Influence of Fasting Plasma Glucose Level on Admission of COVID-19 Patients: A Retrospective Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) is a serious global health threat and has spread dramatically worldwide. Prolonged viral shedding is associated with a more severe disease course and inflammatory reaction. Blood glucose levels were significantly associated with an increased hazard ratio (HR) for poor outcomes in COVID-19 patients. OBJECTIVE: Previous studies focused primarily on the relationship between blood glucose and mortality or severe outcomes, but there were few research studies on the relationship between fasting plasma glucose (FPG) and duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA positive status. To explore the relationship between FPG levels and prolonged duration of SARS-CoV-2 viral positivity, the clinical data of COVID-19 patients were analyzed. METHOD: In this retrospective study, 99 cases of COVID-19 patients in Beijing Ditan Hospital were recruited, and their clinical and laboratory findings at admission were collected and analyzed. Furthermore, the risk factors for prolonged duration of SARS-CoV-2 RNA shedding were identified, and the relationship between FPG levels and the prolonged presence of SARS-CoV-2 RNA was evaluated. RESULT: We found that elevated FPG levels were correlated with longer duration of SARS-CoV-2 RNA positivity, classification of COVID-19, imaging changes of chest CT, inflammation-related biomarkers, and CD8+ T cell number in COVID-19 patients. In a logistic regression model, after adjusting for gender and age, COVID-19 patients with elevated FPG were more likely to had longer duration of SARS-CoV-2 RNA positivity than those with normal FPG levels (OR 3.053 [95% CI 1.343, 6.936]). CONCLUSION: Higher FPG levels (≥6.1 mmol/l) at admission was an independent predictor for prolonged SARS-CoV-2 shedding, regardless of a known history of diabetes. It suggests that intensive monitoring and control of blood glucose are important for all COVID-19 patients.

High Fasting Blood Glucose Level With Unknown Prior History of Diabetes Is Associated With High Risk of Severe Adverse COVID-19 Outcome.

Background: We aimed to understand how glycaemic levels among COVID-19 patients impact their disease progression and clinical complications. Methods: We enrolled 2,366 COVID-19 patients from Huoshenshan hospital in Wuhan. We stratified the COVID-19 patients into four subgroups by current fasting blood glucose (FBG) levels and their awareness of prior diabetic status, including patients with FBG<6.1mmol/L with no history of diabetes (group 1), patients with FBG<6.1mmol/L with a history of diabetes diagnosed (group 2), patients with FBG≥6.1mmol/L with no history of diabetes (group 3) and patients with FBG≥6.1mmol/L with a history of diabetes diagnosed (group 4). A multivariate cause-specific Cox proportional hazard model was used to assess the associations between FBG levels or prior diabetic status and clinical adversities in COVID-19 patients. Results: COVID-19 patients with higher FBG and unknown diabetes in the past (group 3) are more likely to progress to the severe or critical stage than patients in other groups (severe: 38.46% vs 23.46%-30.70%; critical 7.69% vs 0.61%-3.96%). These patients also have the highest abnormal level of inflammatory parameters, complications, and clinical adversities among all four groups (all p<0.05). On day 21 of hospitalisation, group 3 had a significantly higher risk of ICU admission [14.1% (9.6%-18.6%)] than group 4 [7.0% (3.7%-10.3%)], group 2 [4.0% (0.2%-7.8%)] and group 1 [2.1% (1.4%-2.8%)], (P<0.001). Compared with group 1 who had low FBG, group 3 demonstrated 5 times higher risk of ICU admission events during hospitalisation (HR=5.38, 3.46-8.35, P<0.001), while group 4, where the patients had high FBG and prior diabetes diagnosed, also showed a significantly higher risk (HR=1.99, 1.12-3.52, P=0.019), but to a much lesser extent than in group 3. Conclusion: Our study shows that COVID-19 patients with current high FBG levels but unaware of pre-existing diabetes, or possibly new onset diabetes as a result of COVID-19 infection, have a higher risk of more severe adverse outcomes than those aware of prior diagnosis of diabetes and those with low current FBG levels.

