Evaluation of Laboratory Diagnostic Markers in Diabetic Patients With COVID-19

Background : Diabetes mellitus is the most common chronic metabolic disorder that increases both susceptibility and mortality rates in patients with the coronavirus disease 2019 (COVID-19). We conducted a study on diabetic patients with COVID-19 to investigate the relationship between laboratory indicators and peripheral oxygen saturation (SPO 2 ). Materials and Methods : In this analytical-cross-sectional study, the required information of diabetic patients with COVID-19 admitted to Taleghani educational hospital in Abadan from March 20, 2020 to March 19, 2021 was obtained by referring to the hospital information system of Abadan University of Medical Sciences and patient files. Results: Two hundred patients were studied, of which 88 (44%) were men and 112 (56%) were women. The mean age of the studied patients was 60.57 ± 14.84. Among all the investigated markers, blood urea nitrogen (BUN), serum glutamate oxalate transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lactate dehydrogenase (LDH), and respiratory rate (RR) were higher than the normal range, while SPO 2 was lower than the normal range. Based on the linear regression analysis results, a significant relationship was observed between the decrease in SPO 2 of patients with disease outcome, duration of hospitalization in the intensive care unit ( P < 0.001), RR ( P < 0.001), mean corpuscular volume (MCV) ( P = 0.02), CRP + 3 ( P = 0.002), platelet (PTT) ( P = 0.03), alkaline phosphatase (ALP) ( P = 0.002), and LDH ( P = 0.003). Conclusion : The results showed that some laboratory diagnostic markers were higher than the normal range, while SPO 2 was lower than the normal range. Moreover, a significant relationship was found between SPO 2 index and disease outcome, duration of hospitalization in intensive care unit (ICU), and some diagnostic markers of the liver, inflammation, and coagulation.

diabetes in that diabetes is associated with an increased risk of severe COVID-19, and on the other hand, sudden diabetes and severe metabolic complications of diabetes such as diabetic ketoacidosis have been observed in patients with COVID-19 (9). The most important mechanisms that cause immune system dysfunction in diabetics are reduced chemotaxis, reduced production of interleukins in response to infection, immobility of polymorphonuclear leukocytes, and reduced phagocytic activity (10)(11)(12).
Diabetes mellitus is associated with increased severity of COVID-19 and increased mortality; accordingly, diabetes-related complications (e.g., cardiovascular disease and chronic kidney disease) increase COVID-19 mortality. In addition to paying attention to clinical findings and the relationship between COVID-19 and diabetes, Paraclinical evaluations in these patients are necessary and valuable. Paraclinical examinations play an important role in the diagnosis, treatment, and evaluation of the patient's condition; therefore, laboratory tests should be done on them (13)(14)(15)(16)(17).
Since coronavirus 2 has the ability and potential to damage various vital organs such as the liver and kidneys, the analysis of various clinical and laboratory markers such as renal, liver, biochemical, hematologic, and inflammatory markers makes the performance of these organs better evaluated and avoids damage to these organs. Accordingly, this study was conducted on diabetic patients with COVID-19 to investigate the relationship between peripheral oxygen saturation (SPO2) and laboratory indicators such as renal, liver, biochemical, hematologic, and inflammatory markers.

Materials and Methods
The current research is a cross-sectional analytical study in which the information on 200 hospitalized diabetic patients with COVID-19 was obtained from March 20, 2020  , and renal factors such as blood urea nitrogen (BUN), creatinine (Cr), serum sodium, and serum potassium. Information was sorted based on gender, age, and date of admission, and then duplicate data was removed, and the information was recorded in Excel software.
The inclusion criteria in this study included diabetic patients with COVID-19 who were admitted to Taleghani educational hospital in Abadan, Iran, and information about their laboratory diagnostic markers such as liver, kidney, cardiac, and coagulation markers was available in hospital information system. Patients with nasopharyngeal swabs positive for severe acute respiratory syndrome coronavirus 2 in reverse transcription polymerase chain reaction and with fasting blood sugar above 120 mg/dL were included. If this information was incomplete or unavailable, these patients were excluded from the study.
To describe the data, mean and standard deviation were used for quantitative variables, and frequency and percentage were used for qualitative variables. Further, the normality of quantitative variables was checked using the Kolmogorov-Smirnov test. Multiple linear regressions were also run to check the correlation between variables and the SPO 2 index. Then, data analysis was done via SPSS version 24 software, and P > 0.05 was considered statistically significant.

Relationship Between SPO 2 and the Laboratory and Clinical Markers in Diabetic Patients with COVID-19
The findings obtained from the linear regression analysis showed that the SPO2 level of diabetic patients with COVID-19 has a significant relationship with the Dis Diagn. Vol  In general, among other investigated factors, the relationship of SPO 2 patients with outcome variables, duration of hospitalization in the intensive care unit (P < 0.001), RR (P < 0.001), MCV (P = 0.02), CRP + 3 (P = 0.002), PTT (P = 0.03), ALP (P = 0.002), and LDH (P = 0.003) was statistically significant. In this regard and according to the estimated regression coefficients, for each unit increase in SPO 2 , the mean of ALP and LDH decreased by 0.01 and 0.004, respectively. The mean of SPO 2 in patients with CRP + 3 was 1.796 units less than that in those with negative CRP. Further, for each unit increase in SPO 2 , the mean MCV, RR, and PTT decreased by 0.074, 0.82, and 0.067, respectively. For each SPO 2 unit increase, the duration of hospitalization in the intensive care unit was also shortened by 0.419 days ( Table 2).

