METabolic FLEXibility in PMOS
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Change in Normalized Relative Plasma Metabolite Abundance From Baseline to 2 Hours Post-Glucose Ingestion
研究概览
简要总结
Polyendocrine metabolic ovarian syndrome (PMOS), previously known as polycystic ovary syndrome (PCOS), is a common endocrine and metabolic condition affecting women of reproductive age. It is associated with hormonal imbalances, irregular menstrual cycles, elevated androgen levels, and metabolic disturbances such as insulin resistance. These metabolic changes can increase the risk of type 2 diabetes and cardiovascular disease.
Insulin resistance means that the body's cells respond less effectively to insulin, a hormone that regulates blood glucose. This leads to compensatory increases in insulin levels, which can further disrupt hormonal balance and contribute to the clinical features of PMOS.
This study aims to investigate how the bodies of women with PMOS respond dynamically to glucose intake compared with women without PMOS. A standard clinical test, the oral glucose tolerance test (oGTT), will be used. Participants consume a glucose solution, and blood samples are collected before and two hours afterward. This procedure is routinely used in clinical practice.
Women with PMOS will be compared with age- and body mass index (BMI)-matched control participants without PMOS. Blood and urine samples will be analyzed using advanced multi-omics technologies to measure proteins, metabolites, extracellular vesicles, and immune-related signals.
The main objective is to understand how metabolic, hormonal, and immune pathways respond over time to a glucose challenge and whether these responses differ in PMOS. Special attention is given to inter-organ communication and systemic metabolic regulation.
The study includes two visits. The first visit involves health assessments, questionnaires, and body composition measurements. The second visit includes the glucose tolerance test and blood sampling. In total, approximately 100 mL of blood will be collected across both visits.
Participation is voluntary, and participants may withdraw at any time without affecting their medical care. The procedures involve minimal risk and consist of standard clinical methods.
The results of this study may improve understanding of PMOS and contribute to better diagnostic and therapeutic strategies in the future.
详细描述
Background and Rationale: Polyendocrine metabolic ovarian syndrome (PMOS), previously referred to as polycystic ovary syndrome (PCOS), is a common endocrine disorder in women of reproductive age. PMOS is characterized by a heterogeneous clinical phenotype involving reproductive, endocrine, and metabolic disturbances, including hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology.
A central feature of PMOS is insulin resistance. Compensatory hyperinsulinemia can enhance ovarian androgen production and reduce hepatic sex hormone-binding globulin synthesis, thereby increasing circulating free androgen levels. This endocrine-metabolic interaction contributes to the reproductive and metabolic manifestations of PMOS.
Beyond reproductive dysfunction, PMOS is associated with impaired glucose metabolism, dyslipidemia, low-grade inflammation, and an increased long-term risk of type 2 diabetes and cardiovascular disease. Metabolic dysfunction in PMOS may not be fully captured by fasting measurements alone, because fasting assessments provide only a static snapshot of systemic physiology.
The oral glucose tolerance test provides a standardized metabolic challenge for assessing dynamic glucose homeostasis. Glucose ingestion induces coordinated physiological responses involving pancreatic insulin secretion, hepatic glucose regulation, peripheral glucose uptake, endocrine adaptation, and immune-metabolic signaling. Dynamic molecular profiling during an oral glucose tolerance test may therefore reveal regulatory abnormalities that are not apparent under fasting conditions.
Plasma represents an integrative biological compartment reflecting metabolic, endocrine, inflammatory, and inter-organ communication processes. Advances in high-resolution molecular profiling now allow simultaneous characterization of circulating metabolites, plasma proteins, steroid hormones, inflammatory mediators, and extracellular vesicle-associated molecular cargo. Extracellular vesicles are of particular interest because extracellular vesicles may contribute to intercellular and inter-organ communication by transporting proteins, nucleic acids, lipids, and metabolites between tissues.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Age: 18-35 years
- •Body weight (BMI): between BMI 18.5-39.9 kg/m2
- •Ability to consent and to provide written informed consent
- •CG: History of regular MCs (21 to 35 days) 3 months prior to study enrollment
- •PCOS-G: Existing or new established diagnosis of PCOS. Diagnosis is verified in accordance with the ESHRE/ASRM Rotterdam consensus (2003)23, phenotype A (hyperandrogenism, oligo-/anovulation, and polycystic ovarian morphology). PCOS is diagnosed when at least the following three criteria are present, after exclusion of other etiologies:
- •Oligo- or anovulation
- •Clinical and/or biochemical signs of hyperandrogenism
- •Polycystic ovaries on ultrasound (≥12 follicles per ovary measuring 2-9 mm in diameter and/or ovarian volume >10 mL)
排除标准
- •Use of systemic hormonal contraceptives within the last 3 months prior to study enrollment. Use of levonorgestrel-releasing intrauterine devices is permitted; all other hormonal contraceptive methods are excluded.
