Mild Hyperglycaemia in Hospitalised Children with Moderate COVID-19 Infection.

Background and Objectives: COVID-19 infection may influence many physiological processes, including glucose metabolism. Acute hyperglycaemia has been related to a worse prognosis in patients with severe COVID-19 infection. The aim of our study was to find out if moderate COVID-19 infection is associated with hyperglycaemia. Materials and Methods: A total of 235 children were enrolled in the study between October 2021 and October 2022, 112 with confirmed COVID-19 infection and 123 with other RNA viral infection. In all patients, types of symptoms, glycaemia at the time of admission, and basic anthropometric and biochemical parameters were recorded. Results: Average glycaemia was significantly higher in COVID-19 patients compared to other viral infections (5.7 ± 1.12 vs. 5.31 ± 1.4 mmol/L, p = 0.011). This difference was more obvious in subgroups with gastrointestinal manifestations (5.6 ± 1.11 vs. 4.81 ± 1.38 mmol/L, p = 0.0006) and with fever (5.76±1.22 vs. 5.11±1.37 mmol/L, p = 0.002), while no significant difference was found in subgroups with mainly respiratory symptoms. The risk of hyperglycaemia (>5.6 mmol/L) was higher in COVID-19 patients compared to other viral infections (OR = 1.86, 95%CI = 1.10-3.14, p = 0.02). The risk of hyperglycaemia was significantly higher in COVID-19 compared to other viral infections in the subgroups of patients with fever (OR = 3.59, 95% CI 1.755-7.345, p = 0.0005) and with gastrointestinal manifestations (OR = 2.48, 95% CI 1.058-5.791, p = 0.036). Conclusion: According to our results, mild hyperglycaemia was significantly more common in children with moderate COVID-19 infection compared to other RNA virus respiratory and gastrointestinal infections, especially when accompanied by fever or gastrointestinal symptoms.

Increased risk of new-onset diabetes in patients with COVID-19: a systematic review and meta-analysis.

Background: There is growing evidence that patients with COVID-19 are at increased risk of new-onset diabetes. The limited preliminary studies do not provide strong evidence. To assess the association of the SARS-CoV-2 virus with new-onset diabetes and to characterize the population. Methods: Search PubMed, Embase, Cochrane Library, and Web of Science electronic databases for a limited period from December 2019 to July 2022. Two independent reviewers conducted a thorough review of eligible articles and extracted relevant information. Pooled proportions, risk ratios (RR), and 95% confidence intervals (95% CI) indicated the incidence and risk ratios of events. Results: The incidence of new-onset diabetes and hyperglycemia in patients with COVID-19 was 5% (P < 0.001) (3 and 30% for new-onset diabetes and hyperglycemia, respectively), with age, ethnicity, time of diagnosis, and study type all having an impact on the incidence (P < 0.05). New-onset diabetes and hyperglycemia were 1.75 times higher in COVID-19 patients than in non-COVID-19 patients. In new-onset diabetes and hyperglycemia population, the percentage of men is 60% (40% for women), with a mortality rate of 17%. The proportion of new-onset diabetes and hyperglycemia after infection with COVID-19 was 25% in men and 14% in women. Conclusions: The incidence and relative risk of new-onset diabetes and hyperglycemia are elevated after COVID-19 infection, especially in the early COVID-19 and male populations. Systemic review registration: PROSPERO registration no.: CRD42022382989 https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=382989.

COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis.

Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. Postmortem liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from postmortem liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients.

Dichotomising the risk of hyperglycaemia into diabetes and prediabetes may render a disservice to patient care.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, accounting for one-third of global mortality. Prediabetes increases the risk of CVDs as well as several other conditions, yet people with prediabetes may not seek intervention, thinking that they do not have diabetes, as the risk of progression may have not been emphasised by the healthcare professional. Accumulating evidence indicates that hyperglycaemia represents a continuum of CVD risk and dichotomising the risk into type 2 diabetes and prediabetes may deter early clinical intervention. It is proffered that the term 'prediabetes' is a misnomer that may disguise a serious condition, fostering complacency and undermining its prognostic significance.

Glucose variability is a marker for COVID-19 severity and mortality.

