Diabetes Mellitus, Constipation - Functional
Conditions
Keywords
Diabetes, Constipation, Lactulose, Gut Microbiota, Metabolism
Brief summary
Constipation is the most common gastrointestinal manifestation in diabetic patients. Emerging evidence suggests that gut microbiota dysbiosis may contribute to the pathogenesis of diabetes, highlighting the need to investigate its role in diabetic constipation, though current research remains limited. Current management of diabetic constipation primarily relies on bulk-forming and osmotic laxatives. Additionally, microbiome-modulating agents (e.g., probiotics, prebiotics, and synbiotics) may serve as adjunctive therapies by regulating gut microbiota and enhancing intestinal motility. Lactulose, a well-tolerated osmotic laxative with prebiotic effects, is widely recommended in clinical guidelines. It promotes short-chain fatty acid production, increases fecal volume, and accelerates colonic transit, thereby alleviating constipation. However, its specific impact on gut microbiota composition and metabolic pathways in diabetic constipation remains unclear. This study aims to explore changes in fecal microbiota and metabolomic profiles in diabetic patients with chronic constipation following treatment with lactulose alone or in combination with Bacillus subtilis-Enterococcus faecium probiotics, providing mechanistic insights into prebiotic therapy for this condition.
Interventions
Oral, 30 mL once daily administered during breakfast.
DRUGLive Combined B. Subtilis and E. Faecium Enteric-coated Capsules
Oral, 2 tablets (500 mg per tablet) three times daily (TID).
Sponsors
Beijing Hospital
Beijing Huaxin Hospital
Beijing Luhe Hospital
Beijing Huairou Hospital
Peking Union Medical College Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Age: 18-70 years * Type 2 Diabetes Diagnosis (per 2017 ADA criteria), meeting ≥1 of: 1. Fasting plasma glucose (FPG) ≥7.0 mmol/L 2. hour plasma glucose ≥11.1 mmol/L during 75g anhydrous oral glucose tolerance test (OGTT) 3. Random plasma glucose ≥11.1 mmol/L with hyperglycemia symptoms or hyperglycemic crisis * Functional Constipation (Rome IV criteria), requiring: 1. ≥2 of the following 1. occurring in ≥25% of defecations 2. Straining 3. Lumpy/hard stools (Bristol Stool Scale 1-2) 4. Sensation of incomplete evacuation 5. Anorectal obstruction/blockage 6. Manual maneuvers required 7. \<3 spontaneous bowel movements/week 2. No loose stools without laxatives 3. Exclusion of IBS diagnosis. Symptom duration \>6 months, with active symptoms meeting criteria for last 3 months. * Stable Glycemic Control: No anticipated antidiabetic medication adjustments during study * Dietary Stability: Maintain consistent diet; avoid yogurt, fermented foods, prebiotic-containing processed foods, or other items that may confound results
Exclusion criteria
* Secondary Constipation due to organic diseases or medication effects. * Constipation-predominant Irritable Bowel Syndrome (IBS-C). * Concurrent gastrointestinal disorders (e.g., inflammatory bowel disease, colorectal cancer). * Type 1 Diabetes Mellitus. * Severe chronic comorbidities, including: 1. Cardiopulmonary insufficiency 2. Cerebrovascular diseases 3. Psychiatric disorders * Recent use (within 1 month) of confounding medications: 1. Probiotics/prebiotics 2. Antibiotics 3. Laxatives (e.g., osmotic/stimulant agents) 4. Prokinetics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Constipation Symptom Scores Pre- and Post-Treatment | From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment | Assessment of treatment efficacy on constipation symptoms: Changes in symptom scores from baseline to post-treatment within each treatment arm and comparative analysis between the lactulose monotherapy group and lactulose+Medilac-S combination therapy group |
| Changes in Fecal Microbiota Composition (16S rRNA and Metagenomics) | From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment | Comparison of Fecal Microbiota Composition Changes (16S rRNA and Metagenomics): Pre- vs. Post-Treatment Alterations and Intergroup Differences Between Lactulose Monotherapy and Lactulose+Medilac-S Combination Therapy |
| Temporal Changes in Fecal Untargeted Metabolomics Profiles | From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment | Temporal Changes in Fecal Untargeted Metabolomics Profiles: Pre- vs. post-treatment alterations and comparative analysis between lactulose monotherapy and lactulose+Medilac-S combination groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Fasting Blood Glucose and Glycated Albumin Levels | From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment | Changes in Fasting Blood Glucose and Glycated Albumin Levels: Pre- vs. post-treatment variations and comparative analysis between lactulose monotherapy and lactulose+Medilac-S combination groups |
| Changes in Blood Lipid Profiles (Total Cholesterol, Triglycerides, HDL-C, and LDL-C) | From enrollment (0 week) to 2 weeks, and 4 Weeks at the end of treatment | Changes in Blood Lipid Profiles (Total Cholesterol, Triglycerides, HDL-C, and LDL-C): Pre- vs. post-treatment alterations and comparative analysis between lactulose monotherapy and lactulose+Medilac-S combination therapy groups |
Countries
China
Contacts
Primary ContactYaowen Hu
Outcome results
None listed