The Effect of the 14:10-Hour Time-Restricted Feeding Regimen on Selected Markers of Glucose Homeostasis in Diet-Induced Prediabetic Male Sprague Dawley Rats.

Abstract

Background Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by persistent high blood glucose levels due to either impaired insulin secretion, reduced insulin sensitivity, or a combination of both. It is strongly linked to insulin resistance, leptin resistance, obesity, elevated fasting glucose levels, and glucose intolerance. The global incidence of T2DM is increasing rapidly, currently affecting approximately 500 million people worldwide. Projections indicate a 25% rise by 2030 and a 51% increase by 2045. Management of T2DM typically involves pharmacological interventions, such as metformin, combined with lifestyle changes, including enhanced physical activity and dietary modifications. However, poor patient adherence to these approaches often compromises their effectiveness, underscoring the need for alternative treatment options. Recently, intermittent fasting (IF) has garnered interest as a potential management strategy for T2DM. The IF protocols alternate between periods of eating and fasting, which may involve caloric restriction or complete fasting during the fasting phases. The duration and structure of fasting and eating windows differ across various IF regimens, including the 5:2 diet, alternate-day fasting, and time-restricted feeding (TRF). In TRF, individuals typically fast for 14 hours followed by a 10-hour eating window (14:10) or a 16-hour fasting period with an 8-hour eating window (16:8). Studies have demonstrated that the 14:10 TRF regimen effectively reduces body weight, leptin resistance, glucose intolerance, insulin resistance, and blood glucose levels in individuals with T2DM. While the positive effects of 14:10 TRF on T2DM are well-established, its impact on glycemic control during the prediabetic stage remains to be studied. Materials and Methods Twenty-four male (120g to 180g) Sprague Dawley rats were obtained and randomly divided into two dietary groups: Group 1 (n=6) received a standard diet and water. In contrast, group 2 (n=18) was provided a high-fat, high-carbohydrate (HFHC) diet supplemented with 15% fructose for 20 weeks to induce prediabetes. After confirming prediabetes, an additional 12 weeks of treatment took place during which an intermittent fasting (IF) regimen was assigned to the rats while also having untreated and metformin-treated prediabetic rats serving as controls. The IF regimen assigned in this study is TRF where Sprague Dawley rats were exposed to fasting for 14 hours, then had a 10-hour window to eat (14:10). Every 4 weeks during the treatment period, body weight, calorie intake, oral glucose response, and fasting glucose were measured for all groups. Following study termination after 12 weeks of treatment, organs such as the skeletal muscle and the liver were harvested from the animals along with blood. Glycogen concentrations were measured in the liver and skeletal muscle tissues. Additionally, the expression levels of insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), protein kinase A (Akt), Phosphoinositide 3-Kinase (PI3K), and Mechanistic Target of Rapamycin Complex 1 (mTORC1) were assessed in liver tissue, while glucose transporter 4 (GLUT4). Moreover, plasma was extracted to assess fasting insulin and leptin concentrations and computed as well as determined Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).