Objective: We aimed to investigate the association between glucose coefficient of variation (CV) and mortality and disease severity in hospitalized patients with coronavirus disease-19 (COVID-19). Subjects and Methods: Retrospective cohort study in a tertiary center of patients with COVID-19 admitted to designated departments between March 11th, 2020, and November 2nd, 2020. We divided patients based on quartiles of glucose CV after stratification to those with and without diabetes mellitus (DM). Main outcomes were length of stay and in-hospital mortality. Results: The cohort included 565 patients with a mean age of 67.71 ± 15.45 years, and 62.3% were male. Of the entire cohort, 44.4% had DM. The median glucose CV was 32.8% and 20.5% in patients with and without DM, respectively. In patients with DM, higher glucose CV was associated with a longer hospitalization in the unadjusted model (OR = 2.7, 95% CI [1.3,5.6] for Q4), and when adjusted for age, sex, comorbidities, and laboratory markers, this association was no longer statistically significant (OR = 1.3, 95% CI [0.4,4.5] for Q4). In patients with and without DM, higher glucose CV was associated with higher rates of in-hospital mortality in the unadjusted model, but adjustment for comorbidities and laboratory markers eliminated the association (OR = 0.5, 95% CI [0.1,3.4] for Q4 in patients with DM). Conclusion: Higher glucose CV was associated with increased in-hospital mortality and length of stay, but this association disappeared when the adjustment included laboratory result data. Glucose CV can serve as a simple and cheap marker for mortality and severity of disease in patients with COVID-19.

Malnutrition management of hospitalized patients with diabetes/hyperglycemia and COVID-19 infection.

Diabetes mellitus and/or hyperglycemia are highly prevalent medical conditions in patients hospitalized for coronavirus disease 2019 (COVID-19) and are associated with adverse outcomes. In addition, COVID-19 itself can provoke fluctuating and high glucose levels that can be difficult to manage upon hospitalization. Hospitalized patients with COVID-19 are at high risk of malnutrition due to an increase in nutritional requirements and a severe acute inflammatory response. The management of patients with diabetes/hyperglycemia and COVID-19 is challenging and requires a specific nutritional approach, the purpose of which is to fulfill the nutritional requirements while maintaining an optimal glycemic control. In this study, an expert group of nutritional endocrinologists carried out a qualitative literature review and provided recommendations based on evidence and guidelines, when available, or on their own experience. The optimal care based on these recommendations was compared with the routine bedside care as reported by a panel of physicians (mainly, endocrinologists, geriatricians, and internists) treating patients with diabetes/hyperglycemia and COVID-19 in their daily practice. Early screening and diagnosis, a diabetes-specific therapeutic approach, and a close malnutrition monitoring are essential to improve the clinical outcomes of these patients. In conclusion, the proposed recommendations are intended to provide a useful guide on the clinical management of malnutrition in patients with COVID-19 and diabetes/hyperglycemia, in order to improve their outcomes and accelerate their recovery. The comparison of the recommended optimal care with routine clinical practice could aid to identify gaps in knowledge, implementation difficulties, and areas for improvement in the management of malnutrition in this population.

Adult-Onset Type 1 Diabetes Development Following COVID-19 mRNA Vaccination.

During the coronavirus disease 2019 (COVID-19) pandemic, COVID-19 vaccination-induced hyperglycemia and related complications have been reported. However, there have been few reports of type 1 diabetes triggered by COVID-19 vaccines in subjects without diabetes. Here, we report the case of a 56-year-old female patient who developed hyperglycemia after the second dose of COVID-19 mRNA-based vaccination without a prior history of diabetes. She visited our hospital with uncontrolled hyperglycemia despite administration of oral hyperglycemic agents. Her initial glycated hemoglobin level was high (11.0%), and fasting serum C-peptide level was normal. The fasting serum C-peptide level decreased to 0.269 ng/mL 5 days after admission, and the anti-glutamic acid decarboxylase antibody was positive. The patient was discharged in stable condition with insulin treatment. To our knowledge, this is the first case of the development of type 1 diabetes without diabetic ketoacidosis after mRNA-based COVID-19 vaccination, and is the oldest case of type 1 diabetes development under such circumstances.

Post-COVID syndrome, inflammation, and diabetes.

