Diabetes and coccidioidomycosis:

February 1, 2007

Although most persons infected with Coccidioides immitis (Figure) are asymptomatic or have only mild illness, those who are immunocompromised are at increased risk for more severe disease. This is also true for patients with diabetes mellitus.

Although most persons infected with Coccidioides immitis (Figure) are asymptomatic or have only mild illness, those who are immunocompromised are at increased risk for more severe disease. This is also true for patients with diabetes mellitus.

Although the relationship between diabetes mellitus and coccidioidomycosis has not been extensively studied, some reports indicate that patients who have diabetes are at increased risk for more severe infection and for complications.1,2 A study by Rosenstein and colleagues,1 for example, demonstrated that diabetes is an independent risk factor for severe pulmonary coccidioidomycosis.

Additional evidence was reported by Baker and associates,2 who retrospectively studied 52 diabetic patients who had undergone surgery for pulmonary coccidioidomycosis. The incidence of more severe, progressive disease was 4 times higher in patients who had insulin-dependent diabetes than in those who had non-insulin-dependent diabetes.

Recent findings

A recent study by Santelli and associates3 found that poor glycemic control is associated with an increased risk of complications in patients with coccidioidomycosis. The authors retrospectively studied 329 immunocompetent patients who had this fungal infection; 44 had diabetes (40 had type 2 diabetes). The risk of cavitary lung disease was increased in patients with diabetes compared with those who did not have diabetes (relative risk [RR], 2.94; P < .001).

The risk of disseminated disease was significantly increased in patients who had serum glucose concentrations of 220 mg/dL or higher compared with those who had lower glucose concentrations (RR, 2.8; P = .05). The patients with higher glucose levels also were more likely to require treatment (RR, 9.85; P = .005), and their infection was less likely to resolve (RR, 0.24; P = .002).

The authors recommended that serum glucose concentrations be routinely measured in patients with coccidioidomycosis.3

Potential mechanisms

Patients with diabetes are at increased risk for a variety of infections. Although the immunologic mechanisms for the increased risk of infection have not been fully elucidated, possible explanations include the following3:

•Decreased polymorphonuclear adherence, chemotaxis, phagocytosis, and bactericidal activity.

•Impaired innate and adaptive cellular immunity, particularly T-cell function.

•Cytokine-related changes.

In addition, the hyperglycemic environment may enhance the virulence of certain microorganisms.3

Glucose control

Strict glucose control is recommended for all patients with diabetes, since glucose toxicity clearly increases the risk of complications.4,5 Several studies have shown that improved glycemic control can strengthen immune function and reduce the risk of infection.6-9 These findings are not limited to patients with diabetes. For example, Van den Berghe and colleagues7 found that intensive insulin therapy aimed at maintaining serum glucose levels at less than 110 mg/dL helped prevent complications in a surgical ICU population. Intensive insulin therapy also reduced complication and mortality rates in a medical ICU population.9

References:

REFERENCES

1. Rosenstein NE, Emery KW, Werner SB, et al. Risk factors for severe pulmonary and disseminated coccidioidomycosis: Kern County, California, 1995-1996. Clin Infect Dis. 2001;32:708-715.

2. Baker EJ, Hawkins JA, Waskow EA. Surgery for coccidioidomycosis in 52 diabetic patients with special reference to related immunologic factors. J Thorac Cardiovasc Surg. 1978;75: 680-687.

3. Santelli AC, Blair JE, Roust LR. Coccidioidomycosis in patients with diabetes mellitus. Am J Med. 2006;119:964-969.

4. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329:977-986.

5. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group [published correction appears in Lancet. 1999;354:602]. Lancet. 1998;352:837-853.

6. Joshi N, Caputo GM, Weitekamp MR, Karchmer AW. Infections in patients with diabetes mellitus. N Engl J Med. 1999;341:1906-1912.

7. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359-1367.

8. Van den Berghe G, Wouters P, Bouillon R, et al. Outcome benefit of intensive insulin therapy in the critically ill: insulin dose versus glycemic control. Crit Care Med. 2003;31:359-366.

9. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354:449-461.

10. Stafford CM, Lim ML, Lamb C, et al. Fever and a chest wall mass in a young man. J Respir Dis. 2005;26:342-344.