Diabetes and Sepsis: Preclinical Findings and Clinical Relevance

  1. Nathan I. Shapiro, MD, MPH1,2
  1. 1Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  2. 2Center for Vascular Biology Research, Harvard Medical School, Boston, Massachusetts
  3. 3Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Basel, Basel, Switzerland
  4. 4Medical Intensive Care Unit, Hospital Clinic de Barcelona, Barcelona, Spain
  1. Corresponding author: Nathan I. Shapiro, nshapiro{at}bidmc.harvard.edu.

Because of its high prevalence and potential to alter critical elements of sepsis pathophysiology, diabetes is likely an important comorbid condition in this disease; yet the exact influence of diabetes on infection and the development of sepsis remain undefined. The aim of this article is to review evidence from preclinical and clinical trials to discuss the influence of diabetes on sepsis pathophysiology, susceptibility, and clinical outcomes.

Evidence from animal and in vitro studies

Diabetes has reduced bacterial clearance in animal models.

A series of studies investigated whether diabetic mice responded differently to sepsis compared with mice without diabetes. Thereby, 1–2 weeks prior to the experiment, diabetic conditions were induced with streptozotocin, a cytotoxic antibiotic substance isolated from Streptomyces achromogenes, which produces irreversible damage to pancreatic β-cells resulting in hyperglycemia. When mice were experimentally infected with group B streptococcal bacteria, diabetic mice had reduced clearance of bacteria and higher mortality rates (1). Remarkably, the increased mortality in diabetic animals occurred later in the course of the disease (after 72 h) and was associated with persistent bacteremia and prolonged sequestration of viable microorganisms in the hepatic and splenic reticuloendothelial system. Similar findings were reported after infecting diabetic mice with Pseudomonas aeruginosa, where there was a direct association between increased numbers of microorganisms in liver, kidney, and spleen, and mortality (2). A more recent study investigated the host defense against tuberculosis (3). Diabetic mice had a significantly higher bacterial burden and increased inflammation in the lung. Production of γ-interferon (IFN-γ) was reduced by the presence of fewer antigen–responsive T-cells. Interestingly, Yamashiro et al. (4) expanded upon these findings by demonstrating increased numbers of live mycobacteria in lung, liver, and spleen, and lower IFN-γ and interleukin (IL)-12 cytokine levels in diabetic mice. Importantly, the control of blood glucose levels by insulin therapy in this study resulted in improvement of the impaired host protection and T helper type 1-related …

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