Bioequivalence and food effect of a fixed-dose combination of macitentan and tadalafil: Adaptive design in the COVID-19 pandemic.

The COVID-19 pandemic has forced clinical studies to accommodate imposed limitations. In this study, the bioequivalence part could not be conducted as planned. Thus, the aim was to demonstrate bioequivalence, using an adaptive study design, of tadalafil in fixed-dose combination (FDC) tablets of macitentan/tadalafil with single macitentan and tadalafil (Canadian-sourced) tablets and assess the effect of food on FDC tablets in healthy subjects. This Phase 1, single-center, open-label, single-dose, two-part, two-period, randomized, crossover study enrolled 62 subjects. Tadalafil bioequivalence as part of FDC of macitentan/tadalafil (10/40 mg) with single-component tablets of macitentan (10 mg) and tadalafil (40 mg) was determined by pharmacokinetic (PK) assessment under fasted conditions. The effect of food on FDC was evaluated under fed and fasted conditions. Fasted 90% confidence intervals (CIs) for geometric mean ratios (GMRs) were within bioequivalence limits for tadalafil and macitentan. Fed and fasted 90% CIs for area under the curve (AUC) GMR were within bioequivalence limits. However, 90% CIs for maximum plasma concentration (Cmax ) GMR for macitentan and tadalafil were outside bioequivalence limits. One FDC-treated subject experienced a serious adverse event of transient ischemic attack (bioequivalence part). To address pandemic-imposed limitations, an adaptive study design was implemented to demonstrate that the FDC tablet was bioequivalent to the free combination of macitentan and tadalafil (Canadian-sourced). No clinically significant differences in PK were determined between fed and fasted conditions; the FDC formulation could be taken irrespective of meals. The FDC formulation under fasted and fed conditions was well tolerated with no clinically relevant differences in safety profiles between the treatment groups. NCT Number: NCT04235270.

Both high and low pre-infection glucose levels associated with increased risk for severe COVID-19: New insights from a population-based study.

IMPORTANCE: Patients with diabetes are known to be at increased risk for infections including severe coronavirus disease 2019 (COVID-19) but the relationship between COVID-19 severity and specific pre-infection glucose levels is not known. OBJECTIVE: To assess the differential effects of pre-infection glucose levels on the risk for severe COVID-19 amongst patients with and without diabetes. DESIGN: Population based historical cohort study. SETTING: National state-mandated HMO. PATIENTS: All adult patients with a positive SARS-COV2 test between March-October 2020. EXPOSURE: Recent fasting blood glucose (FBG) and glycated hemoglobin (HBA1C), age, gender, body mass index (BMI) and diagnoses of diabetes, hypertension, ischemic heart disease. OUTCOME: Risk for severe COVID-19, defined as resulting in ≥10 hospitalization days, ICU admission or death. RESULTS: 37,121 patients with a positive SARS-COV2 test were identified; 707 defined as severe (1.9%). Unadjusted risk factors for severe disease were age (OR = 1.1 for every year increase; 95% CI 1.09-1.11, p < 0.001), male gender (OR = 1.34, 95% CI 1.06-1.68, p = 0.012); BMI (OR = 1.02 for 1 kg/m2 increase, 95% CI 1.00-1.04, p = 0.025). Controlling for these factors, we found an association between pre-infection FBG and the risk of severe COVID-19, with a differential effect in patients with and without a diagnosis of diabetes. For patients without diabetes, elevated FBG in the pre-diabetes range (106-125 mg/dl) was associated with severe COVID-19 (OR 1.55 95% CI 1.04-2.26 p = 0.027). For patients with a diagnosis of diabetes, we found a J-shaped association between pre-infection glucose control and the risk for severe COVID-19 where the lowest risk for was for patients with FBG 106-125 mg/dl; the risk increased with higher pre-infection glucose levels but strikingly also for patients with a low pre-infection FBG (<100mg/dl) or HbA1C (<5.7%). CONCLUSIONS AND RELEVANCE: Elevated pre-infection blood glucose is a risk factor for severe COVID-19 even in non-diabetics. For patients with a diagnosis of diabetes both high as well as low pre-infection glucose levels are risk factors for severe COVID-19. Further research is required to assess whether these associations are causal, but we believe these findings can already have clinical implications for COVID-19 risk assessment and stratification.

