Overfeeding Induced Fat-tissue Stimulation

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-40
SponsorGerman Diabetes Center

About this trial

Type 2 diabetes is the most common metabolic disease worldwide, characterized by hyperglycemia, decreased whole body insulin sensitivity, and white adipose tissue (WAT) dysfunction. A key factor in its development is chronic overnutrition, usually with a high-fat diet (HFD), leading to disturbances of glucose and lipid metabolism. However, the mechanism of short-term HFD-induced tissue-specific insulin resistance remains poorly understood. This project aims to further unravel the underlying mechanisms of short-term HFD overnutrition-mediated WAT insulin resistance. The model described here corresponds to a randomized, single- blinded parallel-grouped trial, consisting of two interventions: a macronutrient-balanced diet and or a hypercaloric diet over three weeks in order to investigate differences in interorgan fatty acid and glucose metabolism between the studied groups. Based on recent studies, the hypothesis is that 21-day hypercaloric HFD induces WAT insulin resistance via a diacylglycerol, novel protein kinase C-insulin receptor signaling model in both fasting and insulin-stimulated states.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Age between 18 and 40 years

BMI < 29 kg/m2

Sport inactive (<1x /week)

Capacity to consent

Disqualifiers

Diabetes mellitus disease

Acute coronary heart syndrome (myocardial infarction, unstable angina pectoris, stroke or transient ischemic attack in the last 3 months before study participation)

Acute infectious disease

Taking blood glucose-lowering drugs

Trial design

Design model

Parallel

Treatments tested in this trial

  • High-fat overnutrition

    Behavioral

    Overnutrition: 40% higher lipid consumption per day than required

  • Normocaloric macronutrient-balanced nutrition

    Behavioral

    Normocaloric, macronutrient-balanced nutrition: Calories requirement for weight maintenance \[(kcal/d) 55% carbohydrates, 15% proteins, 30% fat\]

Treatment groups

32 Participants
are divided into 2 treatment groups
Group A: High-fat overnutritionActive comparator 1 intervention
Group B: Normocaloric macronutrient-balanced nutritionActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Whole-body insulin sensitivity and WAT insulin sensitivity

Hyperinsulinemica-euglycemia clamp tests with deuterated glucose to measure fasting and insulin-stimulated whole-body insulin sensitivity and measurement of the index ADIPO-IR (fasting insulin x free fatty acid concentration) before and after dietary intervention period.

Time frame
3 weeks intervention period each

Secondary outcomes

1

WAT insulin signaling pathways

Adipose tissue biopsies are planned to be taken during the fasting and insulin-stimulated state before and after the dietary intervention period. DAG and ceramide subcellular fractionation assay is planned to be performed. Expressionanalyses for activation /membrane translocation of novel and atypical protein kinase C isoforms will be done. Determination of the degree of phosphorylation of various components of the insulin pathway via Western blot are planned.

Time frame
3 weeks intervention time

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

German Diabetes Center

Lead sponsor

Yale University

Collaborator