Thromboembolism risk among patients with diabetes/stress hyperglycemia and COVID-19

Abstract

Purpose: Individuals with diabetes/stress hyperglycemia carry an increased risk for adverse clinical outcome in case of SARS-CoV-2 infection. The purpose of this study was to evaluate whether this risk is, at least in part, modulated by an increase of thromboembolic complications.

Methods: We prospectively followed 180 hospitalized patients with confirmed COVID-19 pneumonia admitted to the Internal Medicine Units of San Raffaele Hospital. Data from 11 out of 180 patients were considered incomplete and excluded from the analysis. We analysed inflammation, tissue damage biomarkers, hemostatic parameters, thrombotic events (TEs) and clinical outcome according to the presence of diabetes/stress hyperglycemia.

Results: Among 169 patients, 51 (30.2%) had diabetes/stress hyperglycemia. Diabetes/stress hyperglycemia and fasting blood glucose (FBG) were associated with increased inflammation and tissue damage circulating markers, higher D-dimer levels, increased prothrombin time and lower antithrombin III activity. Forty-eight venous and 10 arterial TEs were identified in 49 (29%) patients. Diabetes/stress hyperglycemia (HR 2.71, p = 0.001), fasting blood glucose (HR 4.32, p < 0.001) and glucose variability (HR 1.6, p < 0.009) were all associated with an increased risk of thromboembolic complication. TEs significantly increased the risk for an adverse clinical outcome only in the presence of diabetes/stress hyperglycemia (HR 3.05, p = 0.010) or fasting blood glucose ≥7 mmol/L (HR 3.07, p = 0.015).

Conclusions: Thromboembolism risk is higher among patients with diabetes/stress hyperglycemia and COVID-19 pneumonia and is associated to poor clinical outcome. In case of SARS-Cov-2 infection patients with diabetes/stress hyperglycemia could be considered for a more intensive prophylactic anticoagulation regimen.

Keywords: COVID-19; Clinical outcome; Diabetes; Humoral response; SARS-CoV-2; Thromboembolism.

Fig. 1

TEs in patients with COVID-19. Univariate Cox regression analysis for thrombosis risk adjusted for sex and age. The forest plots (panel a) show the Hazard Ratios (HR) for thrombosis for each factor tested. Dots represent the HR, lines represent 95% confidence interval (CI), and solid dots indicate P < 0.05. Kaplan-Meier thrombosis-free survival estimates for patients with COVID-19 pneumonia (panel b). Survival rate was estimated for the presence of diabetes. The log-rank test was used to test differences in the estimated survival rate. Crosses indicate censored patients (censoring for death end of follow-up data).

Fig. 2

TEs in patients with COVID-19. Multivariate Cox regression analysis adjusted for sex and age including variables significant at the level of <0.1 in the univariate analysis. The forest plots show the Hazard Ratios (HR) for thrombosis for each factor tested. Dots represent the HR, lines represent 95% confidence interval (CI), and solid dots indicate P < 0.05.

Fig. 3

Thrombosis-free survival and survival in the absence of adverse clinical outcome in patients with COVID-19 with or without TEs, according to diabetes and stress hyperglycemia. Kaplan-Meier thrombosis-free survival estimates for patients with COVID-19 pneumonia (panel a). Survival rate was estimated for the presence of diabetes or stress hyperglycemia. The log-rank test was used to test differences in the estimated survival rate. Crosses indicate censored patients (censoring for death end of follow-up data). The forest plots (panel b) show the hazard ratios for survival in the absence of adverse clinical outcome according to presence/absence of diabetes/stress hyperglycemia. The presence of thrombotic events was considered as a time-varying covariate in Cox proportional hazards models. The effect estimates were reported as Hazard Ratios with the corresponding 95% CI, estimated according to the Wald approximation. Cox regression analysis was adjusted for sex and age. Dots represent the HR, lines represent 95% confidence interval (CI), and * P < 0.01.

Fig. 4

Survival in the absence of adverse clinical outcome in patients with COVID-19 with or without TEs, according to diabetes/stress hyperglycemia or fasting glucose levels. Kaplan-Meier patient survival estimates for 169 patients with COVID-19 pneumonia (panel a). Survival rate in the absence of adverse clinical outcome (defined by composite endpoint of transfer to ICU or death, whichever occurred first) was estimated for the presence of any thrombotic event (TE) separately according diabetes/stress hyperglycemia or fasting glucose levels. The log-rank test was used to test differences in the estimated survival rate between groups. Crosses indicate censored patients (censoring for death or end of follow-up data). The forest plots (panel b) show the hazard ratios for survival in the absence of adverse clinical outcome according to presence/absence of diabetes/stress hyperglycemia or fasting glucose levels (FBG) categories. The presence of thrombotic events (TE) was considered as a time-varying covariate in Cox proportional hazards models. The effect estimates were reported as Hazard Ratios (HRs) with the corresponding 95% CI, estimated according to the Wald approximation. Cox regression analysis was adjusted for sex and age. Dots represent the HR, lines represent 95% confidence interval (CI), and solid dots indicate P < 0.05.