European Journal of Cardiovascular Medicine

COVID-19, caused by the SARS-CoV-2 virus, had resulted in a global health crisis, with a wide spectrum of clinical manifestations ranging from mild respiratory symptoms to life-threatening complications. The severity of COVID-19 is influenced by a multitude of factors, including pre-existing comorbidities and metabolic disturbances. Among these, diabetic ketoacidosis (DKA), renal failure, chronic kidney disease (CKD), and glycemic variations have emerged as critical determinants of outcomes in hospitalized patients.

DKA, a life-threatening complication of diabetes mellitus, involves severe hyperglycemia, ketonemia, and metabolic acidosis. It is associated with an exaggerated inflammatory response, which can amplify the severity of COVID-19. Similarly, renal dysfunction, including acute kidney injury (AKI) and CKD, exacerbates systemic inflammation and impairs immune defense mechanisms, leading to poorer outcomes. Glycemic control, particularly during acute illness, is another key factor influencing COVID-19 progression, with both hyperglycemia and hypoglycemia linked to adverse effects.

This study aims to elucidate the relationship between COVID-19 severity, glycemic excursions including DKA and the presence of renal failure (acute or chronic). By analysing these factors in a cohort of hospitalized COVID-19 patients, we seek to identify patterns and predictors of severe outcomes, thereby contributing to improved clinical management strategies.

This study utilized a retrospective design to analyze data from COVID-19 patients admitted to a tertiary care hospital. The initial dataset comprised 272 cases, from which a cohort of 150 patients was selected based on strict inclusion and exclusion criteria. Inclusion required complete biomarker data for COVID-19 severity, glycemic indices, and renal function, along with demographic details such as age and gender.

Clinical and laboratory data were extracted from electronic medical records, including demographics, comorbidities, glycemic indices (random blood sugar, HbA1c, fasting glucose), renal function markers (serum creatinine, urea, estimated glomerular filtration rate [eGFR]), and COVID-19 severity indicators (ICU admission, mechanical ventilation, mortality).

DKA: Defined as hyperglycemia (blood glucose >250 mg/dL), ketonemia, and metabolic acidosis (serum bicarbonate <18 mmol/L). Renal Failure: Acute kidney injury (AKI) was diagnosed based on KDIGO criteria, while CKD was defined as eGFR <60 mL/min/1.73 m² persisting for more than 3 months. Glycemic Variations: Included hyperglycemia (>180 mg/dL), hypoglycemia (<70 mg/dL), and high glycemic variability (>20% coefficient of variation).

Descriptive statistics were used to summarize baseline characteristics. Pearson’s and Spearman’s correlations assessed relationships between glycemic and renal parameters and COVID-19 severity. Multivariate logistic regression identified independent predictors of ICU admission and mortality. Kaplan-Meier survival analysis compared outcomes in patients with and without metabolic complications. A p-value <0.05 was considered statistically significant.

Glycemic variability was analyzed across the cohort to assess its impact on COVID-19 severity. Patients with hyperglycemia (>180 mg/dL) had significantly higher rates of ICU admission (59.4%) and mortality (29.7%) compared to those with normoglycemia. Among hypoglycemic episodes (<70 mg/dL), patients exhibited a trend toward prolonged ICU stays but did not show statistically significant differences in mortality. High glycemic variability (>20% coefficient of variation) was observed in 18.9% of patients and correlated strongly with ICU admission (p < 0.01).

Chronic kidney disease (CKD) patients demonstrated heightened vulnerability to severe COVID-19 outcomes. The ICU admission rate among CKD patients was 64.7%, significantly higher than in non-CKD patients (41.2%). Mortality in CKD patients was also elevated at 34.4% compared to 18.2% in the non-CKD cohort (p = 0.003). Regression analysis identified CKD as an independent predictor of mortality (OR: 2.72, 95% CI: 1.47-5.01, p = 0.002), underscoring its role in exacerbating disease severity. CKD patients were also more likely to exhibit hyperglycemia and elevated markers of inflammation (CRP and D-dimer).

