权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Type 2 diabetes, sodium glucose, cotransporter-2 (SGLT2) inhibitors and the vaginal microbiota

2 型糖尿病、葡萄糖钠、协同转运蛋白 2 (SGLT2) 抑制剂和阴道微生物群

基本信息

批准号：
10749868
负责人：
Sarah Robbins
金额：
$ 3.09万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-01 至 2024-02-02
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10749868
关键词：
16S ribosomal RNA sequencing Adult Affect Aftercare Age Age Years American Amish Anaerobic Bacteria Anti-Inflammatory Agents Antibiotics Antidiabetic Drugs Atopobium vaginae Bacteria Bacterial Vaginosis Baltimore Biogenic Amines Biological Assay Biological Response Modifier Therapy Cell membrane Chronic Disease Clinic Cohort Studies Communities Cross-Over Studies Cross-Sectional Studies Data Development Diabetes Mellitus Diabetic Nephropathy Endocrinology Epidemiology Epithelium Erectile dysfunction Ethnic Origin Excretory function Feeling Female Frequencies Future Genital Genitalia Genitourinary System Infection Genitourinary system Gestational Diabetes Glucose Glycosuria Growth Gynecologic HIV Health Heart failure High Prevalence Hospitalization Human Human Microbiome Hyperglycemia In Vitro Incidence Individual Isomerism Kidney Knowledge Lactic acid Lactobacillus Maryland Measures Mediating Meta-Analysis Metabolic Methods Molecular Molecular Epidemiology Morbidity - disease rate Non-Insulin-Dependent Diabetes Mellitus Odors Oral Outcome Output Participant Patient Care Patients Pharmaceutical Preparations Play Premature Birth Prevalence Prevention Prevotella Production Property Publishing Quality of life Questionnaires Race Recurrence Reporting Reproductive Health Research Research Design Risk Risk Factors Role Sampling Sexual Health Sexually Transmitted Diseases Sodium Symptoms Time Training Universities Urinary tract infection Urine Vagina Vaginitis Vulvovaginal Candidiasis Woman Women&apos s Health absorption adverse outcome aged cervicovaginal cis-female diabetes management diabetic dysbiosis effective therapy improved infection risk inhibitor intraamniotic infection irritation men microbiota non-diabetic obstetric outcomes pathogen pregnant prevent randomized trial recruit repository reproductive screening guidelines side effect symporter urogenital tract vaginal lactobacilli vaginal microbiota

项目摘要

PROJECT SUMMARY Studies have shown that cisgender women with type 2 diabetes (T2D) are at greater risk for recurrent urogenital infections, including urinary tract infections and vulvovaginal candidiasis (VVC), but it is unknown whether individuals with T2D have disproportionately higher rates of bacterial vaginosis (BV). BV is a common form of vaginitis with a 30% prevalence among North American women. BV is characterized by a Lactobacillus-deficient vaginal microbiota and is associated with increased risk for sexually transmitted infections, including HIV, as well as vulvovaginal symptoms that significantly affect quality of life. Sodium glucose cotransporter-2 (SGLT2) inhibitors, a favorable oral antidiabetic medication, function by inhibiting reabsorption of glucose in the kidneys, causing increased excretion of glucose in urine. This mechanism has been associated with increased incidence of VVC, but the influence of SGLT2 inhibitors on the genitourinary microbiota has not been investigated with molecular methods. In this F31, I propose a molecular epidemiologic project which assesses the vaginal microbiota associated with T2D and after SGLT2 inhibitor use. I hypothesize that T2D and SGLT2 inhibitors are associated with molecular-BV and a vaginal microenvironment low in lactic acid. The production of lactic acid by lactobacilli is an important function because it provides protection by acidifying the vaginal microenvironment (to pH <4.5). The specific aims are: 1) To assess the vaginal microenvironment in non-pregnant individuals with T2D compared to ethnicity/race-matched individuals without T2D. Cisgender women aged 45 years and greater will be recruited to a cross-sectional study at the University of Maryland Center for Diabetes and Endocrinology and a general health clinic at the Baltimore Midtown campus. Self-collected vaginal samples will be assessed for bacterial composition utilizing 16S rRNA gene amplicon sequencing, pan-bacterial quantitative PCR and lactic acid isomer assays. Questionnaires will collect important covariate information. 2) To compare the genitourinary microbiota of women before and after treatment with SGLT2 inhibitors, utilizing a repository of urine samples collected from an ongoing study in the Old Order Amish (R01-DK118942, PI: Taylor, co-sponsor). The single cross-over study design allows for assessment of changes in the genitourinary microbiota following SGLT2 inhibitors and eliminates confounding on time-independent factors because it allows each participant to serve as their own control. Aim 2 is based on repository urine samples, making it highly feasible; recently published studies suggest urine samples demonstrate high concordance with vaginal microbiota. The studies proposed in this F31 will provide the first characterization of the vaginal microbiota in the setting of T2D and assess the impact of SGLT2 inhibitors on the genitourinary microbiota. These findings will contribute to BV screening guidelines and gynecologic care for patients with T2D and those taking SGLT2 inhibitors. The F31 will provide unique training in the molecular epidemiology of the human microbiome and studies of diabetes and chronic disease epidemiology.

项目总结