PURPOSE OF REVIEW: Type 1 diabetes (T1D) is characterized by autoimmune-mediated destruction of pancreatic beta cells culminating in absolute insulin deficiency. Despite enhanced knowledge of the natural history of type 1 diabetes we have yet to develop an intervention to consistently and safely prevent or reverse type 1 diabetes. This review explores the lessons learned from recent type 1 diabetes interventional studies, sets out controversial issues and seeks to provide a roadmap for future interventions. RECENT FINDINGS: The type 1 diabetes intervention studies of the 1980s demonstrated potential for preserving c-peptide, but were abandoned due to unacceptable side-effect profiles of the agents being used. Pilot studies of new immunosuppressive and immunomodulatory agents with improved side-effect profiles have recently demonstrated promise in preserving c-peptide in new-onset type 1 diabetes patients. Several of these agents, including insulin, anti-CD3, mycophenolate mofetil, daclizumab and anti-CD20, are currently being tested in multicenter intervention trials. SUMMARY: The inability to cure type 1 diabetes underscores the complex pathophysiology of the disease, and our poor knowledge of the precise etiological triggers and immunological mechanisms which culminate in the disease. While ongoing efforts to test individual agents with potential to ameliorate diabetes are needed, combination therapies employing multiple safe agents are likely to be the future of type 1 diabetes intervention studies.
PURPOSE OF REVIEW: Type 1 diabetes (T1D) is characterized by autoimmune-mediated destruction of pancreatic beta cells culminating in absolute insulin deficiency. Despite enhanced knowledge of the natural history of type 1 diabetes we have yet to develop an intervention to consistently and safely prevent or reverse type 1 diabetes. This review explores the lessons learned from recent type 1 diabetes interventional studies, sets out controversial issues and seeks to provide a roadmap for future interventions. RECENT FINDINGS: The type 1 diabetes intervention studies of the 1980s demonstrated potential for preserving c-peptide, but were abandoned due to unacceptable side-effect profiles of the agents being used. Pilot studies of new immunosuppressive and immunomodulatory agents with improved side-effect profiles have recently demonstrated promise in preserving c-peptide in new-onset type 1 diabetespatients. Several of these agents, including insulin, anti-CD3, mycophenolate mofetil, daclizumab and anti-CD20, are currently being tested in multicenter intervention trials. SUMMARY: The inability to cure type 1 diabetes underscores the complex pathophysiology of the disease, and our poor knowledge of the precise etiological triggers and immunological mechanisms which culminate in the disease. While ongoing efforts to test individual agents with potential to ameliorate diabetes are needed, combination therapies employing multiple safe agents are likely to be the future of type 1 diabetes intervention studies.
Authors: Ming S Lin; Hubert M Tse; Meghan M Delmastro; Suzanne Bertera; Caterina T Wong; Robert Lakomy; Jing He; Martha M Sklavos; Gina M Coudriet; Massimo Pietropaolo; Massimo M Trucco; Jon D Piganelli Journal: Immunol Res Date: 2011-08 Impact factor: 2.829
Authors: Kristina I Rother; Rebecca J Brown; Miriam M Morales; Elizabeth Wright; Zhigang Duan; Carol Campbell; Dana S Hardin; Jadranka Popovic; Robert C McEvoy; David M Harlan; Philip R Orlander; Staley A Brod Journal: Diabetes Care Date: 2009-07 Impact factor: 19.112
Authors: Michael J Haller; Desmond A Schatz; Jay S Skyler; Jeffrey P Krischer; Brian N Bundy; Jessica L Miller; Mark A Atkinson; Dorothy J Becker; David Baidal; Linda A DiMeglio; Stephen E Gitelman; Robin Goland; Peter A Gottlieb; Kevan C Herold; Jennifer B Marks; Antoinette Moran; Henry Rodriguez; William Russell; Darrell M Wilson; Carla J Greenbaum Journal: Diabetes Care Date: 2018-07-16 Impact factor: 19.112