Mechanisms of Fasting-Induced Insulin Resistance

During prolonged fasting, the body shifts from using glucose toward using fat as its main energy source. At the same time, skeletal muscle becomes less sensitive to insulin, a hormone that helps regulate blood glucose levels. Although this response is a normal adaptation to fasting, the mechanisms responsible for it are not fully understood. The DELIVER study aims to investigate how changes in fat metabolism, communication between tissues, and liver energy metabolism contribute to reduced insulin sensitivity during prolonged fasting. In this randomized crossover study, 18 healthy adults will complete two conditions in random order: a 60-hour fasting period and a control condition involving a standard overnight fast. The conditions will be separated by at least four weeks. During both conditions, researchers will assess insulin sensitivity, energy metabolism, and fat metabolism using blood and urine samples, magnetic resonance spectroscopy (MRS), measurements of energy expenditure, and small samples of skeletal muscle and abdominal fat tissue (biopsies). Insulin sensitivity will be measured using a hyperinsulinemic-euglycemic clamp, a procedure in which insulin and glucose are administered intravenously while blood glucose levels are closely monitored. By comparing the two conditions, the study aims to improve understanding of how the body adapts to fasting and whether some of the mechanisms involved resemble those observed in insulin resistance associated with obesity and type 2 diabetes.

Inclusion Criteria: 1. Healthy men and women, age 18-40 years 2. BMI 20-25 kg/m² 3. Sedentary lifestyle (\