About this Research Topic
We have previously presented a proposal for a new, beta-cell centric classification of diabetes based on a consilience of genetic, metabolic, and clinical research that have accrued since the current classification was instituted . It recognizes that the beta-cell is THE core defect in all patients with diabetes. Differences in the genetics, insulin resistance, environment and inflammation/immune characteristics that damage the beta-cell in each individual will determine the phenotypic presentation of hyperglycemia and allow for a patient-centric, precision medicine therapeutic approach , part of which we have labeled ‘the Egregious Eleven’.
We now recognize the same pathophysiologic mechanisms that account for damage to the beta-cells govern the susceptibility of the cells involved in the complications of diabetes by the now well-defined abnormal metabolic environment that typifies beta-cell dysfunction. This abnormal metabolic environment is typified by oxidative stress which alters metabolic pathways a la Brownlee’s Hypothesis model, alterations in gene expression, epigenetics, and inflammation. This Unified Pathophysiologic Approach to The Complications of Diabetes in The Context of the B-cell–Classification of diabetes allows us to understand the varied risk of developing complications of diabetes with similar levels of glycemic control, how non-glycemic effects of some medications for diabetes result in marked complication risk modification and the value treating co-morbidities of diabetes in effecting complication risk.
Principles we outlined in using ‘the Egregious Eleven’ model- use agents that preserve beta-cell function, treat with least number of agents that treat most number of mechanisms of hyperglycemia without hypoglycemia- can be extended to use those agents, in combination, that also engender weight loss, and decrease CV outcomes. This approach allows for a more accurate assessment of each patient’s disease via markers for genomics, proteomics, and metabolomics and effecting true precision medicine.
We aim to publish a collection of articles -original research, perspective pieces, opinion pieces, reviews- discuss – positively as well as critically- these principles and their implications for refinement, future research , education , and most importantly, care for our patients with Diabetes Mellitus.