In the 100 years since isolation and administration of animal insulin to sustain life in Type 1 diabetes, there has been increasing progress in the administration of exogenous insulin to lower glucose levels.

We reviewed using standard search engines and PubMed present-day techniques of management of type 1 diabetes.

Long-acting insulin formulations have been developed to maintain basal glucose levels in the normal range, while rapid acting insulins have been synthesized to address the sharp rise in glucose levels after a meal. Insulin pumps administer insulin continuously subcutaneously guided by continuous glucose monitoring systems. These almost closed loop systems achieve near normal glucose levels other than at meal times where the rapid glucose rise and then fall pose a significant challenge due to the extended duration of subcutaneous insulin depots. Implanted insulin pumps with intraperitoneal delivery may eventually permit improved post meal glucose control. Type 1 diabetes has now been redefined as an autoimmune disease which may be diagnosed purely from the presence of anti-beta cell antibodies with no abnormality of glucose levels. The future will see an intensification of efforts to combat the immune process which destroys beta cells.

To assess the association between exanthematous diseases, and an earlier age at Type 1 diabetes mellitus diagnosis (T1DM) in a cohort of Brazilian patients.

This was a retrospective cohort study including 812 patients diagnosed with T1DM in Bauru, São Paulo, Brazil, between 1981 and 2023. Data regarding sociodemographic parameters such as age, sex, ethnicity, socioeconomic status, as well as the occurrence of a previous exanthematous diseases, such as chickenpox, measles, rubella, mumps and scarlet fever were collected. An adapted survival analysis was performed to evaluate the impact of each variable on the age of T1DM diagnosis.

Overall, 596 patients were evaluated. Their average age at T1DM diagnosis was 12 ± 7.69 years. It was found that presenting rubella, measles, and mumps, as well as belonging to non-high socioeconomic class, were associated with 35%, 40%, 39%, and 34% lower age at T1DM diagnosis, respectively.

This study has found that rubella, measles, mumps, and belonging to non-high socioeconomic classes were significantly associated with earlier age at T1DM diagnosis in a cohort of Brazilian patients with T1DM. Future studies with other populations are warranted to confirm our findings.

Pancreas, a vital organ with intricate endocrine and exocrine functions, is central to the regulation of the body's glucose levels and digestive processes. Disruptions in its endocrine functions, primarily regulated by islets of Langerhans, can lead to debilitating diseases such as diabetes mellitus. Murine models of pancreatic dysfunction have contributed significantly to the understanding of insulitis, islet-relevant immunological responses, and the optimization of cell therapies. However, genetic differences between mice and humans have severely limited their clinical translational relevance. Recent advancements in tissue engineering and microfabrication have ushered in a new era of in vitro models that offer a promising solution. This paper reviews the state-of-the-art engineered tools designed to study endocrine dysfunction of the pancreas. Islet on a chip devices that allow precise control of various culture conditions and noninvasive readouts of functional outcomes have led to the generation of physiomimetic niches for primary and stem cell derived islets. Live pancreatic slices are a new experimental tool that could more comprehensively recapitulate the complex cellular interplay between the endocrine and exocrine parts of the pancreas. Although a powerful tool, live pancreatic slices require more complex control over their culture parameters such as local oxygenation and continuous removal of digestive enzymes and cellular waste products for maintaining experimental functionality over long term. The combination of islet-immune and slice on chip strategies can guide the path toward the next generation of pancreatic tissue modeling for better understanding and treatment of endocrine pancreatic dysfunctions.