The raging COVID-19 pandemic is in its third year of global impact. The SARS CoV 2 virus has a high rate of spread, protean manifestations, and a high morbidity and mortality in individuals with predisposing risk factors. The pathophysiologic mechanisms involve a heightened systemic inflammatory state, cardiometabolic derangements, and varying degrees of glucose intolerance. The latter can be evident as significant hyperglycemia leading to new-onset diabetes or worsening of preexisting disease. Unfortunately, the clinical course beyond the acute phase of the illness may persist in the form of a variety of symptoms that together form the so-called "Long COVID" or "Post-COVID Syndrome". It is thought that a chronic, low-grade inflammatory and immunologic state persists during this phase, which may last for weeks or months. Although numerous insights have been gained into COVID-related hyperglycemia and diabetes, its prediction, course, and management remain to be fully elucidated.

Association of hyperglycaemia at-admission & diabetes mellitus with 28 day mortality in patients admitted with moderate-severe SARS-CoV-2 infection: A retrospective study.

Background & objectives: The association between hyperglycaemia at admission, diabetes mellitus (DM) status and mortality in hospitalized SARS-CoV-2 infected patients is not clear. The purpose of this study was to determine the relationship between DM, at-admission hyperglycaemia and 28 day mortality in patients admitted with moderate-severe SARS-CoV-2 infection requiring intensive care. Methods: All consecutive moderate-to-severe patients with SARS-CoV-2 infection admitted to the intensive care units (ICUs) over six months were enrolled in this single-centre, retrospective study. The predicators for 28 day mortality were analysed from the independent variables including DM status and hyperglycaemia at-admission. Results: Four hundred and fifty two patients with SARS-CoV-2 were admitted to the ICU, with a mean age of 58.5±13.4 yr, 78.5 per cent being male, HbA1c of 7.2 per cent (6.3-8.8) and 63.7 per cent having DM. Overall, 28 day mortality was 48.9 per cent. In univariate analysis, mortality in diabetes patients was comparable with non-diabetes (47.9 vs. 50.6%, P=0.58), while it was significantly higher in hyperglycaemic group (60.4 vs. 35.8%, P<0.001). In multivariate Cox regression analysis, after adjusting for age, sex and comorbidities, hyperglycaemia at-admission was an independent risk factor of mortality [hazard ratio (HR) 1.45, 95% confidence interval (CI) (1.06-1.99), P<0.05]. Interpretation & conclusions: This study showed that the presence of hyperglycaemia at-admission in critically ill SARS-CoV-2 patients was an independent predictor of 28 day mortality. However, the findings may be susceptible to unmeasured confounding, and more research from prospective studies is required.

Hyperglycemia and steroid use increase the risk of rhino-orbito-cerebral mucormycosis regardless of COVID-19 hospitalization: Case-control study, India.

BACKGROUND: In the ongoing COVID-19 pandemic, an increased incidence of ROCM was noted in India among those infected with COVID. We determined risk factors for rhino-orbito-cerebral mucormycosis (ROCM) post Coronavirus disease 2019 (COVID-19) among those never and ever hospitalized for COVID-19 separately through a multicentric, hospital-based, unmatched case-control study across India. METHODS: We defined cases and controls as those with and without post-COVID ROCM, respectively. We compared their socio-demographics, co-morbidities, steroid use, glycaemic status, and practices. We calculated crude and adjusted odds ratio (AOR) with 95% confidence intervals (CI) through logistic regression. The covariates with a p-value for crude OR of less than 0·20 were considered for the regression model. RESULTS: Among hospitalised, we recruited 267 cases and 256 controls and 116 cases and 231 controls among never hospitalised. Risk factors (AOR; 95% CI) for post-COVID ROCM among the hospitalised were age 45-59 years (2·1; 1·4 to 3·1), having diabetes mellitus (4·9; 3·4 to 7·1), elevated plasma glucose (6·4; 2·4 to 17·2), steroid use (3·2; 2 to 5·2) and frequent nasal washing (4·8; 1·4 to 17). Among those never hospitalised, age ≥ 60 years (6·6; 3·3 to 13·3), having diabetes mellitus (6·7; 3·8 to 11·6), elevated plasma glucose (13·7; 2·2 to 84), steroid use (9·8; 5·8 to 16·6), and cloth facemask use (2·6; 1·5 to 4·5) were associated with increased risk of post-COVID ROCM. CONCLUSIONS: Hyperglycemia, irrespective of having diabetes mellitus and steroid use, was associated with an increased risk of ROCM independent of COVID-19 hospitalisation. Rational steroid usage and glucose monitoring may reduce the risk of post-COVID.

