Hyperglycemia Is an Independent Risk Factor of COVID-19 Mortality

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Even in individuals who don't have diabetes, hyperglycemia is an independent risk factor for COVID-19 mortality after 28 days of hospitalization, according to a study published in Diabetolgia.

Hyperglycemia is an independent predictor of mortality after 28 days in patients who contract coronavirus disease 2019 (COVID-19), according to a study published in Diabetolgia, underscoring the importance of addressing elevated fasting blood glucose at an early stage.

Since the beginning of the pandemic, diabetes has been one of the most prominent risk factors potentially resulting in severe outcomes for those who contract COVID-19. However, hyperglycemia alone “is associated with an elevated risk of mortality in community-acquired pneumonia, stroke, acute myocardial infarction, trauma and surgery, among other conditions,” researchers write.

Previous studies showed hyperglycemia was a risk factor for high morbidity and mortality in those who contracted severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), while most COVID-19 patients are prone to glucose metabolic disorders.

In a retrospective study, investigators assessed the relationship between fasting blood glucose (FBG) and 28-day mortality in COVID-19 patients. In total, data from 605 patients admitted to 2 hospitals in Wuhan, China between January 24 and February 10, 2020 were included in the study.

In addition to 28-day outcomes, demographic and clinical data, in-hospital complications, and CRB-65 scores were analyzed. CRB-65 is a measurement used to asses pneumonia severity based on 4 indicators: confusion, respiratory rate, systolic blood pressure or diastolic blood pressure, and age.

All patients included had no previous diagnosis of diabetes and exhibited laboratory-confirmed infections of COVID-19. All patients also received standard treatment, including antiviral therapy, respiratory support, symptomatic and supportive treatment, and antimicrobial therapy, as necessary. After 28 days, all participants were either discharged, remained in the hospital, or passed away (114 [18.8%]). Two hundred and thirty-seven (39.2%) developed one or more in-hospital complication including acute respiratory distress syndrome (ARDS), acute cardiac injury, acute kidney injury, acute liver injury, cerebrovascular accident, coagulopathy and secondary infection.

Median patient age was 59 and the majority (53.2%) were men, while hypertension was the most commonly reported comorbidity on admission. Patients were categorized based on their glucose levels: those with FBG <6.1 mmol/l (n  =  329, 54.4%), patients with FBG 6.1—6.9 mmol/l (n  = 100, 16.5%) and patients with FBG ≥7.0 mmol/l (n =176, 29.1%).

Multivariable Cox regression analyses found:

Age (hazard ratio [HR] 1.02 [95% CI, 1.00-1.04]), male sex (HR 1.75 [95% CI, 1.17- 2.60]), CRB-65 score 1—2 (HR 2.68 [95% CI, 1.56-4.59]), CRB-65 score 3–4 (HR 5.25 [95% CI, 2.05-13.43]) and FBG ≥7.0 mmol/l (HR 2.30 [95% CI, 1.49-3.55]) were independent predictors for 28-day mortality
Odds ratio (OR) for 28-day in-hospital complications in those with FBG ≥7.0 mmol/l and 6.1—6.9 mmol/l vs <6.1 mmol/l was 3.99 (95% CI, 2.71-5.88) or 2.61 (95% CI, 1.64-4.41), respectively
The number of patients who had complications within 28 days in the groups with FBG <6.1 mmol/l, 6.1—6.9 mmol/l and ≥7.0 mmol/l was 86 (14.2%), 48 (7.9%) and 103 (17.0%), respectively

This study shows for the first time, "that elevated FBG (≥7.0 mmol/l) at admission is independently associated with increased 28-day mortality and percentages of in-hospital complications in COVID-19 patients without previous diagnosis of diabetes,” authors conclude.

Researchers hypothesize those with COVID-19 may experience stress hyperglycemia, while critically ill patients may develop acute insulin resistance, manifested by hyperglycemia and hyperinsulinemia.

The lack of HbA1c assessment, a long-term glycemic control indicator, poses a limitation to the study. The effects of any glucose lowering treatment administered in-hospital were also not included. However, authors argue acute hyperglycemia is more important than long-term glycemic control in predicting the prognosis of hospitalized patients with COVID-19.

“Glycemic testing and control should be recommended for all COVID-19 patients even if they do not have pre-existing diabetes, as most COVID-19 patients are prone to glucose metabolic disorders,” researchers state. “During a pandemic of COVID-19, FBG can facilitate the assessment of prognosis and early intervention of hyperglycemia to help improve the overall outcomes in treatment of COVID-19.”

Reference

Wang S, Ma P, Zhang S, et al. Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study. Diabetologia. Published online July 10, 2020. doi:10.1007/s00125-020-05209-1