Effect of Dietary SFA and Fructose on Hepatic Insulin Sensitivity

Insulin Resistance Clinical Trial

Official title:

Comparing the Effect of a High SFA Diet and High Fructose Diet on Hepatic Insulin Sensitivity

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05017675
• Other study ID #: NL78281.068.21
• Status: Recruiting
• Phase: N/A
• Start date: November 8, 2021
• Est. completion date: December 2023

Study information

• Verified date: March 2023
• Source: Maastricht University Medical Center
• Contact: Vera Schrauwen-Hinderling, Dr
• Phone: 0031 43 3875149
• Email: v.schrauwen[@]maastrichtuniversity.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: December 2023
• Est. primary completion date: October 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 45 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Insulin Resistance

Intervention

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
• 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

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Center	Maastricht	Limburg

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Liver fat content measured by proton magnetic resonance spectroscopy	Difference in liver fat content after the high SFA diet and the high fructose diet	after 28 days of each diet
Other	Peripheral and whole-body Insulin sensitivity measured by hyperinsulinemic-euglycemic clamp	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	after 28 days of each diet
Other	Fat oxidation measured by indirect calorimetry	Fat oxidation as determined by indirect calorimetry, will be compared between the high SFA and high fructose diet	after 25 and 28 days of each diet
Other	Carbohydrate oxidation measured by indirect calorimetry	Carbohydrate oxidation as determined by indirect calorimetry will be compared between the high SFA and high fructose diet	after 25 and 28 days of each diet
Other	Sleeping metabolic rate measured by indirect calorimetry	Sleeping metabolic rate as determined by indirect calorimetry will be compared between the high SFA and high fructose diet	after 25 days of each diet
Other	Body composition measured by BodPod	Body composition is measured using the BodPod technique and percentage fat mass will be determined for participant characterization.	day 1
Primary	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	Hepatic fat composition measured by proton magnetic resonance spectroscopy	The change in liver fat composition (%SFA, %MUFA and %PUFA) after the high SFA diet and the high fructose diet	first day of each diet - after 28 days of each diet
Secondary	De novo lipogenesis measured by deuterated water	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.	after 25 days of each diet