Impact of glycemia and insulin treatment in fatal outcome of severe fever with thrombocytopenia syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high fatality rate. How the glucose level might affect the clinical outcome remains obscure. METHODS: A multicenter study was performed in 2 hospitals from 2011 to 2021. Patients with SFTS and acute hyperglycemia (admission fasting plasma glucose [FPG] ≥7 mmol/L), postadmission hyperglycemia (admission FPG <7 mmol/L but FPG ≥7 mmol/L after admission), and euglycemia (FPG <7 mmol/L throughout hospitalization) were compared for their clinical progress and outcomes. RESULTS: A total of 3225 patients were included in this study, 37.9% of whom developed acute hyperglycemia and 7.6% postadmission hyperglycemia. The presence of acute hyperglycemia, with or without known diabetes, was associated with increased risk of death (odds ratio [OR]: 1.63; 95% confidence interval [CI]: 1.29-2.05) compared with euglycemia. This effect, however, was only determined in female patients (OR: 2.15; 95% CI: 1.54-2.93). Insulin treatment of patients with SFTS and acute hyperglycemia without previous diabetes was associated with significantly increased mortality (OR: 1.58; 95% CI: 1.16-2.16). CONCLUSION: Acute hyperglycemia can act as a strong predictor of SFTS-related death in female patients. Insulin treatment of hyperglycemia in patients with SFTS without pre-existing diabetes has adverse effects.

In-Hospital Hyperglycemia Is Associated With Worse Outcomes in Patients Admitted With COVID-19.

OBJECTIVE: Diabetes and the outpatient diabetes treatment regimen have been identified as risk factors for poor outcomes in patients with sepsis. However, little is known about the effect of tight inpatient glycemic control in the setting of coronavirus disease 2019 (COVID-19). Therefore, we examined the effect of hyperglycemia in patients with diabetes hospitalized because of COVID-19. RESEARCH DESIGN AND METHODS: We analyzed data from 1,938 COVID-19 patients with diabetes hospitalized for COVID-19 from March to May 2020 at a large academic medical center in New York City. Patients were divided into two groups based on their inpatient glycemic values, and a Cox proportional hazards regression model was used to assess the independent association of inpatient glucose levels with mortality (primary outcome) and the risk of requiring mechanical ventilation (MV) (secondary outcome). RESULTS: In our analysis, 32% of the patients were normoglycemic and 68% hyperglycemic. Moreover, 31% of the study subjects died during hospitalization, and 14% required MV, with inpatient hyperglycemia being significantly associated with both mortality and the requirement for MV. Additionally, in the Cox regression analysis, after adjustment for potential confounders, including age, sex, race, BMI, HbA1c, comorbidities, inflammatory markers, and corticosteroid therapy, patients with uncontrolled hyperglycemia had a higher risk of dying (hazard ratio [HR] 1.54, 95% CI 1.00-2.36, P = 0.049) and of requiring MV (HR 4.41, 95% CI 1.52-2.81, P = 0.006) than those with normoglycemia. CONCLUSIONS: A tight control of inpatient hyperglycemia may be an effective method for improving outcomes in patients with diabetes hospitalized for COVID-19.

In-hospital hyperglycemia but not diabetes mellitus alone is associated with increased in-hospital mortality in community-acquired pneumonia (CAP): a systematic review and meta-analysis of observational studies prior to COVID-19.

The objective of this review was to quantify the association between diabetes, hyperglycemia, and outcomes in patients hospitalized for community-acquired pneumonia (CAP) prior to the COVID-19 pandemic by conducting a systematic review and meta-analysis. Two investigators independently screened records identified in the PubMed (MEDLINE), EMBASE, CINAHL, and Web of Science databases. Cohort and case-control studies quantitatively evaluating associations between diabetes and in-hospital hyperglycemia with outcomes in adults admitted to hospital with CAP were included. Quality was assessed using the Newcastle-Ottawa Quality Assessment Scale, effect size using random-effects models, and heterogeneity using I2 statistics. Thirty-eight studies met the inclusion criteria. Hyperglycemia was associated with in-hospital mortality (adjusted OR 1.28, 95% CI 1.09 to 1.50) and intensive care unit (ICU) admission (crude OR 1.82, 95% CI 1.17 to 2.84). There was no association between diabetes status and in-hospital mortality (adjusted OR 1.04, 95% CI 0.72 to 1.51), 30-day mortality (adjusted OR 1.13, 95% CI 0.77 to 1.67), or ICU admission (crude OR 1.91, 95% CI 0.74 to 4.95). Diabetes was associated with increased mortality in all studies reporting >90-day postdischarge mortality and with longer length of stay only for studies reporting crude (OR 1.50, 95% CI 1.11 to 2.01) results. In adults hospitalized with CAP, in-hospital hyperglycemia but not diabetes alone is associated with increased in-hospital mortality and ICU admission. Diabetes status is associated with increased >90-day postdischarge mortality. Implications for management are that in-hospital hyperglycemia carries a greater risk for in-hospital morbidity and mortality than diabetes alone in patients admitted with non-COVID-19 CAP. Evaluation of strategies enabling timely and effective management of in-hospital hyperglycemia in CAP is warranted.

