**6. Insulin resistance**

IR, defined as a lower biological activity of the hormone in its different metabolic actions for a certain concentration, is the first abnormality detected in the evolution of DM2 and is already present in the prediabetes state.

IR plays a main role in DM2 development together with the insulin secretion defect, both disorders having genetic bases that have been extensively studied but not well defined to date, influenced by epigenetic factors that can act since intrauterine life.

IR, obesity, and DM2 are highly interrelated. In 95% of the cases, IR presents in subjects with excess weight or obesity will subsequently develop DM2. Although IR is present in almost all patients with DM2, the degrees of IR are very variable in different individuals; besides, a proportion of IR comes from obesity itself, and the other is characteristic of DM2.

IR is expressed in the liver, muscle, and adipose tissue with different intensities in the different individuals.

In DM2 due to IR, hyperglycemia occurs through three mechanisms: excessive hepatic production of glucose (gluconeogenesis), decrease in its uptake by peripheral tissues (muscle and adipose tissue), and increase in FFA resulting from a greater lipolysis in the adipocytes. FFA competes with glucose as a source of energy contributing to increase glycemia and inhibit glucose entry through the cell membrane [3].