Evaluation of glycemic traits in susceptibility to COVID-19 risk: a Mendelian randomization study.

BACKGROUND: Observational studies suggest poorer glycemic traits and type 2 diabetes associated with coronavirus disease 2019 (COVID-19) risk although these findings could be confounded by socioeconomic position. We conducted a two-sample Mendelian randomization to clarify their role in COVID-19 risk and specific COVID-19 phenotypes (hospitalized and severe cases). METHOD: We identified genetic instruments for fasting glucose (n = 133,010), 2 h glucose (n = 42,854), glycated hemoglobin (n = 123,665), and type 2 diabetes (74,124 cases and 824,006 controls) from genome wide association studies and applied them to COVID-19 Host Genetics Initiative summary statistics (17,965 COVID-19 cases and 1,370,547 population controls). We used inverse variance weighting to obtain the causal estimates of glycemic traits and genetic predisposition to type 2 diabetes in COVID-19 risk. Sensitivity analyses included MR-Egger and weighted median method. RESULTS: We found genetic predisposition to type 2 diabetes was not associated with any COVID-19 phenotype (OR: 1.00 per unit increase in log odds of having diabetes, 95%CI 0.97 to 1.04 for overall COVID-19; OR: 1.02, 95%CI 0.95 to 1.09 for hospitalized COVID-19; and OR: 1.00, 95%CI 0.93 to 1.08 for severe COVID-19). There were no strong evidence for an association of glycemic traits in COVID-19 phenotypes, apart from a potential inverse association for fasting glucose albeit with wide confidence interval. CONCLUSION: We provide some genetic evidence that poorer glycemic traits and predisposition to type 2 diabetes unlikely increase the risk of COVID-19. Although our study did not indicate glycemic traits increase severity of COVID-19, additional studies are needed to verify our findings.

Determinants of Increased Fibrinogen in COVID-19 Patients With and Without Diabetes and Impaired Fasting Glucose.

BACKGROUND: To investigate the factors associated with elevated fibrinogen (Fbg) levels in COVID-19 patients with and without diabetes (DM) and impaired fasting glucose (IFG). METHODS: According to whether or not their glucose metabolism was impaired, COVID-19 patients were subdivided into 2 groups: 1) with DM and IFG, 2) control group. Their demographic data, medical history, signs and symptoms, laboratory results, and final clinical results were analyzed retrospectively. RESULTS: 28 patients (16.3%) died during hospitalization, including 21 (29.2%) in group 1 and 7 (7.0%) in group 2 (P < 0.001). Fbg levels in groups 1 and 2 were higher than the normal range, at 5.6 g/L (IQR 4.5-7.2 g/L) and 5.0 g/L (IQR 4.0-6.1 g/L), respectively (P = 0.009). Serum ferritin levels, C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), triglycerides (TG) were significantly increased in group 1 compared to those in the control. TG levels were 1.3 mmol/L in the control, while that in group 1 was 1.8 mmol/L. Multiple linear regression showed that the predicting factors of Fbg in the control group were serum ferritin and CRP, R2 = 0.295; in group 1, serum ferritin, CRP, and TG, R2 = 0.473. CONCLUSIONS: Fbg in all COVID-19 patients is related to serum ferritin and CRP involved in inflammation. Furthermore, in COVID-19 patients with insulin resistance, Fbg is linearly positively correlated with TG. This suggests that regulation of TG, insulin resistance, and inflammation may reduce hypercoagulability in COVID-19 patients, especially those with insulin resistance.

Impact of undiagnosed type 2 diabetes and pre-diabetes on severity and mortality for SARS-CoV-2 infection.

