Higher values of fasting blood glucose and glycated hemoglobin are not associated with mortality in Covid-19 Mexican patients

Published:November 05, 2020DOI:https://doi.org/10.1016/j.pcd.2020.10.014
      To the editor:
      The SARS-CoV-2 has left a huge impact on death balance associated with Covid-19 around the world. There is a high proportion of these patients with diabetes, who have been documented to have more significant mortality and serious complications [
      • Apicella M.
      • Campopiano M.C.
      • Mantuano M.
      • Mazoni L.
      • Coppelli A.
      • Del Prato S.
      COVID-19 in people with diabetes: understanding the reasons for worse outcomes.
      ]. Type 2 diabetes mellitus (T2DM) is the most frequent among this disease spectrum. T2DM is characterized by β-cell dysfunction, insulin resistance, and a chronic pro-inflammatory process that culminates in micro and macrovascular complications. Diabetes is a capital health problem in México, where approximately one out of ten adults older than 20 years has this disease [
      • Secretaría de Salud
      • Instituto Nacional de Salud Pública
      • Instituto Nacional de Estadística y Geografía
      Encuesta Nacional de Salud y Nutrición 2018. Presentación de resultados.
      ].
      Recently, abnormal fasting blood glucose (FBG) levels have been associated with increased death risk in Covid-19 patients [
      • Wang S.
      • Ma P.
      • Zhang S.
      • Song S.
      • Wang Z.
      • Ma Y.
      • et al.
      Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study.
      ]. Besides, high HbA1c levels in those patients during admission, with diabetes or without as well. These results are associated with pro-inflammatory activity, prothrombotic states, and low levels of oxygen saturation (SaO2) [
      • Wang Z.
      • Du Z.
      • Zhu F.
      Glycosylated hemoglobin is associated with systemic inflammation, hypercoagulability, and prognosis of COVID-19 patients.
      ]. Additionally, it has been observed a relationship between increased risk of mortality and higher levels of HbA1c. Thus, HbA1c has been proposed as a risk stratification marker [
      • Klein S.J.
      • Fries D.
      • Kaser S.
      • Mathis S.
      • Thomé C.
      • Joannidis M.
      Unrecognized diabetes in critically ill COVID-19 patients.
      ]. Nonetheless, the mechanism and clinical meaning of accelerated hemoglobin glycation in this phenomenon are uncertain yet. This work objective was to evaluate HbA1c as a complication and risk predictive mortality marker in patients with or without diabetes with Covid-19 at admission.
      A retrospective analysis of clinical and laboratory data obtained from Covid-19 patients at admission to intensive care services in the IMSS Hospital in Celaya, from August 13 to September 02, 2020. Real-Time PCR confirmed the diagnosis for SARS-CoV-2 in nasopharyngeal specimen, performed at the Mexican Diagnostic and Epidemiological Reference Institute. Patients with history of hemolytic anemia, recent hemorrhage or hemoglobinopathy were excluded. Statistical analysis was done in NCSS 2007 by using two-samples Student t-test for continuous data and Aspin-Welch test when unequal variances. Tukey’s rule was applied for normalization when needed. The χ2 test for trend analysis resolved qualitative categorical data. Results are shown in Table 1.
      Table 1Comparison among clinical and laboratory outcomes of hospitalized Covid-19 patients at admission.
      Diabetes (n = 26)SEMNon-diabetes (n = 56)SEMPNC (n = 21)SEMPDeaths (n = 26)SEMRecovered (n = 56)SEMPCovid-19 (n = 82)SEMNon-Covid-19 (n = 25)SEMP
      Age (years)
      Median (lower limit–upper limit).
      66 [33–87]59 [21–87]59 [40–87]62 [34–81]61 [21–87]61 [21–87]65 [32–87]
      Sex (M:F)1.22.52.07.71.21.90.7
      Hb (g/dL)13.560.4614.140.300.283914.190.610.407514.030.5613.920.260.849613.950.2512.120.47<0.05
      Statistical difference with significance level of 0.05 according to t-test or chi-square.
      Plt (×109/L)225.8524.42226.4518.950.4926195.5727.440.7932170.1524.36252.317.92<0.05
      Statistical difference with significance level of 0.05 according to t-test or chi-square.
      226.2615.00269.623.430.0764
      Glu (mg/dL)243.8116.03138.234.69<0.05
      Statistical difference with significance level of 0.05 according to t-test or chi-square.
      159.1917.35<0.05
      Statistical difference with significance level of 0.05 according to t-test or chi-square.
      167.9513.39184.1411.110.8052179.018.6985.442.25<0.05
      Statistical difference with significance level of 0.05 according to t-test or chi-square.
      HbA1c (%) (mmol/mol)10.70.426.90.14<0.05
      Statistical difference with significance level of 0.05 according to t-test or chi-square.
      7.10.18<0.05
      Statistical difference with significance level of 0.05 according to t-test or chi-square.
      8.20.418.20.350.49138.20.275.70.11<0.05
      Statistical difference with significance level of 0.05 according to t-test or chi-square.
      935254[1–5]66666639
      CRP (mg/L)0.59100.56700.3808<0.05
      Statistical difference with significance level of 0.05 according to t-test or chi-square.
      <50373281010
      50–18071978182613
      >1801630111630462
      DD (ng/mL)1549.17205.421037.6394.63<0.05
      Statistical difference with significance level of 0.05 according to t-test or chi-square.
      1433.74298.700.37222395.81508.921130.599.64<0.05
      Statistical difference with significance level of 0.05 according to t-test or chi-square.
      1206.4795.84251.9633.86<0.05
      Statistical difference with significance level of 0.05 according to t-test or chi-square.
      Iron (mg/dL)103.7711.3289.466.170.230980.8110.300.148994.9611.1993.626.310.9109
      TS (%)34.553.4434.652.520.490833.693.490.568530.93.4236.382.490.1038
      IBC (mg/dL)222.156.17221.415.000.9302229.337.930.4716220.57.18222.184.710.8432
      SaO2 (%)891.5890.50.800.174689.861.430.347887.621.5591.580.65<0.05
      Statistical difference with significance level of 0.05 according to t-test or chi-square.
      Complications
      ARDS6836814
      BP131404
      MI011101
      Sepsis031213
      HbA1c (%) (mmol/mol)
      ≤5.7 (39)04004
      5.7–6.4 (39–47)014377
      ≥6.5 (≥48)2638181945
      <7 (<53)03411925
      ≥7 (≥53)2622101731
      Mortality (%)26.933.90.704423.80.9259
      Deaths7195
      Recovered193716
      NC = no comorbidities; Hb = hemoglobin; Plt = platelets; Glu = glucose; CRP = C reactive protein; DD = D-dimers; TS = transferrin saturation; IBC = iron binding capacity; SaO2 = oxygen saturation; ARDS = acute respiratory distress syndrome; BP = bacterial pneumonia; MI = myocardial infarction. SEM = standard error of mean.
      a Median (lower limit–upper limit).
      * Statistical difference with significance level of 0.05 according to t-test or chi-square.
      In conclusion, there are indeed higher values of FBG and HbA1c in Mexican Covid-19 patients, independently if they had been diagnosed with diabetes. However, this finding is not associated with higher mortality, and it is not necessarily dependent on respiratory complications but with prothrombotic activity. Possibly, the survival outcomes might depend on internal care protocol differences among hospitals. Thus, we suggest that the relationship between HbA1c and D-Dimers in patients with Covid-19 must be further analyzed.

      Funding

      No funding to declare.

      Declaration of interests

      None.

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