Diabetic ketoacidosis in patients with SARS-CoV-2: a systematic review and meta-analysis

Abstract

Background One possible reason for increased mortality due to SARS-CoV-2 in patients with diabetes is from the complication of diabetic ketoacidosis (DKA). Objectives To re-evaluate the association of SARS-CoV-2 and development of DKA and analyse the demographic and biochemical parameters and the clinical outcomes in COVID-19 patients with DKA. Design A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was followed. Methods Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature) were searched from 1 December 2019 to 30 June 2021 in the English language using the following keywords alone or in combination: COVID-19 OR SARS-CoV-2 AND diabetic ketoacidosis OR DKA OR ketosis OR ketonemia OR hyperglycaemic emergency OR hyperglycaemic crisis. We included studies in adults and children of all ages in all healthcare settings. Binary logistic regression model was used to explore the effect of various demographic and biochemical parameters variables on patient’s final treatment outcome (survival or death). Results Of the 484 papers that were identified, 68 articles were included in the systematic review and meta-analysis (54 case report, 10 case series, and 4 cohort studies). Studies involving 639 DKA patients with confirmed SARS-CoV-2 [46 (7.2%) were children and 334 (52.3%) were adults] were analyzed. The median or mean patient age ranged from < 1 years to 66 years across studies. Most of the patients (n = 309, 48.3%) had pre-existing type 2 diabetes mellitus. The majority of the patients were male (n = 373, 58.4%) and belonged to Hispanic (n = 156, 24.4%) and black (n = 98, 15.3%) ethnicity. The median random blood glucose level, HbA1c, pH, bicarbonate, and anion gap in all included patients at presentation were 507 mg/dl [IQR 399–638 mg/dl], 11.4% [IQR 9.9–13.5%], 7.16 [IQR 7.00–7.22], 10 mmol/l [IQR 6.9–13 mmol/l], and 24.5 mEq/l [18–29.2 mEq/l]; respectively. Mortality rate was [63/243, 25.9%], with a majority of death in patients of Hispanic ethnicity (n = 17, 27%; p = 0.001). The odd ratios of death were significantly high in patients with pre-existing diabetes mellitus type 2 [OR 5.24, 95% CI 2.07–15.19; p = 0.001], old age (≥ 60 years) [OR 3.29, 95% CI 1.38–7.91; p = 0.007], and male gender [OR 2.61, 95% CI 1.37–5.17; p = 0.004] compared to those who survived. Conclusion DKA is not uncommon in SARS-CoV-2 patients with diabetes mellitus and results in a mortality rate of 25.9%. Mortality key determinants in DKA patients with SARS-CoV-2 infection are individuals with pre-existing diabetes mellitus type 2, older age [≥ 60 years old], male gender, BMI ≥ 30, blood glucose level > 1000 mg/dl, and anion gap ≥ 30 mEq/l.

The Effects of COVID-19 Pandemic and Lockdown on Pediatric Nutritional and Metabolic Diseases: A Narrative Review

“…In conclusion, a validated mechanism that connects SARS-CoV-2 infection with new onset T1DM has not been yet demonstrated; nevertheless, changes in the availability of healthcare services and parental fears about accessing hospitals due to the SARS-CoV2 epidemic may have created barriers to the accessibility of healthcare services, leading to delayed diagnosis and more severe presentation of T1DM. Information campaigns on T1DM prevention and early diagnosis resulted in effectively reducing these potentially life-threatening acute complications also before the COVID-19 pandemic [ 127 ]. These campaigns might prove to be effective even when health systems are under pressure.…”

Akutkomplikationen des Diabetes mellitus – Schulungsinhalte richtig vermitteln

“…Eine Metaanalyse berichtet für die DKA bei Patient*innen mit COVID-19 eine Sterblichkeitsrate von ca. 25 % [15], wobei diese bei Menschen über 65 Jahren auch auf ca. 50 % steigen kann [13,16].…”

“…50 % steigen kann [13,16]. Interessanterweise scheinen durch COVID-19 besonders Menschen mit Typ-2-Diabetes eine höhere Inzidenz der DKA zu haben [12,14,15], was die Wichtigkeit der DKA-Schulung auch bei Menschen mit Typ-2-Diabetes deutlich zeigt.…”

Relationship between cytokine release and stress hyperglycemia in patients hospitalized with COVID-19 infection

“…Previous studies suggest that hyperglycemia on admission is a strong predictor of poor outcome among patients hospitalized with SARS-CoV-2 infection (6). On the other hand, in patients with type 2 diabetes, SARS-CoV-2 infection has been associated with rapid worsening of glycemic control possibly leading to ketoacidosis or hyperosmolar hyperglycemia (7,8).…”