Effect of Dietary SFA and Fructose on Hepatic Insulin Sensitivity

NCT05017675 | Completed

• 1 other identifier: NL78281.068.21
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

High rates of de novo lipogenesis (DNL) and high saturated fatty acid (SFA) fraction in the liver both have been associated with poor metabolic health and hepatic insulin resistance. Interestingly, the end product of DNL is mainly SFA. So far it is unknown whether it is the process of DNL or the accumulation of SFA per se that leads to hepatic insulin resistance. Therefore, it is of interest to compare the effect of a diet that modifies directly hepatic SFA content (4-week high SFA diet) and a diet that changes SFA indirectly by modifying rates of DNL (4-week high fructose diet). To this end, 18 overweight/obese, but otherwise healthy, males and females will take part in the randomized dietary interventions. The primary outcome is hepatic insulin sensitivity (suppression of EGP during clamp) upon a 4-week high SFA diet versus a 4-week fructose diet.

Conditions

Insulin Resistance

Keywords

High fructose diet; High saturated fat diet; De novo lipogenesis; Hepatic saturated fatty acids

Outcome Measures

Primary Outcomes (1)

• Hepatic insulin sensitivity measured by hyperinsulinemic-euglycemic clamp.

  difference in EGP suppression after the high SFA diet and the high fructose diet

  after 28 days of each diet

Secondary Outcomes (2)

• Hepatic fat composition measured by proton magnetic resonance spectroscopy

  first day of each diet - after 28 days of each diet

• De novo lipogenesis measured by deuterated water

  after 25 days of each diet

Other Outcomes (6)

• Liver fat content measured by proton magnetic resonance spectroscopy

  after 28 days of each diet

• Peripheral and whole-body Insulin sensitivity measured by hyperinsulinemic-euglycemic clamp

  after 28 days of each diet

• Fat oxidation measured by indirect calorimetry

  after 25 and 28 days of each diet

Study Arms (2)

High fructose diet

EXPERIMENTAL

Participants will receive dietary products high in fructose for 4 weeks.

Other: High fructose diet

High saturated fat diet

EXPERIMENTAL

Participants will receive dietary products high in saturated fat for 4 weeks.

Other: High saturated fat diet

Interventions

High fructose diet OTHER

4 week high fructose diet. Intended composition (En%): Carbohydrates: 60-70 Fat: 20-30 Protein: 10-15 Fructose: 20 SFA: 5

High fructose diet

High saturated fat diet OTHER

4 week high saturated fat diet. Intended composition (En%): Carbohydrates: 35-45 Fat: 40-50 Protein: 10-15 Fructose: 5 SFA: 20

High saturated fat diet

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are able to provide signed and dated written informed consent prior to any study specific procedures
• Participants should have suitable veins for cannulation or repeated venipuncture
• Women are post-menopausal (defined as at least 1 year post cessation of menses)
• Aged ≥ 45 and ≤ 75 years
• Body mass index (BMI) 27 - 38 kg/m2
• Stable dietary habits (no weight loss or gain \>5kg in the past 3 months)
• Sedentary lifestyle (not more than 2 hours of sports per week)
• No signs of active cardiovascular disease, liver or kidney malfunction
• Liver fat content ≥ 2% weight/weight.

You may not qualify if:

• Type 2 diabetes
• Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator
• Patients with congestive heart failure and and/or severe renal and or liver insufficiency or another condition that may interfere with outcomes measured in this study.
• Any contra-indication MRI scanning
• Alcohol consumption of \>2 servings per day for men and \>1 servings per day for woman
• Smoking in the past 6 months
• Men: Hb \<8.4 mmol/L, Women: Hb \<7.8 mmol/l
• Vegetarian, vegan, food intolerant to common foods (e.g. gluten intolerant, lactose intolerant)
• Medication use that may influence outcome parameters
• A medical doctor will judge participation eligibility based on the medical history questionnaire, medication use and fasting blood parameters. If the medical doctor advises that a volunteer cannot participate, the volunteer will be excluded from enrollment.

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University Medical Center

Maastricht, Limburg, 6229 ER, Netherlands

Location

MeSH Terms

Conditions

Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Vera Schrauwen-Hinderling, Dr

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2021
• First Posted: August 24, 2021
• Study Start: November 8, 2021
• Primary Completion: April 19, 2024
• Study Completion: May 24, 2024
• Last Updated: August 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)