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ORIGINAL ARTICLE
Year : 2023 | Volume
: 14
| Issue : 1 | Page : 41-47
Glycolyzed hemoglobin as a poor prognostic factor in diabetic COVID-19 patients
Elif Torun Parmaksız1, Ergün Parmaksız2
1 Department of Chest Diseases, Health Sciences University, Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital, Sancaktepe/İstanbul, Turkey
2 Department of Nephrology, Health Sciences University, Kartal Dr Lutfi Kırdar City Hospital, Istanbul, Turkey
Correspondence Address:
Dr. Elif Torun Parmaksız
Department of Chest Diseases, HSU, Sancaktepe Şehit Prof. Dr. İlhan Varank Training and Research Hospital. Emek Mahallesi, Namık Kemal Cd. No:54, 34785 Sancaktepe/İstanbul
Turkey
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jod.jod_120_22
Background: Diabetes mellitus (DM) seems to be conveying increased risk in Coronavirus disease-2019 (COVID-19). We aimed to evaluate the effect of glycemic control on the risk of prevalence and mortality in diabetic COVID-19 patients. Materials and Methods: In this retrospective observational study, the data from diabetic patients admitted to our hospital with the diagnosis of COVID-19 between March 2020 and March 2021 were reviewed. The demographic, clinical, laboratory, and radiological data, and the course and outcomes were recorded. Results: The records of 352 diabetic patients were compared to 333 non-diabetic controls. The mean age of 184 male and 168 female patients was 63.7±13.0 (30–91). The length of hospital stay, rate of Intensive care unit (ICU) admission, and mortality were higher in the diabetic population compared to the non-diabetic counterparts. ICU admission and mortality rates were significantly higher in the group with HbA1c higher than 7%. The rate of ICU admission and mortality was significantly higher in participants with elevated HbA1cConclusions: Uncontrolled DM is among detrimental comorbidities contributing to the severity of SARS-CoV-2 infection and good control of serum glucose levels will improve prognosis in COVID-19. The diabetic population with poor glycemic control succumbed more to COVID-19.
Keywords: Coronavirus disease-2019, diabetes mellitus, glycolyzed hemoglobin
Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. It has emerged in China by the end of the year 2019, and afterward it has spread globally, creating a pandemic in 2020. After about one year period, the number of cases infected with SARS-CoV-2 in Turkey has exceeded 2,700,000, and more than 30,000 people died.[1] The clinical picture differs among infected subjects and there is considerable variability in the outcomes of COVID-19 patients. Although a substantial proportion of the infected population remains asymptomatic, some individuals present with severe pneumonia leading to acute respiratory distress syndrome (ARDS), respiratory failure, multiorgan failure, and death. Some comorbidities are risk factors for adverse clinical outcomes in COVID-19. An overall assessment of the available literature strongly suggests that diabetes mellitus (DM) is an important underlying condition for the risk and severity of COVID-19.[2],[3] However, the factors leading to poor prognosis and death in diabetic patients are not clearly defined. The effect of glycemic control on the higher risk of prevalence and mortality associated with DM in COVID-19 patients needs to be elucidated.
Glycolyzed hemoglobin (HbA1c), which is used to evaluate long-term glycemic control in DM, provides information about the last 3 months’ blood glucose levels concerning the life span of erythrocytes. HbA1c is a reliable test as it is relatively unaffected by acute fluctuations in serum glucose concentrations.[4] We aimed to evaluate the effect of HbA1c levels on the course of the disease in COVID-19 patients.
Materials and MethodsStudy design
We conducted this retrospective observational study on diabetic patients admitted to our hospital with the diagnosis of SARS-CoV-2 between March 2020 and March 2021. The flowchart of the patients reviewed is demonstrated in [Figure 1]. The primary outcomes were ICU admission and/or death during hospitalization period.
The study was approved by the Turkish Republic Ministry of Health and the local ethics committee.
Patients
Diagnosis of COVID-19 infection was confirmed by a positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) test or the presence of ICD-10 code U07.1 based on clinical, laboratory, and radiological findings. Throat-swab specimens from the oropharynx and nasopharynx were obtained from all patients at admission and were put in a viral-transport medium for RT-PCR test.
