Association of transcription factor 7-like 2 gene (TCF7L2) polymorphisms with stress-related hyperglycaemia (SRH) in intensive care and resulting outcomes: the READIAB study - 20/05/19

Doi : 10.1016/j.diabet.2019.05.001

Adrien Ben Hamou, MD ¹, Eric Kipnis, MD PhD ^3,^4,¹², Alexandre Elbaz ², Anne Bignon, MD ⁴, Saad Nseir, MD PhD ^2,³, Fabienne Tamion, MD PhD ^6,⁷, Damien Du Cheyron, MD ¹¹, Emmanuelle Jaillette, MD ², Benoit Voisin, MD ², Laurent Robriquet, MD ², Clement Vanbaelinghem, MD ⁹, Damien Thellier, MD ¹⁰, Henry Abi Rached, MD ¹, Arnaud Jannin, MD ¹, Alain Duhamel, MD PhD ^3,¹⁵, Helene Behal ¹⁵, François Machuron ¹⁵, Stephanie Espiard, MD PhD ^1,³, Jean-Charles Preiser, MD PhD ⁵, Sebastien Preau, MD PhD ², François Pattou ^1,^13,¹⁴, Merce Jourdain, MD PhD ^2,^3,^8,^13,^14,^⁎
¹ CHU Lille, Endocrinology, Diabetology and Metabolism, F-59000 Lille, France
² CHU Lille, Intensive Care Unit, F-59000 Lille, France
³ Univ Lille, Medical School, F-59000 Lille, France
⁴ CHU Lille, Department of Anesthesiology and Critical care, F-59000 Lille, France
⁵ Department of Intensive Care, CUB-Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium
⁶ CHU Rouen, Intensive Care Unit, F-76031, Rouen, France
⁷ UMR 1096 Inserm-Université de Rouen, Biologie, médecine, santé, Endothélium, Valvulopathies et Insuffisance Cardiaque, F-76031 Rouen, France
⁸ Univ Lille, PRESAGE Simulation Center, F-59000 Lille, France
⁹ Intensive Care Unit, Victor Provo Hospital Center, F-59100 Roubaix, France
¹⁰ Intensive Care Unit, Guy Chatiliez Hospital Center, F-59200 Tourcoing, France
¹¹ CHU Caen, Intensive Care Unit, F-14033 Caen, France
¹² Univ Lille, EA 7366, Host Pathogen Translational Research, F-59000 Lille, France
¹³ UMR 1190 INSERM Translational research in diabetes, F-59000 Lille, France
¹⁴ EGID European Genomics Institute for Diabetes, CHU Lille, F-59000 Lille, France
¹⁵ Univ Lille, EA 2694, Public Health, Epidemiology and Quality of Care, F-59000 Lille, France

^⁎Corresponding author: Intensive Care Unit, CHU Lille, Head of Simulation Center, Univ Lille, Avenue du Professeur Emile Laine, 59037 Lille, FranceIntensive Care Unit, CHU Lille, Head of Simulation Center, Univ Lille, Avenue du Professeur Emile LaineLille59037France

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ABSTRACT

Objective. – The study aimed to evaluate the impact of the single nucleotide polymorphism (SNP) rs7903146 on the transcription factor 7-like 2 (TCF7L2) gene in stress-related hyperglycaemia (SRH), defined as blood glucose ≥ 11 mmol/L in at least two blood samples during the first 3 days in the intensive care unit (ICU), and on 28-day and 1-year mortality, and incidence of type 2 diabetes (T2D) at 6 months and 1 year in patients hospitalized in the ICU.

Methods. – This prospective observational (non-interventional) multicentre READIAB study, carried out during 2012–2016 in six French ICUs, involved adult patients admitted to ICUs for at least two organ failures; patients admitted for < 48 h were excluded. During the 3-day ICU observational period, genetic testing, blood glucose values and insulin treatment were recorded.

Main results. – The association of rs7903146 with SRH was assessed using logistic regression models. Cox proportional hazards regression models assessed the associations between rs7903146 and mortality and between SRH and mortality, both at 28 days and 1 year. A total of 991 of the 1000 enrolled patients were included in the READIAB–G4 cohort, but 242 (24.4%) had preexisting diabetes and were excluded from the analyses. SRH occurred within the first 3 days in the ICU for one-third of the non-diabetes patients. The association between the rs7903146 polymorphism and SRH did not reach significance (P = 0.078): OR(per one T copy): 1.24, 95% CI: 0.98–1.58. A significant association was found between rs7903146 and 28-day mortality after adjusting for severity scores (P = 0.026), but was no longer significant at 1 year (P = 0.61). At 28 days, mortality was increased in patients with SRH (HR: 2.09, 95% CI: 1.43–3.06; P < 0.001), and remained significant at 1 year after adjusting for severity scores (HR: 1.73, 95% CI: 1.32–2.28; P < 0.001). On admission, non-diabetes patients with SRH had a higher incidence of T2D at 6 months vs those without SRH (16.0% vs 7.6%, RR: 2.11, 95% CI: 1.07–4.20; P = 0.030). At 1 year, these figures were 13.4% vs 9.2%, RR: 1.45, 95% CI: 0.71–2.96; P = 0.31). Moreover, the rs7903146 polymorphism was not significantly associated with T2D development at either 6 months (P = 0.72) or 1 year (P = 0.64).

Conclusion. – This study failed to demonstrate any significant association between rs7903146 and SRH. Nevertheless, the issue remains an important challenge, as SRH may be associated with increased rates of both mortality and T2D development.

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Key words : Diabetes, Intensive care unit, Long-term mortality, Stress-related hyperglycaemia, TCF7L2 polymorphism