Biochemical mechanisms in the severe prognosis of pa- tients with diabetes mellitus infected by SARS-CoV-2 virus: literature review

Diabetes mellitus (DM) is a metabolic disease characterised mainly by signs and symptoms derived from increased serum glucose or hyperglycemia. The coronavirus disease 2019 (COVID-19) pandemic affected the entire world with reports of severe prognosis in diabetic patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and high hospital admissions in the intensive care unit (ICU) compared to non-diabetic patients. The objective of the bibliographic review was to evaluate and describe some of the biochemical mechanisms that lead to severe prognosis in patients with DM infected by the SARS-CoV-2 virus through a systematic search for information in different databases. The results showed that the high ICU admission with a severe prognosis of diabetic patients infected by the virus was due to excessive inflammation that causes acute respiratory distress syndrome, cytokine storm, severe pneu-monia, impaired immunity, and hyperglycemia. The virus enters the cell mainly through the endocytic and non-endosomal pathway;the central cellular receptors involved in the mechanisms are insulin receptors (IR), glucose transporter type 2 (GLUT-2), dipeptidyl peptidase-4 (DPP4), glucose transporter type 4 (GLUT-4), glucose converting enzyme angiotensin 2 (ACE2), and the serine transmembrane protease co-receptor 2 (TMPRSS2) essential for viral propagation. The increased susceptibility to devel-oping COVID-19 in diabetic patients is due to the overexpression of ACE2, and serious complications are increased at the microvascular and macrovascular levels, such as nephropathies, neuropathies, and cardiovascular diseases.

Ketoacidosis as a primary manifestation of COVID-19.

INTRODUCTION: Diabetic ketoacidosis is the most important metabolic emergency in children. Children mimic many syndromes with a combination of nonspecific symptoms during the COVID-19 pandemic. Many syndromes are triggered by changes in children's body conditions. Reporting specific cases can improve the diagnosis process. The present study reports an 18-month-old paediatric case of COVID-19 who presented ketoacidosis (DKA) symptoms. CASE PRESENTATION: The case is an 18-month-old child with fever and diarrhoea from 3 days before, who did not respond to outpatient treatment. On the day of the visit, he suffered from deep and abdominal breathing and decreased level of consciousness and sugar levels at admission of 420 mg/dl. He was then admitted with the initial diagnosis of DKA and had a positive PCR test result for COVID-19. CONCLUSIONS: Considering the non-specific symptoms of COVID-19, general practitioners and paediatricians are recommended that special attention be paid to these symptoms, especially those that are similar to life-threatening syndromes. They also should not easily ignore these symptoms and follow up patients and their recovery status and, if patients do not recover, consider the risk of COVID-19 given the current COVID-19 pandemic.

Does COVID-19 Infection Increase the Risk of Diabetes? Current Evidence.

PURPOSE OF REVIEW: Multiple studies report an increased incidence of diabetes following SARS-CoV-2 infection. Given the potential increased global burden of diabetes, understanding the effect of SARS-CoV-2 in the epidemiology of diabetes is important. Our aim was to review the evidence pertaining to the risk of incident diabetes after COVID-19 infection. RECENT FINDINGS: Incident diabetes risk increased by approximately 60% compared to patients without SARS-CoV-2 infection. Risk also increased compared to non-COVID-19 respiratory infections, suggesting SARS-CoV-2-mediated mechanisms rather than general morbidity after respiratory illness. Evidence is mixed regarding the association between SARS-CoV-2 infection and T1D. SARS-CoV-2 infection is associated with an elevated risk of T2D, but it is unclear whether the incident diabetes is persistent over time or differs in severity over time. SARS-CoV-2 infection is associated with an increased risk of incident diabetes. Future studies should evaluate vaccination, viral variant, and patient- and treatment-related factors that influence risk.

Impact of coronavirus disease 2019 in seasonal variation of hemoglobin A1c in adults with type 1 diabetes and the effect of the mode of treatment: a single-center retrospective study for 2019 and 2021 and analysis by the mode of treatment.

