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.

项目概要研究表明，患有 2 型糖尿病 (T2D) 的顺性别女性复发的风险更大泌尿生殖系统感染，包括尿路感染和外阴阴道念珠菌病（VVC），但尚不清楚 T2D 患者的细菌性阴道病 (BV) 发病率是否异常高。 BV是一种常见的一种阴道炎，在北美女性中患病率为 30%。 BV的特点是阴道微生物群缺乏乳酸菌，与性传播风险增加有关感染，包括艾滋病毒，以及严重影响生活质量的外阴阴道症状。钠葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂是一种有效的口服抗糖尿病药物，通过抑制肾脏对葡萄糖的重吸收，导致尿液中葡萄糖的排泄增加。这个机制有与 VVC 发生率增加相关，但 SGLT2 抑制剂对泌尿生殖系统的影响尚未用分子方法研究微生物群。在这个 F31 中，我提出了分子流行病学该项目评估与 T2D 以及使用 SGLT2 抑制剂后相关的阴道微生物群。我假设 T2D 和 SGLT2 抑制剂与分子 BV 和阴道微环境有关乳酸含量低。乳酸菌产生乳酸是一项重要功能，因为它提供了通过酸化阴道微环境（pH <4.5）来提供保护。具体目标是： 1) 评估与民族/种族匹配的个体相比，非妊娠 T2D 个体的阴道微环境没有 T2D。 45 岁及以上的顺性别女性将被招募参加一项横断面研究马里兰大学糖尿病和内分泌中心以及巴尔的摩的综合健康诊所市中心校区。将利用 16S rRNA 评估自行采集的阴道样本的细菌组成基因扩增子测序、泛细菌定量 PCR 和乳酸异构体测定。问卷调查将收集重要的协变量信息。 2）比较女性治疗前后的泌尿生殖微生物群使用 SGLT2 抑制剂进行治疗，利用从正在进行的研究中收集的尿液样本库老秩序阿米什人（R01-DK118942，PI：泰勒，共同发起人）。单一交叉研究设计允许评估 SGLT2 抑制剂后泌尿生殖微生物群的变化并消除混杂因素与时间无关的因素，因为它允许每个参与者作为自己的控制者。目标 2 基于储存尿液样本，使其高度可行；最近发表的研究表明尿液样本表现出与阴道微生物群的高度一致性。 F31 中提出的研究将提供第一个描述 T2D 背景下阴道微生物群的特征并评估 SGLT2 抑制剂对泌尿生殖微生物群。这些发现将有助于 BV 筛查指南和妇科护理 T2D 患者和服用 SGLT2 抑制剂的患者。 F31 将提供独特的分子训练人类微生物组的流行病学以及糖尿病和慢性病流行病学的研究。