Maternal transmission of diabetes

Abstract

Type 2 diabetes mellitus represents a heterogeneous group of conditions characterized by impaired glucose homeostasis. The disorder runs in families but the mechanism underlying this is unknown. Many, but not all, studies have suggested that mothers are excessively implicated in the transmission of the disorder. A number of possible genetic phenomena could explain this observation, including the exclusively maternal transmission of mitochondrial DNA (mtDNA). It is now apparent that mutations in mtDNA can indeed result in maternally inherited diabetes. Although several mutations have been implicated, the strongest evidence relates to a point substitution at nucleotide position 3243 (A to G) in the mitochondrial tRNA(leu(UUR)) gene. Mitochondrial diabetes is commonly associated with nerve deafness and often presents with progressive non-autoimmune beta-cell failure. Specific treatment with Coenzyme Q10 or L-carnitine may be beneficial. Several rodent models of mitochondrial diabetes have been developed, including one in which mtDNA is specifically depleted in the pancreatic islets. Apart from severe, pathogenic mtDNA mutations, common polymorphisms in mtDNA may contribute to variations of insulin secretory capacity in normal individuals. Mitochondrial diabetes accounts for less than 1% of all diabetes and other mechanisms must underlie the maternal transmission of Type 2 diabetes. Possibilities include the role of maternally controlled environments, imprinted genes and epigenetic phenomena.

Family-based mitochondrial association study of traits related to type 2 diabetes and the metabolic syndrome in adolescents

“…It has been noted that fewer mitochondria can be seen microscopically in diabetes patients than in controls, and those that can be seen are smaller than normal [6]. Mitochondrial variants have been indirectly linked with diabetes by the observation that there is a bias towards maternal transmission of diabetes, which increases with mean age of onset [7].…”

“…These have included both case-control studies of type 2 diabetes and studies on metabolic traits that are known risk factors for diabetes. More than 25 mitochondrial variants have been posited as being associated with type 2 diabetes [7,12], but in general there have been conflicting findings regarding potential associations. A large study in the UK population using 500 cases and controls showed an association with the T16189C polymorphism, which is found at a frequency of 6-10% in Europe [13].…”

Clinical and genetic features of childhood-onset Type 2 diabetes in Japan

“…33 Interestingly, in our study most of the cases of childhood-onset T2DM were also maternally rather than paternally inherited, suggesting that imprinted genes might affect the development of diabetes.…”

Not every diabetic child has type 1 diabetes mellitus

“…O diabetes mitocondrial é conseqüente à transmissão de um DNA mitocondrial (mtDNA) mutado de herança materna 8,9 . Pacientes portadores de mutações do mtDNA apresentam síndrome clínica que envolve disfunções mitocondriais de reconhecimento relativamente simples, resumidas a seguir:…”