Figure 6.

Vicious cycle leading to progressively increased risk of DM. An individual’s intrinsic mitochondrial oxidative capacity is determined by numerous factors including genetic and ethnic background, intrauterine exposures, and age. Chronic fuel excess, in the setting of suboptimal oxidative activity, results in fatty acid accumulation, incomplete oxidation, increased oxidative stress, and ROS generation leading to impairment in oxidative capacity, compounding the deleterious effects of fuel excess. With time, mitochondrial damage ensues, further exacerbating the process. Together, these factors contribute to progressively impaired insulin sensitivity, insulin secretion, and heightened risk of DM.