naa a22 4500 51077993X CHVBK 20180411083243.0 cr unu---uuuuu 180411e20131001xx s 000 0 eng 10.1007/s11892-013-0407-7 doi (NATIONALLICENCE)springer-10.1007/s11892-013-0407-7 Wilkin Terence University of Exeter Medical School, Exeter, UK aut Is Autoimmunity or Insulin Resistance the Primary Driver of Type 1 Diabetes? [Elektronische Daten] [Terence Wilkin] Diabetes is usually classified as autoimmune or metabolic but, as difficulties have arisen with the taxonomy of diabetes, it may help to forego the conventional classification for a more inclusive model. Thus, all diabetes can be ascribed to beta cell insufficiency—hyperglycemia occurs only when the insulin supply fails to meet demand. Humans enter the world with a reserve of beta cells, which is eroded variably by apoptosis over the course of a lifetime. For most, the loss is slow and inconsequential but, for others fast enough to be critical within a lifetime. The challenge now is to define the factors that vary the tempo of beta cell loss, because tempo, not type, seems likely to determine whether diabetes occurs at all, in adulthood or in childhood. Insulin resistance is generally believed to underpin T2D, but has been a feature of insulin-dependent diabetes as well for nearly 80years, though largely ignored until immunotherapy trials to test the autoimmunity hypothesis persistently failed to bring patient benefit. It seems possible that insulin resistance accelerates beta cell loss generally, its impact modulated by an immune response (autoimmunity) to the beta-cell stress whose intensity varies with immunogenotype. If so, the target for prevention of T1D might more logically lie with insulin sensitivity than with immunoregulation. Springer Science+Business Media New York, 2013 Insulin resistance nationallicence T1D nationallicence Accelerator hypothesis nationallicence Pathophysiology nationallicence Autoimmunity nationallicence Type 1 diabetes nationallicence Current Diabetes Reports Springer US; http://www.springer-ny.com 13/5(2013-10-01), 651-656 1534-4827 13:5<651 2013 13 11892 https://doi.org/10.1007/s11892-013-0407-7 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11892-013-0407-7 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Wilkin Terence University of Exeter Medical School, Exeter, UK aut NATIONALLICENCE 773 0- Current Diabetes Reports Springer US; http://www.springer-ny.com 13/5(2013-10-01), 651-656 1534-4827 13:5<651 2013 13 11892 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer