Clinical trial NCT06384313: Butyrate-enriched Triglyceride and Diabetes Prevention
Official title: Prevention of Diabetes with a Novel Butyrate-enriched Triglyceride
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 2 Diabetes
PreDiabetes
Obesity
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2024-04-25
Enrollment: 48
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: A body of animal studies as well as observational studies in humans demonstrated that butyrate is one SCFA that has pronounced positive effects on body weight control, inflammation, and insulin resistance. Even though the SCFA hexanoate is less researched, it has been shown to be involved in anti-inflammatory processes. Of note, acute human studies showed that fibre-induced metabolic improvements are linked to higher SCFA levels in the systemic circulation. It has been shown that a butyrate/hexanoate-enriched triglyceride oil enhanced systemic butyrate and hexanoate concentrations for a prolonged time. Yet, it remains to be determined whether a chronic increase in circulating butyrate and hexanoate concentrations translate into long-term benefits. In this study it is hypothesized that a chronic increase of butyrate/hexanoate in the circulation may improve host metabolism and metabolic health by improving adipose tissue function, reducing systemic lipid overflow and inflammation thereby increasing peripheral insulin sensitivity in individual with overweight/obesity and prediabetes.


Eligibility criteria: Inclusion Criteria:

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

* Age 20-70 years
* BMI ≥ 28 and \< 40 kg/m2
* Weight stable for at least 3 months
* Normal blood pressure (systolic blood pressure 100-140 mmHg, diastolic blood pressure 60-90 mmHg)
* One or more of the following criteria to determine disturbed glucose/insulin homeostasis

  * Fasting glucose 5.6-6.9 mmol/L
  * Two-hour glucose of 7.8-11.1 mmol/L
  * HOMA-IR ≥ 2.2
  * HbA1c (5.7-6.4%)

Exclusion Criteria:

* Diabetes mellitus (type 1 or 2)

  * Cardiovascular disease: including no history or myocardial infarction, heart failure, arrhythmias
  * Pulmonary disease: no history of chronic obstructive pulmonary disease, emphysema, bronchitis, asthma
  * Kidney (e.g. kidney failure) or liver (e.g. cirrhosis, non-alcoholic fatty acid) malfunction
  * Gastrointestinal disease (no inflammatory bowel disease, irritable bowel syndrome or digestive disorders) or a history of abdominal surgery (except appendectomy and cholecystectomy)
  * Autoimmune disease
  * Any other diseases affecting glucose and/or lipid metabolism or use of any medication that influence glucose or fat metabolism and inflammation
  * Ongoing disease or any disease with a life expectancy ≤ 5 years
  * Abuse of products; alcohol (\>15 units per week) and drugs, excessive nicotine use defined as \>20 cigarettes per week
  * Regular supplementation of pre- or probiotic products, use of pre- or probiotics, antibiotics and laxatives 3 months prior to the start of the study
  * Intensive exercise training more than three hours a week
  * Plan to lose weight or to follow a hypocaloric diet or vegetarian diet
  * Pregnancy

Primary outcomes:
measure: Peripheral insulin sensitivity
timeFrame: Before and 6 months after the start of the intervention
Secondary outcomes:
measure: hepatic insulin sensitivity
timeFrame: Before and 6 months after the start of the intervention
measure: adipose tissue insulin sensitivity
timeFrame: Before and 6 months after the start of the intervention
measure: Energy expenditure (indirect calorimetry)
timeFrame: Before and 6 months after the start of the intervention
measure: Substrate oxidation (indirect calorimetry)
timeFrame: Before and 6 months after the start of the intervention
measure: circulating SCFA
timeFrame: Before and 6 months after the start of the intervention
measure: Faecal SCFA
timeFrame: Before and 6 months after the start of the intervention
measure: Faecal microbiota composition
timeFrame: Before and 6 months after the start of the intervention
measure: Circulating hormones such as insulin
timeFrame: Before and 6 months after the start of the intervention
measure: Circulating metabolites such as glucose
timeFrame: Before and 6 months after the start of the intervention
measure: body composition
timeFrame: Before and 6 months after the start of the intervention
measure: body weight
timeFrame: Before and 6 months after the start of the intervention
measure: Gut permeability
timeFrame: Before and 6 months after the start of the intervention
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University
state: Limburg
Study officials:
References: