Tag: type 1 diabetes

Incidence of immune-mediated inflammatory diseases following COVID-19: a matched cohort study in UK primary care

Abstract:

Background: Some patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) go on to experience post-COVID-19 condition or long COVID. Preliminary findings have given rise to the theory that long COVID may be due in part to a deranged immune response. In this study, we assess whether there is an association between SARS-CoV-2 infection and the incidence of immune-mediated inflammatory diseases (IMIDs).

Methods: Matched cohort study using primary care electronic health record data from the Clinical Practice Research Datalink Aurum database. The exposed cohort included 458,147 adults aged 18 years and older with a confirmed SARS-CoV-2 infection and no prior diagnosis of IMIDs. They were matched on age, sex, and general practice to 1,818,929 adults with no diagnosis of confirmed or suspected SARS-CoV-2 infection. The primary outcome was a composite of any of the following IMIDs: autoimmune thyroiditis, coeliac disease, inflammatory bowel disease (IBD), myasthenia gravis, pernicious anaemia, psoriasis, rheumatoid arthritis (RA), Sjogren’s syndrome, systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1DM), and vitiligo. The secondary outcomes were each of these conditions separately. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the primary and secondary outcomes, adjusting for age, sex, ethnic group, smoking status, body mass index, relevant infections, and medications.

Results: Six hundred and nighty six (0.15%) and 2230 (0.12%) patients in the exposed and unexposed cohort developed an IMID during the follow-up period over 0.29 person-years, giving a crude incidence rate of 4.59 and 3.65 per 1000 person-years, respectively. Patients in the exposed cohort had a 22% increased risk of developing an IMID, compared to the unexposed cohort (aHR 1.22, 95% CI 1.12 to 1.33). The incidence of three IMIDs was significantly associated with SARS-CoV-2 infection. These were T1DM (aHR 1.56, 1.09 to 2.23), IBD (aHR 1.36, 1.18 to 1.56), and psoriasis (1.23, 1.05 to 1.42).

Conclusions: SARS-CoV-2 was associated with an increased incidence of IMIDs including T1DM, IBD and psoriasis. However, these findings could be potentially due to ascertainment bias. Further research is needed to replicate these findings in other populations and to measure autoantibody profiles in cohorts of individuals with COVID-19.

Source: Syed U, Subramanian A, Wraith DC, Lord JM, McGee K, Ghokale K, Nirantharakumar K, Haroon S. Incidence of immune-mediated inflammatory diseases following COVID-19: a matched cohort study in UK primary care. BMC Med. 2023 Sep 21;21(1):363. doi: 10.1186/s12916-023-03049-5. PMID: 37735654; PMCID: PMC10512476. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10512476/ (Full text)

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

Abstract:

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.

Source: Rahmati M, Yon DK, Lee SW, Udeh R, McEVoy M, Kim MS, Gyasi RM, Oh H, López Sánchez GF, Jacob L, Li Y, Koyanagi A, Shin JI, Smith L. 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. J Med Virol. 2023 Jun;95(6):e28833. doi: 10.1002/jmv.28833. PMID: 37264687. https://onlinelibrary.wiley.com/doi/10.1002/jmv.28833

The Role of Microbiota and Intestinal Permeability in the Pathophysiology of Autoimmune and Neuroimmune Processes with an Emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome

Abstract:

BACKGROUND: In steady state conditions intestinal immune homeostasis is maintained by a sophisticated bidirectional dialogue between the microbiota and the intestinal immune system. This “cross talk” is enabled by the presence of highly adapted secretory cells, sampling cells and pattern recognition receptors in the gastric epithelium.

METHODS: Herein we discuss the mechanisms involved in the breakdown of intestinal homeostasis and the development of systemic immune activation and neuroinflammation with a view to discussing the importance of these processes, in tandem with genetic and environmental factors, in the pathophysiology of (auto)immune diseases.Data is presented explaining how immune tolerance is maintained and how it may breakdown.

CONCLUSION: The breakdown of immune homeostasis following the development of gut inflammation, caused for example by gut dysbiosis, and the consequent increased intestinal permeability, is increasingly considered to be the ultimate source of the systemic immune activation and T helper 17/T regulatory cell imbalances, and maybe neurological disturbances, seen in autoimmune diseases such as Type 1 diabetes and inflammatory bowel disease. Increased intestinal permeability and translocation of commensal antigens into the systemic circulation is also a likely cause of the severe fatigue and an almost bewildering range of neurocognitive, neuroimaging and overall symptom presentations seen in patients with a diagnosis of Chronic Fatigue Syndrome.

 

Source: Morris G, Berk M, Carvalho AF, Caso JR, Sanz Y, Maes M. The Role of Microbiota and Intestinal Permeability in the Pathophysiology of Autoimmune and Neuroimmune Processes with an Emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome. Curr Pharm Des. 2016;22(40):6058-6075. https://www.ncbi.nlm.nih.gov/pubmed/27634186

 

Enterovirus infections in new disguise

Abstract:

Enteroviruses (Coxsackie A and B, echovirus, poliovirus) belong to a group of small RNA-viruses, picomavirus, which are widespread in nature. Enteroviruses cause a number of well known diseases and symptoms in humans, from subclinical infections and the common cold to poliomyelitis with paralysis. The development of polio vaccines is the greatest accomplishment within the field of enterovirus research and the background work was awarded the Nobel prize in 1954. New knowledge implies that enteroviruses play a more important part in the morbidity panorama than was previously thought. Chronic (persistent) enteroviruses were formerly unknown.

Serologic and molecular biology techniques have now demonstrated that enteroviral genomes, in certain situations, persist after the primary infection (which is often silent). Persistent enteroviral infection or recurrent infections and/or virus-stimulated autoimmunity might contribute to the development of diseases with hitherto unexplained pathogenesis, such as post polio syndrome, dilated cardiomyopathy, juvenile (type 1) diabetes and possibly some cases of chronic fatigue syndrome.

 

Source: Fohlman J, Friman G, Tuvemo T. Enterovirus infections in new disguise. Lakartidningen. 1997 Jul 9;94(28-29):2555-60. [Article in Swedish] http://www.ncbi.nlm.nih.gov/pubmed/9254324