Discussion
Out of the 200 diabetic patients with COVID-19 in this study, the majority were in their 5th and 6th decades of life (54.5%). Hypertension was reported as the most common disease associated with these patients and was observed in more than a quarter of patients. Further, a significant relationship was found between SPO 2 and disease outcome, duration of hospitalization in ICU, RR, MCV, CRP + 3, LDH, ALP, and PTT. Among the renal markers, the mean BUN in diabetic patients was higher than the normal range. Likewise, SGOT and SGPT were higher than the normal range in this group of patients. CRP + 1, CRP + 2, and CRP + 3 were also reported in 53 (26.5%), 59 (29.5%), and 34 (17%) patients with diabetes, respectively. The mean FBS, LDH, ESR, and RR were also higher than normal in these patients. Conversely, the mean SPO 2 of the patients was lower than the normal range.
In the cohort study by Wu et al in 2020 on diabetes, there was a significant difference in CRP, gender, and common symptoms (e.g., fever, cough, shortness of breath, and fatigue). In diabetic patients with COVID-19 compared to non-diabetic patients, the numbers of white blood cells, neutrophils, D-dimer, and LDH in diabetic COVID-19 patients were not significant (18). In the present study, CRP + 3 and LDH increased in diabetic patients with COVID-19.
The cohort study of Bruce Bode et al in 2020 revealed that uncontrolled diabetes or hyperglycemia occurs frequently among hospitalized patients with COVID-19. In addition, the COVID-19 patients with diabetes/uncontrolled hyperglycemia had a longer length of hospitalization, and  their mortality was more significant and higher than that of patients without diabetes/uncontrolled hyperglycemia (19). In the present study, the mean FBS in hospitalized diabetic coronary patients was observed to be higher than the normal range. Furthermore, low SPO 2 increased the risk of death of patients by 2.7 times. In the research by Javanian et al in 2020, CRP in patients with COVID-19 was significantly higher (20). In the present study, CRP + 1, CRP + 2, and CRP + 3 were also reported in 53 (26.5%), 59 (29.5%), and 34 (17%) diabetic patients with COVID-19 and low SPO 2 significantly increased CRP + 3.
In the study by Alguwaihes et al in 2020, 68.3% of the total examined patients with COVID-19 were men, their mean age was reported to be 55 years, and diabetes significantly increased the death rate of patients (21). In the present study, 54.5% of people were in the age range of 50 to 70 years, and low SPO 2 increased the risk of death of patients by 2.7 times. Additionally, with increasing age, the mean SPO 2 decreased by 0.023 units, and the mean SPO 2 in men was 0.073 units less than that in women.
In a study by Cheng et al in 2020 in Wuhan, China, an increase in serum creatinine and BUN was reported in 14.4 and 13.1% of patients with COVID-19, respectively (22). This result is in line with the result of the present study in which the mean BUN in diabetic patients with COVID-19 was higher than the normal range.
In the study by Fox et al in 2021, 47% of all examined patients with COVID-19 had diabetes and had higher inflammatory markers such as CRP and LDH compared to others, and only age was reported as an independent risk factor for the death of patients (23). In our study, LDH and CRP + 3 significantly increased in diabetic patients with COVID-19, and the SPO 2 level of diabetic patients with COVID-19 had a significant relationship with the outcome of their death. Moreover, with increasing age, the mean SPO 2 decreased.
In another study by Hammad and Alseoudy in 2021, 118 diabetic patients with COVID-19 were studied, of which 54 (45.8%) were men and 64 (54.2%) were women. SGPT increased significantly in men compared to women, while SGOT exhibited no significant difference. Further, BUN and Cr did not increase significantly in both genders (24). In our study, the mean of SGPT, SGOT, and BUN was higher than the normal range.
The results of a study by Wang et al in 2020 showed that ESR and CRP increase in diabetic patients with COVID-19 (25). In the present study, the mean ESR was also higher than normal in diabetic patients with COVID-19.

Conclusion
The results indicated that some laboratory diagnostic markers (e.g., liver, kidney, and inflammation) were higher than the normal range, while SPO 2 was lower than the normal range. Moreover, a significant relationship was found between SPO 2 index and disease outcome, duration of hospitalization in ICU, and some diagnostic markers of the liver, inflammation, and coagulation. Therefore, it is critical to pay attention to these markers in the diagnosis and treatment of coronary patients with diabetes. However, this requires further studies. It is suggested that larger control case designs be implemented to compare laboratory marker indicators in patients with and without diabetes suffering from COVID-19 to determine the independent risk factors affecting the death of this group of patients while comparing these indicators.