Type 1 Diabetes
Conditions
Keywords
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), Short-Chain Fatty Acids (SCFAs), Sodium Butyrate, Type 1 Diabetes (T1D)
Brief summary
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent in individuals with type 1 diabetes (T1D) and is associated with increased cardiovascular and metabolic risk. However, evidence regarding effective therapeutic strategies for MASLD in T1D remains scarce. Lifestyle modification has shown benefits in obesity and type 2 diabetes, whereas butyrate, a microbiota-derived short-chain fatty acid, has emerged as a potential therapeutic approach because of its anti-inflammatory and metabolic effects. This study aims to evaluate the efficacy of intensive lifestyle modification, butyrate supplementation, or their combination on hepatic steatosis in individuals with T1D and MASLD. Methods: BEAM-T1D is a factorial, randomized, 6-month, parallel-group, placebo-controlled clinical trial conducted at the Regional University Hospital of Malaga. A total of 200 adults with T1D and MASLD will be randomized (1:1:1:1) to receive: (1) standard lifestyle recommendations plus placebo; (2) intensive lifestyle modification plus placebo; (3) standard lifestyle recommendations plus butyrate; or (4) intensive lifestyle modification plus butyrate. Intensive lifestyle modification includes a hypocaloric Mediterranean diet and promotion of physical activity. Participants randomized to butyrate will receive 2.25 g/day of microencapsulated sodium butyrate. The primary endpoint will be the change in controlled attenuation parameter (CAP) measured by transient elastography (FibroScan®). Secondary outcomes include changes in liver fat content, insulin resistance, metabolic control, body composition, inflammatory markers, gut microbiota composition, and short-chain fatty acid concentrations. Results: Participant recruitment is expected to begin in October 2025. The study will evaluate the independent and combined effects of butyrate supplementation and intensive lifestyle modification on hepatic steatosis and metabolic outcomes in individuals with T1D and MASLD. Conclusion: The BEAM-T1D study will provide novel evidence regarding the potential role of butyrate and intensive lifestyle modification in the management of MASLD in T1D. If effective, these interventions could represent feasible and scalable therapeutic strategies for a population with limited evidence-based treatment options.
Interventions
OTHERIntensive lifestyle modification (hypocaloric Mediterranean diet and promotion of physical activity)
Participants will be advised to follow a Mediterranean diet, characterized by the use of olive oil as the main source of fat, regular consumption of vegetables, fruits, legumes, and fish, reduced consumption of red meat and processed meats, and elimination of sugar-sweetened beverages, industrial pastries, and confectionery. The Mediterranean diet will include a 30% energy restriction based on estimated energy needs (Harris-Benedict equation). Participants will also be advised to perform ≥150 minutes of moderate-to-vigorous physical activity per week, distributed over at least 3 days, with no more than 2 consecutive days without activity, and to perform 2-3 resistance training sessions per week on non-consecutive days. This group will receive microencapsulated placebo.
DIETARY_SUPPLEMENTButyrate
Participants randomized to this group will receive microencapsulated sodium butyrate (MSB). Each sachet contains 750 mg sodium butyrate and 1750 mg triglyceride matrix (total 2,500 mg). Participants will take 3 sachets daily (total daily dose: 2.25 g butyrate): one in the morning, one at midday, and one in the evening.
DIETARY_SUPPLEMENTIntensive lifestyle modification + butyrate
Participants will undergo both intensive lifestyle modification and receive butyrate as described above. This study will be placebo-controlled: participants not randomized to butyrate will receive placebo sachets identical in size, color, appearance, and taste to the investigational product but without butyrate. Placebo will also be taken three times daily following the same schedule.
Sponsors
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Both butyrate and placebo will be packaged and labeled identically to ensure double blinding of participants and study staff.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-75 years. * Type 1 diabetes. * MASLD: Defined by a Controlled Attenuation Parameter (CAP) measured by Fibroscan® ≥248 dB/m (40). * Signed informed consent.
Exclusion criteria
* History of alcohol consumption \> 50 g/day in men or \> 30 g/day in women for 3 consecutive months in the last year. * Patients with impaired liver function (total bilirubin \> 2.0 mg/dL). * Hemochromatosis, Wilson's disease, or autoimmune hepatitis. * History of cancer (except basal cell carcinoma) in the past 5 years or active cancer of any type. * Known infection with HIV, HBV, HCV, or any other infection that may cause liver disease. * Severe underlying diseases that, in the investigators' judgment, constitute an exclusion criterion for study participation. * Reduced life expectancy. * Pregnant or breastfeeding women. * Documented history of intolerance/allergy to butyrate. * Participation in another clinical trial within 30 days prior to study entry. * Inability to comply with scheduled visits. * Use of antibiotics, prebiotics, or probiotics (in pharmacological form or as supplements, not as part of usual diet) in the month prior to inclusion in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Controlled Attenuation Parameter (CAP) by hepatic elastography (FibroScan®): Controlled Attenuation Parameter (CAP) | Baseline, 3 month and 6 month | Measured in dB/m |
| Changes in Controlled Attenuation Parameter (CAP) by hepatic elastography (FibroScan®): Liver Stiffness Measurement | Baseline, 3 month and 6 month | Measured in : kPa |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in insulin resistance: eGDR | Baseline, 3 months and 6 months | Measured in mg/kg/min |