INTRODUCTION: Diabetes and hyperglycemia are risk factors for critical COVID-19 outcomes; however, the impact of pre-diabetes and previously unidentified cases of diabetes remains undefined. Here, we profiled hospitalized patients with undiagnosed type 2 diabetes and pre-diabetes to evaluate its impact on adverse COVID-19 outcomes. We also explored the role of de novo and intrahospital hyperglycemia in mediating critical COVID-19 outcomes. RESEARCH DESIGN AND METHODS: Prospective cohort of 317 hospitalized COVID-19 cases from a Mexico City reference center. Type 2 diabetes was defined as previous diagnosis or treatment with diabetes medication, undiagnosed diabetes and pre-diabetes using glycosylated hemoglobin (HbA1c) American Diabetes Association (ADA) criteria and de novo or intrahospital hyperglycemia as fasting plasma glucose (FPG) ≥140 mg/dL. Logistic and Cox proportional regression models were used to model risk for COVID-19 outcomes. RESULTS: Overall, 159 cases (50.2%) had type 2 diabetes and 125 had pre-diabetes (39.4%), while 31.4% of patients with type 2 diabetes were previously undiagnosed. Among 20.0% of pre-diabetes cases and 6.1% of normal-range HbA1c had de novo hyperglycemia. FPG was the better predictor for critical COVID-19 compared with HbA1c. Undiagnosed type 2 diabetes (OR: 5.76, 95% CI 1.46 to 27.11) and pre-diabetes (OR: 4.15, 95% CI 1.29 to 16.75) conferred increased risk of severe COVID-19. De novo/intrahospital hyperglycemia predicted critical COVID-19 outcomes independent of diabetes status. CONCLUSIONS: Undiagnosed type 2 diabetes, pre-diabetes and de novo hyperglycemia are risk factors for critical COVID-19. HbA1c must be measured early to adequately assess individual risk considering the large rates of undiagnosed type 2 diabetes in Mexico.

COVID-19 pandemic: Can fasting plasma glucose and HbA1c replace the oral glucose tolerance test to screen for hyperglycaemia in pregnancy?

AIMS: To evaluate proposals considering HbA1c and fasting plasma glucose (FPG) measurement as a substitute for oral glucose tolerance test (OGTT) to diagnose hyperglycaemia in pregnancy (HIP) during COVID-19 pandemic. METHODS: Of the 7,334 women who underwent the OGTT between 22 and 30 weeks gestation, 966 had HIP (WHO diagnostic criteria, reference standard). The 467 women who had an available HbA1c were used for analysis. French-speaking Society of Diabetes (SFD) proposal to diagnose HIP during COVID-19 pandemic was retrospectively applied: HbA1c ≥5.7% (39 mmol/mol) and/or FPG level ≥5.1 mmol/l. SFD proposal sensitivity for HIP diagnosis and the occurrence of HIP-related events (preeclampsia, large for gestational age infant, shoulder dystocia or neonatal hypoglycaemia) in women with false negative (FN) and true positive (TP) HIP-diagnoses were evaluated. RESULTS: The sensitivity was 57% [95% confidence interval 52-62]. FN women had globally lower plasma glucose levels during OGTT, lower HbA1c and body mass index than those TP. The percentage of HIP-related events was similar in FN (who were cared) and TP cases, respectively 19.5 and 16.9% (p = 0.48). We observed similar results when women at high risk for HIP only were considered. CONCLUSION: The SFD proposal has a poor sensitivity to detect HIP. Furthermore, it fails to have any advantages in predicting adverse outcomes.

Independent and combined effects of hypertension and diabetes on clinical outcomes in patients with COVID-19: A retrospective cohort study of Huoshen Mountain Hospital and Guanggu Fangcang Shelter Hospital.

