Type 2 diabetes mellitus (DM2) has become a global epidemic whose incidence is not well known in our population. An important part of DM2 develops as a result of the presence of insulin resistance (RI), although many patients develop it through other mechanisms. The genetic component of this disease is very high, although only a small part has been identified. Both variants in the sequence and alterations of DNA methylation and hydroxymethylation (mC-hmC) may be influencing the development of this disease. Sequence variations, mainly rare variants can have important effects on the functionality of a gene, in addition the mC-hmC of coding and regulating splicing sequences can also have a relevant effect, mainly by regulating the expression of a gene. Therefore, both types of alterations can have a significant effect on the development of DM2. Objectives: 1) Identification of the genetic bases of DM2 (measuring its development or not by IR) by sequencing the exome in 125 patients with IR and 125 without IR followed for 5 years, of which 25 in each group have developed DM2. The mC-hmC study shall be conducted in 40 individuals in each group; 2) Identification of sequence or methylation variations that may help predict the development of DM2; 3) develop the second phase of the study Di@bet.es after 6 years of the first phase with the study of 650 individuals in the Valencian, Murcian and Balearic communities; 4) Validation of the genes identified by sequencing in the samples of the study Di@bet.es. The results will be of great importance since we will identify genes and pathways involved in the development of DM2, predictive changes in the development of DM2, new therapeutic targets, development of new drugs or genetic-epigenetic tests for DM2, etc.