- •CG: A clinically diagnosed or history of a menstrual disorder (e.g., polycystic ovarian syndrome (PCOS), premenstrual dysphoric disorder (PMDD) or amenorrhea)
- •A clinically diagnosed mental disorder (e.g. major depression, anxiety disorder)
- •history of epileptic seizure
- •history of or current manic or psychotic episode
- •existing/current eating disorders (bulimia nervosa, anorexia nervosa) within the past 5 years
- •inability to communicate adequately in speech
- •inability to follow instructions
- •regular use of medication other than thyroxine
- •alcohol consumption as equivalent doses of more than 12 g of pure alcohol per day
- •vegan diet
- •daily nicotine consumption
- •currently or history of (regular) consumption of illegal drugs within the last year
- •pregnancy or breastfeeding
- •known diseases of the cardiovascular system
- •arterial hypertension above 160/90 mm/Hg at rest
- •known pulmonary diseases
- •Arthritis and rheumatic diseases and conditions
- •Hematologic diseases
- •surgery less than 1 month ago
- •having given birth within 12 months before the start of the study
结局指标
主要结局
Change in Normalized Relative Plasma Metabolite Abundance From Baseline to 2 Hours Post-Glucose Ingestion
时间窗: Baseline (fasting, Visit 2) and 2 hours post-glucose ingestion (Visit 2).
Assessment of dynamic changes in circulating metabolites in response to a standardized oral glucose tolerance test (oGTT). Metabolomic profiling includes targeted and untargeted analyses of plasma metabolites involved in glucose metabolism, lipid metabolism, amino acid turnover, and energy homeostasis. Longitudinal changes between fasting state and post-glucose challenge will be compared between PMOS participants and age- and BMI-matched controls. The metabolomic response is used as a central readout of systemic metabolic flexibility.
Change in Normalized Relative Plasma Protein Abundance From Baseline to 2 Hours Post-Glucose Ingestion
时间窗: Baseline (fasting, Visit 2) and 2 hours post-glucose ingestion (Visit 2).
Quantification of dynamic changes in circulating plasma proteins in response to oGTT using nanoparticle-enhanced high-resolution proteomics. The analysis focuses on proteins involved in insulin signaling, inflammatory pathways, lipid metabolism, endocrine regulation, and inter-organ communication. Temporal protein abundance changes between fasting and post-glucose states will be assessed to characterize systemic proteomic adaptations and differences in metabolic flexibility between PMOS and controls.
次要结局
- Change in oGTT-Derived Glucose and Insulin Response Indices From Baseline to 2 Hours Post-Glucose Ingestion(Baseline and 2 hours post-glucose ingestion (Visit 2).)
- Change in Concentration of Plasma Extracellular Vesicles From Baseline to 2 Hours Post-Glucose Ingestion(Baseline and 2 hours post-glucose ingestion (Visit 2).)
- Change in Median Diameter of Plasma Extracellular Vesicles From Baseline to 2 Hours Post-Glucose Ingestion(Baseline and 2 hours post-glucose ingestion (Visit 2).)
- Change in Normalized Relative Abundance of Extracellular Vesicle-Associated Proteins From Baseline to 2 Hours Post-Glucose Ingestion(Baseline and 2 hours post-glucose ingestion (Visit 2).)
- Change in Normalized Relative Abundance of Extracellular Vesicle-Associated Metabolites From Baseline to 2 Hours Post-Glucose Ingestion(aseline and 2 hours post-glucose ingestion (Visit 2).)
- Change in Normalized Relative Abundance of Plasma Inflammatory Proteins From Baseline to 2 Hours Post-Glucose Ingestion(Baseline and 2 hours post-glucose ingestion (Visit 2).)
- Concentrations of Circulating Steroid Hormones from Baseline to 2 Hours Post-Glucose Ingestion(Baseline (fasting state, Visit 1 or Visit 2).)
- Total Body Bone Mineral Density Measured by DXA at Baseline(Baseline assessment (Visit 1).)
- Total Body Fat Mass Measured by DXA at Baseline(Baseline assessment (Visit 1).)
- Score on the State-Trait Anxiety Inventory at Baseline(Baseline assessment (Visit 1).)
- Score on the Beck Depression Inventory-II at Baseline(Baseline assessment (Visit 1).)