Diabetes mellitus (DM) is a metabolic syndrome characterized by hyperglycaemia, polydipsia, polyuria, and weight loss, among others. The pathophysiology for the disorders is complex and results in pancreatic abnormal function. Viruses have also been implicated in the metabolic syndrome. This study charted peptides to investigate and predict the autoimmune potential of shared sequences between 8 viral species proteins (which we termed 'diabetes-viruses') and the human pancreatic proteins. The structure and immunological relevance of shared sequences between viruses reported in DM onset and human pancreatic proteins were analysed. At nonapeptide mapping between human pancreatic protein and 'diabetic-viruses', reveal 1064 shared sequences distributed among 454 humans and 4288 viral protein sequences. The viral results showed herpesviruses, enterovirus (EV), human endogenous retrovirus, influenza A viruses, rotavirus, and rubivirus sequences are hosted by the human pancreatic protein. The most common shared nonapeptide was AAAAAAAAA, present in 30 human nonredundant sequences. Among the viral species, the shared sequence NSLEVLFQG occurred in 18 nonredundant EVs protein, while occurring merely in 1 human protein, whereas LGLDIEIAT occurred in 8 influenza A viruses overlapping to 1 human protein and KDELSEARE occurred in 2 rotaviruses. The prediction of the location of the shared sequences in the protein structures, showed most of the shared sequences are exposed and located either on the surface or cleft relative to the entire protein structure. Besides, the peptides in the viral protein shareome were predicted computationally for binding to MHC molecules. Here analyses showed that the entire 1064 shared sequences predicted 203 to be either HLA-A or B supertype-restricted epitopes. Fifty-one of the putative epitopes matched reported HLA ligands/T-cell epitopes majorly coming from EV B supertype representative allele restrictions. These data, shared sequences, and epitope charts provide important insight into the role of viruses on the onset of DM and its implications.

Microorganisms have long been suspected to influence the outcome of immune-related syndromes, particularly autoimmune diseases. Type 1 diabetes (T1D) results from the autoimmune destruction of the insulin-producing beta cells of pancreatic islets, causing high glycemia levels. Genetics is part of its aetiology, but environmental factors, particularly infectious microorganisms, also play a role. Bacteria, viruses, and parasites influence the outcome of T1D in mice and humans. We used nonobese diabetic (NOD) mice, which spontaneously develop T1D, to investigate the influence of a parasitic infection, leishmaniasis. Leishmania amazonensis is an intracellular eukaryotic parasite that replicates predominantly in macrophages and is responsible for cutaneous leishmaniasis. The implication of Th1 immune responses in T1D and leishmaniasis led us to study this parasite in the NOD mouse model. We previously constructed osteopontin knockout mice with a NOD genetic background and demonstrated that this protein plays a role in the T1D phenotype. In addition, osteopontin (OPN) has been found to play a role in the immune response to various infectious microorganisms and to be implicated in other autoimmune conditions, such as multiple sclerosis in humans and experimental autoimmune encephalomyelitis (EAE) in mice. We present herein data demonstrating the role of OPN in the response to Leishmania in NOD mice and the influence of this parasitic infection on T1D. This exploratory study aimed to investigate the environmental infectious component of the autoimmune response, including Th1 immunity, which is common to both T1D and leishmaniasis.

Diabetes mellitus (DM) is among the four noncommunicable diseases. There are two types-type I and type II. The prevalence of type I DM in India is 0.26/1,000 population (1992). This study was carried out to assess dental caries status and gingival status. The study group was compared with the nondiabetic control group to find any association with metabolic control of the disease.

A total sample size of 200 subjects was selected out of 100 patients referred to treat their poorly controlled type I diabetes mellitus at the tertiary hospital. Another 100 nondiabetic subjects were selected as controls. An oral clinical examination used a mouth mirror, dental explorer, visible light source, and cotton gauze. Decayed, missing, and filled teeth (DMFT), gingival index, plaque index, and calculus index were evaluated.

Comparison of the gingival index between cases and control was found to be significant, where the p-value is <0.001. This points out that type I diabetic patients have more chance of gingival problems than others. The increased plaque index indicates the need to give more importance to oral health as it may lead to an increased calculus index in the future, leading to periodontal problems. It was found that glycosylated hemoglobin (HbA1c) is directly proportional to the gingival index.

Maintaining good oral health through regular check-ups with dental experts and motivating and educating type I diabetic patients as they are more prone to dental issues.

Thankappan N, Chandran V, Venugopal M, et al. Assessment of Oral Health Status among Children with Type I Diabetes Mellitus: A Cross-sectional Study. Int J Clin Pediatr Dent 2024;17(10):1124-1128.