It is widely recognized that hypertension is one of the major risk factor for disease severity and mortality in patients with coronavirus disease 2019 (COVID-19). However, type 2 diabetes mellitus (T2DM) and hypertension are frequent comorbid conditions, complicating the assessment of hypertension's individual contribution to the risk. The aims of this study were to evaluate the contributions of hypertension alone, T2DM alone, or their combination to the risk of death, acute respiratory distress syndrome (ARDS)/respiratory failure, and severe COVID-19 infection. Additionally, we assessed risks associated with elevated blood pressure and fasting blood glucose on the same three clinical outcomes. Multivariate logistic models were used for these analyses. Among the 3400 patients, 3327(97.9%) survived and 73(2.1%) died. Compared to patients having neither hypertension nor T2DM (n = 1392), the risk of mortality was significantly higher in patients with T2DM alone (n = 226, OR 5.26 [95% CI: 2.39-11.58]) or with T2DM in combination with hypertension (n = 507, OR 3.02, [95% CI: 1.48-6.15]). Similarly, T2DM was a risk factor for development of ARDS/respiratory failure and severe infection. Hypertension alone (n = 1275) only conferred additional risk for the development of severe infection (OR 1.22 [95% CI: 1.00-1.51]). In conclusion, neither hypertension nor elevated blood pressure was independent risk factors for death or ARDS/respiratory failure but hypertension marginally increased the risk of severe COVID-19 infection. The risk associated with hypertension is accentuated through its confounding effect on T2DM.

Women with Mild Fasting Hyperglycemia in Early Pregnancy Have More Neonatal Intensive Care Admissions.

AIMS: To determine impact of mild fasting hyperglycemia in early pregnancy (fasting plasma glucose [FPG] 5.1-5.5 mmol/L) on pregnancy outcomes. METHODS: We measured FPG at 11.9 ± 1.8 weeks in 2006 women from a prospective cohort study. Women with FPG ≥5.6 mmol/L (19) received treatment and were excluded from further analyses. A total of 1838 women with FPG <5.6 mmol/L received a 75 g oral glucose tolerance test (OGTT) between 24 and 28 weeks of pregnancy. RESULTS: Of all participants, 78 (4.2%) had FPG 5.1 to 5.5 mmol/L in early pregnancy, of which 49 had a normal OGTT later in pregnancy (high fasting normal glucose tolerance [NGT] group). Compared with the NGT group with FPG <5.1 mmol/L in early pregnancy (low fasting NGT group, n = 1560), the high fasting NGT group had a higher body mass index (BMI), higher insulin resistance with more impaired insulin secretion and higher FPG and 30 minute glucose levels on the OGTT. The admission rate to neonatal intensive care unit (NICU) was significantly higher in the high fasting NGT group than in the low fasting NGT group (20.4% [10] vs 9.3% [143], P = .009), with no difference in duration (7.0 ± 8.6 vs 8.4 ± 14.3 days, P = .849) or indication for NICU admission between both groups. The admission rate to NICU remained significantly higher (odds ratio 2.47; 95% confidence interval 1.18-5.19, P = .017) after adjustment for age, BMI, and glucose levels at the OGTT. CONCLUSIONS: When provision of an OGTT is limited such as in the Covid-19 pandemic, using FPG in early pregnancy could be an easy alternative to determine who is at increased risk for adverse pregnancy outcomes.

High-density lipoprotein cholesterol as a factor affecting virus clearance in covid-19 patients.

OBJECTIVE: There were COVID-19 patients with SARS-COV-2 nucleic acid long-term positive. This article aims to understand the relevant factors that affect SARS-COV-2 clearance time. METHODS: The clinical data of 115 COVID-19 patients with SARS-COV-2 nucleic acid positive time exceeding 14 days were collected retrospectively, and the relationship between clinical characteristics, chest CT scans, blood cells, biochemical indicators, and the time of viral nucleic acid turning negative were analyzed. RESULTS: The time from symptom onsets to nucleic acid turning negative was (32.5 ± 8.7) days in this group of patients. The time of nucleic acid turning negative: no fever group was longer than fever group, diabetes group was longer than no comorbidity group, elevated levels of ALT (alanine aminotransferase), or GLU (fasting blood glucose) group, decreased levels of ALB (albumin) group or HDLC (high-density lipoprotein cholesterol) group was longer than it's normal group separately (P < 0.05). Cox multivariate regression analysis showed that ALT [odds ratio (OR): 2.164 (95% CI: 1.276-3.670), P = 0.004], GLU [OR: 2.064 (95% CI: 1.195-3.566), P = 0.009] and HDLC [OR: 0.527 (95% CI: 0.307-0.907), P = 0.021] were independent factors which affected the time of nucleic acid turning negative. CONCLUSIONS: ALT, GLU and HDLC were independent factors that influenced the time of nucleic acid turning negative. Although diabetes or hyperglycemia is a known risk factor, HDLC is the first to be identified, clinicians should be aware of dyslipidemia in covid-19 patients.

