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© Borgis - New Medicine 1/2001, s. 12-15
Agnieszka Szypowska
Fungal infections in diabetes
The Second Department of Paediatrics - Department of Paediatric Diabetology and Birth Defects The Medical University of Warsaw
Head: Lech Korniszewski MD, PhD Warsaw University Medical School
Patients with diabetes mellitus have increased susceptibility to certain mycotic infections. In this article the author describes predisposing factors and presents a clinical picture of fungal infections frequently reported in diabetics.
It is generally known that patients with diabetes mellitus are more prone to fungal infections and that the course of the disease may be more severe. This occurs in some mycoses e.g. mucocutaneous candidiasis or mucormycosis, which are more frequent in diabetes. Most patients, especially those with good metabolic control, show no increased risk. Apart from diabetes, many factors predispose to fungal infections: long-term antibiotic therapy, immunosuppresion, AIDS, neutropaenia, burns, cardiosurgical operations, organ transplantation, renal dialysis, prematurity, pregnancy and others.
One of the causes of increased susceptibility to infections in diabetic patients is an impaired immune function. Impaired leukocyte function is associated with inadequate glucose metabolism. Normal phagocytosis requires energy which is a product of glycolysis. Energy supplies used by phagocytes are small, and therefore the substrate must be obtained from external sources. Glucose is transported via the leukocyte cell membrane without the participation of insulin. However, insulin is required to activate enzymes of the glycolytic cycle i.e., glucokinase and pyruvate kinase. Insulin deficiency leads to impaired glycolysis and this impairs the process of phagocytosis (12).
The disturbed glucose metabolism inside the leukocytes results in a decreased ability of phagocytes to destroy microorganisms. In the aerobic processes which play a significant role in fungal infections, phagocytosis of micoorganisms stimulates respiratory processes within a few minutes, which produces toxic oxidants (14). The action of the NADPH oxidase and displacement of an electron with NADPH onto the molecular oxygen leads to the formation of a superoxide anion, which gives rise to hydrogen peroxide. With the participation of ferrous ions, hydroxyl radicals are formed from hydrogen peroxide and in the myoloperoxidase-catalyse reaction hypochlorous acid is formed. This in reaction with amines, produces cholaramins (4). Reactive oxygen compounds are toxic for bacteria, parasitic fungi and tumour cells. A high level of glycaemia in patients with diabetes means that most glucose is metabolised by aldose reductase, by means of NADPH. These transformations lead to the consumption of NADPH which is indispensible in the oxygen processes involved in destroying microorganisms by phagocytes (14). The significance of these disturbances may be evidenced by the fact that among individuals with myeloperoxidase deficiency who develop severe fungal infections, a large number is represented by patients with diabetes (3).
Patients with diabetes mellitus also have impaired chemotaxis. This seems to have no association with poor metabolic control, but with an independent congenital defect. Impaired chemotaxis has been found in the offspring of patients with diabetes (9).
Factors contributing to the development of mycoses also include vascular alterations and neuropathy which are chronic complications of diabetes.
There are over 150 fungi from the Candida species which are present in our environment as saprophites. Merely a few of those are pathogenic for man, and those most frequenly isolated are: C. albicans, C. tropicalis, C krusei, C. parapsilosis, C. stellatoidea, C. glabrata and the primarily amphotericin B-resistant C. lusitanie (21). The Candida species are commensals on the mucous membranes and the skin. The most frequently isolated are C. albicans (80% jointly with C. tropicalis), whereas C. glabrata and C. parapsilosis are found in 10%-15% of cases (2). In intensive care units in the USA infections due to the Candida species are the fourth most frequent, following Pseudomonas aeruginosa, Staphylococcus aureus and coagulase-negative staphylococci (5). High mortality rates are also noted among patients with systemic candidiasis (10, 11).
Table 1. Types of fungal infections in patients with diabetes.
Significantly increased incidence
a. rhinocerebral
b. cutaneous
a. vulvovaginal
b. oral
c. candiduria
d. ascending pyelonephritis
a. external otitis

Slightly increased incidence

a. cutaneous
b. prostatic abscess
c. peritonitis in patients undergoing peritoneal dialysis

Possible increased incidence(?)

a. biliary tract infection
b. postoperative peritonitis
Pulmonary mucormycosis
Invasive aspergillosis

Incidence similar to that in general population
a. systemic candidiasis
b. candidaemia
c. Candida sinusitis
according to J.A. Vazquez, J.D. Sobel
Cutaneous candidiasis
Colonisation and infection of the skin with the Candida species occurs most frequently in patients with diabetes mellitus as compared with the remaining population (2). The most frequently isolated pathogen is C. albicans. Lesions are localised mainly in the skin folds. The most frequent sites are under the breasts, between the toes, in the groin, in the gluteal folds, and around the anus, where increased moisture is a predisposing factor. The lesions are intertriginous, primarily with a white surface which desquamates leaving a moist bright red area and festoon-like rims. A painful and deep fissure develops in the folds. Typical of the condition is the presence of distant, red, erythematous eruptions known as satellites (6).
Infection of the nail and the wall around the nail begins as a painful red swelling which develops scanty mucopurulent pus on pressure. The nail becomes grey, obliquely furrowed and may be separated from the nail bed (10).
Oral candidiasis
Vascular lesions, diabetic neuropathy, impaired collagen synthesis and genetic predisposition contribute to the development of diseases of the oral cavity. Patients with diabetes are more susceptible to gingivitis, paradontitis and caries than a healthy population (20). A high sugar concentration contributtes to oral fungal infections. In their epidemiological study of 439 patients with diabetes, Aly et al. confirmed the presence of fungi in the oral cavity in 54% of the subjects. The most frequent pathogen was C. albicans (67%). Other fungi included C. glabrata, C. parapsilosis, Sacharomyces cervisiae, C. tropicalis, C. pseudotropicalis and C. guilliermondi (1).
Patients with a poor control of diabetes develop persistent perleche at the corners of the mouth. A creamy white coating may appear on the buccal, lingual and palatal mucosa. The patients often experience, a burning sensationin in the oral mucosa, especially of the tongue. The gums and palate reveal redness, particularly at the sites in contact with a prosthetic plate (2).
Vulvovaginal candidiasis
A high glucose level in the discharge from the reproductive tract in women with diabetes predisposes to the development of fungal infections. The course of infection in patients with poor metabolic control may be persistent - chronic with frequent relapses. The presence of fungi without symptoms of infection may often be noted. It is considered that infections of the reproductive tract may be the initial manifestation of hyperglycaemia in women with undiagnosed diabetes (21). The most frequently - recognised pathogen is C. albicans which infrequently accompanies C. glabrata (18). Poor metabolic control is generally considered to be a predisposing factor in fungal infections. However, not all researchers confirm that view. Liotta et al. conducted a study of a group of children and adults with insulin-dependent diabetes. They did not find any statistically significant correlation between the duration and the degree of metabolic control and existing infection of the reproductive tract. However, they confirmed an increased incidence of infections in patients at puberty (7).

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New Medicine 1/2001
Strona internetowa czasopisma New Medicine