The study was aimed to investigate the seasonal variation of hemoglobin A1c (HbA1c) in adults with type 1 diabetes (T1D) and the impact of coronavirus disease 2019 (COVID-19) by comparing 2019 and 2021 data and differences in treatment modes. This was a single-center retrospective observational study including 52 adult patients with T1D who regularly visited hospital in 2019 and 2021. Twenty-five patients used multiple daily injections (MDI)/self-measurement of blood glucose (SMBG), 16 used MDI/intermittently scanned continuous glucose monitoring (isCGM), 9 used sensor-augmented pump (SAP), and 2 used continuous subcutaneous insulin infusion (CSII)/isCGM. The mean HbA1c level was calculated for each month. The correlation between monthly means of temperature and HbA1c was investigated. Similar analyses were performed for the MDI/SMBG, MDI/isCGM, and SAP + CSII/isCGM groups. HbA1c levels in 2019 decreased in summer and increased in winter and showed a significant negative correlation with temperature (r = -0.652, p = 0.022). However, HbA1c in 2021 showed no seasonal variation and no correlation with temperature (r = -0.134, p = 0.678) and tended to decline after the three emergency declarations. HbA1c in the MDI/SMBG group showed the same trend as the whole group in 2019 and 2021. However, the effect of seasonal variation in HbA1c was lower in the MDI/isCGM group and the lowest in the SAP + CSII/isCGM group in 2019. The impact of emergency declaration on HbA1c level was small for the MDI/isCGM group and smaller for the SAP + CSII/isCGM group in 2021. The COVID-19 pandemic has affected the seasonal variation of HbA1c levels in T1D; the variation differed according to the treatment mode.

Type 1 diabetes patient experiences and management practices during the COVID-19 pandemic in rural Uganda.

Background: The COVID-19 pandemic has impacted various aspects of the lives of persons with chronic diseases, including type 1 diabetes (T1D). However, the diabetes care experiences and practices adopted by persons living with T1D after the declaration of the COVID-19 pandemic in Uganda have not been well documented. Objectives: We investigated diabetes management practices and experiences of persons with T1D during the COVID-19 pandemic lockdown in a rural district of southwestern Uganda. Methods: Using interactive sequential explanatory mixed methods, we conducted a cross-sectional study of persons with T1D aged 18-25 years, their caregivers and health workers. Quantitative data was exclusively collected from patients with T1D using Kobo Toolbox™ and analysed with SPSS™ version 26; qualitative interviews were used to elicit responses from purposively selected patients with T1D, plus caregivers and health workers that were analysed using a thematic framework approach. Results: The study enrolled 51 (24 males) patients with T1D; diabetes duration (mean ± SD) 6.6 ± 5 years. Access to insulin syringes significantly worsened in 19.6% of participants (p = 0.03). Insulin injection frequency (p = 0.01), blood glucose monitoring (p = 0.001) and meal frequency (p = 0.0001) significantly decreased. Qualitative interviews highlighted COVID-19 restriction measures had reduced household income, frequency of clinic visits, and access to food, diabetes support and social services. Conclusions: Experiences and practices were consistent with decisions to prioritise survival, even with known risks around metabolic control. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01222-4.

Longitudinal study of the flash glucose monitoring system in type 1 diabetics: An mHealth ally in times of COVID-19.

