Diabetes mellitus, sodium glucose cotransporter-2 inhibitors and the vaginal microbiota

Abstract

Women with type 2 diabetes (T2D) face increased risk for urinary tract infections and vulvovaginal candidiasis (VVC). It is unknown whether women with T2D have higher rates of another prevalent vaginal condition: bacterial vaginosis (BV). BV is characterized by a low-Lactobacillus vaginal microbiota with a higher abundance of anaerobic bacteria. Vaginal Lactobacillus species are essential for urogenital health. Aim 1 sought to assess the association between diabetes and the vaginal microbiota. Biannual mid-vaginal swabs and annual sera from 811 women followed for two years were utilized. The vaginal samples underwent 16S rRNA gene amplicon sequencing and pan-bacterial qPCR. Diabetes cases (N=45) were identified through self-reported medication, medical history, or glycated albumin levels exceeding 16.5%. Compared to participants without diabetes, cases had lower odds of L. iners-dominated vaginal microbiota relative to Lactobacillus-dominated microbiota (aOR: 0.51, 95% CI:0.29-0.74). Among postmenopausal individuals without diabetes, those with low-Lactobacillus/high diversity microbiota had higher odds of vulvovaginal atrophy (aOR=1.65, 95% CI: 1.07-2.53) compared to those with Lactobacillus-dominated microbiota; this estimate was non-significant in diabetes cases (N=22), although sample size was small. Aim 2 evaluated whether there was a short-term effect of the sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin on the genitourinary microbiota. SGLT2 inhibitors are a popular oral antidiabetic drug, and while they have been linked with increased VVC risk, their impact on the genitourinary microbiota is unknown. This aim utilized archived urine samples from a trial which administered canagliflozin (300 mg/day for five days) to an Amish cohort without diabetes. Vaginal samples were not collected in the parent study, but urine samples provide an adequate approximation of vaginal microbiota. The samples showed no significant bacterial community changes following SGLT2 treatment and no associations with adverse outcomes of a low-Lactobacillus/high diversity or L. iners-dominated states. Although, further exploratory compositional analyses indicated slight changes over 6 days. This dissertation reveals novel insights into possible impacts of diabetes on the vaginal microbiota, and while no short-term effects of SGLT2 inhibitors were observed on the genitourinary microbiota, further research is essential. Larger, long-term studies are needed to comprehensively understand the impact of diabetes and SGLT2 inhibitors on urogenital health.