Type 2 diabetes (DM2) is already a global epidemic and its prevalence is constantly increasing. Its genetic component is very high but only 10-15 % has been identified. Numerous rare genetic variants (PFVs) may be influencing the risk of DM2 and many may be located in the exome. People over 80 without DM2 and risk factors appear to be protected against DM2. Objectives: The overall objective is to identify new genetic variants and genes involved in DM2. 1) Recruitment of 300 octogenarians with BMI between 27 and 35, without DM2 or alterations in glycid metabolism and analyse their exome. Recruit a similar sample of 2000 octogenarians and 2000 patients under 55 years of age. 2) Comparison of genetic variants with more than 525 exomas already analysed by our group. 3) Verification of VPFs in all exome samples and analysis of their distribution. 4) selection of 50 variants/genes using Systems Biology and their validation (sequencing of exons and contiguous regions) in 2,000 octogenaries and 2,000 cases. 5) Analysis of 14,000 general population samples of genes that maintain the association under Objective 4. The results will identify vairants, genes and routes involved in DM2 (especially protective ones), new therapeutic targets and improve knowledge of DM2 and, in the future, improve the health of the population.