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A common UCP2 polymorphism predisposes to stress hyperglycaemia in severe sepsis
  1. A Pyle1,
  2. I M Ibbett1,
  3. C Gordon2,
  4. S M Keers1,
  5. M Walker3,
  6. P F Chinnery1,
  7. S V Baudouin2
  1. 1
    Mitochondrial Research Group, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
  2. 2
    Institute of Cellular Medicine, Newcastle University & Department of Anaesthesia, Leazes Wing, Royal Victoria Infirmary, Newcastle upon Tyne, UK
  3. 3
    Diabetes Research Group, Newcastle University, Newcastle upon Tyne, UK
  1. Correspondence to Dr P F Chinnery, Mitochondrial Research Group, The Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK; p.f.chinnery{at}ncl.ac.uk

Abstract

Background: Insulin resistance and hyperglycaemia are common in severe sepsis. Mitochondrial uncoupling protein 2 (UCP2) plays a role in insulin release and sensitivity.

Objectives: To determine if a common, functional polymorphism in the UCP2 gene promoter region (the −866 G/A polymorphism) contributes to the risk of hyperglycaemia in severe sepsis.

Results: In the prospective group 120 non-diabetic patients who were carriers of the G allele had significantly higher maximum blood glucose recordings than non-carriers (mean (SD) AA 8.5 (2.2) mmol/l; GA 8.5 (2.4) mmol/l; GG 10.1 (3.1) mmol/l; p = 0.0042) and required significantly more insulin to maintain target blood glucose (p = 0.0007). In the retrospective study 103 non-diabetic patients showed a similar relationship between maximum glucose and UCP genotype (AA 6.8 (2.3) mmol/l; GA 7.8 (2.2) mmol/l; GG 9.2 (2.9) mmol/l; p = 0.0078).

Conclusions: A common, functional polymorphism in the promoter region of the UCP2 gene is associated with hyperglycaemia and insulin resistance in severe sepsis. This has implications for our understanding of the genetic pathophysiology of sepsis and is of use in the stratification of patients for more intensive management.

https://doi.org/10.1136/jmg.2009.067173

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    Footnotes

    • Funding This work was supported by an unconditional research grant from the United States Army. PFC is a Wellcome Trust Senior Clinical Fellow who also receives funding from the Medical Research Council (UK), the UK Parkinson’s Disease Society, and the UK NIHR Biomedical Research Centre for Ageing and Age-related disease award to the Newcastle upon Tyne Foundation Hospitals NHS Trust.

    • Competing interests None.

    • Provenance and Peer review Not commissioned; externally peer reviewed.

    • Patient consent Not required.