Elevated blood glucose levels as a primary risk factor for the severity of COVID-19

SARS-CoV-2 started spreading towards the end of 2019 causing COVID-19, a disease that reached pandemic proportions among the human population within months. The reasons for the spectrum of differences in the severity of the disease across the population, and in particular why the disease affects more severely the aging population and those with specific preconditions are unclear. We developed machine learning models to mine 240,000 scientific papers openly accessible in the CORD-19 database, and constructed knowledge graphs to synthesize the extracted information and navigate the collective knowledge in an attempt to search for a potential common underlying reason for disease severity. The literature repeatedly pointed to elevated blood glucose as a key facilitator in the progression of COVID-19. Indeed, when we retraced the steps of the SARS-CoV-2 infection we found evidence linking elevated glucose to each step of the life-cycle of the virus, progression of the disease, and presentation of symptoms. Specifically, elevations of glucose provide ideal conditions for the virus to evade and weaken the first level of the immune defense system in the lungs, gain access to deep alveolar cells, bind to the ACE2 receptor and enter the pulmonary cells, accelerate replication of the virus within cells increasing cell death and inducing an pulmonary inflammatory response, which overwhelms an already weakened innate immune system to trigger an avalanche of systemic infections, inflammation and cell damage, a cytokine storm and thrombotic events. We tested the feasibility of the hypothesis by analyzing data across papers, reconstructing atomistically the virus at the surface of the pulmonary airways, and performing quantitative computational modeling of the effects of glucose levels on the infection process. We conclude that elevation in glucose levels can facilitate the progression of the disease through multiple mechanisms and can explain much of the variance in disease severity seen across the population. The study proposes diagnostic recommendations, new areas of research and potential treatments, and cautions on treatment strategies and critical care conditions that induce elevations in blood glucose levels.

Detailed analysis of ‘work as imagined’ in the use of intravenous insulin infusions in a hospital: a hierarchical task analysis

ObjectiveVariable rate intravenous insulin infusions (VRIII) is a high-risk medication that has a potential to cause significant patient harm if used in error. Complex preparation of VRIII in clinical areas and the need for frequent monitoring and adjustment increase the complexity of using VRIII. An emerging approach, called Resilient Healthcare, proposes understanding complexity of work by exploring how work is assumed to be done and compare it with everyday work. This study aimed to explore how VRIII is perceived to be used by healthcare practitioners, focusing on one aspect of Resilient Healthcare: understanding how work is assumed to be done, using a method called hierarchical task analysis (HTA).DesignA qualitative study using document analysis and focus groups.SettingA vascular surgery unit in an acute National Health Service teaching hospital in the UK.ParticipantsStakeholders/users in different professional roles involved in the process of using VRIII.ResultsThe HTA showed the complexity of using VRIII and highlighted more than 115 steps required to treat elevated blood glucose. The process of producing hospital-specific guidelines was iterative. Careful consideration was taken to coordinate the development and implementation of guidelines. Documents provided detailed clinical instructions related to the use of VRIII but practitioners selectively used them, often in deference to senior colleagues. Intentional adaptations, for example, proactively asking for a VRIII prescription occurred and were acknowledged as part of providing individualised patient care.ConclusionUsing VRIII to treat elevated blood glucose is a complex but necessary process mediated by a range of factors such as organisational influences. Adaptive strategies to mitigate errors were common and future research can build on insights from this study to develop a broader understanding of how VRIII is used and to understand how adaptations are made in relation to the use of VRIII.

Potential role of liver enzymes for predicting elevated blood glucose levels

Background This study was to explore the potential effect of different liver enzymes on elevated blood glucose with the use of a more detailed blood glucose grouping. Methods This cross-sectional study enrolled 144,135 participants who had biochemical examinations from 2014–2018. Participants were classified by sex and different blood glucose levels (< 5.0 mmol/L, 5.0-5.5 mmol/L, 5.6–6.2 mmol/L, 6.3–6.9 mmol/L, and ≥ 7.0 mmol/L). The associations between liver function indicators and occurrence of type 2 diabetes (T2DM) were analyzed through multivariate linear regression and multiple logistic regression. Results There was a significant difference among the biochemical indices between different blood glucose groups in males and females. Liver enzymes such as alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and γ-glutamyl transpeptidase (GGT) were independent risk factors for raised blood glucose, and there were gender differences in the predictive performance of each liver enzyme to elevated blood glucose levels. In men, GGT was the most appropriate to predict progressive elevation of blood glucose or T2DM risk, and ALT and ALP may only be applicable to the prediction of impaired fasting glucose (IFG). By contrast, ALT and ALP were the most appropriate enzymes for the prediction of the risk of elevated blood glucose or T2DM in women, and AST and GGT may only be appropriate for the prediction of IFG. Conclusions Liver enzymes were independent risk factors for elevated blood glucose. There were gender differences in the role of each liver enzyme for elevated blood glucose. GGT was more suitable as a predictor for dynastic elevated blood glucose in men, whereas for women, ALT and ALP were more suitable.

