The double burden of diabetes and bacterial infection - a model to investigate co-morbid disease — ASN Events
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  2. Poster Session B
  3. The double burden of diabetes and bacterial infection - a model to investigate co-morbid disease

The double burden of diabetes and bacterial infection - a model to investigate co-morbid disease (#311)

Tahnee Bridson 1 , Jodie Morris 1 , Kelly Hodgson 1 , Donna Rudd 1 , Catherine Rush 1 , Robert Norton 1 2 , Brenda Govan 1 , Natkunam Ketheesan 1
  1. Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, Australia
  2. Pathology Queensland, Townsville Hospital, Townsville, QLD, Australia

Introduction: Type 2 diabetes (T2D) is a chronic inflammatory condition which induces immune dysfunction through uncontrolled hyperglycaemia and subsequent oxidative stress. Low- to middle-income countries with high burdens of infectious diseases contribute to >80% of the T2D pandemic. Patients with T2D have a significantly increased risk of acquiring intracellular bacterial infections such as tuberculosis (TB) and melioidosis. In tropical Australia co-morbid diabetes was reported in 23% of patients with TB. Whilst this association has been recognised, the host-pathogen interactions contributing to susceptibility remain poorly defined, with current in vivo models inadequate to investigate co-morbid infection.

 Methods: This research involved the development of the Diet-Induced Diabetes Co-Infection (DIDI) murine model, to reflect the pathognomic characteristics of human T2D. Male C57BL/6 mice were fed a high fat, high glycaemic index (HFHG) diet and the biochemical changes, inflammatory status and immune response when challenged with intracellular bacterial pathogens determined over 30 weeks.

 Results: Mice on the HFHG diet demonstrated the cardinal signs of T2D, including glucose intolerance, hyperglycaemia and advanced glycation end product formation. Furthermore, 87.0% of mice (n=20) on the HFHG diet developed dyslipidaemia and evidence of renal impairment, a leading complication associated with T2D. When infected subcutaneously with Burkholderia pseudomallei NCTC 13178 (9x105 CFU), an intracellular bacterial pathogen, mice on the HFHG diet had a significantly higher bacterial burden in the spleen and blood and succumbed to infection more rapidly compared to control animals. The HFHG diet also contributed to baseline immune dysregulation and impaired cytokine responses following infection challenge.

 Conclusion: The development of the DIDI model has facilitated co-morbid infection studies that better reflect the intrinsic host-pathogen interactions involved in the increased susceptibility of patients with T2D.

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