HOST FACTORS — Host-specific factors that are thought to predispose diabetic patients to
infection include the following:
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Hyperglycemia-related impairment of the immune response
Vascular insufficiency
Sensory peripheral neuropathy
Autonomic neuropathy
Skin and mucosal colonization with pathogens such as Staphylococcus aureus and
Candida species
Hyperglycemia-related impairment of immune response — Neutrophil chemotaxis and
adherence to vascular endothelium, phagocytosis, intracellular bactericidal activity,
opsonization, and cell-mediated immunity are all depressed in diabetics with hyperglycemia
[10-12]. Investigations to identify the mechanisms of immune impairment have noted the
following findings:
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Release of tumor necrosis factor-alpha and interleukin-1-beta from
lipopolysaccharide-stimulated macrophages is reduced in diabetic mice compared
with control mice [13].
The level of macrophage inflammatory protein 2, a mediator of lung neutrophil
recruitment, is significantly decreased in diabetic compared to control mice [14]. The
deficiency causes a delay in neutrophil recruitment in the lungs.
Hyperglycemia impairs opsonophagocytosis by diverting NADPH from superoxide
production into the aldose reductase-dependent polyol pathway [15].
Diabetic mice with a bacterial infection of the scalp had greater than two-fold
induction of genes that directly or indirectly induce apoptosis compared with
normoglycemic controls [16]. Blocking apoptosis allows for a significant
improvement in wound healing and bone growth.
Methylglyoxal-glycation, which is a major pathway of glycemic damage in diabetics,
inhibits production of IL-10 from myeloid cells as well as interferon-gamma and
tumor necrosis factor-alpha from T cells; it also reduces MHC class I expression on
the surface of myeloid cells [17].
High glucose concentrations competitively inhibit binding of oligosaccharides by Ctype lectin; such binding is necessary for many functions of the immune system [18].
There has been substantial interest in studying the effects of glucose control in critically ill
non-diabetic patients. This is discussed in detail separately. (See "Glycemic control and
intensive insulin therapy in critical illness".)
Vascular insufficiency — Vascular disease is common in diabetes. When present, vascular
insufficiency may result in local tissue ischemia that in turn enhances the growth of
microaerophilic and anaerobic organisms while simultaneously depressing the oxygendependent bactericidal functions of leukocytes. Vascular disease related to diabetes may also
impair the local inflammatory response and the absorption of antibiotics.
Sensory peripheral neuropathy — Minor local trauma in patients with diabetes-associated
peripheral neuropathy may result in skin ulcers, which, in turn, lead to diabetic foot
infections. Skin lesions in such patient are often either unnoticed or ignored until infection
occurs.
Autonomic neuropathy — Patients with diabetes-associated autonomic neuropathy may
develop urinary retention and stasis that, in turn, predisposes them to develop urinary tract
infections.
Increased skin and mucosal colonization — Patients with diabetes, particularly those who
inject insulin daily, often have asymptomatic nasal and skin colonization with S. aureus.
Furthermore, according to an analysis of data from the National Health and Nutrition
Examination Survey (NHANES) collected between 2001 and 2002, diabetic patients who are
colonized with S. aureus are more likely to have a methicillin-resistant S. aureus isolate than
a susceptible one (odds ratio 2.6; 95% CI, 1.1-6.1) [19]. Colonization may predispose to
cutaneous or incisional staphylococcal infections as well as transient bacteremia, which may
then result in infection at distant sites such as damaged muscle.
Mucosal colonization with Candida albicans is also common. Women with diabetes who
have poor glycemic control are more prone to vulvovaginal candidiasis than euglycemic
women [20,21]. In particular, women with type 2 diabetes appear prone to non-albicans
Candida species [22]. (See "Candida vulvovaginitis", section on 'Risk factors'.)