Acute Effects of an Oral Fat Load on Skeletal Muscle and Hepatic Insulin Sensitivity

Insulin Sensitivity Clinical Trial

— FLAME  

Official title:

Acute Effects of an Oral Fat Load on Skeletal Muscle and Hepatic Insulin Sensitivity (FLAME-study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01736202
• Other study ID #: FLAME
• Status: Completed
• Phase: Phase 4
• Start date: March 2012
• Est. completion date: January 1, 2022

Study information

• Verified date: June 2023
• Source: German Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The development of type 2 diabetes is based on a combination of insulin resistance and beta cell dysfunction. In the last years, elevated FFA were recognized as a key players in the pathogenesis of insulin resistance and type 2 diabetes.

The study compares the acute effects of an oral lipid bolus on insulin sensitivity and hepatic glucose metabolism in healthy humans.

Description:

A dysregulation of lipid metabolism with increased levels of free fatty acids (FFA) represents one key mechanism in the pathogenesis of insulin resistance, which contributes to the development of type 2 diabetes (T2D). In most cases, dyslipidemia is related to obesity and the metabolic syndrome. Not only skeletal muscle glucose uptake, but also hepatic glucose fluxes are altered in insulin resistant states. In obese and T2D subjects, rates of gluconeogenesis (GNG) are increased, but in obese normoglycemic subjects endogenous glucose production (EGP) remains constant because of downregulation of glycogenolysis (GL). However, in T2D subjects, both GNG and GL are elevated, contributing to fasting and postprandial hyperglycemia. Therefore, elevated GNG rates may represent an early event in the pathophysiology of insulin resistance and T2D.

Preliminary studies of our institute show that intravenous lipid infusion with subsequent elevation of FFA results in increased GNG rates without alteration of EGP in lean, non-diabetic subjects. In another recent study we investigated the effects of an oral fat load on hepatic insulin sensitivity. As expected, we did not find any alterations in EGP; however, rates of GNG and GL have not been assessed.

The aim of this study is to analyze the effects of an oral fat load with transiently elevated levels of circulating lipids on hepatic glucose fluxes, especially GNG and GL, to elucidate the role of dietary fat in the induction of insulin resistance in healthy humans.

In this randomized, controlled cross-over study, effects of oral palm oil and canola oil ingestion will be investigated in young, healthy lean subjects. Hepatic glucose fluxes will be assessed by two independent methods, in vivo magnet resonance spectroscopy (MRS) and the deuterated water/acetaminophen method, which also allows for the determination of glycogen cycling rates. Furthermore, hepatic phosphorus metabolites and liver fat content will be monitored by MRS.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: January 1, 2022
• Est. primary completion date: January 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 40 Years

Eligibility

Inclusion Criteria:

• healthy male and female subjects

• age 20-40

• BMI 20-25 kg/m2

Exclusion Criteria:

• hyperlipidemia

• smoking

• pregnancy

• allergy against paracetamol/palm oil/canola oil

• contraindication for MRI investigations

• anaemia

• taking drugs influencing lipid or glucose metabolism, the immune system or antihypertensive treatment

• M. Meulengracht

• Hepatitis/HIV

• chronic diseases

Related Conditions & MeSH terms

• Hypersensitivity
• Insulin Resistance
• Insulin Sensitivity

Intervention

Biological:
• fat orally
Oral ingestion of palm oil or canola oil or water at timepoint zero

Locations

Country	Name	City	State
Germany	German Diabetes Center	Düsseldorf	Nordrhein-Westfalen

Sponsors (2)

Lead Sponsor	Collaborator
German Diabetes Center	German Center for Diabetes Research

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in rate of glucose disappearance (Rd)	Measurement of whole body insulin sensitivity in a hyperinsulinamic euglicamic clamp with deuterated glucose kinetics	6 hours
Secondary	Change in rate of hepatic endogenous glucose production (EGP)	Measurement of hepatic EGP in a hyperinsulinamic euglicamic clamp with deuterated glucose kinetics	6 hours