Butyrate-enriched Triglyceride and Diabetes Prevention

Prevention of Diabetes with a Novel Butyrate-enriched Triglyceride

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.

Study Overview

• Status: Recruiting
• Conditions: Obesity; PreDiabetes; Type 2 Diabetes
• Intervention / Treatment: Dietary supplement: butyrate/hexanoate-enriched triglycerides

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emanuel E Canfora, PhD; Phone Number: 01733061283; Email: e.canfora@freenet.de

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 5229 ER
      • Recruiting
      • Maastricht University
      • Contact: Emanuel Canfora; Phone Number: +31 43 3881 669; Email: emanuel.canfora@maastrichtuniversity.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: butyrate/hexanoate-enriched triglycerides; Oil containing butyrate and hexanoate-enriched triglycerides	Dietary supplement: butyrate/hexanoate-enriched triglycerides; The oils are consumed two times a day for 24 weeks (six months).
Placebo Comparator: placebo; Oil devoid of butyrate and hexanoate but with similar composition as the intervention oil	Dietary supplement: butyrate/hexanoate-enriched triglycerides; The oils are consumed two times a day for 24 weeks (six months).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral insulin sensitivity	The change of peripheral insulin sensitivity as assessed by a hyperinsulinaemic-euglycemic clamp	Before and 6 months after the start of the intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hepatic insulin sensitivity	The change in hepatic insulin sensitivity as assessed by a hyperinsulinaemic-euglycemic clamp	Before and 6 months after the start of the intervention
adipose tissue insulin sensitivity	The change in adipose tissue insulin sensitivity as assessed by a hyperinsulinaemic-euglycemic clamp	Before and 6 months after the start of the intervention
Energy expenditure (indirect calorimetry)	The change in energy expenditure as measured via ventilated hood system	Before and 6 months after the start of the intervention
Substrate oxidation (indirect calorimetry)	The change in substrate oxidation as measured via ventilated hood system	Before and 6 months after the start of the intervention
circulating SCFA	The change in concentrations of circulating SCFA	Before and 6 months after the start of the intervention
Faecal SCFA	The change in concentrations of faecal SCFA	Before and 6 months after the start of the intervention
Faecal microbiota composition	The change in faecal microbiota composition assessing abundances of bacteria and diversity indices as assessed via 16s rRNA gene	Before and 6 months after the start of the intervention
Circulating hormones such as insulin	The change in concentrations of circulating hormones in peripheral blood	Before and 6 months after the start of the intervention
Circulating metabolites such as glucose	The change in concentrations of metabolites in peripheral blood	Before and 6 months after the start of the intervention
body composition	The change in body composition as assessed using DEXA scans	Before and 6 months after the start of the intervention
body weight	The change in body weight in kg using a weight scale	Before and 6 months after the start of the intervention
Gut permeability	The change in gut permeability as assessed using a multi-sugar test	Before and 6 months after the start of the intervention

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: April 22, 2024
• First Submitted That Met QC Criteria: April 22, 2024
• First Posted (Actual): April 25, 2024

Study Record Updates

• Last Update Posted (Actual): October 26, 2024
• Last Update Submitted That Met QC Criteria: October 23, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Prediabetic State
• Other Study ID Numbers: NL86266.068.24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No