Butyrate or Intensive Lifestyle Modification in Type 1 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease

Butyrate or Intensive Lifestyle Modification in Type 1 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Factorial Randomized Clinical Trial

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Other: Intensive lifestyle modification (hypocaloric Mediterranean diet and promotion of physical activity); Dietary supplement: Butyrate; Dietary supplement: Intensive lifestyle modification + butyrate

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jose Carlos Fernández García, MD; Phone Number: 951290343; Email: josec.fernandez.garcia.sspa@juntadeandalucia.es
• Study Contact Backup: Name: Virginia Soria Utrilla, PhD; Email: virginia.soria.sspa@juntadeandalucia.es

Study Locations

• Spain
  • Málaga
    • Málaga, Málaga, Spain, 29009
      • Hospital Regional Universitario de Málaga, FIMABIS
      • Contact: Jose Carlos Fernández García, MD; Phone Number: 951290343; Email: josec.fernandez.garcia.sspa@juntadeandalucia.es

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Placebo + Standard lifestyle recommendations; Participants in this group will not undergo any intervention beyond what is routinely performed in clinical practice. This group will receive microencapsulated placebo.
Placebo Comparator: Placebo + Intensive lifestyle modification	Other: Intensive 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.
Experimental: Butyrate	Dietary supplement: Butyrate; 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.
Experimental: Intensive lifestyle modification + butyrate	Dietary supplement: Intensive 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Controlled Attenuation Parameter (CAP) by hepatic elastography (FibroScan®): Controlled Attenuation Parameter (CAP)	Measured in dB/m	Baseline, 3 month and 6 month
Changes in Controlled Attenuation Parameter (CAP) by hepatic elastography (FibroScan®): Liver Stiffness Measurement	Measured in : kPa	Baseline, 3 month and 6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in insulin resistance: eGDR	Measured in mg/kg/min	Baseline, 3 months and 6 months
Changes in metabolic control: Glucose	Measured in mg/dl	Baseline, 3 months and 6 months
Changes in metabolic control: HbA1c	Measured in mmol/mol	Baseline, 3 months and 6 months
Changes in metabolic control: Average sensor glucose	Measured in mg/dl	Baseline, 3 months and 6 months
Changes in metabolic control: Glucose Management Indicator (GMI)	Measured in %	Baseline, 3 months and 6 months
Changes in metabolic control: Time in range (TIR)	Measured in %	Baseline, 3 months and 6 months
Changes in metabolic control: Time Above Range (TAR)	Measured in %	Baseline, 3 months and 6 months
Changes in metabolic control: Time Below Range (TBR)	Measured in minutes or hours	Baseline, 3 months and 6 months
Changes in body composition: Weight	Measured in kg	Baseline, 3 months and 6 months
Changes in body composition: Body mass index (BMI)	Measured in kg/m2	Baseline, 3 months and 6 months
Changes in body composition: Muscular area of rectus anterior	Measured in cm2	Baseline, 3 months and 6 months
Changes in body composition: Fat mass	Measured in kg	Baseline, 3 months and 6 months
Changes in body composition: Fat-free mass	Measured in kg	Baseline, 3 months and 6 months
Changes in body composition: Body cellular mass	Measured in kg	Baseline, 3 months and 6 months
Changes in body composition: Skeletical muscle mass	Measured in kg	Baseline, 3 months and 6 months
Changes in body composition: Appendicular skeletal muscle mass	Measured in kg	Baseline, 3 months and 6 months
Changes in blood pressure: Systolic blood pressure	Measured in mmHg	Baseline, 3 months and 6 months
Changes in blood pressure: Diastolic blood pressure	Measured in mmHg	Baseline, 3 months and 6 months
Changes in lipid profile: Total cholesterol	Measured in mg/dl	Baseline, 3 months and 6 months
Changes in lipid profile: HDL	Measured in mg/dl	Baseline, 3 months and 6 months
Changes in lipid profile: LDL	Measured in mg/dl	Baseline, 3 months and 6 months
Changes in adipokines: Leptin	Measured in ng/mL	Baseline, 3 months and 6 months
Changes in adipokines: Adiponectin	Measured in μg/mL	Baseline, 3 months and 6 months
Changes in hepatokines: GDF-15	Measured in ng/mL	Baseline, 3 months and 6 months
Changes in hepatokines: FGF-21	Measured in ng/mL	Baseline, 3 months and 6 months
Changes in inflammatory markers: IL-10	Measured in pg/mL	Baseline, 3 months and 6 months
Changes in inflammatory markers: IL-1b	Measured in pg/mL	Baseline, 3 months and 6 months
Changes in inflammatory markers: IL-6	Measured in pg/mL	Baseline, 3 months and 6 months
Changes in inflammatory markers: IL-8	Measured in pg/mL	Baseline, 3 months and 6 months
Changes in inflammatory markers: IL-12	Measured in pg/mL	Baseline, 3 months and 6 months
Changes in inflammatory markers: TNF-α	Measured in pg/mL	Baseline, 3 months and 6 months
Changes in intestinal permeability: Zonuline	Measured in ng/mL	Baseline, 3 months and 6 months
Changes in short-chain fatty acid levels: Butyrate	Measured in μmol/kg	Baseline, 3 months and 6 months
Changes in gut microbiota: phylum, genus, species	Measured in relative abundance, alpha diversity, beta diversity	Baseline, 3 months and 6 months
Change from baseline in Mediterranean Diet Adherence at 3 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.	Baseline, 3 months and 6 months
Change from baseline in Physical Activity Level at 3 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.	Baseline, 3 months and 6 months
Change from baseline in Long-term Physical Activity Patterns at 3 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.	Baseline, 3 months and 6 months
Changes in body composition: Height	Measured in cm	Baseline, 3 months and 6 months

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

Study record dates

Study Major Dates

• Study Start (Estimated): September 15, 2026
• Primary Completion (Estimated): September 15, 2027
• Study Completion (Estimated): February 15, 2028

Study Registration Dates

• First Submitted: June 24, 2026
• First Submitted That Met QC Criteria: July 1, 2026
• First Posted (Actual): July 6, 2026

Study Record Updates

• Last Update Posted (Actual): July 6, 2026
• Last Update Submitted That Met QC Criteria: July 1, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Type 1 Diabetes (T1D); Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD); Short-Chain Fatty Acids (SCFAs); Sodium Butyrate
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 1; Organic Chemicals; Fatty Acids; Lipids; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Butyrates
• Other Study ID Numbers: BEAM-T1D Study

Drug and device information, study documents

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