AIMS AND OBJECTIVES: The aim of this study was to assess the effect of the FreeStyle Libre device implantation in adult type 1 diabetics in a Health Area of Castilla La Mancha (Spain) during the COVID-19 pandemic. BACKGROUND: FreeStyle Libre is a so-called mHealth device that supports health care. During COVID-1 confinement, diabetic patients could have improved their glycaemic monitoring thanks to these devices, although health care in these patients may have been limited due to confinement. METHODS: A 12-month longitudinal study in which a total of 206 type I diabetics participated, belonging to a single health area. Sociodemographic and analytical data and the Self Care Inventory Revised questionnaire (SCI-R) were collected. STROBE checklist was followed. RESULTS: The analysis showed differences related to the use of the sensor. After the study period, patients obtained better levels of basal glucose, glycosylated haemoglobin, creatinine, cholesterol, triglycerides and LDL. In addition, a significant increase in the total score of the SCI-R questionnaire was observed after the use of the monitor (MD -7.77; 95% CI -10.43, -8.29). The same occurred with different SCI-R items such as diet (MD -2.995; 95% CI -3.24, -2.57), glucose determination (MD -3.21; 95% CI -3.52, -2.91), medication administration (MD -2.58; 95% CI -2.53, -1.96) and hypoglycaemic episodes (MD -1.07; 95% CI -1.21, -0.93). In the analysis by groups, worse values of glycosylated haemoglobin and adherence to treatment (p < .05) were observed in overweight/obese subjects versus those with normal weight after one year of study. CONCLUSION: The use of flash monitoring is related to better adherence to most of the recommended habits in diabetes. Nevertheless, there seems to be no relationship with an improvement in physical exercise and preventive aspects of diabetes. A good nursing intervention to support physical exercise and the use of mHealth devices could improve the control of diabetic patients. RELEVANCE TO CLINICAL PRACTICE: The use of this mHealth device has shown positive results and reduced complications. Despite less contact with healthcare facilities due to the pandemic, type 1 diabetic patients have improved their blood results and adherence after using the device for one year. Nursing staff should focus on promoting physical activity and routine disease care in type 1 diabetics.

New-onset type 1 diabetes in children and adolescents as postacute sequelae of SARS-CoV-2 infection: A systematic review and meta-analysis of cohort studies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents may increase risk for a variety of post-acute sequelae including new-onset type 1 diabetes mellitus (T1DM). Therefore, this meta-analysis aims to estimate the risk of developing new-onset type 1 diabetes in children and adolescents as post-acute sequelae of SARS-CoV-2 infection. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched up to March 20, 2023. A systematic review and subsequent meta-analyses were performed to calculate the pooled effect size, expressed as risk ratio (RR) with corresponding 95% confidence interval (CI) of each outcome based on a one-stage approach and the random-effects estimate of the pooled effect sizes of each outcome were generated with the use of the DerSimonian-Laird method. Eight reports from seven studies involving 11 220 530 participants (2 140 897 patients with a history of diagnosed SARS-CoV-2 infection and 9 079 633 participants in the respective control groups) were included. The included studies reported data from four U.S. medical claims databases covering more than 503 million patients (IQVIA, HealthVerity, TriNetX, and Cerner Real-World Data), and three national health registries for all children and adolescents in Norway, Scotland, and Denmark. It was shown that the risk of new-onset T1DM following SARS-CoV-2 infection in children and adolescents was 42% (95% CI 13%-77%, p = 0.002) higher compared with non-COVID-19 control groups. The risk of developing new-onset T1DM following SARS-CoV-2 infection was significantly higher (67%, 95% CI 32 %-112%, p = 0.0001) in children and adolescents between 0 and 11 years, but not in those between 12 and 17 years (RR = 1.10, 95% CI 0.54-2.23, p = 0.79). We also found that the higher risk for developing new-onset T1DM following SARS-CoV-2 infection only exists in studies from the United States (RR = 1.70, 95% CI 1.37-2.11, p = 0.00001) but not Europe (RR = 1.02, 95% CI 0.67-1.55, p = 0.93). Furthermore, we found that SARS-CoV-2 infection was associated with an elevation in the risk of diabetic ketoacidosis (DKA) in children and adolescents compared with non-COVID-19 control groups (RR = 2.56, 95% CI 1.07-6.11, p = 0.03). Our findings mainly obtained from US medical claims databases, suggest that SARS-CoV-2 infection is associated with higher risk of developing new-onset T1DM and diabetic ketoacidosis in children and adolescents. These findings highlight the need for targeted measures to raise public health practitioners and physician awareness to provide intervention strategies to reduce the risk of developing T1DM in children and adolescents who have had COVID-19.

Causal associations between type 1 diabetes and COVID-19 infection and prognosis: a two-sample Mendelian randomization study.

