Glucose Metabolism Disorders, Type 2 Diabetes
Conditions
Keywords
Continuous Glucose Monitoring, CGM, Oral Glucose Tolerance Test, OGTT, Mixed-Meal Tolerance Test, Glycemic Variability, Incretins, Home-Based Testing, GLP-1, GIP
Brief summary
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).
Detailed description
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. In-hospital OGTT and Biomarker Assessment Phase (Day 10-14): Participants will undergo a standard 75g OGTT at the clinic. Venous blood samples will be collected at fasting, 30, 60, 120, and 180 minutes for measuring glucose, insulin, C-peptide, GLP-1, GIP, and blood pressure/heart rate. Group Allocation: This is an observational study with no interventional allocation. After completion, participants will be categorized into three groups based solely on their 2-hour plasma glucose (2hPG) value from the OGTT, following WHO criteria: Normal Glucose Tolerance (NGT, 2hPG \<7.8 mmol/L), Pre-diabetes (Pre-DM, 7.8 ≤ 2hPG \<11.1 mmol/L), and Type 2 Diabetes (T2DM, 2hPG ≥11.1 mmol/L). Comparative analyses will be conducted across these naturally formed groups. Statistical Considerations: The sample size of 225 was calculated using G\*Power for an ANOVA model (effect size f=0.25, α=0.05, power=0.80), accounting for a 20% dropout rate. The primary analysis will use the Full Analysis Set (FAS). Statistical methods will include Spearman correlation to assess the relationship between MMTT-induced CGM parameters and OGTT glucose values, Analysis of Covariance (ANCOVA) to compare CGM metrics across the three glycemic groups (adjusting for covariates like age and BMI), and Receiver Operating Characteristic (ROC) curve analysis to evaluate the predictive power of CGM parameters for OGTT-based diagnosis. Scientific Value: This study is designed as a mechanism-exploratory investigation. It seeks to validate a novel, patient-centric approach (home-based MMTT with CGM) against the diagnostic gold standard (OGTT) and to provide deeper insights into the integrated physiology of glycemic homeostasis, including the role of incretin hormones and its potential link to vascular responses like postprandial hypotension.
Interventions
None listed
Sponsors
Shanghai 6th People's Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
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.
Exclusion criteria
* 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between MMTT-induced glucose AUC and OGTT plasma glucose values | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dietary Macronutrient Intake Composition | From enrollment until the completion of the in-clinic OGTT (approximately 10-14 days). | The daily intake proportion of macronutrients (carbohydrates, protein, and fat), expressed as a percentage of total caloric intake, assessed via a dietary logging application. |
| Caloric Intake per Meal | From enrollment until the completion of the in-clinic OGTT (approximately 10-14 days). | The average energy intake (in kilocalories) per meal, estimated using a dietary logging application. |
| Mean Amplitude of Glycemic Excursions (MAGE) | Entire CGM monitoring period (10-14 days) | Mean Amplitude of Glycemic Excursions, calculated from CGM data to quantify major glucose swings. |
| Complexity of Glucose Time Series | Entire CGM monitoring period (10-14 days) | Complexity of glucose time series (e.g., using multiscale entropy or similar indices) derived from CGM data. |
| Glucose AUC after MMTT | 0-3 hours after each MMTT | Area under the curve of glucose levels after each Mixed-Meal Tolerance Test (MMTT), measured by CGM. |
| Glucose Levels During OGTT | OGTT: 0, 30, 60, 120, 180 minutes | Plasma levels of glucose at OGTT time points |
| Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) | Baseline (OGTT 0-minute sample) | Insulin resistance index calculated from fasting glucose and fasting insulin levels. |
