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Lookup NU author(s): Dr Angela Pyle,
Professor Mark Walker,
Professor Patrick Chinnery,
Dr Simon Baudouin
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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 2866 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.
Author(s): Pyle A, Ibbett IM, Gordon C, Keers SM, Walker M, Chinnery PF, Baudouin SV
Publication type: Article
Publication status: Published
Journal: Journal of Medical Genetics
ISSN (print): 0022-2593
ISSN (electronic): 1468-6244
Publisher: BMJ Group
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