Type 2 diabetes mellitus (DM2) is a complex, polygenic disease with genetic heterogeneity. Susceptibility has been evaluated for over 250 potentially involved genes, with linkage found to different chromosomes depending on ethnicity. Mitochondrial DNA (mtDNA) mutations account for less than 2% of DM2 cases with maternal inheritance patterns. The study aims to evaluate the association between DM2 and mtDNA polymorphisms through a case-control study, comparing allele and haplotype frequencies of polymorphic loci in mtDNA between case and control groups. High frequencies of Amerindian mitochondrial haplotypes in the Antioquian population suggest that DM2 incidence may be explained by the interaction between nuclear gene polymorphisms and ancestral mitochondrial haplotypes, leading to DM2 and obesity.