Prevalence and risk factors for vaginal Candidacolonization in women with type 1 and type 2 diabetes

Diabetes mellitus predisposes individuals to bacterial and fungal infections, including those caused by Candida species. Many investigators have suggested that vulvovaginal candidiasis (VVC) occurs more frequently in diabetics [1–8]. Further, chronic recurring VVC may be a marker of diabetes [9]. Several studies report increased rates of asymptomatic vaginal carriage rates of Candida species and incidence of symptomatic infection in diabetic women, but results are inconsistent [5, 10–14]. While some show no increase in carriage of vaginal Candida[5], those demonstrating increased Candida carriage in female diabetes patients do not examine the effect of glucose control or diabetes type [12, 14]. However, in vitro studies demonstrating impaired host response directed against Candida in diabetics support the idea of increased rates of Candida colonization among diabetics [4, 6, 7]. Whether diabetes leads to more symptomatic and/or more recurrent VVC episodes is a subject of controversy.

Potential risk factors for VVC include diabetes type, severity, and degree of glucose control.[26–30] In addition to diabetes mellitus, a number of VVC risk factors have been identified, including African-American heritage [15–17], previous history of VVC [15], higher education degree, intermediate age, oral contraceptive pills [3, 10, 16, 18], use of commercially available solutions for cleansing of external genitalia or vaginal douching, frequent sexual intercourse [17, 19, 10], sexual behavior (age at first intercourse, frequency of oral-genital contact) [20], contraception devices (diaphragm, vaginal contraceptive sponge, intrauterine device), and antibiotics [3, 15, 19]. Whether these factors increase risk ofCandida colonization or symptomatic infection following colonization, or both, is unknown, however, it should be emphasized that a prerequisite for symptomatic vaginitis is vaginal colonization.

Few studies have addressed the relationship between Candida colonization, VVC, and diabetes; none we are aware of have examined the role of behavioral VVC risk factors for colonization among persons with diabetes. To evaluate the relationship between Candida colonization and hypothesized risk factors for vulvovaginal candidiasis colonization in diabetics, we conducted a cross-sectional study among female diabetes patients receiving care at one of two diabetes clinics. We describe the associations between Candida colonization, sociodemographics, health behaviors, diabetes type, diabetes severity, and Hemoglobin A_1c level among women with type 1 and type 2 diabetes.

Among women with diabetes, Candida carriage increased with older age, type 1 diabetes, abnormal HbA_1c level, oral antibiotic use in the previous two weeks, and ever history of chlamydia. Other VVC risk factors, including African American descent, lifetime history of VVC, higher education, oral contraceptive use, and frequency of vaginal intercourse were not significantly associated with Candida colonization after adjustment for other variables. These data suggest that behavioral factors, as well as HbA_1c, are important determinants of Candida colonization among women with diabetes.

Women with type 1 diabetes had higher Candida colonization rates than those with type 2, even after adjusting for age, behavioral factors and HbA_1c. One possible explanation is difference in duration of Candida carriage: women with type 1 and type 2 diabetes may be equally likely to acquire Candida, but those with type 1 may be less able to clear it. Similar to previous reports, C. albicans was isolated from the majority of colonized type 1 participants, while C. glabrata was the most common isolate in type 2 participants, but our numbers are small [1]. Whether this is due to diabetes type or reflects different distributions of Candida species by age or both is uncertain.

The observation that hyperglycemia in type 1 diabetes increases risk for Candida colonization is consistent with previous reports [1, 5, 6, 31]. A New Zealand study of 124 women with type 1 diabetes found 7 of 7 women with elevated glycated hemoglobin reported vaginal symptoms for the previous year, compared with 60% overall [10]. Hyperglycemia limits neutrophil function among persons with type 1 diabetes, including neutrophils' ability to phagocytose and kill Candida organisms. With the oxidative killing ability of neutrophils hindered, diabetics may not be able to clear pathogens as well as non-diabetics [1, 6, 7, 31]. Hyperglycemic individuals may also have increased risk for Candida colonization because their secretions contain glucose, which can serve as nutrients for Candida organisms. Sobel and colleagues reported a fucose (6-deoxy-galactose) vaginal epithelial cell receptor that aids in adhesion of Candida to vaginal epithelial cells [32]. Since fucose contains an isomer of glucose and acts as one form of receptor site for Candida adhesion, it is possible that increased Candida colonization is proportional to glucose level. Receptor avidity may be a reflection of increased glucose levels in the blood and tissues. Glycemia, however, does not fully explain the observed increased risk of Candida colonization.

We found a borderline significant association with performing oral sex associated with an almost five-fold increase in vaginal colonization with Candida. Receiving but not performing oral sex has been previously reported as a risk factor for VVC [15]. Oral sex may facilitate transmission of yeast, as Candida often colonizes the oral cavity [15, 33]. Diabetics may be more likely to carry Candida in the oral cavity than their sex partner; thus, performing oral sex on their sex partner prior to vaginal intercourse may serve to inoculate the vaginal cavity. Douching has also been previously associated with Candida colonization [17, 19, 20]. The practice is hypothesized to disrupt vaginal flora; vaginal symptoms may also lead a women to douche so the direction of effect is unclear. The association we observed with chlamydia is probably a marker of sexual behavior rather than a causal factor; for example, women who reported a history of chlamydia were more likely to douche and to report engaging in oral sex, although it is possible that chlamydia carriage adversely affects the vaginal flora increasing the chance of Candida colonization. Recent antibiotic use is a well-described correlate of symptomatic Candida vaginitis [3, 15–18, 34]. While asymptomatic infection is not equivalent to disease, antibiotic use may act to alter the vaginal microenvironment to facilitate Candida colonization in the same way it is hypothesized to promote VVC.

Women aged 45 years and older in our study were more likely to be colonized with Candida species. We are unaware of colonization studies in women of comparable age; most have emphasized women of childbearing age [8, 35, 36]. Whether our observation is a real finding or a reflection of our age distribution (18–84) or unknown selection biases which led to inclusion in our study requires further investigation. However, incidence of symptomatic infection is higher in younger (18–44) women [15].

This study is small and was intended to be hypothesis generating. The study population is in no way representative of all females with diabetes, although the age and racial distribution of participants reflected that of the participating clinics. Although it is possible that women with a history of symptomatic infection might have been more likely to participate, we have no reason to believe that women differentially participated by both symptomatic history and other variables under study which would have biased our results. Further, as women were unaware of whether they carried Candida at the time of completing the questionnaire, it seems unlikely that a differential recall of behaviors among colonized and non-colonized might have occurred. A final concern is that Candida colonization, while the first step toward VVC, is not equivalent to symptomatic infection. Larger, more definitive studies, which include a non-diabetic control group and prospective follow-up, are planned.

We found strong, statistically significant associations between vaginal Candida colonization and antibiotic use, lifetime history of chlamydia, diabetes type and HbA_1c level and a borderline significant association with performing oral sex. More non-albicans species were observed among women with type 2 diabetes. Improving glucose control and possibly modifying sexual behavior may reduce risk of Candida colonization, and potentially symptomatic infection, among women with diabetes.