PMC:7347402 / 24328-30720 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7347402","sourcedb":"PMC","sourceid":"7347402","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7347402","text":"Discussion\nThe ongoing COVID-19 pandemic is taking a heavy toll worldwide and effective measures have to be taken to minimise its impact and to lower mortality. Previous studies have shown that diabetes and acute uncontrolled hyperglycaemia (defined as blood glucose \u003e10 mmol/l twice within any 24 h period) are related to morbidity and/or mortality from COVID-19 [13, 21, 25]. Nonetheless, so far, no research effort has been directed at whether the admission FBG level is an independent predictor of mortality in COVID-19 patients without previously diagnosed diabetes. This two-centre retrospective study shows, for the first time, that elevated FBG (≥7.0 mmol/l) at admission is independently associated with increased 28-day mortality and percentages of in-hospital complications in COVID-19 patients without previous diagnosis of diabetes.\nOur multivariable Cox regression analysis showed that FBG, CRB-65 score, age and sex were independently associated with 28-day mortality in COVID-19 patients without previous diagnosis of diabetes. In a study involving 191 COVID-19 patients, advanced age, a high Sequential Organ Failure Assessment (SOFA) score and a D-dimer level greater than 1 μg/l were risk factors for mortality [21]. Because of differences in patient composition, their study failed to reveal any significant difference for sex, although the proportion of male patients in the non-survivor group was higher than in the surviving group (68.4% vs 49.7%). Hyperglycaemia and/or diabetes were identified to be risk factors for morbidity and mortality caused by infection with community-acquired pneumonia (CAP), SARS and MERS [9–12]. Consistent with the studies on CAP [9, 10], our results indicate that admission FBG is a significant prognostic factor for COVID-19. Another analysis of COVID-19 patients with ARDS showed that FBG is related to the occurrence of ARDS, but not associated with the death of patients with ARDS [26]. We have, for the first time, performed a stratified analysis of different FBG levels in a larger population and demonstrated that FBG ≥7.0 mmol/l is critical to the prognosis of patients with COVID-19. Our data also show that non-survivors are more likely to have serious complications. In addition, we demonstrate that the incidence of in-hospital complications increases with the elevation of FBG. The CRB-65 score is a quick and convenient indicator for judging the severity of pneumonia [27]; we have also shown that FBG ≥7.0 mmol/l is associated with increased mortality in participants, regardless of whether the patient’s CRB-65 score is 0 or greater.\nPatients with FBG \u003e6.1 mmol/l accounted for 45.6% (276/605) and a total of 29.1% (176/605) patients had blood glucose ≥7.0 mmol/l. These results indicate that our study included both undiagnosed diabetic patients and non-diabetic patients with hyperglycaemia caused by an acute blood-glucose disorder. Similarly to a previous study, COVID-19 patients might suffer from stress hyperglycaemia [10] and critically ill patients may develop acute insulin resistance, manifested by hyperglycaemia and hyperinsulinaemia [28]. Patients with conditions not related to diabetes, such as severe sepsis, systemic inflammatory response syndrome (SIRS) and traumatic brain injury tend to have hyperglycaemia [28]. Hyperglycaemia at admission to the intensive care unit (ICU) is directly related to increased mortality or morbidity [29]. At the same time, drugs, such as antibiotics and corticosteroids, could also elevate serum glucose concentration [30, 31]. In particular, corticosteroids may impair glucose tolerance by promoting gluconeogenesis in the liver, reducing glucose uptake and utilisation in peripheral tissues and increasing the effects of other glycaemic hormones [31]. It is recommended that close attention be paid to hospitalised patients, regardless of whether they have been previously diagnosed as having diabetes.\nAlthough insulin treatment for critically ill patients has become a standard of care, efficacy might well vary with different ICUs. A study published in 2001 reported that intensive insulin therapy with blood glucose maintained at or below 6 mmol/l reduced morbidity and mortality in critically ill patients in surgical ICUs [32]. However, subsequent studies on intensive insulin therapy of critically ill patients in medical ICUs showed that this treatment could reduce morbidity but not mortality [33]. The debate over this issue remains, and a study published in 2009 found that intensive glycaemic control could increase mortality in adults in ICUs, but increasing target glucose levels to 10 mmol/l could reduce mortality [34]. A recent review separately examined surgical and medical patients and suggested that, to treat hyperglycaemia, insulin therapy should be used to maintain the glucose level between 8 mmol/l and 10 mmol/l. This treatment could reduce the mortality and morbidity resulting from high FBG and lower the occasional risk of hypoglycaemia associated with intensive insulin therapy [35].\nThis study has several limitations. First, this was a retrospective study. Second, we did not cover HbA1c, a long-term glycaemic control indicator that helps distinguish patients with poor long-term glycaemic control from those with stress hyperglycaemia. Finally, because our results were premised only on the glucose levels at admission, we might have underestimated the risks associated with hyperglycaemia (assuming that patients with the highest glucose levels are more likely to be treated in the hospital), and we did not have sufficient data to study the effect of glucose-lowering treatment (e.g. insulin, metformin) on the outcome of our patients. However, we believe that acute hyperglycaemia is more important than long-term glycaemic control in predicting the prognosis of hospitalised COVID-19 patients.\nIn conclusion, FBG ≥7.0 mmol/l at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes. Glycaemic testing and control should be recommended for all COVID-19 patients even if they do not have pre-existing diabetes, as most COVID-19 patients are prone to glucose metabolic disorders. During a pandemic of COVID-19, FBG can facilitate the assessment of prognosis and early intervention of hyperglycaemia to help improve the overall outcomes in treatment of 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