An Exploratory Investigation Into the Mechanism of Glycemic Homeostasis Regulation Under the Synergistic Conditions of Continuous Glucose Monitoring (CGM) and Oral Glucose Tolerance Test (OGTT)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 225
- 主要终点
- Correlation between MMTT-induced glucose AUC and OGTT plasma glucose values
研究概览
简要总结
This is a prospective, exploratory, observational study aimed at investigating the mechanisms of glycemic homeostasis by comparing continuous glucose monitoring (CGM) data with results from the oral glucose tolerance test (OGTT).
The study plans to enroll approximately 225 participants aged 18-70 years who are at risk for or suspected of having glucose metabolism disorders, but without a prior diagnosis of diabetes. Participants will be equipped with a blinded CGM device for 10-14 days. During this period, they will perform two standardized mixed-meal tolerance tests (MMTT) at home. Subsequently, they will undergo a standard 75g OGTT at the hospital, where blood samples will be collected at multiple time points to measure glucose, insulin, C-peptide, and gastrointestinal hormones (GLP-1, GIP).
Based on the 2-hour blood glucose value from the OGTT, participants will be naturally categorized into three groups for comparative analysis: Normal Glucose Tolerance (NGT), Pre-diabetes (Pre-DM), and Newly Diagnosed Type 2 Diabetes (T2DM).
The primary objective is to establish a quantitative relationship between CGM-derived parameters (e.g., glycemic variability, time-in-range) after the MMTT and the OGTT diagnostic results. Secondary objectives include assessing the feasibility and correlation between home-based MMTT and standard OGTT, exploring the impact of gastrointestinal hormone responses on daily glucose fluctuations, and investigating the association between postprandial glucose dynamics and vascular reactivity (e.g., postprandial hypotension).
详细描述
Background and Rationale:
The oral glucose tolerance test (OGTT) is the gold standard for diagnosing diabetes but has limitations, including its inability to reflect daily glycemic variability and the discomfort caused by a high glucose load, which may not represent physiological conditions. Continuous glucose monitoring (CGM) captures comprehensive glycemic fluctuations in free-living settings. The mixed-meal tolerance test (MMTT), containing macronutrients like fat and protein, better simulates a physiological meal and may be better tolerated. However, the quantitative relationship between CGM-derived parameters from home-based MMTTs and the diagnostic outcomes of the standard OGTT remains unclear. Furthermore, the role of gastrointestinal hormone responses (e.g., GLP-1, GIP) during an OGTT in modulating subsequent daily glycemic homeostasis is an area of exploratory interest. This study aims to bridge these gaps by synergistically utilizing CGM, MMTT, and OGTT to investigate the mechanisms of glycemic regulation.
Study Design and Methodology:
This is a single-center, prospective, exploratory, observational study. Participants will wear a blinded CGM sensor for 10-14 days to prevent behavioral bias. The study comprises three sequential phases:
At-home MMTT Phase (Day 2 and another day prior to hospital visit): Participants will perform two standardized MMTTs (a standard formula and a high-protein formula) at home after an overnight fast. Adherence and any adverse events will be monitored remotely via a dedicated mini-program and daily communication.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To be eligible to participate in this study, an individual must meet ALL of the following criteria:
- •Is aged between 18 and 70 years, inclusive.
- •And meets at least ONE of the following conditions:
- •Presents with diabetes-related clinical symptoms or signs (e.g., unexplained ·polydipsia, polyphagia, polyuria, weight loss) and has been advised by a ·clinician to undergo an OGTT for diagnostic clarification.
- •Has indicators of abnormal glucose metabolism:Impaired Fasting Glucose (IFG): Fasting venous plasma glucose ≥ 6.1 mmol/L and < 7.0 mmol/L.and/or Glycated hemoglobin (HbA1c) in the pre-diabetes range of 5.7% to 6.4%.
- •Has at least one of the following diabetes risk factors:Body Mass Index (BMI) ≥ 24 kg/m²；Has a first-degree relative (parent, sibling, or child) with a history of diabetes；Has a history of hypertension (or undergoing antihypertensive treatment) or dyslipidemia.