| Changes in metabolic control: Glucose | Baseline, 3 months and 6 months | Measured in mg/dl |
| Changes in metabolic control: HbA1c | Baseline, 3 months and 6 months | Measured in mmol/mol |
| Changes in metabolic control: Average sensor glucose | Baseline, 3 months and 6 months | Measured in mg/dl |
| Changes in metabolic control: Glucose Management Indicator (GMI) | Baseline, 3 months and 6 months | Measured in % |
| Changes in metabolic control: Time in range (TIR) | Baseline, 3 months and 6 months | Measured in % |
| Changes in metabolic control: Time Above Range (TAR) | Baseline, 3 months and 6 months | Measured in % |
| Changes in metabolic control: Time Below Range (TBR) | Baseline, 3 months and 6 months | Measured in minutes or hours |
| Changes in body composition: Weight | Baseline, 3 months and 6 months | Measured in kg |
| Changes in body composition: Body mass index (BMI) | Baseline, 3 months and 6 months | Measured in kg/m2 |
| Changes in body composition: Muscular area of rectus anterior | Baseline, 3 months and 6 months | Measured in cm2 |
| Changes in body composition: Fat mass | Baseline, 3 months and 6 months | Measured in kg |
| Changes in body composition: Fat-free mass | Baseline, 3 months and 6 months | Measured in kg |
| Changes in body composition: Body cellular mass | Baseline, 3 months and 6 months | Measured in kg |
| Changes in body composition: Skeletical muscle mass | Baseline, 3 months and 6 months | Measured in kg |
| Changes in body composition: Appendicular skeletal muscle mass | Baseline, 3 months and 6 months | Measured in kg |
| Changes in blood pressure: Systolic blood pressure | Baseline, 3 months and 6 months | Measured in mmHg |
| Changes in blood pressure: Diastolic blood pressure | Baseline, 3 months and 6 months | Measured in mmHg |
| Changes in lipid profile: Total cholesterol | Baseline, 3 months and 6 months | Measured in mg/dl |
| Changes in lipid profile: HDL | Baseline, 3 months and 6 months | Measured in mg/dl |
| Changes in lipid profile: LDL | Baseline, 3 months and 6 months | Measured in mg/dl |
| Changes in adipokines: Leptin | Baseline, 3 months and 6 months | Measured in ng/mL |
| Changes in adipokines: Adiponectin | Baseline, 3 months and 6 months | Measured in μg/mL |
| Changes in hepatokines: GDF-15 | Baseline, 3 months and 6 months | Measured in ng/mL |
| Changes in hepatokines: FGF-21 | Baseline, 3 months and 6 months | Measured in ng/mL |
| Changes in inflammatory markers: IL-10 | Baseline, 3 months and 6 months | Measured in pg/mL |
| Changes in inflammatory markers: IL-1b | Baseline, 3 months and 6 months | Measured in pg/mL |
| Changes in inflammatory markers: IL-6 | Baseline, 3 months and 6 months | Measured in pg/mL |
| Changes in inflammatory markers: IL-8 | Baseline, 3 months and 6 months | Measured in pg/mL |
| Changes in inflammatory markers: IL-12 | Baseline, 3 months and 6 months | Measured in pg/mL |
| Changes in inflammatory markers: TNF-α | Baseline, 3 months and 6 months | Measured in pg/mL |
| Changes in intestinal permeability: Zonuline | Baseline, 3 months and 6 months | Measured in ng/mL |
| Changes in short-chain fatty acid levels: Butyrate | Baseline, 3 months and 6 months | Measured in μmol/kg |
| Changes in gut microbiota: phylum, genus, species | Baseline, 3 months and 6 months | Measured in relative abundance, alpha diversity, beta diversity |
| Change from baseline in Mediterranean Diet Adherence at 3 and 6 months | Baseline, 3 months and 6 months | The 17-item Mediterranean Diet Adherence Questionnaire assesses dietary habits through 17 questions regarding the consumption of traditional Mediterranean diet components (e.g., olive oil, vegetables, fruits, fish). Each item is scored as 0 (does not meet the criterion) or 1 (meets the criterion), with a total score ranging from 0 (minimum score) to 17 (maximum score). Higher scores indicate greater adherence to the Mediterranean diet. |
| Change from baseline in Physical Activity Level at 3 and 6 months | Baseline, 3 months and 6 months | The Short version of the International Physical Activity Questionnaire (IPAQ) assesses physical activity across three intensities (vigorous, moderate, and walking) over the last 7 days. Total physical activity is calculated as a continuous variable expressed in Metabolic Equivalent of Task minutes per week (MET-minutes/week), summing the duration (minutes/week) of each activity type multiplied by its specific MET value (walking = 3.3, moderate = 4.0, vigorous = 8.0). Higher MET-minutes/week indicate higher levels of physical activity. Sedentary behavior is assessed by measuing the total time spent sitting during a typical weekday over the last 7 days (including time at work, home, study, or leisure). The score is expressed as total minutes or hours of sitting time per day. Higher values indicate greater sedentary behavior. |
| Change from baseline in Long-term Physical Activity Patterns at 3 and 6 months | Baseline, 3 months and 6 months | The validated version of the Nurses' Health Study and Health Professionals' Follow-up Study physical activity questionnaire assesses the average time per week spent on specific recreational activities (e.g., walking, jogging, cycling, swimming, running) over a longer recall period. Each activity is assigned a standard MET value based on intensity (the number of METs corresponding to each activity were calculated using the Compendium of Physical Activities). Total activity is computed as the sum of MET-hours per week (MET-hours/week) by multiplying the weekly hours dedicated to each activity by its corresponding MET value. Higher scores reflect greater energy expenditure from physical activity. |
| Changes in body composition: Height | Baseline, 3 months and 6 months | Measured in cm |
Countries
Spain
Contacts
CONTACTJose Carlos Fernández García, MD
CONTACTVirginia Soria Utrilla, PhD
Outcome results
None listed