Chronic dysglycaemia and diabetes type : impact in critical illness and sepsis

Sammanfattning: Diabetes is a common disease in the general population. Higher susceptibility to infection and increased morbidity can lead to severe illness and intensive care unit (ICU) admission. Glycated haemoglobin A1c (HbA1c), a marker of chronic glycaemic control, taken at ICU admission, allows for the identification of individuals with chronic dysglycaemia (diabetes, pre-diabetes and those with previously unknown diabetes). This is important, as recent evidence suggests that HbA1c is associated with worse prognosis among critically ill patients and patients with Covid-19. Additionally, increased susceptibility to infections can lead to sepsis and increased mortality in individuals with diabetes types 1 and 2. However, if and how HbA1c per se modulates the risk of sepsis and subsequent mortality are insufficiently investigated. The aim of this thesis was to determine the prevalence of chronic dysglycaemia (pre-diabetes, unknown and known diabetes), by additional measurement of HbA1c at ICU admission, in general ICU patients and critically ill Covid-19 patients, respectively. Furthermore, we aimed to assess the association of chronic dysglycaemia with different domains of glycaemic control, patient-centred outcomes during ICU stay and 90-days mortality. Finally, we aimed to describe the nature of the relationship of HbA1c with sepsis and mortality in a nationwide cohort of individuals with diabetes types 1 and 2, recorded in the National Diabetes Register (NDR) over a period of 11 years. We found a high prevalence of chronic dysglycaemia in the general ICU population, encompassing one-third of all admitted patients, with 9% having pre-diabetes and 4,5% having previously undiagnosed diabetes. Chronic dysglycaemia was associated with a higher average blood glucose, greater glucose variability, increased risk of hypoglycaemia, and acute renal failure requiring renal replacement therapy in the ICU. Among critically ill Covid-19 patients, the prevalence of chronic dysglycaemia reached 80%, with 40% having pre-diabetes and 21% having undiagnosed diabetes. Chronic dysglycaemia was not associated with mortality in either population. In our cohort of more than half a million individuals with type 1 or 2 diabetes, we found a U-shaped relationship between HbA1c and sepsis, with the lowest risk around a value of 53 mmol/mol. Sepsis was associated with a four-fold higher risk of death in type 2 diabetes. However, HbA1c was not associated with mortality among individuals with type 1 or type 2 diabetes who developed sepsis. HbA1c is a valuable tool in revealing the true prevalence of chronic dysglycaemia in the critically ill patients with or without Covid-19. Describing the relationship between a potentially modifiable risk factor (HbA1c) and sepsis has implications for millions of people suffering from diabetes worldwide and will hopefully lead to improved care in this population.