Postprandial VLDL-triglyceride Metabolism in Type 2 Diabetes Patients With and Without NAFLD

Type 2 Diabetes Clinical Trial

Official title:

Postprandial Hepatic Fatty Acid Metabolism During Oral High-fat Mixed-meal Challenge Test in Patients With Type 2 Diabetes With and Without NAFLD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05044130
• Other study ID #: 01072021
• Status: Completed
• Phase: N/A
• Start date: September 14, 2021
• Est. completion date: April 23, 2023

Study information

• Verified date: March 2024
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum from simple reversible hepatic steatosis to inflammation and fibrosis termed steatohepatitis (NASH). The mechanisms behind why some subjects progress from NAFLD to NASH are not clear and the responsible mechanism for storage of excess amounts of liver fat in patients with NAFLD are poorly understood.

Patients with type 2 diabetes mellitus (T2D) and abdominally obese subjects very often have accumulation of liver fat (NAFLD).

T2D is also associated with abnormal lipid metabolism (dyslipidemia), including free fatty acids (FFA), hypertriglyceridemia and excessive postprandial hyperlipidemia which increases the risk of ischemic cardiovascular disease (CVD) and heart failure.

In healthy, insulin sensitive subjects the postprandial increase in triglycerides (TG) is primarily caused by meal derived chylomicrons, whereas endogenously produced TG (VLDL-TG) and decreased peripheral TG clearance only becomes quantitatively important in insulin resistant subjects .Thus, postprandial lipidemia in T2D results from both chylomicronemia as well as a reduction in both insulin mediated suppression of VLDL-TG secretion and lipoprotein lipase (LPL) mediated peripheral clearance. A recent study demonstrated that the ability of insulin to suppress hepatic VLDL-TG after a fat-enriched meal and the duration of the postprandial hyperlipidemia was similar in patients with T2D compared with age- and BMI matched individuals without T2D, indicating that the degree of insulin mediated VLDL-TG secretion and hyperlipidemia primarily depends on insulin sensitivity and not the presence of T2D diabetes per se.

In these studies, the investigators want to examine the effect of a fat enriched mixed-meal on hepatic VLDL-TG handling and adipose storage capacity in patients with T2D with and without NAFLD. Investigators will address these questions using carboxyl-14C triolein labeled VLDL-TG, magnetic resonance (MR) spectroscopy of liver, muscle and fat biopsies in combination with state-of-the art muscle and adipose tissue enzyme kinetics, gene- and protein expression.

The overarching goals are to define abnormalities and differences between patients with T2D with and without NAFLD in terms of hepatic lipid metabolism.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: April 23, 2023
• Est. primary completion date: February 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

Inclusion Criteria:

• Subjects with Type 2 Diabetes with and without NAFLD (steatosis FF% > 5,6% on MR spectroscopy for NAFLD and NASH groups)

Exclusion Criteria:

• Active smoking

• Comorbidity other than hypertension and hyperlipidemia

• Fixed medical drug consumption (including insulin) except statins and anti-diabetic medications. However, statins must be paused 2 weeks before the examination date and other antidiabetic medication on examination date.

• Patients with cancer or former cancer patients

• Blood donation within the last 3 months prior to the study

• Participation in experiments involving radioactive isotopes within the last 3 months

• Alcohol abuse (over 21 items per week for men and over 14 for women)

• Pregnancy

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• NAFLD
• Non-alcoholic Fatty Liver Disease
• Type 2 Diabetes

Intervention

Dietary Supplement:
• High-fat mixed-meal tolerance test (HF-MMTT)
The test meal consists of a standardized HF-MMTT (791 cal) with 197 g cream (38 % fat), 18 g sugar and 1 g vanilla sugar for taste (75 g fat, 25 g carbohydrate and 4 g protein)

Locations

Country	Name	City	State
Denmark	Department of Endocrinology and Internal Medicine	Aarhus N

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Danish Diabetes Academy

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	VLDL-triglyceride secretion - Ex vivo labeled VLDL - [14C]-triolein tracer technique.	(µmol/min)	1 day
Primary	VLDL-triglyceride uptake in muscle - Measurement of fatty acid concentration and specific activity in muscle biopsies	(percent)	1 day
Primary	VLDL-triglyceride uptake in adipose tissue - Measurement of fatty acid concentration and specific activity in adipose tissue biopsies	(percent)	1 day
Secondary	VLDL-triglyceride oxidation - Oxidation is measured by specific activity in exhaled air.	(µmol/min)	1 day
Secondary	Adipose cell size measurement	(µl)	1 day
Secondary	Insulin sensitivity	(mg/kg/min)	1 day