INTRODUCTION: It has been suggested that type 1 diabetes was associated with increased COVID-19 morbidity and mortality. However, their causal relationship is still unclear. Herein, we performed a two-sample Mendelian randomization (MR) to investigate the causal effect of type 1 diabetes on COVID-19 infection and prognosis. RESEARCH DESIGN AND METHODS: The summary statistics of type 1 diabetes were obtained from two published genome-wide association studies of European population, one as a discovery sample including 15 573 cases and 158 408 controls, and the other data as a replication sample consisting of 5913 cases and 8828 controls. We first performed a two-sample MR analysis to evaluate the causal effect of type 1 diabetes on COVID-19 infection and prognosis. Then, reverse MR analysis was conducted to determine whether reverse causality exists. RESULTS: MR analysis results showed that the genetically predicted type 1 diabetes was associated with higher risk of severe COVID-19 (OR=1.073, 95% CI: 1.034 to 1.114, pFDR=1.15×10-3) and COVID-19 death (OR=1.075, 95% CI: 1.033 to 1.119, pFDR=1.15×10-3). Analysis of replication dataset showed similar results, namely a positive association between type 1 diabetes and severe COVID-19 (OR=1.055, 95% CI: 1.029 to 1.081, pFDR=1.59×10-4), and a positively correlated association with COVID-19 death (OR=1.053, 95% CI: 1.026 to 1.081, pFDR=3.50×10-4). No causal association was observed between type 1 diabetes and COVID-19 positive, hospitalized COVID-19, the time to the end of COVID-19 symptoms in the colchicine treatment group and placebo treatment group. Reverse MR analysis showed no reverse causality. CONCLUSIONS: Type 1 diabetes had a causal effect on severe COVID-19 and death after COVID-19 infection. Further mechanistic studies are needed to explore the relationship between type 1 diabetes and COVID-19 infection and prognosis.

Comparing Glucose Outcomes Following Face-to-Face and Remote Initiation of Flash Glucose Monitoring in People Living With Diabetes.

BACKGROUND: When launched, FreeStyle Libre (FSL; a flash glucose monitor) onboarding was mainly conducted face-to-face. The COVID-19 pandemic accelerated a change to online starts with patients directed to online videos such as Diabetes Technology Network UK for education. We conducted an audit to evaluate glycemic outcomes in people who were onboarded face-to-face versus those who were onboarded remotely and to determine the impact of ethnicity and deprivation on those outcomes. METHODS: People living with diabetes who started using FSL between January 2019 and April 2022, had their mode of onboarding recorded and had at least 90 days of data in LibreView with >70% data completion were included in the audit. Glucose metrics (percent time in ranges) and engagement statistics (previous 90-day averages) were obtained from LibreView. Differences between glucose variables and onboarding methods were compared using linear models, adjusting for ethnicity, deprivation, sex, age, percent active (where appropriate), and duration of FSL use. RESULTS: In total, 935 participants (face-to-face 44% [n = 413]; online 56% [n = 522]) were included. There were no significant differences in glycemic or engagement indices between onboarding methods and ethnicities, but the most deprived quintile had significantly lower percent active time (b = -9.20, P = .002) than the least deprived quintile. CONCLUSIONS: Online videos as an onboarding method can be used without significant differences in glucose and engagement metrics. The most deprived group within the audit population had lower engagement metrics, but this did not translate into differences in glucose metrics.

A serological survey of pathogens associated with the respiratory and digestive system in the Polish European bison (Bison bonasus) population in 2017-2022.

BACKGROUND: The European bison (Bison bonasus) is a near threatened species and requires health monitoring. The aim of the present study was to determine the prevalence of antibodies to pathogens known to cause respiratory and digestive illness in ruminants. RESULTS: In the studied 328 European bison, the highest seroprevalence was observed for Bovine herpesvirus-1 (BoHV-1) (50.27%), Bovine Coronavirus (BCoV) (26.36%), and Bluetongue Virus (BTV) (12.83%). For Mycoplasma bovis strains and Bovine Viral Diarrhea Virus (BVDV), positive results were rare. Interestingly, a higher prevalence of BTV antibodies was noted in the northeastern populations and older animals. CONCLUSIONS: Our findings indicate that the Polish European bison population appears to have considerable contact with BoHV-1; however, this does not appear to be of great significance, as clinical symptoms and post-mortem lesions are rarely noted in Polish European bison population. The high seroprevalence of BTV in the north-east of Poland is an ongoing trend, also noted in previous studies. It is possible that European bison may perpetuate the virus in this region. This is the first report of antibodies for BCoV in European bison.

