Defining the Human Insulin Resistance Molecular Network; SIGNATURE
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age25-55
SponsorUniversity of Copenhagen
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Age: 25-55 years
Body Mass Index (BMI): 18-30 kg/m²
Healthy (no diagnosed chronic diseases)
Able and willing to comply with study procedures
Disqualifiers
Smoking or nicotine use, current or within the past 5 years
Alcohol intake exceeding 10 units per week
Hemoglobin A1c (HbA1c) > 48 mmol/mol (indicative of diabetes or prediabetes)
Chronic diseases (e.g., cardiovascular disease, diabetes, etc.)
Trial design
Design model
Parallel
Treatments tested in this trial
Physical Inactivity
BehavioralParticipants 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.
Hypercaloric High-Fat Diet
BehavioralParticipants 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.
Treatment groups
80 Participants
are divided into 2 treatment groupsGroup A: Baseline CharacterizationNo intervention 0 interventions
Group B: Lifestyle InterventionsExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Whole-body insulin action
Glucose disposal rates during hyperinsulinemic euglycemic conditions as a marker of whole-body insulin action
Time frame
Baseline characterization & immediately following intervention (either 14 days of physical inactivity or 3 days of hypercaloric high-fat diet)Secondary outcomes
1
Identification of proteins and posttranslational modification of proteins in blood as well as skeletal muscle and adipose tissue biopsies
The obtained samples will be subjected to mass spectrometry-based proteomic and phosphoproteomic analyses. These measurements show protein abundance and posttranslational modifications that regulates protein function. Ultimately, revealing the signaling network underlying the interventions studied. Unit of measure is log2-transformed arbitrary units.
Time frame
Baseline & immediately following the intervention (14 days of physical inactivity or 3 days of hypercaloric high-fat diet)2
Whole-Body Glucose Tolerance
Whole-body glucose tolerance will be assessed by an oral glucose tolerance test (OGTT). Blood glucose and insulin concentrations will be measured at multiple time points following oral glucose ingestion to determine glucose and insulin responses. Glucose and insulin areas under the curve (AUC) values will be used to evaluate changes in glucose tolerance.
Time frame
Baseline3
Beta Cell Function
Beta cell function will be evaluated using an intravenous glucose tolerance test (IVGTT). Following intravenous glucose administration, arterial glucose and insulin concentrations will be measured at multiple time points to assess first-phase insulin secretion and beta cell responsiveness.
Time frame
Baseline & immediately following the intervention (14 days of physical inactivity or 3 days of hypercaloric high-fat diet)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Copenhagen
Lead sponsor
University of Sydney
Collaborator
Queen Mary University of London
Collaborator
Novo Nordisk A/S
Collaborator
Source ClinicalTrials.gov