The incidence of global obesity and Type 2 diabetes has increased and is predicted to rise to 30% of the global population. Diet and lifestyle factors are incapable to resolve the increased incidence for obesity and diabetes in various populations of the world. Developing countries have come to the forefront because of the higher diabetic epidemic. The urbanization may possibly provide an explanation for the global diabetic epidemic. In Western countries the metabolic syndrome and non alcoholic fatty liver disease (NAFLD) have reached 30 % of the population and now at present NAFLD afflicts 20% of developing populations. Western diets and sedentary lifestyles cause metabolic disorders in developing countries which may increase neurodegenerative diseases by the disrupted metabolism of xenobiotics in urban populations. In developing countries access to high calorie diets in urban areas down regulate liver nuclear receptors that are responsible for glucose, lipid and toxicological sensing and interrupt the metabolism of xenobiotics that become toxic to various tissues such as the pancreas, heart, kidney, brain and liver. Xenobiotics in urban areas induce epigenetic changes that involve chromatin remodelling by alterations in transcriptional regulators with modification of histones. Dysfunction of nuclear receptors such as the calorie sensitive sirtuin 1 (Sirt 1) gene involves abnormal nutrient metabolism with insulin resistance, NAFLD, energy balance and circadian rhythm disorders. In obesity and diabetes insulin resistance has been connected to poor xenobiotic metabolism with the toxic affects of increased xenobiotic transport to the brain associated with neurodegeneration. Dietary interventions to increase xenobiotic metabolism are likely to reduce oxidative stress and neuroendocrine disease in developing countries. Prevention programs are an important goal of international health organizations and in developing countries the plans to adapt a healthy diet, active lifestyle and reduced exposure to xenobiotics are important to manage the global epidemic for obesity and diabetes.