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

NCT ID: NCT05044130

Last Updated: 2024-03-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-14
• Study Completion Date: 2023-04-23

Brief 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.

Conditions

NAFLD; Type 2 Diabetes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Type 2 Diabetes with NAFLD

Patients with Type 2 Diabetes with NAFLD

MR spectroscopy verified steatosis

Group Type: ACTIVE_COMPARATOR

High-fat mixed-meal tolerance test (HF-MMTT)

Intervention Type: DIETARY_SUPPLEMENT

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)

Type 2 Diabetes without NAFLD

Patients with Type 2 Diabetes without NAFLD

MR spectroscopy verified no steatosis

Group Type: ACTIVE_COMPARATOR

High-fat mixed-meal tolerance test (HF-MMTT)

Intervention Type: DIETARY_SUPPLEMENT

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)

Interventions

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)

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Danish Diabetes Academy

OTHER

Sponsor Role: collaborator

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Department of Endocrinology and Internal Medicine

Aarhus N, , Denmark

Countries

Denmark

Other Identifiers

01072021

Identifier Type: -

Identifier Source: org_study_id