Gut Microbiota and Serum Metabolites as Predictors of Glycemic Variability and Outcomes in Diabetic Kidney Disease

Prospective Cohort Study on the Impact of Gut Microbiota and Serum Metabolites on Glycemic Variability and Clinical Outcomes in Patients With Diabetic Kidney Disease

Diabetic kidney disease (DKD) is one of the main complications of diabetes and a leading cause of end-stage kidney disease. Blood glucose variability is closely associated with disease progression in individuals with DKD. Recent evidence suggests that gut bacteria and their circulating metabolites may play important roles in regulating blood glucose variability and clinical outcomes. However, it remains unclear whether gut bacteria and blood metabolites influence DKD progression through effects on blood glucose variability.

This study aims to (1) characterize gut bacteria and blood metabolites in individuals with DKD at different stages and levels of disease severity, and evaluate their value in predicting adverse outcomes; (2) assess the relationships among gut bacteria, blood metabolites, and blood glucose variability; and (3) determine whether gut bacteria and blood metabolites affect clinical outcomes by modulating blood glucose variability.

A total of 270 individuals with DKD will be enrolled in a prospective observational cohort. The investigators will conduct continuous glucose monitoring and collect stool and blood samples for advanced analyses of gut microbiota and blood metabolites. The objective is to clarify how gut bacteria and circulating metabolites relate to blood glucose variability and disease prognosis, and to develop tools to identify high-risk individuals at an early stage. Ultimately, the findings may provide new insights and strategies to improve clinical care and quality of life for individuals with DKD.

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetic Kidney Disease

Detailed Description

Diabetic kidney disease (DKD) is a major microvascular complication of diabetes and a leading cause of end-stage kidney disease. Blood glucose variability (GV) has been shown to be closely associated with disease progression in individuals with DKD. Recent studies suggest that gut microbiota and their serum metabolites may play important roles in regulating GV and influencing clinical outcomes. However, it remains unclear whether gut microbiota and serum metabolites affect DKD progression through GV.

This prospective observational cohort study aims to address three key questions:

1. Characterize gut microbiota and serum metabolites in individuals with DKD at different disease stages and severities, and evaluate their prognostic value for adverse outcomes.
2. Examine the relationships among gut microbiota, serum metabolites, and blood glucose variability.
3. Determine whether gut microbiota and serum metabolites influence clinical outcomes by affecting blood glucose variability.
4. A total of 270 individuals with DKD will be enrolled. The investigators will conduct continuous glucose monitoring (CGM), collect blood and stool samples, and analyze these samples using 16S rRNA high-throughput sequencing and untargeted serum LC-MS. These data will be used to assess GV, characterize gut microbiota and serum metabolites, and develop predictive models for adverse outcomes in DKD. The study aims to clarify the impact of gut microbiota and blood glucose variability on DKD prognosis and to develop tools for early identification of high-risk individuals, ultimately improving disease management and clinical outcomes.

• Study Type: Observational
• Enrollment (Estimated): 270

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of adult patients diagnosed with Diabetic Kidney Disease (DKD), aged between 18 and 65 years. All participants will have a confirmed diagnosis of Type 2 Diabetes Mellitus (T2DM) in accordance with the 1999 World Health Organization diagnostic criteria, and meet the diagnostic criteria for DKD as outlined in the 2021 Chinese Guidelines for the Prevention and Treatment of Diabetic Kidney Disease.

Description

Inclusion Criteria:

1. Age 18-65 years
2. Diagnosis of Diabetic Kidney Disease (DKD)
3. Type 2 Diabetes Mellitus
4. Stable Antidiabetic Regimen:The antidiabetic regimen must have been stable for at least 3 months prior to study enrollment.
5. Willingness to Provide Informed Consent:

Participants must voluntarily sign an informed consent form to participate in the study. -

Exclusion Criteria:

1. Acute Diabetic Complications:

   Participants with acute diabetic complications, such as diabetic ketoacidosis (DKA), or with primary kidney diseases like primary glomerulonephritis, nephrotic syndrome, or lupus nephritis.

2. Infection or Stress Conditions:

   Participants in a state of infection, trauma, or other stress conditions.

3. Pregnancy or Lactation:

   Women who are pregnant, breastfeeding, or planning to become pregnant in the next month.

4. Severe Dermatologic Conditions:

   Participants with severe dermatologic conditions, such as extensive eczema, widespread scars, tattoos, herpetic dermatitis, severe edema, or psoriasis.

5. Skin Issues with Sensor Application:

   Participants with severe skin issues at the site of sensor application, such as burns, injuries, sunburns, ulcers, or scars from prior surgery.

6. Coagulation or Blood Disorders:

   Participants with abnormal coagulation, anemia, or abnormal hematocrit.

7. Chronic Gastrointestinal Diseases or Surgery History:

   Participants with chronic gastrointestinal diseases or a history of gastrointestinal or biliary surgery.

8. Recent Probiotic or Antibiotic Use:

Participants who have used probiotics or prebiotics, or received antibiotic treatment for more than 3 days in the past 3 months, or have consumed yogurt or yogurt-containing foods/beverages in the past week.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Diabetic Kidney Disease (DKD) Progression	DKD progression is defined as the occurrence of at least one of the following events: (1) end-stage kidney disease requiring dialysis or kidney transplantation; or (2) a sustained decline of ≥30% in estimated glomerular filtration rate (eGFR) from baseline. This outcome will be used to assess the predictive value of blood glucose variability, gut microbiota, serum metabolites, and inflammatory markers for long-term DKD progression.	Time Frame: 12 months (from baseline to endpoint assessment) This time frame reflects the follow-up period during which DKD progression will be monitored in the study cohort.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Cardiovascular Mortality	Cardiovascular mortality is defined as death resulting from heart disease or related cardiovascular complications occurring during the follow-up period.	Time Frame: 12 months Adverse events will be monitored over a period of 12 months from baseline to track occurrences and assess their relationship with GV and other biomarkers.
Number of Participants with Major Adverse Cardiovascular Events (MACE)	Major adverse cardiovascular events (MACE) are defined as the occurrence of myocardial infarction, stroke, or unstable angina during the follow-up period.	12 months (from baseline)
Number of Participants Undergoing Kidney Transplantation	Kidney transplantation is defined as receipt of a kidney transplant procedure during the follow-up period.	12 months (from baseline)
Number of Participants with Hypoglycemic Events	Hypoglycemic events are defined as documented episodes of hypoglycemia occurring during the study period, identified by continuous glucose monitoring and/or clinical records.	12 months (from baseline)

Collaborators and Investigators

• Sponsor: Eighth Affiliated Hospital, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): July 30, 2029

Study Registration Dates

• First Submitted: November 24, 2025
• First Submitted That Met QC Criteria: January 12, 2026
• First Posted (Actual): January 20, 2026

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Diabetic Kidney Disease; Gut Microbiota; Glycemic Variability
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Diabetes Mellitus; Diabetes Complications; Diabetic Nephropathies
• Other Study ID Numbers: PY-2025-04

Drug and device information, study documents

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