Despite advancements in medical interventions, the disease burden caused by viral pathogens remains large and highly diverse. This burden includes the wide range of signs and symptoms associated with active viral replication as well as a variety of clinical sequelae of infection. Moreover, there is growing evidence supporting the existence of sex- and ethnicity-based health disparities linked to viral infections and their associated diseases. Despite several well-documented disparities in viral infection rates, our current understanding of virus-associated health disparities remains incomplete. This knowledge gap can be attributed, in part, to limitations of the most commonly used viral detection methodologies, which lack the breadth needed to characterize exposures across the entire virome. Additionally, virus-related health disparities are dynamic and often differ considerably through space and time. In this study, we utilize PepSeq, an approach for highly multiplexed serology, to broadly assess an individual's history of viral exposures, and we demonstrate the effectiveness of this approach for detecting infection disparities through a pilot study of 400 adults aged 30-60 in Phoenix, AZ. Using a human virome PepSeq library, we observed expected seroprevalence rates for several common viruses and detected both expected and previously undocumented differences in inferred rates of infection between our male/female and Hispanic/non-Hispanic White individuals.

Our understanding of population-level virus infection rates and associated health disparities is incomplete. In part, this is because of the high diversity of human-infecting viruses and the limited breadth and sensitivity of traditional approaches for detecting infection events. Here, we demonstrate the potential for modern, highly multiplexed antibody detection methods to greatly increase our understanding of disparities in rates of infection across subpopulations (e.g., different sexes or ethnic groups). The use of antibodies as biomarkers allows us to detect evidence of past infections over an extended period, and our approach for highly multiplexed serology (PepSeq) allows us to measure antibody responses against hundreds of viruses in an efficient and cost-effective manner.

Everyone knows that an infection can make you feel sick. Although we perceive infection-induced changes in metabolism as a pathology, they are a part of a carefully regulated process that depends on tissue-specific interactions between the immune system and organs involved in the regulation of systemic homeostasis. Immune-mediated changes in homeostatic parameters lead to altered production and uptake of nutrients in circulation, which modifies the metabolic rate of key organs. This is what we experience as being sick. The purpose of sickness metabolism is to generate a metabolic environment in which the body is optimally able to fight infection while denying vital nutrients for the replication of pathogens. Sickness metabolism depends on tissue-specific immune cells, which mediate responses tailored to the nature and magnitude of the threat. As an infection increases in severity, so do the number and type of immune cells involved and the level to which organs are affected, which dictates the degree to which we feel sick. Interestingly, many alterations associated with metabolic disease appear to overlap with immune-mediated changes observed following infection. Targeting processes involving tissue-specific interactions between activated immune cells and metabolic organs therefore holds great potential for treating both people with severe infection and those with metabolic disease. In this review, we will discuss how the immune system communicates in situ with organs involved in the regulation of homeostasis and how this communication is impacted by infection.

Viral respiratory infections may precipitate type 1 diabetes (T1D). A possible association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, and the incidence of T1D is being determined. This study was carried out using Portuguese registries, aiming at examining temporal trends between COVID-19 and T1D.

Hospital data, comparing the incidence before and during the COVID-19 pandemic, from children and young adults diagnosed with new-onset T1D, was acquired beginning in 2017 and until the end of 2022. Data was obtained from nine different Portuguese hospital units. The impact of the COVID-19 pandemic, beginning in March 2020, was assessed comparing the annual numbers of new-onset T1D cases. The annual median levels of glucose, glycated hemoglobin (HbA1c) and fasting C-peptide at T1D diagnosis were compared. The annual number of diabetic ketoacidosis (DKA) episodes among new T1D cases was also assessed at two centers.

