A Unified Pathophysiological Construct of Diabetes and its Complications. (September 2017) - Schwartz, Stanley S.
Abstract : Advances in understanding diabetes mellitus (DM) through basic and clinical research have helped clarify and reunify a disease state fragmented into numerous etiologies and subtypes. It is now understood that a common pathophysiology drives the diabetic state throughout its natural history and across its varied clinical presentations, a pathophysiology involving metabolic insults, oxidative damage, and vicious cycles that aggravate and intensify organ dysfunction and damage. This new understanding of the disease requires that we revisit existing diagnostics and treatment approaches, which were built upon outmoded assumptions. 'The Common Pathophysiologic Origins of Diabetes Mellitus and its Complications Construct' is presented as a more accurate, foundational, and translatable construct of DM that helps make sense of the hitherto ambiguous findings of long-term outcome studies. Trends: All cells implicated in DM and its complications undergo the same metabolic insults and injury (Common origin of DM). Existing diagnostics and treatment algorithms for subtypes, including type 1 DM, type 2 DM, and latent autoimmune diabetes of adults (LADA), frustrate care. There is also no functional or therapeutic distinction between 'microvascular' and 'macrovascular' disease, although differences in cardiovascular (CV) effects of various antidiabetes agents are evidenced. In the clinic, this means that we need only regard a single disease; one that can best be addressed by early, aggressive glucose lowering and by targeting the individual mediating pathways of hyperglycemia operative in any specific patient (β Cell-Centric Model). Patient risks and predispositions, drug mode of action, and 'intelligently' designed combined regimens are our current best means of reducing adverse outcomes.