Young people with type 1 diabetes on insulin pump therapy could fast safely during COVID-19 pandemic Ramadan: A telemonitoring experience in Bangladesh.

Our aim was to report our telemedicine experience with type 1 diabetes patients using insulin pumps who fasted for Ramadan 2020 during the COVID-19 pandemic. The routine diabetes outpatient care in our Changing Diabetes in Children (CDiC) Pediatric Diabetes Center at the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders hospital was closed, as there was a lockdown from 26 March in Bangladesh. The diabetes team in our center started telemedicine care for routine follow up of patients. Nine patients who wished to fast for Ramadan contacted our diabetes team over the phone. The mean age was 19.3 ± 5.0 years, and five (55.6%) were female. Most of the patients fasted >20 days. Hyperglycemia and mild hypoglycemia were common complications during fasting. There was no episode of severe hypoglycemia or diabetic ketoacidosis, and none of the patients required admission. During the COVID-19 crisis in Bangladesh, patients with type 1 diabetes using an insulin pump could fast safely for Ramadan with the support of the telemedicine service by the diabetes team.

Admission fasting plasma glucose is an independent risk factor for 28-day mortality in patients with COVID-19.

Hyperglycemia commonly occurs in severe cases with COVID-19. In this study, we explored the associations between admission fasting plasma glucose (FPG) and 28-day mortality in COVID-19 patients. In this single centre retrospective study, 263 adult patients with COVID-19 were included. Demographic and clinical information were collected and compared between patients with and without diabetes. Cox regression analyses were used to investigate the risk factors of 28-day mortality in hospitals. Of 263 patients, 161 (61.2%) were male, 62 (25.6%) had a known history of diabetes, and 135 (51.3%) experienced elevated FPG (>7.0 mmol/L) at hospital admission. The median FPG in patients with diabetes was much higher than in patients without diabetes (12.79 vs. 6.47 mmol/L). Patients with diabetes had higher neutrophil count and D-dimer, less lymphocyte count, lower albumin level, and more fatal complications. Multivariable Cox regression analyses showed that age (per 10-year increase) (hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.13-1.74), admission FPG between 7.0 and 11.0 and ≥11.1 mmol/L (HR, 1.90; 95% CI, 1.11-3.25 and HR, 2.09; 95% CI, 1.21-3.64, respectively), chronic obstructive pulmonary disease (HR, 2.89; 95% CI, 1.31-6.39), and cardiac injury (HR, 2.14; 95% CI, 1.33-3.47) were independent predictors of 28-day mortality in COVID-19 patients. Hyperglycemia on admission predicted worse outcome in hospitalized patients with COVID-19. Intensive monitoring and optimal glycemic control may improve the prognosis of COVID-19 patients.

Fasting Blood Glucose and COVID-19 Severity: Nonlinearity Matters.

OBJECTIVE: Fasting blood glucose (FBG) could be an independent predictor for coronavirus disease 2019 (COVID-19) morbidity and mortality. However, when included as a predictor in a model, it is conventionally modeled linearly, dichotomously, or categorically. We comprehensively examined different ways of modeling FBG to assess the risk of being admitted to the intensive care unit (ICU). RESEARCH DESIGN AND METHODS: Utilizing COVID-19 data from Kuwait, we fitted conventional approaches to modeling FBG as well as a nonlinear estimation using penalized splines. RESULTS: For 417 patients, the conventional linear, dichotomous, and categorical approaches to modeling FBG missed key trends in the exposure-response relationship. A nonlinear estimation showed a steep slope until about 10 mmol/L before flattening. CONCLUSIONS: Our results argue for strict glucose management on admission. Even a small incremental increase within the normal range of FBG was associated with a substantial increase in risk of ICU admission for COVID-19 patients.