In total, data from 574 newly diagnosed T1D patients was analyzed, including 530 (92.3%) children. The mean ages for child and adult patients were 9.1 (SD 4.4) and 32.8 (SD 13.6) years, respectively. 57.8% (331/573) were male, one patient had unknown sex. The overall median (25-75 percentiles) levels of glucose, HbA1c and fasting C-peptide at diagnosis were 454 mg/dL (356-568), 11.8% (10.1-13.4) and 0.50 µg/L (0.30-0.79), respectively. DKA at T1D diagnosis was present in 48.4% (76/157). For eight centers with complete 2018 to 2021 data (all calendar months), no overall significant increase in T1D cases was observed during the COVID-19 pandemic, i.e. 90 cases in 2018, 90 cases in 2019, 112 in 2020 and 100 in 2021 (P for trend = 0.36). Two of the centers, Faro (CHUA) and Dona Estefânia (CHULC) hospitals, did however see an increase in T1D from 2019 to 2020. No significant changes in glucose (P = 0.32), HbA1c (P = 0.68), fasting C-peptide (P = 0.20) or DKA frequency (P = 0.68) at the time of T1D diagnosis were observed over the entire study period.

The T1D incidence did not increase significantly, when comparing the years before and during the COVID-19 pandemic, nor did key metabolic parameters or number of DKA episodes change.

During the coronavirus disease 2019 (COVID-19) pandemic, reports of individuals experiencing new-onset type 1 diabetes (T1D) began to appear in the literature. This spurred subsequent epidemiological studies that demonstrated an increase in new diagnosis of T1D compared to prepandemic. Development of T1D is characterized by the development of an inappropriate T cell response directed against pancreatic beta-cells, leading to eventual loss of insulin secretion. This T cell response occurs in genetically susceptible individuals and may be triggered by viral illnesses. Abnormal cytokine production is another element of the pathogenesis of T1D. Infection with severe acute respiratory syndrome related coronavirus 2 induces a profound increase in the production of inflammatory cytokines and causes significant T-cell dysregulation. These disruptions of the immune system may be linked to the development of T1D following COVID-19. [Pediatr Ann. 2024;53(7):e264-e268.].

Diabetes mellitus (DM) is comprised of two predominant subtypes: type 1 diabetes mellitus (T1DM), accounting for approximately 5 % of cases worldwide and resulting from autoimmune destruction of insulin-producing β-cells, and type 2 (T2DM), accounting for approximately 95 % of cases globally and characterized by the inability of pancreatic β-cells to meet the demand for insulin due to a relative β-cell deficit in the setting of peripheral insulin resistance. Both types of DM involve derangement of glucose metabolism and are metabolic diseases generally considered to be initiated by a combination of genetic and environmental factors. Viruses have been reported to play a role as infectious etiological factors in the initiation of both types of DM in predisposed individuals. Among the reported viral infections causing DM in humans, the most studied include coxsackie B virus, cytomegalovirus and hepatitis C virus. The recent COVID-19 pandemic has highlighted the diabetogenic potential of SARS-CoV-2, rekindling interest in the field of virus-induced diabetes (VID). This review discusses the reported mechanisms of viral-induced DM, addressing emerging concepts in VID, as well as highlighting areas where knowledge is lacking, and further investigation is warranted.

Type 1 diabetes results from autoimmune events influenced by environmental variables, including changes in diet. This study investigated how feeding refined versus unrefined (aka 'chow') diets affects the onset and progression of hyperglycaemia in non-obese diabetic (NOD) mice.

Female NOD mice were fed either unrefined diets or matched refined low- and high-fat diets. The onset of hyperglycaemia, glucose tolerance, food intake, energy expenditure, circulating insulin, liver gene expression and microbiome changes were measured for each dietary group.

NOD mice consuming unrefined (chow) diets developed hyperglycaemia at similar frequencies. By contrast, mice consuming the defined high-fat diet had an accelerated onset of hyperglycaemia compared to the matched low-fat diet. There was no change in food intake, energy expenditure, or physical activity within each respective dietary group. Microbiome changes were driven by diet type, with chow diets clustering similarly, while refined low- and high-fat bacterial diversity also grouped closely. In the defined dietary cohort, liver gene expression changes in high-fat-fed mice were consistent with a greater frequency of hyperglycaemia and impaired glucose tolerance.

Glucose intolerance is associated with an enhanced frequency of hyperglycaemia in female NOD mice fed a defined high-fat diet. Using an appropriate matched control diet is an essential experimental variable when studying changes in microbiome composition and diet as a modifier of disease risk.