The patients were not vaccinated, because the study was conducted in the period before vaccination was started in our country. Hospital admission was defined as patient presence and treatment in a dedicated COVID-19 unit in the hospital. The study population had a personal history of DM. The diagnosis of DM was based on criteria established by American Diabetes Association.[5]
All participants were selected from 962 diabetic COVID-19 patients admitted between March 2020 and March 2021. Data from diabetic patients without HbA1c results were excluded from the study. Patients who were under treatment with corticosteroids were not included. The restriction method was used to eliminate the confounding effect. After this exclusion, 352 diabetic patients were included. The control group consisted of 333 age- and gender-matched non-diabetic COVID-19 cases.
Data collection
The demographic data were recorded. Data regarding the clinical symptoms on admission (i.e., cough, fever, dyspnea, fatigue, headache, chest pain, gastrointestinal symptoms such as nausea, vomiting, or diarrhea) and comorbidities (i.e., hypertension, cardiovascular disease, chronic respiratory disease, chronic renal failure, malignancy) were collected. The physical examination findings on initial admission were recorded; these included fever, blood pressure, heart rate, and oxygen saturation. The laboratory tests included complete blood count, fasting blood glucose (FBG), C-reactive protein (CRP), procalcitonin, D-dimer, ferritin, lactate dehydrogenase, renal and hepatic function tests, electrolytes, and HbA1c. The radiological findings were based on CT findings and classified as no involvement, unilateral involvement, or bilateral involvement. Length of hospital stay, need for admission to intensive care unit, the course, and outcomes during hospitalization were recorded. Treatment protocols were applied according to the COVID-19 guide of the Turkish Ministry of Health.[6]
Statistical analysis
Statistical sample size calculation was not performed, because the sample size was equal to all the diabetic COVID-19 patients hospitalized and had undergone HbA1c testing. Categorical variables were expressed as the number of patients and percentages with 95% confidence intervals (CI). Continuous variables were analyzed parametrically by means and standard deviations and compared by T-tests. The distribution of clinical and laboratory data was made over the HbA1c subgroups, and patients were grouped by HbA1c as under 7%; 7 through 8%; 8 through 9%; 9 through 10%; 10 through 11%; and above 11%. Differences between categorical variables were calculated using the χ2 method and Fisher’s exact test. All statistical tests were 2-tailed, and statistical significance was considered as a p-value under 0.05. Statistical analyses were performed using SPSS software (version 17.0).
ResultsData were collected from 352 diabetic patients and 333 non-diabetic patients (control group). The control group was adjusted for age and gender. The mean age of the study population was 63.7 ± 13.0 (30–91); 184 patients (52%) were male and 168 (48%) were female. The comparison of the demographic, clinical, laboratory, and radiologic data and outcomes in diabetic and control groups are demonstrated in [Table 1]. The length of hospital stay, rate of ICU admission, and mortality were higher in the diabetic population compared to the non-diabetic counterparts.
Table 1: Clinical, radiological and biological characteristics of the participants on admissionWhen the diabetic population was grouped based on HbA1c and HbA1c under 7% was considered as good glycemic control, age was significantly higher (65.7 vs. 62.3; p = 0.02) and duration of hospital stay was significantly shorter (5.5 vs. 7.6 days; p = 0.005) in subjects with good glycemic control. The number of patients who required ICU admission and the number of deceased were significantly higher in the group with HbA1c higher than 7%. SpO2 levels measured at the time of hospital admission were significantly decreased in subjects with HbA1c higher than 7%. The laboratory findings assumed as prognostic factors such as CRP, D-dimer, ferritin, LDH, and lymphocyte count did not seem to differ significantly in groups based on HbA1c.