Fasting Plasma Glucose Level Independently Predicts the Mortality of Patients with Coronavirus Disease 2019 Infection: A Multicenter, Retrospective Cohort Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic, which prompts a consensus for the necessity to seek risk factors for this critical disease. Risk factors affecting mortality of the disease remain elusive. Diabetes and hyperglycemia are known to negatively affect a host's antiviral immunity. We evaluated the relationship between a history of diabetes, fasting plasma glucose (FPG) levels and mortality among severely ill patients with COVID-19. METHODS: This was a retrospective cohort study that assessed 106 adult inpatients (aged ≥18 years) from two tertiary hospitals in Daegu, South Korea. The participants were transferred to tertiary hospitals because their medical condition required immediate intensive care. The demographic and laboratory data were compared between COVID-19 patients who survived and those who did not. RESULTS: Compared with the survivor group, age, and the proportions of diabetes, chronic lung disease and FPG were significantly higher in the deceased group. In the Cox proportional hazards regression model for survival analysis, FPG level and age were identified as significant predictors of mortality (P<0.05). The threshold values for predicting high mortality were age >68 years and FPG of 168 mg/dL, respectively. Among those without diabetes, high FPG remained a significant predictor of mortality (P<0.04). CONCLUSION: High FPG levels significantly predicted mortality in COVID-19, regardless of a known history of diabetes. These results suggest intensive monitoring should be provided to COVID-19 patients who have a high FPG level.

J-shaped association between fasting blood glucose levels and COVID-19 severity in patients without diabetes.

AIMS: Coronavirus disease 2019 (COVID-19) has become a recognized worldwide pandemic. Researchers now know that mortality from COVID-19 can be reduced through early prevention measures. This retrospective, multi-centered study of 293 COVID-19 patients without diabetes explores the association between fasting blood glucose (FBG) levels and the risk of COVID-19 disease progression, with the goal of providing clinical evidence for glycemic targets in patients. METHODS: The multivariate stepwise binary logistic regression analysis was used to test the dose-response effects of FBG levels on the risk of severe and critical condition in COVID-19 patients. RESULTS: FBG levels were plotted in quintiles with set at <4.74, 4.74-5.21, 5.21-5.78, 5.78-7.05, and ≧7.05 mmol/L. The constituent ratio of severe or critical cases in each FBG quintile was 20.7%, 1.7%, 13.8%, 27.1%, and 67.2%, respectively (P < 0.0001). When the second quintile was used as the reference, the adjusted odds ratios (AORs) (95%CI) for the risk of severe/critical condition in COVID-19 was 25.33 (2.77, 231.64), 1.00 (Reference), 3.13 (0.33, 29.67), 10.59 (1.23, 91.24), 38.93 (4.36, 347.48) per FBG quintile respectively (P < 0.001). CONCLUSIONS: We provide evidence of J-shaped associations between FBG and risk of severe and critical condition in non-diabetes patients with COVID-19, with nadir at 4.74-5.78 mmol/L.

Approaches to screening for hyperglycaemia in pregnant women during and after the COVID-19 pandemic.