Infections may affect the course of autoimmune inflammatory diseases of the central nervous system (CNS), such as multiple sclerosis (MS). Infections with lactate dehydrogenase-elevating virus (LDV) protected mice from developing experimental autoimmune encephalomyelitis (EAE), a mouse counterpart of MS. Uninfected C57BL/6 mice immunized with the myelin oligodendrocyte glycoprotein peptide (MOG35-55) experienced paralysis and lost weight at a greater rate than mice who had previously been infected with LDV. LDV infection decreased the presentation of the MOG peptide by CD11b+CD11c+ dendritic cells (DC) to pathogenic T lymphocytes. When comparing non-infected mice to infected mice, the histopathological examination of the CNS showed more areas of demyelination and CD45+ and CD3+, but not Iba1+ cell infiltration. These results suggest that the protective effect of LDV infection against EAE development is mediated by a suppression of myelin antigen presentation by a specific DC subset to autoreactive T lymphocytes. Such a mechanism might contribute to the general suppressive effect of infections on autoimmune diseases known as the hygiene hypothesis.

Diabetes, a chronic metabolic disorder disrupting blood sugar regulation, has emerged as a prominent silent pandemic. Uncontrolled diabetes predisposes an individual to develop fatal complications like cardiovascular disorders, kidney damage, and neuropathies and aggravates the severity of treatable infections. Escalating cases of Type 1 and Type 2 diabetes correlate with a global upswing in diabetes-linked mortality. As a growing global concern with limited preventive interventions, diabetes necessitates extensive research to mitigate its healthcare burden and assist ailing patients. An altered immune system exacerbated by chronic hyperinflammation heightens the susceptibility of diabetic individuals to microbial infections, including notable viruses like SARS-CoV-2, dengue, and influenza. Given such a scenario, we scrutinized the literature and compiled molecular pathways and signaling cascades related to immune compartments in diabetics that escalate the severity associated with the above-mentioned viral infections in them as compared to healthy individuals. The pathogenesis of these viral infections that trigger diabetes compromises both innate and adaptive immune functions and pre-existing diabetes also leads to heightened disease severity. Lastly, this review succinctly outlines available treatments for diabetics, which may hold promise as preventive or supportive measures to effectively combat these viral infections in the former.

Diabetic neuropathy is one of the prevalent and debilitating microvascular complications of diabetes mellitus, affecting a significant portion of the global population. Relational preclinical animal models are essential to understand its pathophysiology and develop effective treatments. This abstract provides an overview of current knowledge and advancements in such models. Various animal models have been developed to mimic the multifaceted aspects of human diabetic neuropathy, including both type 1 and type 2 diabetes. These models involve rodents (rats and mice) and larger animals like rabbits and dogs. Induction of diabetic neuropathy in these models is achieved through chemical, genetic, or dietary interventions, such as diabetogenic agents, genetic modifications, or high-fat diets. Preclinical animal models have greatly contributed to studying the intricate molecular and cellular mechanisms underlying diabetic neuropathy. They have shed light on hyperglycemia-induced oxidative stress, neuroinflammation, mitochondrial dysfunction, and altered neurotrophic factor signaling. Additionally, these models have allowed for the investigation of morphological changes, functional alterations, and behavioral manifestations associated with diabetic neuropathy. These models have also been crucial for evaluating the efficacy and safety of potential therapeutic interventions. Novel pharmacological agents, gene therapies, stem cell-based approaches, exercise, dietary modifications, and neurostimulation techniques have been tested using these models. However, limitations and challenges remain, including physiological differences between humans and animals, complex neuropathy phenotypes, and the need for translational validation. In conclusion, preclinical animal models have played a vital role in advancing our understanding and management of diabetic neuropathy. They have enhanced our knowledge of disease mechanisms, facilitated the development of novel treatments, and provided a platform for translational research. Ongoing efforts to refine and validate these models are crucial for future treatment developments for this debilitating condition.

