The CGM-OGTT Glycemic Homeostasis Study

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)

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Glucose Metabolism Disorders; Type 2 Diabetes

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.

• Study Type: Observational
• Enrollment (Estimated): 225

Contacts and Locations

• Study Contact: Name: Yue Zhang, Master's Degree; Phone Number: +86 17851180860; Email: zyzy931@sjtu.edu.cn
• Study Contact Backup: Name: Jian Zhou, PhD; Phone Number: +86 021 24056515; Email: zhoujian@sjtu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This monocentric, prospective, observational study will enroll 225 adult participants (aged 18-70 years) who are at high risk for diabetes or present with abnormal glucose metabolism, but have not been previously diagnosed with diabetes.

Participants must meet specific eligibility criteria, including having diabetes-related symptoms, impaired fasting glucose, elevated HbA1c in the pre-diabetes range, or established risk factors (e.g., obesity, family history of diabetes, hypertension, or dyslipidemia).

Key Exclusion Criteria include a prior diagnosis of diabetes, use of medications affecting glucose metabolism, significant organ dysfunction, or pregnancy.

Upon enrollment, all participants will undergo a standardized 75g Oral Glucose Tolerance Test (OGTT). Based on the OGTT results, they will be retrospectively categorized into three natural groups for comparative analysis: Normal Glucose Tolerance (NGT), Pre-Diabetes (Pre-DM), and Newly Diagnosed Type 2 Diabetes (T2DM).

Description

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).

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Normal Glucose Tolerance (NGT); Participants with normal glucose tolerance as defined by a 2-hour plasma glucose value < 7.8 mmol/L during the oral glucose tolerance test (OGTT).
Pre-diabetes (Pre-DM); Participants with pre-diabetes (intermediate hyperglycemia) as defined by a 2-hour plasma glucose value between 7.8 mmol/L and 11.0 mmol/L during the OGTT.
Newly Diagnosed Type 2 Diabetes (T2DM); Participants with newly diagnosed type 2 diabetes as defined by a 2-hour plasma glucose value ≥ 11.1 mmol/L during the OGTT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between MMTT-induced glucose AUC and OGTT 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).	MMTT: 0-3 hours post-meal (for AUC calculation). OGTT: 0, 30, 60, 120, and 180 minutes (for plasma glucose values).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic Variability (GV)	Coefficient of variation (CV) of glucose levels, calculated from Continuous Glucose Monitoring (CGM) data.	Entire CGM monitoring period (10-14 days)
Dietary Macronutrient Intake Composition	The daily intake proportion of macronutrients (carbohydrates, protein, and fat), expressed as a percentage of total caloric intake, assessed via a dietary logging application.	From enrollment until the completion of the in-clinic OGTT (approximately 10-14 days).
Caloric Intake per Meal	The average energy intake (in kilocalories) per meal, estimated using a dietary logging application.	From enrollment until the completion of the in-clinic OGTT (approximately 10-14 days).
Mean Amplitude of Glycemic Excursions (MAGE)	Mean Amplitude of Glycemic Excursions, calculated from CGM data to quantify major glucose swings.	Entire CGM monitoring period (10-14 days)
Complexity of Glucose Time Series	Complexity of glucose time series (e.g., using multiscale entropy or similar indices) derived from CGM data.	Entire CGM monitoring period (10-14 days)
Glucose AUC after MMTT	Area under the curve of glucose levels after each Mixed-Meal Tolerance Test (MMTT), measured by CGM.	0-3 hours after each MMTT
Glucose Levels During OGTT	Plasma levels of glucose at OGTT time points	OGTT: 0, 30, 60, 120, 180 minutes
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	Insulin resistance index calculated from fasting glucose and fasting insulin levels.	Baseline (OGTT 0-minute sample)
Incidence of Postprandial Hypotension during OGTT	Occurrence of postprandial hypotension, defined as a maximum decrease in systolic blood pressure ≥ 20 mmHg from baseline after the OGTT.	OGTT: 0, 30, 60, 120, 180 minutes
Maximum reduction in systolic blood pressure (SBP) during OGTT	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.	OGTT: 0, 30, 60, 120, 180 minutes
Completion Rate of Home-based MMTT	Proportion of participants who successfully complete both home-based MMTTs.	Through study completion (up to 14 days)
Adverse Events during OGTT /MMTT	Incidence of adverse events (e.g., nausea, vomiting, bloating) occurring during the OGTT/MMTT procedure.	During the OGTT/MMTT procedure (approximately 3 hours)
GLP-1 serum concentration during OGTT	Serum concentration of Glucagon-like peptide-1 (GLP-1) at each standard time point in response to the Oral Glucose Tolerance Test (OGTT).	OGTT: 0, 30, 60, 120, and 180 minutes
GIP serum concentration during OGTT	Serum concentration of Glucose-dependent insulinotropic polypeptide (GIP) at each standard time point in response to the Oral Glucose Tolerance Test (OGTT).	OGTT: 0, 30, 60, 120, and 180 minutes
Insulin serum concentration during OGTT	Plasma insulin concentration at each time point of the Oral Glucose Tolerance Test (OGTT).	OGTT: 0, 30, 60, 120, 180 minutes
C-peptide serum concentration during OGTT	Plasma C-peptide concentration at each time point of the Oral Glucose Tolerance Test (OGTT).	OGTT: 0, 30, 60, 120, 180 minutes
Total GLP-1 AUC during OGTT	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).	OGTT: 0, 30, 60, 120, and 180 minutes
Total GIP AUC during OGTT	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).	OGTT: 0, 30, 60, 120, and 180 minutes
Association between Incretin Secretion and Glycemic Complexity	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.	During the in-clinic OGTT （0 to 180 minutes）
Time to Peak Glucose after Each 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.	Throughout the CGM monitoring period (10-14 days), following each main meal.
Maximum reduction in diastolic blood pressure (DBP) during OGTT	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.	OGTT: 0, 30, 60, 120, and 180 minutes
Glycated hemoglobin (HbA1c) level	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	OGTT day (single time point, e.g., at the fasting blood draw)
Glycated albumin (GA) level	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	OGTT day (single time point, e.g., at the fasting blood draw)

Collaborators and Investigators

• Sponsor: Shanghai 6th People's Hospital
• Investigators: Study Chair: Jian Zhou, Shanghai Sixth People's Hospital, Shanghai, Shanghai 200233

Study record dates

Study Major Dates

• Study Start (Estimated): December 18, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): August 10, 2027

Study Registration Dates

• First Submitted: December 4, 2025
• First Submitted That Met QC Criteria: December 15, 2025
• First Posted (Estimated): December 17, 2025

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 21, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: GLP-1; Continuous Glucose Monitoring; CGM; Incretins; GIP; OGTT; Oral Glucose Tolerance Test; Glycemic Variability; Mixed-Meal Tolerance Test; Home-Based Testing
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders
• Other Study ID Numbers: 20251120

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The individual participant data (IPD) collected in this study are highly sensitive, containing detailed glycemic profiles, hormone levels, and personal health information. To protect participant confidentiality and privacy as strictly stipulated in the informed consent form and approved by the ethics committee, the IPD will not be made publicly available. The data will be de-identified and stored securely for analysis by the principal investigative team only. In the future, requests for access to anonymized data may be considered on a case-by-case basis for legitimate scientific collaboration, subject to a formal data sharing agreement and approval from the institutional ethics committee.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No