The Diabetes Syndrome – A Collection of Conditions with Common, Interrelated Pathophysiologic Mechanisms

Abstract

The four basic pathophysiologic mechanisms which damage the β-cell within diabetes (ie, genetic and epigenetic changes, inflammation, an abnormal environment, and insulin resistance [IR]) also contribute to cell and tissue damage and elevate the risk of developing all typical diabetes-related complications. Genetic susceptibility to damage from abnormal external and internal environmental factors has been described including inflammation and IR. All these mechanisms can promote epigenetic changes, and in total, these pathophysiologic mechanisms interact and react with each other to cause damage to cells and tissues ultimately leading to disease. Importantly, these pathophysiologic mechanisms also serve to link other common conditions including cancer, dementia, psoriasis, atherosclerotic cardiovascular disease (ASCVD), nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). The "Diabetes Syndrome", an overarching group of interrelated conditions linked by these overlapping mechanisms, can be viewed as a conceptual framework that can facilitate understanding of the interrelationships of superficially disparate conditions. Recognizing the association of the conditions within the Diabetes Syndrome due to common pathophysiologies has the potential to provide both benefit to the patient (eg, prevention, early detection, precision medicine) and to the advancement of medicine (eg, driving education, research, and dynamic decision-based medical practice).

Hyperinsulinemia and age-related diseases: interrelations and approaches to treatment

“…Обзоры последних лет указывают, что имеет смысл рассматривать эти синдромы не как коморбидные, а как клинические маски единого системного процесса, в рамках биологического старения [9,11]. Некоторые авторы предлагают для него название «диабетический синдром» [45], «метаболический сосудистый синдром» [46].…”

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“…Rather than feel stuck in the mud with single medication therapies for DM, we should fell emboldened to approach its management with multimodal approaches. Think of the money wasted trying to determine which drug was "better" when we could be considering drugs with complimentary benefits and mechanisms of action that address the multifaceted etiology of the DM spectrum [6]. In addition, some newer therapeutic classes not only have proven benefits for managing hyperglycemia, but also reduce cardiovascular and kidney risk as well as promote weight loss [6].…”

“…Think of the money wasted trying to determine which drug was "better" when we could be considering drugs with complimentary benefits and mechanisms of action that address the multifaceted etiology of the DM spectrum [6]. In addition, some newer therapeutic classes not only have proven benefits for managing hyperglycemia, but also reduce cardiovascular and kidney risk as well as promote weight loss [6]. Furthermore, moving our understanding of a patient "unlucky enough" to get more than 1 disease besides DM toward recognizing the interconnection between common conditions allows us to further add to our armamentarium of potential drugs to address common etiologies across disease [6].…”

“…In addition, some newer therapeutic classes not only have proven benefits for managing hyperglycemia, but also reduce cardiovascular and kidney risk as well as promote weight loss [6]. Furthermore, moving our understanding of a patient "unlucky enough" to get more than 1 disease besides DM toward recognizing the interconnection between common conditions allows us to further add to our armamentarium of potential drugs to address common etiologies across disease [6]. This broader view brings us closer to precision medicine for our patients.…”

“…Additionally, it is imperative to realize our ability to detect frank complications is limited and the damage and processes begin early in the disease continuum [4]. Further, it is important to widen our view of the causes of diabetes and its complications to incorporate common pathophysiologic processes beyond "just metabolic" [5,6]. Indeed the pathologic mechanisms that damage the b-cell (i.e.…”