Diabetes mellitus, commonly referred to as diabetes, is a group of metabolic disorders characterized by chronic elevation in blood glucose levels, resulting from inadequate insulin production, defective cellular response to extracellular insulin, and/or impaired glucose metabolism. The two main types that account for most diabetics are type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), each with their own pathophysiological features. T1D is an autoimmune condition where the body's immune system attacks and destroys the insulin-producing beta cells in the pancreas. This leads to lack of insulin, a vital hormone for regulating blood sugar levels and cellular glucose uptake. As a result, those with T1D depend on lifelong insulin therapy to control their blood glucose level. In contrast, T2DM is characterized by insulin resistance, where the body's cells do not respond effectively to insulin, coupled with a relative insulin deficiency. This form of diabetes is often associated with obesity, sedentary lifestyle, and/or genetic factors, and it is managed with lifestyle changes and oral medications. Animal models play a crucial role in diabetes research. However, given the distinct differences between T1DM and T2DM, it is imperative for researchers to employ specific animal models tailored to each condition for a better understanding of the impaired mechanisms underlying each condition, and for assessing the efficacy of new therapeutics. In this review, we discuss the distinct animal models used in type 1 and type 2 diabetes mellitus research and discuss their strengths and limitations.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes enhanced mortality in people with metabolic and cardiovascular diseases. Other highly infectious RNA viruses have demonstrated dependence on glucose transport and utilization, so we hypothesized that SARS-CoV-2 infection could lead to alterations in cellular and whole-body glucose metabolism. Twenty-four healthy domestic cats were intratracheally inoculated with B.1.617.2 (delta) SARS-CoV-2 and samples were collected at 4- and 12-days post-inoculation (dpi). Blood glucose and circulating cortisol concentrations were elevated at 4 and 12 dpi. Serum insulin concentration was statistically significantly decreased, while angiotensin 2 concentration was elevated at 12 dpi. SARS-CoV-2 RNA was detected in the pancreas and skeletal muscle at low levels; however, no change in the number of insulin-producing cells or proinflammatory cytokines was observed in the pancreas of infected cats through 12 dpi. SARS-CoV-2 infection statistically significantly increased GLUT protein expression in both the heart and lungs, correlating with increased AMPK expression. In brief, SARS-CoV-2 increased blood glucose concentration and cardio-pulmonary GLUT expression through an AMPK-dependent mechanism, without affecting the pancreas, suggesting that SARS-CoV-2 induces the reprogramming of host glucose metabolism. A better understanding of host cell metabolism and virus crosstalk could lead to the discovery of novel metabolic therapeutic targets for patients affected by COVID-19.

Type 1 diabetes (T1D) is caused by an autoimmune process which culminates in the destruction of insulin-producing beta cells in the pancreas. It is widely believed that a complex and multifactorial interplay between genetic and environmental factors, such as viruses, play a crucial role in the development of the disease. Research over the past few decades has shown that there is not one single viral culprit, nor one single genetic pathway, causing the disease. Rather, viral infections, most notably enteroviruses (EV), appear to accelerate the autoimmune process leading to T1D and are often seen as a precipitator of clinical diagnosis. In support of this hypothesis, the use of anti-viral drugs has recently shown efficacy in preserving beta cell function after onset of diabetes. In this review, we will discuss the various pathways that viral infections utilize to accelerate the development of T1D. There are three key mechanisms linking viral infections to beta-cell death: One is modulated by the direct infection of islets by viruses, resulting in their impaired function, another occurs in a more indirect fashion, by modulating the immune system, and the third is caused by heightened stress on the beta-cell by interferon-mediated increase of insulin resistance. The first two aspects are surprisingly difficult to study, in the case of the former, because there are still many questions about how viruses might persist for longer time periods. In the latter, indirect/immune case, viruses might impact immunity as a hit-and-run scenario, meaning that many or all direct viral footprints quickly vanish, while changes imprinted upon the immune system and the anti-islet autoimmune response persist. Given the fact that viruses are often associated with the precipitation of clinical autoimmunity, there are concerns regarding the impact of the recent global coronavirus-2019 (COVID-19) pandemic on the development of autoimmune disease. The long-term effects of COVID-19 infection on T1D will therefore be discussed, including the increased development of new cases of T1D. Understanding the interplay between viral infections and autoimmunity is crucial for advancing our knowledge in this field and developing targeted therapeutic interventions. In this review we will examine the intricate relationship between viral infections and autoimmunity and discuss potential considerations for prevention and treatment strategies.

