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

German Diabetes Center

Status and phase: Completed; Phase 4

Conditions: Insulin Sensitivity

Treatments: Biological: fat orally

Study type: Interventional

Funder types: Other

Identifiers

NCT01736202

FLAME

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 20 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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20 participants in 3 patient groups, including a placebo group

Palm oil orally

Active Comparator group

Description:

oral fat load

Treatment:

Biological: fat orally

Canola oil orally

Active Comparator group

Description:

Oral fat load

Treatment:

Biological: fat orally

Water orally

Placebo Comparator group

Description:

oral water administration as control

Treatment:

Biological: fat orally