Using a Screening Toolkit to Determine the Prevalence of Non-Communicable Diseases in an Urban Slum of Mumbai, India: A Cross-Sectional Study

Background: Higher than national rates of non-communicable diseases have been found in some urban slums of India. This has been attributed to potentially lower levels of education and decreased access to preventative care. We sought to assess the prevalence of NCDs in a Mumbai slum compared to national averages and understand the association with social determinants of health.Methods: We used a screening toolkit called THULSI (Toolkit for Healthy Urban Life in Slums Initiative) in a community health-camp setting to screen 266 slum dwellers for obesity (BMI above 25 kg/m2), elevated blood pressure (SBP > 120 mm of Hg and DBP > 80 mm of Hg), and elevated blood glucose (RPG > 200 mg/dL). A health survey was administered to understand the demographic data and information about health-seeking behavior of the slum dwellers. The collected data was analyzed to determine the prevalence of each condition and associations with different social determinants of health such as literacy and education level, diagnosis and marital status, age, gender, place of care, employment, availability of toilet, and languages spoken. Results: Of the screened population, 72.6% had elevated blood pressure, 9.0% had elevated blood glucose, 63.2% were obese, and 12.4% were overweight. These rates were 2.81, 1.04, and 3.84 times higher than the national averages, respectively. Of the study population, 26.7% had one condition, 53.4% had two conditions, and 7.9% had all the three conditions we screened for. Male gender (OR: 3.33, 95% CI: 1.37, 8.07) and older age (35-49 years OR: 3.03, 95% CI: 1.52, 6.05, 49-63 years OR: 7.22, 95% CI: 3.06, 17.05, >= 63 years OR: 6.82, 95% CI: 2.12, 22.00) were associated with increased odds of elevated blood pressure, not being previous diagnosed (OR: 0.04, 95% CI: 0.01, 0.13) was associated with lower odds of elevated blood glucose, and older age (35-49 years OR: 2.51, 95% CI: 1.21, 5.21, 49-63 years OR: 4.95, 95% CI: 2.06, 11.92) was associated with increased odds of obesity.Conclusion: We found higher than national rates of the NCDs and high comorbidity in the screened slum population of Mumbai. This signifies the need for screening services and the importance of awareness and education in this population.

Amelioration of Olanzapine-Induced Impaired Glucose Tolerance in Mice with Methanol Extract of Steamed Brassica Oleracea (Cabbage) Leaves

Olanzapine is an antipsychotic drug and has been reported to induce impaired glucose tolerance leading to high blood glucose levels. In oral glucose tolerance tests (OGTT), methanolic extract of steamed cabbage (Brassica oleracea L. var. capitata) (MEBO) leaves have been shown to reduce elevated blood glucose levels in glucose-loaded mice. It was thus of interest to determine whether MEBO leaves can ameliorate olanzapineinduced impaired glucose tolerance in mice, which have been administered olanzapine for 28 days. Impaired glucose tolerance was measured through OGTT in mice. Olanzapine (28 days)-administered mice showed elevated blood glucose in OGTT. MEBO leaves showed significant reduction of blood glucose level in OGTT in mice (compared to vehicle or olanzapine treated mice for 28 days, Groups 2 and 3, respectively) both when administered for 28 days along with olanzapine, as well when administered 60 min prior to glucose loading in OGTT (positive control glibenclamide administered at 10 mg/kg). A single dose of MEBO (400 mg/kg) was used based on previous studies. Thus, MEBO leaves can be beneficial for improving glucose tolerance and reduce blood glucose levels in olanzapine-induced elevated blood glucose levels.

