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Glycemic Control and Risk of Sepsis and Subsequent Mortality in Type 2 Diabetes

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posted on 29.10.2021, 17:13 by Anca Balintescu, Marcus Lind, Mikael Andersson Franko, Anders Oldner, Maria Cronhjort, Ann-Marie Svensson, Björn Eliasson, Johan Mårtensson
Objective

To investigate the nature of the relationship between HbA1c and sepsis among individuals with type 2 diabetes and to assess the association of sepsis and all-cause mortality in such patients.

Research design and methods

We included 502,871 individuals with type 2 diabetes recorded in the Swedish National Diabetes Register and used multivariable Cox regression and restricted cubic spline analyses to assess the association between time-updated HbA1c values and sepsis occurrence between January 1, 2005 and December 31, 2015. The association between sepsis and death was examined using multivariable Cox regression analysis.

Result

Overall, 14,534 (2.9%) patients developed sepsis during the study period. On multivariable Cox regression analysis, compared with an HbA1c of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was 1.15 (95% CI 1.07-1.24) for HbA1c <43 mmol/mol (6.1%); 0.93 (0.87-0.99) for HbA1c 53-62 mmol/mol (7.0-7.8%); 1.05 (0.97-1.13) for HbA1c 63-72 mmol/mol (7.9-8.7%); 1.14 (1.04-1.25) for HbA1c 73-82 mmol/mol (8.8-9.7%); and 1.52 (1.37-1.68) for HbA1c >82 mmol/mol (9.7%). In the cubic spline model, a reduction of the adjusted risk was observed within the lower HbA1c range until 53 mmol/mol (7.0%), with a hazard ratio of 0.78 (0.73-0.82) per standard deviation, and increased thereafter (P for non-linearity <0.001). As compared to patients without sepsis, the adjusted hazard ratio for death among patients with sepsis was 4.16 (4.03-4.30).

Conclusions

In a nationwide cohort of individuals with type 2 diabetes, we found a U-shaped association between HbA1c and sepsis and a four-fold increased risk of death among those developing sepsis.

Funding

A.B. and J.M. were supported by Region Stockholm (clinical research appointment and ALF project grants). M.L. has received research grants from DexCom and Novonordisk and personal fees from Astra Zeneca, Boehringer Ingelheim, DexCom, Eli Lilly, MSD and Novonordisk outside the submitted work.

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