AIM: To evaluate the diagnostic and prognostic performance of alternative diagnostic strategies to oral glucose tolerance tests, including random plasma glucose, fasting plasma glucose and HbA1c , during the COVID-19 pandemic. METHODS: Retrospective service data (Cambridge, UK; 17 736 consecutive singleton pregnancies, 2004-2008; 826 consecutive gestational diabetes pregnancies, 2014-2019) and 361 women with ≥1 gestational diabetes risk factor (OPHELIA prospective observational study, UK) were included. Pregnancy outcomes included gestational diabetes (National Institute of Health and Clinical Excellence or International Association of Diabetes and Pregnancy Study Groups criteria), diabetes in pregnancy (WHO criteria), Caesarean section, large-for-gestational age infant, neonatal hypoglycaemia and neonatal intensive care unit admission. Receiver-operating characteristic curves and unadjusted logistic regression were used to compare random plasma glucose, fasting plasma glucose and HbA1c performance. RESULTS: Gestational diabetes diagnosis was significantly associated with random plasma glucose at 12 weeks [area under the receiver-operating characteristic curve for both criteria 0.81 (95% CI 0.79-0.83)], fasting plasma glucose [National Institute of Health and Clinical Excellence: area under the receiver-operating characteristic curve 0.75 (95% CI 0.65-0.85); International Association of Diabetes and Pregnancy Study Groups: area under the receiver-operating characteristic curve 0.92 (95% CI 0.85-0.98)] and HbA1c at 28 weeks' gestation [National Institute of Health and Clinical Excellence: 0.83 (95% CI 0.75-0.90); International Association of Diabetes and Pregnancy Study Groups: 0.84 (95% CI 0.77-0.91)]. Each measure predicts some, but not all, pregnancy outcomes studied. At 12 weeks, ~5% of women would be identified using random plasma glucose ≥8.5 mmol/l (sensitivity 42%; specificity 96%) and at 28 weeks using HbA1c ≥39 mmol/mol (sensitivity 26%; specificity 96%) or fasting plasma glucose ≥5.2-5.4 mmol/l (sensitivity 18-41%; specificity 97-98%). CONCLUSIONS: Random plasma glucose at 12 weeks, and fasting plasma glucose or HbA1c at 28 weeks identify women with hyperglycaemia at risk of suboptimal pregnancy outcomes. These opportunistic laboratory tests perform adequately for risk stratification when oral glucose tolerance testing is not available.

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.

AIMS/HYPOTHESIS: Hyperglycaemia is associated with an elevated risk of mortality in community-acquired pneumonia, stroke, acute myocardial infarction, trauma and surgery, among other conditions. In this study, we examined the relationship between fasting blood glucose (FBG) and 28-day mortality in coronavirus disease 2019 (COVID-19) patients not previously diagnosed as having diabetes. METHODS: We conducted a retrospective study involving all consecutive COVID-19 patients with a definitive 28-day outcome and FBG measurement at admission from 24 January 2020 to 10 February 2020 in two hospitals based in Wuhan, China. Demographic and clinical data, 28-day outcomes, in-hospital complications and CRB-65 scores of COVID-19 patients in the two hospitals were analysed. CRB-65 is an effective measure for assessing the severity of pneumonia and is based on four indicators, i.e. confusion, respiratory rate (>30/min), systolic blood pressure (≤90 mmHg) or diastolic blood pressure (≤60 mmHg), and age (≥65 years). RESULTS: Six hundred and five COVID-19 patients were enrolled, including 114 who died in hospital. Multivariable Cox regression analysis showed that age (HR 1.02 [95% CI 1.00, 1.04]), male sex (HR 1.75 [95% CI 1.17, 2.60]), CRB-65 score 1-2 (HR 2.68 [95% CI 1.56, 4.59]), CRB-65 score 3-4 (HR 5.25 [95% CI 2.05, 13.43]) and FBG ≥7.0 mmol/l (HR 2.30 [95% CI 1.49, 3.55]) were independent predictors for 28-day mortality. The OR for 28-day in-hospital complications in those with FBG ≥7.0 mmol/l and 6.1-6.9 mmol/l vs <6.1 mmol/l was 3.99 (95% CI 2.71, 5.88) or 2.61 (95% CI 1.64, 4.41), respectively. CONCLUSIONS/INTERPRETATION: 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 are important to all COVID-19 patients even where they have no pre-existing diabetes, as most COVID-19 patients are prone to glucose metabolic disorders. Graphical abstract.