Incidence, characteristics, risk factors and outcomes of diabetic ketoacidosis in COVID-19 patients: Comparison with influenza and pre-pandemic data.

AIMS: This study characterized incidence, patient profiles, risk factors and outcomes of in-hospital diabetic ketoacidosis (DKA) in patients with COVID-19 compared with influenza and pre-pandemic data. METHODS: This study consisted of 13 383 hospitalized patients with COVID-19 (March 2020-July 2022), 19 165 hospitalized patients with influenza (January 2018-July 2022) and 35 000 randomly sampled hospitalized pre-pandemic patients (January 2017-December 2019) in Montefiore Health System, Bronx, NY, USA. Primary outcomes were incidence of in-hospital DKA, in-hospital mortality, and insulin use at 3 and 6 months post-infection. Risk factors for developing DKA were identified. RESULTS: The overall incidence of DKA in patients with COVID-19 and influenza, and pre-pandemic were 2.1%, 1.4% and 0.5%, respectively (p < .05 pairwise). Patients with COVID-19 with DKA had worse acute outcomes (p < .05) and higher incidence of new insulin treatment 3 and 6 months post-infection compared with patients with influenza with DKA (p < .05). The incidence of DKA in patients with COVID-19 was highest among patients with type 1 diabetes (12.8%), followed by patients with insulin-dependent type 2 diabetes (T2D; 5.2%), non-insulin dependent T2D (2.3%) and, lastly, patients without T2D (1.3%). Patients with COVID-19 with DKA had worse disease severity and higher mortality [odds ratio = 6.178 (4.428-8.590), p < .0001] compared with those without DKA. Type 1 diabetes, steroid therapy for COVID-19, COVID-19 status, black race and male gender were associated with increased risk of DKA. CONCLUSIONS: The incidence of DKA was higher in COVID-19 cohort compared to the influenza and pre-pandemic cohort. Patients with COVID-19 with DKA had worse outcomes compared with those without. Many COVID-19 survivors who developed DKA during hospitalization became insulin dependent. Identification of risk factors for DKA and new insulin-dependency could enable careful monitoring and timely intervention.

SARS-CoV-2 Positive Serology and Islet Autoantibodies in Newly Diagnosed Pediatric Cases of Type 1 Diabetes Mellitus: A Single-Center Cohort Study.

Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although presenting less severe forms of the disease in children, seems to play a role in the development of other conditions, including type 1 diabetes mellitus (T1DM). After the beginning of the pandemic, an increase in the number of T1DM pediatric patients was observed in several countries, thus leading to many questions about the complex relationship between SARS-CoV-2 infection and T1DM. Our study aimed to highlight possible correlations between SARS-CoV-2 serology and T1DM onset. Therefore, we performed an observational retrospective cohort study that included 158 children diagnosed with T1DM in the period April 2021-April 2022. The presence or absence of SARS-CoV-2 and T1DM-specific antibodies and other laboratory findings were assessed. In the group of patients with positive SARS-CoV-2 serology, a higher percentage had detectable IA-2A antibodies, more children were positive for all three islet autoantibodies determined (GADA, ICA, and IA-2A), and a higher mean HbA1c value was found. No difference existed between the two groups regarding DKA presence and severity. A lower C-peptide level was found in the patients presenting diabetic ketoacidosis (DKA) at T1DM onset. When compared to a group of patients diagnosed before the pandemic, an increased incidence of both DKA and severe DKA, as well as a higher age at diagnosis and higher levels of HbA1c were present in our study group. These findings have important implications for the ongoing monitoring and management of children with T1DM after the COVID-19 pandemic and highlight the need for further research to better understand the complex relationship between SARS-CoV-2 infection and T1DM.

Synthesis and Antiviral Efficacy of Pyrimidine Analogs Targeting Viral Pathways

To date, viruses are known to cause chronic to acute pathogenesis. Nevertheless, antiviral drugs have been known for their medicinal applications for the last few decades to treat infections caused by these pathogens. Despite advancements in the field of vaccination and antiviral drugs, there is a need for a molecule that can eradicate or control viral infection without getting resistance from pathogens will be a real challenge. This review covers possible ways to treat viral infections with pyrimidine and its mimics compared to known antiviral drugs. A comprehensive study of the report accomplished synthetic routes of pyrimidine analogs and their target-specific antiviral potential. The present review article covers literature from 2018 to 2022.

