Mitochondrial (mt) gene abnormalities cause disease due to defects in oxidative production of energy (1). In 1990, Goto and colleagues (2) described the co-segregation of a syndrome called mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (which is sometimes associated with diabetes) and an A to G transition at position 3243 of mtDNA, encoding transfer RNA leucine (tRNALeu [UUR]). In 1992, a subtype of diabetes called maternally inherited diabetes and deafness (MIDD) was reported to co-segregate with the same point mutation (3–4). Maternally inherited diabetes and deafness was initially characterized by matrilineal transmission, associated hearing loss, or both, without major neurologic defects. In MIDD, diabetes seems to be due primarily to a defect in insulin secretion (4–9), while insulin sensitivity is unaltered (8, 10). An estimated 0.5% to 2.8% of diabetic patients have MIDD (9, 11–16). Because most reported series have been small, the clinical description of MIDD and its course, particularly the occurrence of diabetic complications, remains incomplete. The aims of our study were to delineate the clinical presentation of MIDD, including involvement of other organs, in a large series of patients and to assess the prevalence of diabetic microvascular and macrovascular complications.