Effects of Exercise Intervention on Type 2 Diabetes Patients With Abdominal Obesity and Low Thigh Circumference (EXTEND): Study Protocol for a Randomized Controlled Trial

INTRODUCTION: Type 2 diabetes patients have abdominal obesity and low thigh circumference. Previous studies have mainly focused on the role of exercise in reducing body weight and fat mass, improving glucose and lipid metabolism, with a lack of evaluation on the loss of muscle mass, diabetes complications, energy metabolism, and brain health. Moreover, whether the potential physiological benefit of exercise for diabetes mellitus is related to the modulation of the microbiota-gut-brain axis remains unclear. Multi-omics approaches and multidimensional evaluations may help systematically and comprehensively correlate physical exercise and the metabolic benefits. METHODS AND ANALYSIS: This study is a randomized controlled clinical trial. A total of 100 sedentary patients with type 2 diabetes will be allocated to either an exercise or a control group in a 1:1 ratio. Participants in the exercise group will receive a 16-week combined aerobic and resistance exercise training, while those in the control group will maintain their sedentary lifestyle unchanged. Additionally, all participants will receive a diet administration to control the confounding effects of diet. The primary outcome will be the change in body fat mass measured using bioelectrical impedance analysis. The secondary outcomes will include body fat mass change rate (%), and changes in anthropometric indicators (body weight, waist, hip, and thigh circumference), clinical biochemical indicators (glycated hemoglobin, blood glucose, insulin sensitivity, blood lipid, liver enzyme, and renal function), brain health (appetite, mood, and cognitive function), immunologic function, metagenomics, metabolomics, energy expenditure, cardiopulmonary fitness, exercise-related indicators, fatty liver, cytokines (fibroblast growth factor 21, fibroblast growth factor 19, adiponectin, fatty acid-binding protein 4, and lipocalin 2), vascular endothelial function, autonomic nervous function, and glucose fluctuation. DISCUSSION: This study will evaluate the effect of a 16-week combined aerobic and resistance exercise regimen on patients with diabetes. The results will provide a comprehensive evaluation of the physiological effects of exercise, and reveal the role of the microbiota-gut-brain axis in exercise-induced metabolic benefits to diabetes. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR2100046148.