Defining the Human Insulin Resistance Molecular Network; SIGNATURE

Summary

The goal of this intervention study is to learn more about what causes insulin resistance in otherwise healthy adults, and how short-term changes in physical activity or diet may influence it. The study includes healthy male and female participants aged 25 to 55 years, who meet specific health criteria.

The main questions it aims to answer are:

Does the cause of insulin resistance vary between individuals due to their genes and lifestyle?

Can the investigators identify different types (sub-phenotypes) of insulin resistance at the molecular level?

Researchers will compare groups who either reduce their physical activity for 14 days or consume a high-fat diet for 3 days, to see how these changes affect insulin sensitivity and related biological markers.

Participants will:

* Complete a health screening and be assessed for eligibility
* Undergo baseline testing to measure insulin sensitivity, physical activity, diet, and metabolic health
* Be randomly assigned to one of two short-term interventions (14 days of reduced physical activity, or 3 days of a high-fat, high-calorie diet)
* Repeat selected tests after the intervention to assess changes

This study will help researchers better understand how lifestyle and biology interact in the development of insulin resistance, even in people who are otherwise healthy.

Conditions

• Metabolic Health
• Insulin Sensitivity/Resistance

Interventions

BEHAVIORAL

Physical Inactivity

Participants assigned to the physical inactivity intervention will reduce their daily physical activity to fewer than 1,500 steps per day for 14 consecutive days. This strict limitation significantly decreases overall movement and muscle activity, mimicking a sedentary lifestyle. The aim is to assess the short-term effects of reduced physical activity on insulin sensitivity and related metabolic processes. Compliance will be monitored using activity trackers and daily logs. Baseline metabolic and physiological assessments will be repeated after the intervention to evaluate changes.

BEHAVIORAL

Hypercaloric High-Fat Diet

Participants assigned to the high-fat diet intervention will consume a hypercaloric diet rich in fat for 3 consecutive days. The diet is designed to significantly increase caloric intake and fat consumption beyond habitual levels to induce short-term metabolic stress. This intervention aims to assess how a brief period of high-fat overfeeding affects insulin sensitivity and related molecular pathways. Participants' dietary intake will be carefully controlled and monitored to ensure adherence. Baseline metabolic and physiological assessments will be repeated after the intervention to evaluate changes.

Sponsors & Collaborators

• University of Sydney

  collaborator OTHER

• Queen Mary University of London

  collaborator OTHER

• Novo Nordisk A/S

  collaborator INDUSTRY

• University of Copenhagen

  lead OTHER

Principal Investigators

• Jørgen F.P. Wojtaszewski, Ph.D. · University of Copenhagen

• Ylva Hellsten, Ph.D. · University of Copenhagen

• Henriette Pilegaard, Ph.D. · University of Copenhagen

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

25 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-12-01

Primary Completion

2028-06-30

Completion

2038-06-30

Countries

• Denmark

Study Locations