Effect of Dietary SFA and Fructose on Hepatic Insulin Sensitivity

Sponsor
Maastricht University Medical Center (Other)
Overall Status
Recruiting
CT.gov ID
NCT05017675
Collaborator
(none)
24
1
2
15.7
1.5

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Other: High fructose diet
  • Other: High saturated fat diet
N/A

Detailed Description

Rationale: 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. This is a clinically relevant question, as it will give novel insights towards the best strategy for prevention and treatment of hepatic insulin resistance. Therefore, it is of interest to compare the effect of a diet that modifies directly hepatic SFA content (high SFA diet) and a diet that changes SFA indirectly by modifying rates of DNL (high fructose diet).

Objective: To determine the effect of a 4-week high SFA diet compared to a 4-week high fructose diet on hepatic insulin sensitivity, on hepatic SFA fraction and DNL.

Study design: This is a randomized intervention study comparing the effects of a 4-week high SFA diet compared to a 4-week high fructose diet on hepatic insulin sensitivity.

Study population: 24 overweight/obese, but otherwise healthy, males and females (BMI 27-38 kg/m2), 45-75 years, will participate in the study. Of these 24 included participants, 18 are expected to meet the study criteria and take part in the measurements following the screening, of these 14 need to complete the study.

Intervention: Participants follow a 4-week high SFA diet and a 4-week high fructose diet.

Main study parameters/endpoints: 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. Secondary outcomes are DNL upon 4-week high SFA versus 4-week high fructose, and delta (baseline-end intervention) hepatic SFA fraction upon 4-week high SFA versus 4-week high fructose.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
24 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
Comparing the Effect of a High SFA Diet and High Fructose Diet on Hepatic Insulin Sensitivity
Actual Study Start Date :
Nov 8, 2021
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Mar 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: High fructose diet

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

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

Experimental: High saturated fat diet

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

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

Outcome Measures

Primary Outcome Measures

  1. Hepatic insulin sensitivity measured by hyperinsulinemic-euglycemic clamp. [after 28 days of each diet]

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

Secondary Outcome Measures

  1. Hepatic fat composition measured by proton magnetic resonance spectroscopy [first day of each diet - after 28 days of each diet]

    The change in liver fat composition (%SFA, %MUFA and %PUFA) after the high SFA diet and the high fructose diet

  2. De novo lipogenesis measured by deuterated water [after 25 days of each diet]

    Difference between overnight DNL after the high SFA diet and the high fructose diet. Measured as relative contribution of newly synthesized palmitate in the VLDL-TG pool expressed as %DNL.

Other Outcome Measures

  1. Liver fat content measured by proton magnetic resonance spectroscopy [after 28 days of each diet]

    Difference in liver fat content after the high SFA diet and the high fructose diet

  2. Peripheral and whole-body Insulin sensitivity measured by hyperinsulinemic-euglycemic clamp [after 28 days of each diet]

    Whole body insulin sensitivity is measured as GIR in μmol/kg/min and peripheral insulin sensitivity is measured as Rd in μmol/kg/min. Difference in GIR and Rd after the high SFA diet and the high fructose diet will be determined

  3. Fat oxidation measured by indirect calorimetry [after 25 and 28 days of each diet]

    Fat oxidation as determined by indirect calorimetry, will be compared between the high SFA and high fructose diet

  4. Carbohydrate oxidation measured by indirect calorimetry [after 25 and 28 days of each diet]

    Carbohydrate oxidation as determined by indirect calorimetry will be compared between the high SFA and high fructose diet

  5. Sleeping metabolic rate measured by indirect calorimetry [after 25 days of each diet]

    Sleeping metabolic rate as determined by indirect calorimetry will be compared between the high SFA and high fructose diet

  6. Body composition measured by BodPod [day 1]

    Body composition is measured using the BodPod technique and percentage fat mass will be determined for participant characterization.

Eligibility Criteria

Criteria

Ages Eligible for Study:
45 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  • 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.

Exclusion Criteria:
  • 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Maastricht University Medical Center Maastricht Limburg Netherlands 6229 ER

Sponsors and Collaborators

  • Maastricht University Medical Center

Investigators

  • Principal Investigator: Vera Schrauwen-Hinderling, Dr, Maastricht University Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT05017675
Other Study ID Numbers:
  • NL78281.068.21
First Posted:
Aug 24, 2021
Last Update Posted:
Nov 23, 2021
Last Verified:
Nov 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Maastricht University Medical Center
Additional relevant MeSH terms:

Study Results

No Results Posted as of Nov 23, 2021