problem is substantial:

• Approximately two-thirds of hospitalized patients with acute illness develop stress-induced hyperglycemia, which independently predicts higher mortality and morbidity 2
• Influenza infection raises abnormal glucose excursions by roughly 75% in type 2 diabetics 2
• Perioperative hyperglycemia (>180 mg/dL or 10 mmol/L) increases morbidity, particularly infection risk, and mortality 1
• Diabetic patients have a 4.4-times greater risk of systemic infection than non-diabetics, and poorly controlled glucose (elevated HbA1c) correlates positively with infection severity 7

Blood Glucose Monitoring During Infection

Measure blood glucose in every patient presenting with sepsis or any acute infection, regardless of diabetes history 2

High-Risk Populations Requiring Routine Glucose Monitoring:

• Age >60 years 1, 2
• Known diabetes or metabolic syndrome 1, 2
• Prior episode of transient hyperglycemia 1, 2
• Altered mental status (predicts hypoglycemia with 86% specificity in septic patients) 2

Monitoring Frequency:

• Every 2-4 hours during acute infection if hyperglycemia is present 1
• Continuous glucose monitoring or frequent self-monitoring for insulin-treated patients 1
• Regular monitoring even after apparent metabolic stabilization, as late-stage sepsis can paradoxically cause hypoglycemia 2

Target Blood Glucose Levels During Infection

Maintain serum glucose between 70-180 mg/dL (4-10 mmol/L) for all infected patients 2

Specific Thresholds:

• Lower limit: Keep glucose ≥70 mg/dL (≥4 mmol/L) to avoid hypoglycemia 2
• Upper limit in diabetics: Mortality rises when glucose exceeds 180 mg/dL (10 mmol/L) 1, 2
• Upper limit in non-diabetics: Mortality rises when glucose exceeds 140 mg/dL (7.8 mmol/L) 1, 2

Do NOT aim for tight control <150 mg/dL (<8.3 mmol/L) because this significantly increases the risk of dangerous hypoglycemic events without proven mortality benefit 2

Treatment Approach

For Patients Without Pre-Existing Diabetes:

Initiate continuous insulin infusion via electronic syringe (IVES) when glucose persistently exceeds 180 mg/dL (10 mmol/L) 1, 2

• Target glucose 90-180 mg/dL (5-10 mmol/L) 1
• Monitor for new-onset diabetes that may be triggered by the virus itself 1, 2
• Screen for diabetic ketoacidosis if severe hyperglycemia develops, as infection can unmask previously undiagnosed diabetes 1

For Patients With Pre-Existing Diabetes:

Continue insulin therapy without interruption and adjust based on frequent glucose monitoring 1

• Type 1 diabetes or insulin-requiring type 2 diabetes: Use continuous insulin infusion (IVES) during severe infection 1
• Patients on insulin pumps: If pump must be stopped, immediately transition to IVES insulin 1
• Tremendous insulin requirements are commonly observed during severe COVID-19 and other serious infections, often disproportionate to critical illness from other causes 1

Medication Adjustments During Infection:

Stop metformin during acute infection due to dehydration risk and lactic acidosis potential 1

Stop SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) due to diabetic ketoacidosis and dehydration risk 1

Continue DPP-4 inhibitors (alogliptin, linagliptin, saxagliptin, sitagliptin) as they are generally well tolerated 1

Monitor GLP-1 receptor agonists closely for dehydration; encourage adequate fluid intake and regular meals 1

Critical Pitfalls to Avoid

Hypoglycemia Risk:

• Certain infections (malaria) and late-stage sepsis can cause hypoglycemia, especially in malnourished individuals, children, or those with chronic liver disease 2
• If glucose measurement is impossible in a patient with impaired consciousness, presume hypoglycemia and administer 30-50 g of intravenous glucose immediately 2
• Altered mental status in septic patients should trigger immediate glucose assessment 2

Diabetic Ketoacidosis Recognition:

• Italian clinicians report frequent severe DKA at hospital admission during COVID-19, suggesting potential direct β-cell damage from certain viral infections 1
• Monitor for ketones when glucose exceeds 250 mg/dL (13.9 mmol/L), particularly in type 1 diabetes 8
• Vomiting with ketosis requires immediate emergency intervention 8

Infection-Specific Considerations:

• Urinary tract infections are the most common infection in diabetics (70% of cases), followed by respiratory infections (11.8%) and soft tissue infections (10.3%) 7
• Soft tissue infections in diabetics are strongly associated with diabetic microangiopathy (85.7% of cases) 7
• Perioperative stress hyperglycemia increases surgical site infection risk and requires perioperative glucose control between 90-180 mg/dL 1

Immune Function Impairment:

Acute hyperglycemia directly impairs innate immunity through multiple mechanisms:

• Inhibits neutrophil migration, phagocytosis, superoxide production, and microbial killing via protein kinase C activation 5
• Decreases neutrophil extracellular trap formation 5
• Causes direct glycosylation of complement proteins, inhibiting opsonization and bacterial clearance 5
• Increases vascular permeability and decreases dilation during inflammatory responses 5

This creates a vicious cycle: infection causes hyperglycemia, which impairs immune function, which worsens infection severity 9, 5

Prevention and Long-Term Management

Intensify metabolic control in diabetic patients who have not yet been infected as primary prevention of severe infection complications 1

• Maintain HbA1c <6.5% when possible, as poorly controlled diabetes (elevated HbA1c and fructosamine) correlates with increased infection frequency and severity 1, 7
• Continue strict blood pressure and lipid control 1
• Utilize remote consultations (Connected Health models) to reduce infection exposure while maintaining diabetes management 1