Gene Networks of Hyperglycemia, Diabetic Complications, and Human Proteins Targeted by SARS-CoV-2: What Is the Molecular Basis for Comorbidity?

People with diabetes are more likely to have severe COVID-19 compared to the general population. Moreover, diabetes and COVID-19 demonstrate a certain parallelism in the mechanisms and organ damage. In this work, we applied bioinformatics analysis of associative molecular networks to identify key molecules and pathophysiological processes that determine SARS-CoV-2-induced disorders in patients with diabetes. Using text-mining-based approaches and ANDSystem as a bioinformatics tool, we reconstructed and matched networks related to hyperglycemia, diabetic complications, insulin resistance, and beta cell dysfunction with networks of SARS-CoV-2-targeted proteins. The latter included SARS-CoV-2 entry receptors (ACE2 and DPP4), SARS-CoV-2 entry associated proteases (TMPRSS2, CTSB, and CTSL), and 332 human intracellular proteins interacting with SARS-CoV-2. A number of genes/proteins targeted by SARS-CoV-2 (ACE2, BRD2, COMT, CTSB, CTSL, DNMT1, DPP4, ERP44, F2RL1, GDF15, GPX1, HDAC2, HMOX1, HYOU1, IDE, LOX, NUTF2, PCNT, PLAT, RAB10, RHOA, SCARB1, and SELENOS) were found in the networks of vascular diabetic complications and insulin resistance. According to the Gene Ontology enrichment analysis, the defined molecules are involved in the response to hypoxia, reactive oxygen species metabolism, immune and inflammatory response, regulation of angiogenesis, platelet degranulation, and other processes. The results expand the understanding of the molecular basis of diabetes and COVID-19 comorbidity.

Impact of Hyperglycemia on Cardiovascular Events and Clinical Outcomes in Patients Hospitalized With COVID-19 Pneumonia.

OBJECTIVE: To study cardiovascular events and clinical outcomes in patients with elevated glycated hemoglobin (HbA1c) levels and/or admission hyperglycemia and those with type 2 diabetes hospitalized with SARS-CoV-2 pneumonia. METHODS: This was a multicenter retrospective study of 1645 patients hospitalized with SARS-CoV-2 pneumonia. Diagnosis of SARS-CoV-2 pneumonia required a positive reverse transcription-polymerase chain reaction result for SARS-CoV-2, presence of new or worsening pulmonary infiltrates on computed tomography scan or chest x-ray, and at least one of following: (1) new or increased cough, (2) temperature of >37.8 °C, or (3) dyspnea. Outcomes included in-hospital cardiovascular events, intensive care unit admission, and mortality. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for association of elevated HbA1c levels and/or admission hyperglycemia and type 2 diabetes for individual outcomes. RESULTS: Among 1645 adults hospitalized with SARS-CoV-2 pneumonia, 18 with type 1 diabetes were excluded from the analysis. Of 1627 adults, 634 (39%) had known diagnosis of type 2 diabetes, and among 993 patients with no diabetes, 107 (10.8%) patients were identified with elevated HbA1c levels and/or admission hyperglycemia. Patients with elevated HbA1c levels and/or admission hyperglycemia had increased odds of developing acute in-hospital cardiovascular events (OR, 1.73; 95% CI, 1.07-2.80), intensive care unit admissions (OR, 1.61; 95% CI, 1.10-2.34), and mortality (OR, 1.77; 95% CI, 1.02-3.07) compared to patients with type 2 diabetes and no diabetes. CONCLUSION: Patients with elevated HbA1c levels and/or admission hyperglycemia hospitalized with SARS-CoV-2 pneumonia have increased risk of developing acute in-hospital cardiovascular complications and overall poor clinical outcomes compared with patients with type 2 diabetes and no diabetes.

