Can Untreated Diabetes Cause Leukocytosis?
Yes, untreated diabetes mellitus can cause leukocytosis, but this elevation is typically modest and occurs through two distinct mechanisms: as a physiological stress response to severe hyperglycemia and metabolic derangement, or as a secondary response to infection (which diabetic patients are more susceptible to developing). 1
Primary Mechanisms of Leukocytosis in Diabetes
Stress-Induced Leukocytosis from Metabolic Derangement
Severe hyperglycemia itself acts as a physiological stressor that can elevate white blood cell counts through the release of stress hormones (cortisol, catecholamines) and inflammatory cytokines, similar to other physical stressors like trauma or surgery. 1, 2
The metabolic instability associated with uncontrolled diabetes—including severe hyperglycemia, acidosis, and hyperosmolar states—triggers a systemic inflammatory response that can produce leukocytosis even without infection. 1
This stress-related leukocytosis is typically mild to moderate (usually WBC counts in the 11,000-15,000 range), as the peripheral white blood cell count can double within hours in response to metabolic stress due to mobilization from bone marrow storage pools. 2, 3
Infection-Related Leukocytosis
Diabetic patients have increased susceptibility to infections due to impaired leukocyte function (decreased phagocytosis, impaired bacterial killing, and reduced chemotaxis) caused by hyperglycemia. 1
When infection is present—particularly in diabetic foot infections, pneumonia, or urinary tract infections—leukocytosis becomes more pronounced and is accompanied by other signs of infection such as fever, purulent drainage, or cellulitis. 1
Critical Clinical Pitfalls
The Unreliability of Leukocytosis in Diabetic Infections
A major pitfall: normal white blood cell counts do NOT exclude serious infection in diabetic patients. In one study of diabetic patients with acute osteomyelitis of the foot, 54% had normal WBC counts on admission despite confirmed bone infection. 4
In diabetic foot infections specifically, leukocytosis is present in only about 46% of cases with confirmed osteomyelitis, making it a poor screening tool for infection in this population. 4
The absence of fever is equally unreliable—82% of diabetic patients with acute osteomyelitis had normal oral temperatures. 4
Distinguishing Infection from Metabolic Stress
When evaluating a diabetic patient with leukocytosis, look for these specific infection indicators: purulent drainage, erythema extending >2 cm from wound edges, warmth, tenderness, induration, and the ability to probe to bone. 1
C-reactive protein (CRP) is more reliable than WBC count for identifying concurrent bacterial infection in diabetic patients, as CRP levels correlate with infection presence rather than just metabolic derangement. 5
Erythrocyte sedimentation rate (ESR) is elevated in 96% of diabetic patients with osteomyelitis, making it more sensitive than WBC count for detecting bone infection. 4
Practical Clinical Algorithm
When Encountering Leukocytosis in a Diabetic Patient:
First, assess for metabolic instability: Check blood glucose, pH, bicarbonate, anion gap, and serum osmolality to identify severe hyperglycemia, diabetic ketoacidosis, or hyperosmolar hyperglycemic state. 1
Second, systematically search for infection sources: Examine feet for ulcers and probe wounds to bone; assess for pneumonia, urinary symptoms, or other focal infections. 1
Third, obtain adjunctive markers: Order CRP and ESR, as these are more reliable than WBC count alone for identifying infection in diabetic patients. 4, 5
Fourth, recognize that hospitalization criteria include: systemic toxicity (fever AND leukocytosis together), metabolic instability, rapidly progressive infection, or substantial tissue necrosis—not leukocytosis alone. 1
Important Nuances
The degree of leukocytosis correlates with glycemic control: Higher HbA1c levels are associated with elevated neutrophil-to-lymphocyte ratios, suggesting chronic poor glucose control contributes to baseline inflammatory cell elevation. 6
In diabetic ketoacidosis, leukocytosis is common but does NOT reliably indicate infection—the metabolic acidosis itself causes WBC elevation, and CRP should be used instead to identify concurrent bacterial infection. 5
Medications matter: Corticosteroids (often used in severe illness) can independently cause leukocytosis and worsen hyperglycemia, creating a confounding clinical picture. 2, 3