| Incidence of Postprandial Hypotension during OGTT | OGTT: 0, 30, 60, 120, 180 minutes | Occurrence of postprandial hypotension, defined as a maximum decrease in systolic blood pressure ≥ 20 mmHg from baseline after the OGTT. |
| Maximum reduction in systolic blood pressure (SBP) during OGTT | OGTT: 0, 30, 60, 120, 180 minutes | The maximum decrease (Δ) in systolic blood pressure from the baseline (pre-glucose ingestion) value at any standard time point during the Oral Glucose Tolerance Test. |
| Completion Rate of Home-based MMTT | Through study completion (up to 14 days) | Proportion of participants who successfully complete both home-based MMTTs. |
| Adverse Events during OGTT /MMTT | During the OGTT/MMTT procedure (approximately 3 hours) | Incidence of adverse events (e.g., nausea, vomiting, bloating) occurring during the OGTT/MMTT procedure. |
| Glycemic Variability (GV) | Entire CGM monitoring period (10-14 days) | Coefficient of variation (CV) of glucose levels, calculated from Continuous Glucose Monitoring (CGM) data. |
| GIP serum concentration during OGTT | OGTT: 0, 30, 60, 120, and 180 minutes | Serum concentration of Glucose-dependent insulinotropic polypeptide (GIP) at each standard time point in response to the Oral Glucose Tolerance Test (OGTT). |
| Insulin serum concentration during OGTT | OGTT: 0, 30, 60, 120, 180 minutes | Plasma insulin concentration at each time point of the Oral Glucose Tolerance Test (OGTT). |
| C-peptide serum concentration during OGTT | OGTT: 0, 30, 60, 120, 180 minutes | Plasma C-peptide concentration at each time point of the Oral Glucose Tolerance Test (OGTT). |
| Total GLP-1 AUC during OGTT | OGTT: 0, 30, 60, 120, and 180 minutes | Total area under the curve (AUC) for the Glucagon-like peptide-1 (GLP-1) serum concentration profile in response to the Oral Glucose Tolerance Test (OGTT). |
| Total GIP AUC during OGTT | OGTT: 0, 30, 60, 120, and 180 minutes | Total area under the curve (AUC) for the Glucose-dependent insulinotropic polypeptide (GIP) serum concentration profile in response to the Oral Glucose Tolerance Test (OGTT). |
| Association between Incretin Secretion and Glycemic Complexity | During the in-clinic OGTT （0 to 180 minutes） | An exploratory analysis using multiple linear regression to assess the influence of GLP-1 AUC and GIP AUC (during OGTT) on the complexity of the glycemic time series (e.g., CGI) during the OGTT period, adjusting for covariates such as age, sex, and BMI. |
| Time to Peak Glucose after Each Meal | Throughout the CGM monitoring period (10-14 days), following each main meal. | The time (in minutes) from the start of a meal to the maximum postprandial glucose concentration, as determined by CGM data. The average for breakfast, lunch, and dinner will be calculated. |
| Maximum reduction in diastolic blood pressure (DBP) during OGTT | OGTT: 0, 30, 60, 120, and 180 minutes | The maximum decrease (Δ) in diastolic blood pressure from the baseline (pre-glucose ingestion) value at any standard time point during the Oral Glucose Tolerance Test. |
| Glycated hemoglobin (HbA1c) level | OGTT day (single time point, e.g., at the fasting blood draw) | The concentration of glycated hemoglobin (HbA1c) in venous blood samples collected on the day of the Oral Glucose Tolerance Test (OGTT). HbA1c reflects the average blood glucose level over the preceding 2 to 3 months |
| Glycated albumin (GA) level | OGTT day (single time point, e.g., at the fasting blood draw) | The concentration of glycated albumin (GA) in venous blood samples collected on the day of the Oral Glucose Tolerance Test (OGTT). GA reflects the average blood glucose level over the preceding 2 to 3 weeks |
| GLP-1 serum concentration during OGTT | OGTT: 0, 30, 60, 120, and 180 minutes | Serum concentration of Glucagon-like peptide-1 (GLP-1) at each standard time point in response to the Oral Glucose Tolerance Test (OGTT). |
Contacts
Primary ContactJian Zhou, PhD
Backup ContactYue Zhang, Master's Degree
Outcome results
None listed