Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia - A systematic review, meta-analysis, and meta-regression

Abstract

Background and aims: Diabetes Mellitus (DM) is chronic conditions with devastating multi-systemic complication and may be associated with severe form of Coronavirus Disease 2019 (COVID-19). We conducted a systematic review and meta-analysis in order to investigate the association between DM and poor outcome in patients with COVID-19 pneumonia.

Methods: Systematic literature search was performed from several electronic databases on subjects that assess DM and outcome in COVID-19 pneumonia. The outcome of interest was composite poor outcome, including mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care, and disease progression.

Results: There were a total of 6452 patients from 30 studies. Meta-analysis showed that DM was associated with composite poor outcome (RR 2.38 [1.88, 3.03], p < 0.001; I²: 62%) and its subgroup which comprised of mortality (RR 2.12 [1.44, 3.11], p < 0.001; I²: 72%), severe COVID-19 (RR 2.45 [1.79, 3.35], p < 0.001; I²: 45%), ARDS (RR 4.64 [1.86, 11.58], p = 0.001; I²: 9%), and disease progression (RR 3.31 [1.08, 10.14], p = 0.04; I²: 0%). Meta-regression showed that the association with composite poor outcome was influenced by age (p = 0.003) and hypertension (p < 0.001). Subgroup analysis showed that the association was weaker in studies with median age ≥55 years-old (RR 1.92) compared to <55 years-old (RR 3.48), and in prevalence of hypertension ≥25% (RR 1.93) compared to <25% (RR 3.06). Subgroup analysis on median age <55 years-old and prevalence of hypertension <25% showed strong association (RR 3.33) CONCLUSION: DM was associated with mortality, severe COVID-19, ARDS, and disease progression in patients with COVID-19.

Keywords: COVID-19; Coronavirus; Diabetes mellitus; Mortality; SARS-CoV-2.

Fig. 1

Prisma flowchart.

Fig. 2

Diabetes Mellitus and Poor Outcome. Forest-plot shows that diabetes mellitus was associated with increased composite poor outcome and its subgroup which comprises of mortality, severe COVID-19, ARDS, need for ICU care, and disease progression in patients with COVID-19. ARDS: Acute Respiratory Distress Syndrome, COVID-19: Coronavirus Disease 2019, ICU: Intensive Care Unit.

Fig. 3

Bubble-plot for Meta-regression. Meta-regression analysis showed that the association between diabetes mellitus and composite poor outcome was affected by age [A] and hypertension [B], but not by cardiovascular diseases [C].

Fig. 4

Publication Bias Analysis. The Begg’s funnel-plot analysis showed a qualitatively symmetrical inverted funnel-plot for the association between diabetes mellitus and composite poor outcome [A]. Regression-based Harbord’s test showed indication of small-study effects for hypertension and composite poor outcome.