J-shaped associations and joint effects of fasting glucose with inflammation and cytokines on COVID-19 mortality.

OBJECTIVES: The aim of this study was to investigate the dose-response relationship of admission fasting glucose (FBG) with corona virus disease 2019 (COVID-19) mortality and to further evaluate potential interactions of hyperglycemia with inflammation and hypercoagulation on COVID-19 outcomes. METHODS: This retrospective study included 2555 consecutively hospitalized patients with COVID-19, until death or discharge, in Wuhan Union hospital between January 1 and April 9, 2020. The poor early outcomes included admission to intensive care unit, intubation, and deaths occurring within 28 days. We used splines nested in Cox regression to visualize dose-response associations and generalized additive models to fit three-dimensional (3D) trend plots for joint effects of FBG with markers of inflammation and coagulation. RESULTS: J-shaped associations existed between hospitalized mortality or poor early outcomes and FBG with a nadir at 5 mmol/L, which were more evident in women. 3D plots demonstrated significant joint effect trends, and patients with hyperglycemia and high neutrophil-lymphocyte ratio, C-reactive protein, lactate dehydrogenase, procalcitonin, d-dimer, and interleukin-6 had 7.4-25.3-fold risks; the proportions of joint associations attributed to additive interactions reached 30% to 54%. CONCLUSIONS: FBG was associated with hospitalized mortality and poor early outcomes in a J-shaped manner, and a combination of hyperglycemia, inflammation, hypercoagulation, and cytokines conferred a dramatically higher risk.

Effect of linagliptin plus insulin in comparison to insulin alone on metabolic control and prognosis in hospitalized patients with SARS-CoV-2 infection.

To evaluate the effect of the combination of linagliptin and insulin on metabolic control and prognosis in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hyperglycemia. A parallel double-blind randomized clinical trial including hospitalized patients with SARS-CoV-2 infection and hyperglycemia, randomized to receive 5 mg linagliptin + insulin (LI group) or insulin alone (I group) was performed. The main outcomes were the need for assisted mechanical ventilation and glucose levels during hospitalization. Subjects were screened for eligibility at hospital admission if they were not with assisted mechanical ventilation and presented hyperglycemia, and a total of 73 patients with SARS-CoV-2 infection and hyperglycemia were randomized to the LI group (n = 35) or I group (n = 38). The average hospital stay was 12 ± 1 vs 10 ± 1 days for the I and LI groups, respectively (p = 0.343). There were no baseline clinical differences between the study groups, but the percentage of males was higher in the LI group (26 vs 18, p = 0.030). The improvements in fasting and postprandial glucose levels were better in the LI group that the I group (122 ± 7 vs 149 ± 10, p = 0.033; and 137 ± 7 vs 173 ± 12, p = 0.017, respectively), and insulin requirements tended to be lower in the LI group than the I group. Three patients in the LI group and 12 in the I group required assisted mechanical ventilation (HR 0.258, CI 95% 0.092-0.719, p = 0.009); 2 patients in the LI group and 6 in the I group died after a follow-up of 30 days (p = 0.139). No major side effects were observed. The combination of linagliptin and insulin in hospitalized patients with SARS-CoV-2 infection and hyperglycemia reduced the relative risk of assisted mechanical ventilation by 74% and improved better pre and postprandial glucose levels with lower insulin requirements, and no higher risk of hypoglycemia.This study is registered at clinicaltrials.gov, number NCT04542213 on 09/03/2020.

Hyperglycemia and Loss of Redox Homeostasis in COVID-19 Patients.