The association between acute-to-chronic glycemic ratio and outcome in acute heart failure

Introduction Elevated blood glucose level on admission worsen outcome in acute heart failure (AHF). The admission blood glucose (ABG)/ the estimated average glucose (eAG) ratio which combines both acute and chronic glucose levels is attracting attention as a newly introduced glycemic index. It may be accepted as indicating the true acute glycemic rise in critically in all patients. Purpose The aim of this study was to assess the association between acute-to-chronic glycemic ratio and outcome in AHF. Methods This study assessed consecutive patients with AHF. The ABG/ eAG ratio was determined as ABG divided by eAG. We examined the relationship between ABG/ eAG ratio and all-cause mortality and readmission for heart failure within 30 days. Results A total of 249 patients with AHF (mean age; 81 years, 50% male and 37% DM) were studied. 31 (12.4%) patients had events within 30 days [18 (7.2%) died and 13 (5.2%) readmitted for HF]. We divided into three tertiles [T1 (&lt;0.93), T2 (0.93–1.21) and T3 (&gt;1.21)] based on the ABG/ eAG ratio. There was a stepwise worsening of the 30 days outcome [1 patient (0.4%) vs 7 patients (2.8%) vs 23 patients (9.2%), p&lt;0.0001]. In multiple variable analysis, ABG/ eAG ratio was an independent predictor of the events (p=0.002). A cut-off value of the ABG/ eAG ratio &lt;1.11 had a sensitivity of 94% and specificity of 67% for the increase of events within 30 days. In full model, the ABG/ eAG ratio was independent predictor of 30 days outcome in AHF (odds ratio: 11.7; 95% confidence interval: 3.65–37.5; p&lt;0.0001). Conclusion ABG/ eAG ratio was one of the strong predictors 30 days outcome in AHF. Elevated blood glucose in the acute phase evaluated using the ABG/ eAG ratiocan enhance affect outcome and it could be a potential therapeutic target in patients of AHF. Funding Acknowledgement Type of funding source: None

Prevalence and Risk Factors of Elevated Blood Pressure and Elevated Blood Glucose among Residents of Kajiado County, Kenya: A Population-Based Cross-Sectional Survey

Kenya is experiencing a rising burden of non-communicable diseases (NCDs), yet data to inform effective interventions are limited. We investigated the prevalence of elevated blood pressure, elevated blood glucose and their determinants in a rapidly urbanizing area in Kenya. Data on socio-demographics, dietary and behavioural risk factors, anthropometric measurements, blood pressure, blood glucose, plasma lipids and urinary biomarkers were collected from 221 men and 372 women (25–64 years). Multivariable logistic regression models assessed correlates of elevated blood pressure (EBP) and elevated blood glucose (EBG). Participants’ mean age was 38.0. ± 11.1 years. The prevalence rates of pre-hypertension and hypertension were 49.0% and 31.6% in men and 43.7% and 20.1% in women, respectively, while those of pre-diabetes and diabetes were 8.4% and 8.0% in men and 11.6% and 7.4% in women, respectively. The prevalence of Body Mass Index (BMI) ≥ 25 kg/m2 was higher in women (60.2%) than in men (39.7%). However, both the risk of EBP and EBG were stronger among men than among women. The high prevalence rates of EBP, EBG and overweight/obesity coupled with low physical activity and low fruit and vegetable intake predispose this population to a higher NCD risk. Interventions to mitigate this risk considering the sex differences are urgently required.

Blood glucose testing in the community: who are the users and do they have elevated blood glucose?

ABSTRACT INTRODUCTIONOn-the-spot blood glucose testing is a health service performed in public spaces to raise diabetes awareness and screen for elevated blood glucose levels. AIMTo describe the users of this service and the frequency of detecting elevated blood glucose. METHODSData collected at point-of-testing on a standardised form over 20 months in two regions of New Zealand were audited. Descriptive and simple inferential statistics report on population demographics and presence of elevated blood glucose (mmol/L). RESULTSData from 2156 individuals were audited. Most (1680, 78%) were female, the mean age was 52 years (standard deviation 18 years) and all major ethnic groups and socioeconomic quintiles were represented. For 53% of responders, this was their first blood glucose test. In total, 153 (7.1%) cases with elevated blood glucose were identified, including 94 who did not report a previous pre-diabetes or diabetes diagnosis. Blood glucose was not correlated with socioeconomic status (r=0.04; P=0.07), but weakly correlated with age (r=0.19; P&lt;0.001). Blood glucose values did not appear to differ between ethnicities (P=0.052). Men had a higher mean value than women (P=0.003). People with elevated blood glucose access their general practitioner more often than people with normal blood glucose, irrespective of a diabetes diagnosis (P=0.002). DISCUSSIONOn-the-spot blood glucose testing is a health service accessed by a wide range of people, although more commonly by women than men. Future interventions targeting men may better engage them in health screening. Alongside awareness raising, on-the-spot community testing identified previously unknown elevated blood glucose levels at a rate of 1-in-22, and may lead to the earlier identification and treatment of prediabetes or diabetes.