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

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:

• Characterize gut microbiota and serum metabolites in individuals with DKD at different disease stages and severities, and evaluate their prognostic value for adverse outcomes.
• Examine the relationships among gut microbiota, serum metabolites, and blood glucose variability.
• Determine whether gut microbiota and serum metabolites influence clinical outcomes by affecting blood glucose variability.
• 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.

Inclusion criteria

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

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

Exclusion criteria

• 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.

• Infection or Stress Conditions:

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

• Pregnancy or Lactation:

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

• Severe Dermatologic Conditions:

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

• 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.

• Coagulation or Blood Disorders:

Participants with abnormal coagulation, anemia, or abnormal hematocrit.

• Chronic Gastrointestinal Diseases or Surgery History:

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

• 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.