Glycemic Control in Type 1 Diabetes Mellitus and COVID-19: What We Learned From the Lockdown Experience.

INTRODUCTION: Confinement measures that were imposed during the COVID-19 pandemic drastically changed the routines of the population. Some studies on the impact of confinement on glycemic control suggest a reduction of 0.1 to 0.5% in glycated hemoglobin. The objective of this study was to evaluate the impact of the COVID-19 pandemic lockdown on glycemic control in adult patients with type 1 diabetes mellitus. METHODS: An observational retrospective cohort study of patients with type 1 diabetes mellitus followed in a Diabetes Unit was performed. The study compared the metabolic control of these patients before (between January 1st and March 18th, 2020) and after (between May 3rd and July 31st, 2020) the lockdown. RESULTS: The study included 102 patients with type 1 diabetes mellitus (51% females), with a median age of 36 years (interquartile range 18.75, (24.25-43)) and a median duration of diabetes of 15 years (interquartile range 13, (8-21)). After lockdown, a significant decrease of 0.28±0.71% in glycated hemoglobin was observed (7.88±1.33% vs 7.59±1.23%, p=<0.001). In patients using continuous glucose monitoring a significant improvement in time in range was also noted (47.25±17.33% vs 49.97±18.61%, p=0.008). CONCLUSIONS: This study demonstrated an improvement in glycemic control after the lockdown. This might be explained by the positive impact of stable schedules, healthy meals and greater availability to make therapeutic adjustments to glycemic control. The fact that diabetes was considered a risk factor for the development of severe COVID-19 disease might also influence patients to increase their efforts to optimize their glycemic control.

In This Issue of Diabetes Care

The article provides information on a digital health care platform for diabetes that showed improvements in blood glucose levels and weight loss over 24 weeks. The platform includes an Artificial Intelligence system that recognizes foods in photographs and estimates their nutritional values. Additionally, the use of sulfonylureas as an add-on therapy for diabetes does not appear to increase cardiovascular or all-cause mortality risks.

Association between Covid-19 vaccination and incidence of type 1 diabetes in China: Evidence from 14.14 million registered residents between 2007 and 2021.

AIMS: Reports have suggested that COVID-19 vaccination may cause Type 1 diabetes (T1D), particularly fulminant T1D (FT1D). This study aimed to investigate the incidence of T1D in a general population of China, where>90% of the people have received three injections of inactivated SARS-Cov-2 vaccines in 2021. METHODS: A population-based registry of T1D was performed using data from the Beijing Municipal Health Commission Information Center. Annual incidence rates were calculated by age group and gender, and annual percentage changes were assessed using Joinpoint regression. RESULTS: The study included 14.14 million registered residents, and 7,697 people with newly diagnosed T1D were identified from 2007 to 2021. T1D incidence increased from 2.77 in 2007 to 3.84 per 100,000 persons in 2021. However, T1D incidence was stable from 2019 to 2021, and the incidence rate did not increase when people were vaccinated in January-December 2021. The incidence of FT1D did not increase from 2015 to 2021. CONCLUSIONS: The findings suggest that COVID-19 vaccination did not increase the onset of T1D or have a significant impact on T1D pathogenesis, at least not on a large scale.

An Overview of Laboratory Testing for ADAMTS13.

ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) is also called von Willebrand factor (VWF) cleaving protease (VWFCP). ADAMTS13 acts to cleave VWF multimers and thus reduce plasma VWF activity. In the absence of ADAMTS13 (i.e., in thrombotic thrombocytopenia purpura, TTP), plasma VWF can accumulate, in particular as "ultra-large" VWF multimers, and this can lead to thrombosis. Relative deficiencies in ADAMTS13 can also occur in a variety of other conditions, including secondary thrombotic microangiopathies (TMA). Of contemporary interest, COVID-19 (coronavirus disease 2019) may also be associated with relative reduction of ADAMTS13 and also pathological accumulation of VWF, with this likely contributing to the thrombosis risk seen in affected patients. Laboratory testing for ADAMTS13 can assist in the diagnosis of these disorders (i.e., TTP, TMA), as well as in their management, and can be achieved using a variety of assays. This chapter therefore provides an overview of laboratory testing for ADAMTS13 and the value of such testing to assist the diagnosis and management of associated disorders.

