This review integrates new developments in psychology with updated physiological insight on the complex relationships among chronic psychological stress (arising from weight stigmatization and body shaming), food composition, physical activity and metabolic health for the example of diabetes. We address how visual measures of health, such as body mass index (BMI) and waist-to-hip ratio, do not adequately capture metabolic health and can instead contribute to weight stigmatization, chronic stress, and system-wide impairment of metabolic health. We also emphasize the importance of food composition over calorie counting. We summarize how chronic stress interacts with nutritional deficiencies and physical inactivity to disrupt the stress response, immune response, gut microbiome, and function of fat depots. We specifically address how interactions among lifestyle factors and the gut microbiome regulate whether fat stored around the waist has a negative or positive effect on metabolic health. We aim to provide a resource and updated framework for diabetes prevention and health promotion by (i) highlighting metabolic imbalances triggered by lifestyle changes during the transition to industrialized society and (ii) detailing the potential to support metabolic health through access to modest, but comprehensive lifestyle adjustments.