The comparison and distribution of the demographic, clinical, laboratory, and radiologic data and outcomes in groups based on HbA1c are shown in [Table 2] and [Table 3]. We grouped the patients with respect to HbA1c with different cut-off values, that is, 7%, 8%, and 9%. The rate of ICU admission and mortality was significantly higher in participants with elevated HbA1c. Eighteen of 145 (12%) subjects with HbA1c <7% and 52 of 207 (25%) subjects with HbA1c ≥7% required ICU admission. The number of deceased was 10 (7%) in subjects with HbA1c <7% and 26 (13%) in subjects with HbA1c ≥7%. In the subset with HbA1c <8%, 35 of 205 subjects (17%) required ICU admission and 16 subjects (8%) died. In the group with HbA1c ≥8%, 35 of 147 subjects (24%) required ICU admission and 20 subjects (14%) died. When 9% was considered as the cut-off value, 43 of 247 (17%) subjects with HbA1c <9% were admitted to ICU and 18 subjects (7%) were deceased. In the group with HbA1c ≥9%, 27 of 105 subjects were admitted to ICU and 18 subjects (17%) were deceased [Figure 2] and [Figure 3].
Table 2: The comparison of the demographic, clinical, laboratory and radiologic data and outcomes in groups based on HbA1c
Table 3: The distribution of patient characteristics with respect to HbA1c levels
Figure 2: The distribution of prognostic laboratory markers with respect to HbA1c values
Figure 3: The demonstration of gender distribution and study outcomes of HbA1c groupsThe association between HbA1c measurements and outcomes is presented in [Table 4]. Correlation analyses revealed that HbA1c was positively correlated to CRP (r = 0.11, p = 0.05); ferritin (r = 0.11, p = 0.05) and length of hospital stay (r = 0.08, p = 0.11).
DiscussionIn this study, we have evaluated a large group of diabetic patients admitted to the hospital with SARS-CoV-2 infection. The subjects with poor glycemic control, that is, higher HbA1c cases were found to have a worse prognosis in COVID-19. The hospital stay was longer and ICU admission and death rates were higher in these patients. FBG levels on the morning of admission were significantly higher in subjects with higher HbA1c levels. Other widely used laboratory tests that are considered to have an impact on prognosis (e.g., CRP, D-dimer, ferritin, LDH, and lymphocyte count) did not seem to differ in groups with poor and good glycemic control. Our data revealed that the whole diabetic population is not at equal risk of severe disease due to COVID-19. This makes HbA1c an important prognostic factor in diabetic patients with COVID-19.
Earlier identification of individuals with an elevated risk of severe SARS-CoV-2 disease is crucial. DM has been identified as a leading factor associated with higher mortality compared with non-diabetic subjects in COVID-19.[7],[8] In a meta-analysis conducted in China, the prevalence of DM was found to vary between 7.4% and 20% in SARS-CoV-2 infected population and it was the second most common comorbidity after hypertension.[9] Vascular compromise is a cardinal feature of both diabetes and COVID-19. The interaction between COVID-19 and DM has been reviewed and multiple pathophysiological explanations have been put forward. DM stimulates the production and release of cytokines, compromises innate immunity, and reduces the expression of angiotensin-converting enzyme. These can be expressed as potential factors that exacerbate the severity of COVID-19.[10] A recent study has shown that elevated HbA1c level is associated with inflammation, hypercoagulability, and desaturation in COVID-19 patients. DM was associated with increased mortality rates in SARS-CoV-2 infection.[11] In a large cohort of COVID-19 patients, it has been shown that well-controlled diabetic subjects had lower mortality compared with subjects with poor glycemic control.[12] These reports are consistent with our findings and confer an increased risk of mortality in uncontrolled DM. However, several studies have claimed that having unsuccessful glycemic control was not associated with poor outcomes in COVID-19 patients.[13],[14] This is contradictory with our results as we have demonstrated that better glycemic control is crucial to avoid death from COVID-19. The diabetic population with poor glycemic control succumbed more to COVID-19.
There are several limitations of the study. This is a retrospective study; therefore, some electronic data of the participants may be missing. The study does not include a follow-up period; therefore, the outcome measures represent early period prognosis and in-hospital mortality. However, this fact is similar to a substantial number of similar investigations.
ConclusionPoorly controlled diabetes has a significantly higher risk of severe COVID-19, longer hospital admission, and increased mortality. Uncontrolled DM is among detrimental comorbidities contributing to the severity of SARS-CoV-2 infection and good control of serum glucose levels will improve prognosis in COVID-19. Blood glucose monitoring and achievement of glycemic control promote better prognosis.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
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