排除标准
- •An individual who meets ANY of the following criteria will be excluded from participation in this study:
- •Previously diagnosed with diabetes.
- •Use of medications that significantly affect glucose metabolism or gastrointestinal hormones (e.g., GLP-1 receptor agonists, DPP-4 inhibitors, glucocorticoids) within a specified washout period prior to enrollment.
- •History of gastrointestinal surgery (e.g., gastrectomy) or chronic pancreatic disease.
- •Presence of severe hepatic or renal impairment (e.g., ALT > 3 times the upper limit of normal, or eGFR < 45 mL/min/1.73m²).
- •Pregnant or lactating women, or women planning to become pregnant during the study period.
- •Known allergy to soy (as the standardized meal may contain soy-based components).
结局指标
主要结局
Correlation between MMTT-induced glucose AUC and OGTT plasma glucose values
时间窗: MMTT: 0-3 hours post-meal (for AUC calculation). OGTT: 0, 30, 60, 120, and 180 minutes (for plasma glucose values).
To establish a quantitative relationship by assessing the correlation between the area under the curve (AUC) of postprandial glucose derived from Continuous Glucose Monitoring (CGM) after a standardized Mixed-Meal Tolerance Test (MMTT) and the plasma glucose values at all standard time points during the Oral Glucose Tolerance Test (OGTT).
次要结局
- GIP serum concentration during OGTT(OGTT: 0, 30, 60, 120, and 180 minutes)
- Glycemic Variability (GV)(Entire CGM monitoring period (10-14 days))
- Dietary Macronutrient Intake Composition(From enrollment until the completion of the in-clinic OGTT (approximately 10-14 days).)
- Caloric Intake per Meal(From enrollment until the completion of the in-clinic OGTT (approximately 10-14 days).)
- Mean Amplitude of Glycemic Excursions (MAGE)(Entire CGM monitoring period (10-14 days))
- Complexity of Glucose Time Series(Entire CGM monitoring period (10-14 days))
- Glucose AUC after MMTT(0-3 hours after each MMTT)
- Glucose Levels During OGTT(OGTT: 0, 30, 60, 120, 180 minutes)
- Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)(Baseline (OGTT 0-minute sample))
- Incidence of Postprandial Hypotension during OGTT(OGTT: 0, 30, 60, 120, 180 minutes)
- Maximum reduction in systolic blood pressure (SBP) during OGTT(OGTT: 0, 30, 60, 120, 180 minutes)
- Completion Rate of Home-based MMTT(Through study completion (up to 14 days))
- Adverse Events during OGTT /MMTT(During the OGTT/MMTT procedure (approximately 3 hours))
- GLP-1 serum concentration during OGTT(OGTT: 0, 30, 60, 120, and 180 minutes)
- Insulin serum concentration during OGTT(OGTT: 0, 30, 60, 120, 180 minutes)
- Total GLP-1 AUC during OGTT(OGTT: 0, 30, 60, 120, and 180 minutes)
- Glycated hemoglobin (HbA1c) level(OGTT day (single time point, e.g., at the fasting blood draw))
- C-peptide serum concentration during OGTT(OGTT: 0, 30, 60, 120, 180 minutes)
- Time to Peak Glucose after Each Meal(Throughout the CGM monitoring period (10-14 days), following each main meal.)
- Glycated albumin (GA) level(OGTT day (single time point, e.g., at the fasting blood draw))
- Total GIP AUC during OGTT(OGTT: 0, 30, 60, 120, and 180 minutes)
- Association between Incretin Secretion and Glycemic Complexity(During the in-clinic OGTT （0 to 180 minutes）)
- Maximum reduction in diastolic blood pressure (DBP) during OGTT(OGTT: 0, 30, 60, 120, and 180 minutes)
研究者
Jian Zhou
Principal Investigator, Professor, Chief Physician, Head of Department
Shanghai 6th People's Hospital