Lipid-induced Insulin Resistance Clinical Trial
— OVID_FASTIOfficial title:
Short-term High-fat Overnutrition Induces Insulin Resistance in White Adipose Tissue
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.
| Status | Recruiting |
| Enrollment | 32 |
| Est. completion date | December 31, 2030 |
| Est. primary completion date | December 31, 2025 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 18 Years to 40 Years |
| Eligibility | Inclusion Criteria: - Age between 18 and 40 years - BMI < 29 kg/m2 - Sport inactive (<1x /week) - Capacity to consent Exclusion Criteria: - 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 - Diseases or drugs affecting the immune system and allergies to drugs used in the study - Drugs with potential metabolic effects - Chronic liver disease (hepatitis, gallbladder disease, elevated liver enzymes (ALT > 300 U/L)) - Chronic inflammatory bowel diseases - Rheumatic diseases - Hyper- or hypothyroidism of the thyroid gland - Renal insufficiency, administration of iodine-containing contrast media in the last 2 days - Chronic lung diseases - cancerous diseases - Addictive diseases, psychiatric diseases - Pregnancy, breastfeeding - Shift workers - Anemia (Hb <12 g/dl) - Disorders of hemostasis - Regular use of antithrombotic drugs - Alcohol consumption, smoking - Conditions that do not permit an MRI examination |
| Country | Name | City | State |
|---|---|---|---|
| Germany | Georgia Xourafa | Düsseldorf | Nordrhein-Westfalen |
| Lead Sponsor | Collaborator |
|---|---|
| German Diabetes Center | Yale University |
Germany,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. | 3 weeks intervention period each | |
| Secondary | 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. | 3 weeks intervention time |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01482455 -
Fat and Transcapillary Insulin Transport
|
N/A |