What is the role of admission HbA1c in managing COVID-19 patients?

To the Editor,

Some recent articles published in the Journal of Diabetes have raised concerns about the importance of checking glycosylated hemoglobin (HbA1c) upon hospital admission for coronavirus disease 2019 (COVID‐19) patients. , , It is now undoubtedly clear that absolute hyperglycemia at the time of admission increases the risk of severe outcomes of COVID‐19, independent of prior diabetes status, , and tight glycemic control improves the prognosis of these patients significantly. , However, the role of admission HbA1c, which reflects average glycemia over the preceding 2 to 3 months, in the management of COVID‐19 patients remains uncertain.

Some studies have shown a significant association between admission HbA1c and disease progression or mortality in COVID‐19 patients, whereas a few others did not (Table 1). While the reasons for this discrepancy are not clear, most of these studies are constrained by a small number of patients, , a large proportion of missing HbA1c data, and inadequate adjustment of potential confounders. , Previous research has shown that background glycemia mediates the association between admission glucose and outcomes in patients with a variety of medical conditions. , , Thus, correcting admission glucose levels for background glycemia estimated by HbA1c, the so‐called relative hyperglycemia predicts outcomes in acute health conditions better than absolute hyperglycemia, , albeit not yet proven in the COVID‐19 context.

TABLE 1

Admission HbA1c and clinical outcomes in COVID‐19 patients

Authors and country	N	Known diabetes, n (%)	Mean (SD) or median (IQR) HbA1c (%)	Outcome (s)	Findings	Variables adjusted for
Liu L et al, 7 China	77	33 (43.0)	NR	Mortality	1% increase in HbA1c was significantly associated with mortality with an hazard ratio of 1.58 (95% CI 1.16, 2.15), P = .004	Age, lactate dehydrogenase, lymphocyte count, NT‐proBNP, and serum ferritin
Liu Z et al, 6 China	64	64 (100)	8.1 (6.6‐9.7)	Disease progression (transferred to ICU or death) during hospitalization	1% increase in HbA1c was significantly associated with disease progression with an OR of 3.29 (95% CI 1.19, 9.13), P = .022	Maximum of in‐hospital blood glucose, lymphocytes, CRP, and prothrombin time
Wang Z et al, 9 China	132	31 (23.5)	6.4 (5.8‐7.2)	Mortality Markers of inflammation and hypercoagulability, and oxygen saturation	Higher mortality rate with increasing HbA1c levels: 9.8% in group A (n = 41, no diabetes and HbA1c ≤6.0%), 11.4% in group B (n = 44, no diabetes and HbA1c >6.0‐ < 6.5%), and 27.7% in group C (n = 47, diabetes and/or HbA1c ≥6.5%), P = .04 Negative correlation between HbA1c and SaO2 (r = −0.22, P = .01). Positive correlation between HbA1c and ferritin (r = 0.24, P = .01), CRP (r = 0.22, P = .01), fibrinogen (r = 0.27, P < .01), and ESR (r = 0.27, P < .01)	None
Cariou B et al, 8 France	1317	1317 (100)	8.1 (1.9)	Invasive mechanical ventilation or death within 7 days of admission	No significant association: compared with HbA1c <7%, OR for 7%‐7.9% was 0.84 (95% CI 0.55, 1.27), OR for 8%‐8.9% was 0.92 (95% CI 0.59, 1.45), and OR for ≥9.0% was 0.78 (95% CI 0.51, 1.21)	None
Ling P et al, 1 China	51	51 (100)	8.0 (1.5)	Disease progression (nonsevere to severe illness)	No significant association	Age, sex, blood glucose, smoking status, and blood pressure

Abbreviations: CI, confidence interval; COVID‐19, coronavirus disease 2019; CRP, C‐reactive protein; ESR, erythrocyte sedimentation rate; HbA1c, glycosylated hemoglobin; ICU, intensive care unit; IQR, interquartile range; NR, not reported; NT‐proBNP, N‐terminal prohormone natriuretic peptide; OR, odds ratio; SaO2, oxygen saturation; SD, standard deviation.

Since HbA1c is relatively unaffected by the stress of acute illness, it may help identify newly diagnosed diabetes cases in COVID‐19 patients. Newly diagnosed diabetes (new onset or previously undiagnosed) is now increasingly recognized as a common phenomenon in COVID‐19 patients. , More importantly, COVID‐19 patients with newly diagnosed diabetes appear to be at a greater risk for poor prognosis not only compared with those without diabetes but also individuals with known diabetes. , ,

To summarize, admission blood glucose is certainly a key biomarker to risk stratify and guide the clinical management of COVID‐19 patients, with or without known diabetes. Thus, it is essential that all COVID‐19 patients be screened for absolute hyperglycemia upon admission so that early and appropriate treatment can be initiated if required. While the role of admission HbA1c as a marker of COVID‐19 severity is yet to be fully established, HbA1c assists in identifying patients with newly diagnosed diabetes. , These patients are a high‐risk group and should be closely monitored for the emergence of cardiometabolic disorders in the long term.

DISCLOSURE

None declared.