Automated and Rapid ADAMTS13 Testing Using Chemiluminescence: Utility for Identification or Exclusion of TTP and Beyond.

Thrombotic thrombocytopenic purpura (TTP) is a prothrombotic condition caused by a significant deficiency of the enzyme, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). In the absence of adequate levels of ADAMTS13 (i.e., in TTP), plasma VWF accumulates, in particular as "ultra-large" VWF multimers, and this leads to pathological platelet aggregation and thrombosis. In addition to TTP, ADAMTS13 may be mildly to moderately reduced in a range of other conditions, including secondary thrombotic microangiopathies (TMA) such as those caused by infections (e.g., hemolytic uremic syndrome (HUS)), liver disease, disseminated intravascular coagulation (DIC), and sepsis, during acute/chronic inflammatory conditions, and sometimes also in COVID-19 (coronavirus disease 2019)). ADAMTS13 can be detected by a variety of techniques, including ELISA (enzyme-linked immunosorbent assay), FRET (fluorescence resonance energy transfer) and by chemiluminescence immunoassay (CLIA). The current report describes a protocol for assessment of ADAMTS13 by CLIA. This protocol reflects a rapid test able to be performed within 35 min on the AcuStar instrument (Werfen/Instrumentation Laboratory), although certain regional approvals may also permit this testing to be performed on a BioFlash instrument from the same manufacturer.

The use of alanine, free carnitine and IGFBP-1 as potential biomarkers for glycogen storage disease type I

Background: Glycogen Storage Disease Ia (GSDIa) and Ib (GSDIb) are inborn errors of carbohydrate metabolism due to a deficiency of glucose-6-phosphatase (G6Pase) or glucose-6-phosphate translocase (G6PT), respectively. Consuming prescribed amounts of uncooked cornstarch (UCCS) to prevent hypoglycemia is the standard of care for GSDIa and GSDIb. Patients followed in our GSD Program are admitted to the hospital annually for evaluation of their metabolic control by measuring glucose and lactate levels and revising treatment regimens accordingly. Lack of bed space due to the COVID-19 pandemic has created a need for alternate markers of metabolic control as lactate measurements are unreliable in the outpatient setting. This research aims to identify alternative biomarkers to show degree of metabolic control in individuals with GSDI. Method(s): A retrospective chart review was conducted on 45 adults and children with GSDI using data from January 1, 2014 toMay 6, 2021. Plasma alanine and free carnitine levels were compared with laboratory reference ranges. Results from the three tests were not available on every subject. Plasma alanine was evaluated on 24 subjects (16-GSDIa, 8-GSDIb) and free carnitine was evaluated on 25 subjects (17-GSDIa, 8-GSDIb). Result(s): Alanine levels in subjects with GSDIa ranged from 378 to 786 umol/L, while alanine levels in subjects with GSDIb ranged from 254 to 506 umol/L (reference range = 103-528 umol/L). Free carnitine levels ranged from26 to 72 umol/L in subjects with GSDIa and from 44 to 90 umol/L in subjects with GSDIb (reference range = 19-55 umol/L). Conclusion(s): Our analysis showed that plasma alanine and free carnitine have potential to be used as biomarkers of metabolic control. For plasma alanine, there seemed to be differences between subjects with GSDIa and GSDIb, as the majority of subjects with GSDIa had elevations in plasma alanine, while subjects with GSDIb did not. Elevated plasma alanine levels indicate lactic acidosis. For GSDIb, we hypothesize that there may be some type of G6Pase enzyme activity that occurs outside of the endoplasmic reticulum. When looking at both groups, free carnitine levels were mostly elevated. This indicates that there could be inhibition of fatty acid oxidation.Copyright © 2022 Elsevier Inc. All rights reserved.