The CGM-OGTT Glycemic Homeostasis Study

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.

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).