Diabetes-related acute metabolic emergencies in COVID-19 patients: a systematic review and meta-analysis

Papadopoulos, Vasileios P.; Koutroulos, Marios-Vasileios; Zikoudi, Dimitra-Georgia; Bakola, Stefania-Aspasia; Avramidou, Peny; Touzlatzi, Ntilara; Filippou, Dimitrios K.

AIMS: COVID-19 is associated with diabetic ketoacidosis (DKA), hyperglycaemic hyperosmolar state (HHS) and euglycaemic DKA (EDKA); however, evidence regarding parameters affecting outcome and mortality rates is scarce. METHODS: A systematic literature review was conducted using EMBASE, PubMed/Medline, and Google Scholar from January 2020 to 7 January 2021 to identify all studies describing clinical profile, outcome and mortality rates regarding DKA, HHS, DKA/HHS and EDKA cases in COVID-19 patients. The appropriate Joanna Briggs Institute tools were used for quality assessment; quality of evidence was approached using GRADE. Univariate and multivariate analyses were used to assess correlations between clinical characteristics and outcome based on case reports. Combined mortality rates (CMR) were estimated from data reported in case report series, cross-sectional studies, and meta-analyses. The protocol was submitted to PROSPERO (ID: 229356/230737). RESULTS: From 312 identified publications, 44 were qualitatively and quantitatively analyzed. Critical COVID-19 necessitating ICU (P = 3 × 10(–8)), DKA/HHS presence (P = 0.021), and AKI (P = 0.037) were independently correlated with death. Increased COVID-19 severity (P = 0.003), elevated lactates (P < 0.001), augmented anion gap (P < 0.001), and AKI (P = 0.002) were associated with DKA/HHS. SGLT-2i were linked with EDKA (P = 0.004) and negatively associated with AKI (P = 0.023). CMR was 27.1% (95% CI 11.2–46.9%) with considerable heterogeneity (I(2) = 67%). CONCLUSION: Acute diabetes-related metabolic emergencies in COVID-19 patients lead to increased mortality; key determinants are critical COVID-19 illness, coexistence of DKA/HHS and AKI. Previous SGLT-2i treatment, though associated with EDKA, might preserve renal function in COVID-19 patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00502-9.