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Review
. 2017 Oct 30:8:271.
doi: 10.3389/fendo.2017.00271. eCollection 2017.

Diabetes and Sepsis: Risk, Recurrence, and Ruination

Lynn M Frydrych  1 , Fatemeh Fattahi  2 , Katherine He  1 , Peter A Ward  2 , Matthew J Delano  1
Affiliations
Review

Diabetes and Sepsis: Risk, Recurrence, and Ruination

Lynn M Frydrych et al. Front Endocrinol (Lausanne). .

Abstract

Sepsis develops when an infection surpasses local tissue containment. A series of dysregulated physiological responses are generated, leading to organ dysfunction and a 10% mortality risk. When patients with sepsis demonstrate elevated serum lactates and require vasopressor therapy to maintain adequate blood pressure in the absence of hypovolemia, they are in septic shock with an in-hospital mortality rate >40%. With improvements in intensive care treatment strategies, overall sepsis mortality has diminished to ~20% at 30 days; however, mortality continues to steadily climb after recovery from the acute event. Traditionally, it was thought that the complex interplay between inflammatory and anti-inflammatory responses led to sepsis-induced organ dysfunction and mortality. However, a closer examination of those who die long after sepsis subsides reveals that many initial survivors succumb to recurrent, nosocomial, and secondary infections. The comorbidly challenged, physiologically frail diabetic individuals suffer the highest infection rates. Recent reports suggest that even after clinical "recovery" from sepsis, persistent alterations in innate and adaptive immune responses exists resulting in chronic inflammation, immune suppression, and bacterial persistence. As sepsis-associated immune defects are associated with increased mortality long-term, a potential exists for immune modulatory therapy to improve patient outcomes. We propose that diabetes causes a functional immune deficiency that directly reduces immune cell function. As a result, patients display diminished bactericidal clearance, increased infectious complications, and protracted sepsis mortality. Considering the substantial expansion of the elderly and obese population, global adoption of a Western diet and lifestyle, and multidrug resistant bacterial emergence and persistence, diabetic mortality from sepsis is predicted to rise dramatically over the next two decades. A better understanding of the underlying diabetic-induced immune cell defects that persist following sepsis are crucial to identify potential therapeutic targets to bolster innate and adaptive immune function, prevent infectious complications, and provide more durable diabetic survival.

Keywords: complications; diabetes; infections; resource utilization; sepsis; septic shock.

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Figures

Figure 1
Figure 1
Immune dysregulation in Type II diabetes and sepsis. Diabetes is a functional immune deficiency with chronic inflammation and immune suppression that affects an individuals’ overall immune system homeostasis. The development of patient management protocols in sepsis has decreased early organ failure and sepsis mortality, allowing highly comorbid elderly patients to survive the initial insult. Furthermore, sepsis studies have demonstrated an enduring inflammatory state driven by dysfunctional innate and suppressed adaptive immunity that culminates in persistent organ injury and patient death. Subsequently, the highly comorbid elderly patient population that initially survived now experiences significant morbidity and mortality several months to a year later. Multiple hypotheses for these observations exist, with persistent derangements in the innate and adaptive immune system cellular functions as the main contributors to this long-term mortality.
Figure 2
Figure 2
Innate versus adaptive immune responses in sepsis and Type II diabetes. (A) During an acute episode of sepsis, the innate and adaptive immune systems are in a constant state of fluctuation. They respond to an invading pathogen and attempt to recover homeostasis after the pathogen is cleared. This continual seesaw effect is thought to drive ongoing inflammation, facilitate organ injury, and enable infectious complications. (B) In diabetes, the innate and adaptive immune systems experience chronic derangements secondary to chronic inflammation, also placing these systems in constant flux. When these two systems (sepsis and diabetes) are superimposed, patients have increased morbidity and mortality; however, we do not know why. There are unclear synergistic versus antagonistic changes occurring that leads to worsened immune system perturbations and the inability to return to homeostasis.
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