ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Diabetes Care. 2020. doi: 10.2337/dc20-0723

Short summary: In this observational cohort of hospitalised COVID-19 patients in Italy, patients who had hyperglycaemia, with or without diabetes, were at higher risk for severe COVID disease than normoglycaemic patients. Insulin infusion was effective for achieving glycaemic targets and reducing mortality in patients with COVID-19.

Comment: Hyperglycaemia and insulin resistance are common in critically ill patients, even in those without diabetes. Twenty years ago Van den Berghe et al. first reported that intensive insulin therapy to maintain blood glucose at or below 110 mg/dl (6.1 mmol/l) reduces morbidity and mortality among critically ill patients in the surgical intensive care unit.¹ The recent epidemic of COVID-19 enabled reassessment of these findings.

In December 2019, clusters of pneumonia cases of unknown etiology emerged in Wuhan, Hubei Province, China. A novel coronavirus was identified as the causative agent, which was named severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), and the disease it causes was called COVID-19. On March 11, 2020, the World Health Organization declared COVID-19 as a pandemic.

Among patients with COVID-19, hyperglycaemia is found among those without a previous diagnosis of diabetes, as well as in those with diabetes. To determine whether tight glycaemic control is beneficial in patients with COVID-19 with moderate disease, patients with COVID-19 with moderate pneumonia were stratified to 4 groups based on diabetes status and on normoglycaemia or hyperglycaemia (an admission plasma glucose level >7.7 mmol/l) at admission: 1. Prior diabetes, with normoglycaemia, n =18; 2. prior diabetes, with hyperglycaemia n=8; 3. No prior diabetes, with normoglycaemia n =26; 4. No prior diabetes with hyperglycaemia n =7.

At admission, mean IL-6 and D-dimer levels were significantly and persistently higher in the hyperglycaemia than normoglycaemia group, despite the same treatment for COVID-19. One week after admission, pneumonia had progressed in 40% of those with hyperglycaemia compared to only 9% of those with normoglycaemia. Death occurred in 20% of the patients with hyperglycaemia compared to 5.9% of those with normoglycaemia. Furthermore, hyperglycaemic patients treated with insulin infusion (n =15) had lower IL-6 and D-dimer levels, and less severe lung disease than those not treated with insulin infusion (n =10). The composite end point (admission to intensive care, invasive ventilation, or death) occurred in 33% of hyperglycaemic patients treated with insulin infusion compared with 80% of hyperglcaemic patients without insulin infusion. Death occurred in 0% in the hyperglycaemic group treated with insulin infusion and 50% in the hyperglcaemic group without insulin infusion.

These findings suggest that in the context of COVID-19, elevated blood glucose, with or without diabetes, may cause an inflammatory response associated with increased severity of disease and higher risk of death. These findings highlight the extreme importance of tight glycaemic control for patients with diabetes.

Reference:

1. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. The New England Journal of Medicine 2001;345(19):1359–67. doi: 10.1056/NEJMoa011300 [published Online First: 2002/01/17].