The infection with SARS-CoV-2 impairs the glucose-insulin axis and this contributes to oxidative (OS) and nitrosative (NSS) stress. Here, we evaluated changes in glucose metabolism that could promote the loss of redox homeostasis in COVID-19 patients. This was comparative cohort and analytical study that compared COVID-19 patients and healthy subjects. The study population consisted of 61 COVID-19 patients with and without comorbidities and 25 healthy subjects (HS). In all subjects the plasma glucose, insulin, 8-isoprostane, Vitamin D, H2S and 3-nitrotyrosine were determined by ELISA. The nitrites (NO2-), lipid-peroxidation (LPO), total-antioxidant-capacity (TAC), thiols, glutathione (GSH) and selenium (Se) were determined by spectrophotometry. The glucose, insulin and HOMA-IR (p < 0.001), 8-isoprostanes, 3-nitrotyrosine (p < 0.001) and LPO were increased (p = 0.02) while Vitamin D (p = 0.01), H2S, thiols, TAC, GSH and Se (p < 0.001) decreased in COVID-19 patients in comparison to HS. The SARS-CoV-2 infection resulted in alterations in the glucose-insulin axis that led to hyperglycemia, hyperinsulinemia and IR in patients with and without comorbidities. These alterations increase OS and NSS reflected in increases or decreases in some oxidative markers in plasma with major impact or fatal consequences in patients that course with metabolic syndrome. Moreover, subjects without comorbidities could have long-term alterations in the redox homeostasis after infection.

Impact of newly diagnosed diabetes on coronavirus disease 2019 severity and hyperglycemia.

AIMS/INTRODUCTION: Diabetes is associated with poor clinical outcomes of coronavirus disease 2019 (COVID-19). However, the impact of newly diagnosed diabetes on prognosis has not been clarified. The objective of this study was to show the features and outcome of COVID-19 patients with newly diagnosed diabetes in Japan. MATERIALS AND METHODS: We retrospectively analyzed 62 patients with diabetes hospitalized for COVID-19 between 1 April and 18 August 2021 at the National Center for Global Health and Medicine in Tokyo, Japan. We evaluated the worst severity of COVID-19 and plasma blood glucose levels in patients with newly diagnosed diabetes or pre-existing diabetes. RESULTS: This study included 62 confirmed COVID-19 patients with diabetes, including 19 (30.6%) patients with newly diagnosed diabetes and 43 (69.4%) patients with pre-existing diabetes. Patients with newly diagnosed diabetes significantly progressed to a critical condition more frequently during hospitalization than patients with pre-existing diabetes (52.6% vs 20.9%, P = 0.018). In addition, patients with newly diagnosed diabetes had significantly higher average plasma blood glucose levels for the first 3 days after admission than those with pre-existing diabetes. CONCLUSIONS: Our study suggests that the proportion of COVID-19 patients who are newly diagnosed with diabetes is high, and they have an increased risk of developing severe disease than those with pre-existing diabetes. It might be advisable that at the point of COVID-19 diagnosis, blood glucose and glycated hemoglobin levels be assessed in all patients.

The association of admission random blood glucose concentration and body-mass index with mortality in COVID-19 patients.

OBJECTIVE: This study aimed to investigate the association between hyperglycemia and body mass index (BMI), along with other associated comorbidities in hospitalized COVID-19 patients among the Indonesian population. PATIENTS AND METHODS: This was a retrospective study conducted at Hasan Sadikin Hospital, Bandung between March 1, 2020, and August 30, 2020. Data were analyzed using the chi-square test for categorical data and unpaired t-test and Mann-Whitney alternative test for numerical data using SPSS version 24.0 (IBM SPSS Statistics for Windows, Version 24.0. IBM, Armonk, NY, USA) and GraphPad Prism version 7.0 for Windows. RESULTS: A total of 142 hospitalized COVID-19 patients were documented between March and August 2020 at the Hasan Sadikin Hospital. Among the 142 patients, 116 (81.7%) survived, while 26 (18.3%) died. Sex, age, BMI, number of comorbidities, heart rate, respiratory rate, peripheral oxygen saturation, platelet count, random blood glucose (RBG), and length of stay (LOS) were significantly associated with mortality. Multivariate analyses demonstrated that admission RBG levels > 140 mg/dl were independently associated with an increased risk of mortality in COVID-19 patients (OR 4.3, 95% CI 1.1-17.5, p = 0.043), while BMI > 25 kg/m2 was significantly associated with reduced mortality (OR, 0.22; 95% CI 0.05-0.88, p = 0.033). CONCLUSIONS: Admission hyperglycemia, indicated by an increase in RBG levels >140 mg/dL, is independently associated with an increased risk of mortality in hospitalized COVID-19 patients, while obesity (BMI >25 kg/m2) might have protective properties against the risk of death.