Table 1: Patient Demographics and Clinical Characteristics

Table 2. Multivariate Logistic Regression Analysis for Predictors of Severe COVID-19 Outcomes

Notes:

• Adjusted for age, sex, and comorbidities (hypertension, diabetes).
• Model fit assessed using Hosmer–Lemeshow test (p = 0.64, good fit).
• Nagelkerke R² = 0.42, indicating good explanatory power.

Table 3: Kaplan-Meier Survival Analysis

This study highlights the significant impact of metabolic and renal complications on COVID-19 severity and outcomes. DKA was strongly associated with ICU admission and mortality, likely due to the exacerbation of systemic inflammation and metabolic acidosis. CKD and AKI independently predicted worse outcomes, emphasizing the vulnerability of patients with renal dysfunction to severe COVID-19. Glycemic variations, particularly hyperglycemia, were significant predictors of adverse outcomes, consistent with prior studies linking glucose dysregulation to immune dysfunction and pro-inflammatory states.

Comparison with other studies reveals consistent patterns. For instance, Hirsch et al. (2020) reported that AKI was a major complication in hospitalized COVID-19 patients, with a mortality rate exceeding 50% in those requiring renal replacement therapy. This aligns with our finding that AKI significantly increases ICU admission and mortality risk. Regarding renal complications, multiple studies have confirmed our findings. Jewell et al. (2021) reported a 39% AKI incidence in 1,248 COVID-19 inpatients, with AKI being a strong predictor of 30-day mortality across all stages of severity. The study found increasing mortality risk across AKI stages, with stage 3 AKI carrying a 3-fold higher risk of death. This pattern closely mirrors our survival analysis findings

Similarly, Zhang et al. (2021) highlighted hyperglycemia as an independent predictor of adverse outcomes, emphasizing the role of glycemic control in mitigating disease severity. Bornstein et al. (2020) also underscored the importance of managing diabetes in COVID-19, as hyperglycemia was linked to an amplified inflammatory response and poor prognosis. The elevated mortality rates in DKA patients observed in our study are consistent with findings from Yang et al. (2020), who demonstrated that metabolic acidosis exacerbates cytokine release, worsening disease outcomes. Yang et al. (2021) conducted a comprehensive meta-analysis of 16 observational studies with 6,386 COVID-19 patients, demonstrating that hyperglycemia at admission was associated with significantly increased mortality (OR = 3.45, 95% CI, 2.26–5.26) and severe complications (OR = 2.08, 95% CI, 1.45–2.99). This finding is consistent with our results showing hyperglycemia as a predictor of adverse outcomes. Saand et al. (2020) further supported these findings in critically ill COVID-19 patients, reporting that blood glucose ≥140 mg/dL was associated with increased mortality rates, prolonged ICU length of stay, and higher need for mechanical ventilation .Interestingly, hypoglycemia, while trending toward worse outcomes, did not reach statistical significance in this study. This is in contrast to findings by Gupta et al. (2020), who suggested that hypoglycemia may indicate a dysregulated metabolic response to infection, warranting further investigation. Our Kaplan-Meier survival analysis adds to the growing evidence of cumulative risks associated with DKA, CKD, and AKI, underscoring the need for integrated management of these conditions.

Patients with DKA, renal failure, CKD, and glycemic variations face significantly higher risks of severe COVID-19 outcomes. These findings underscore the need for vigilant monitoring and proactive management of metabolic and renal complications in COVID-19 patients. Integrating glycemic control and renal function optimization into COVID-19 care protocols could mitigate the burden of severe disease and improve survival rates. Future studies should focus on prospective designs and larger cohorts to validate these findings and explore therapeutic strategies.

1. Gupta R, et al. Clinical considerations for patients with diabetes in times of COVID-19 epidemic. Diabetes Metab Syndr. 2020;14(3):211-212.
2. Hirsch JS, et al. Acute kidney injury in patients hospitalized with COVID-19. Kidney Int. 2020;98(1):209-218.
3. Zhang JJ, et al. Associations of hypertension, diabetes, dyslipidemia, and COVID-19 severity. Am J Epidemiol. 2021;190(8):1642-1652.
4. Bornstein SR, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020;8(6):546-550.
5. Yang X, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475-481.