The coronavirus disease 2019 (COVID-19) pandemic became superimposed on the pre-existing obesity and diabetes mellitus (DM) pandemics. Since COVID-19 infection alters the metabolic equilibrium, it may induce pathophysiologic mechanisms that potentiate new-onset DM, and we evaluated this issue.

A systematic review of the literature published from the 1 January 2020 until the 20 July 2023 was performed (PROSPERO registration number CRD42022341638). We included only full-text articles of both human clinical and randomized controlled trials published in English and enrolling adults (age > 18 years old) with ongoing or preceding COVID-19 in whom hyperglycemia was detected. The search was based on the following criteria: "(new-onset diabetes mellitus OR new-onset DM) AND (COVID-19) AND adults".

Articles on MEDLINE (n = 70) and the Web of Science database (n = 16) were included and analyzed by two researchers who selected 20 relevant articles. We found evidence of a bidirectional relationship between COVID-19 and DM.

This link operates as a pathophysiological mechanism supported by epidemiological data and also by the clinical and biological findings obtained from the affected individuals. The COVID-19 pandemic raised the incidence of DM through different pathophysiological and psychosocial factors.

Diabetes mellitus can be subdivided into several categories based on origin and clinical characteristics. The most common forms of diabetes are type 1 (T1D), type 2 diabetes (T2D) and gestational diabetes mellitus (GDM). T1D and T2D are chronic diseases affecting around 537 million adults worldwide and it is projected that these numbers will increase by 12% over the next two decades, while GDM affects up to 30% of women during pregnancy, depending on diagnosis methods. These forms of diabetes have varied origins: T1D is an autoimmune disease, while T2D is commonly associated with, but not limited to, certain lifestyle patterns and GDM can result of a combination of genetic predisposition and pregnancy factors. Despite some pathogenic differences among these forms of diabetes, there are some common markers associated with their development. For instance, gut barrier impairment and inflammation associated with an unbalanced gut microbiota and their metabolites may be common factors in diabetes development and progression. Here, we summarize the microbial signatures that have been linked to diabetes, how they are connected to diet and, ultimately, the impact on metabolite profiles resulting from host-gut microbiota-diet interactions. Additionally, we summarize recent advances relating to promising preventive and therapeutic interventions focusing on the targeted modulation of the gut microbiota to alleviate T1D, T2D and GDM.

Laboratory mice live in specific pathogen-free (SPF) conditions, resulting in an immature immune system comparable to that of newborns rather than adult humans or mice from pet shops. This condition may compromise their translational value. Reintroducing pathogens would lead to the uncontrolled spread of infections and associated diseases, so research facilities should seek safer alternatives. We immunized laboratory mice with a cocktail of pathogens, which were inactivated by ultraviolet irradiation and mixed with the adjuvant AddaVax. This immunization resulted in a higher percentage of CD8+ effector memory T cells compared to untreated mice, although the response was not as robust as in pet shop mice. In a model of skin inflammation, pre-immunization led to an increased skin inflammatory response compared to non-immunized mice. All immunized mice seroconverted to the pathogens in the mixture, while none of the non-immunized mice housed together seroconverted to the pathogens applied to the pre-immunized mice. In conclusion, pre-immunization of mice impacts the immune system, which includes increasing the levels of CD8+ effector memory T cells.

To determine if cellulose nanofibrils (CNF) have potential applications as food additives.

Male C57BL/6 mice on a Western diet were exposed to CNF for one month at a dose of 30 mg/kg by gavage. Male NOD mice, a model for type 1 diabetes (T1D), were used in a six-month study.

Sequencing analysis of 16S rRNA genes suggested significant changes in gut microbiome of male C57BL/6 mice exposed to CNF. Analysis of functional metagenomics indicated that many of the functional contents that might be altered following CNF ingestion were associated with lipid and carbohydrate processing. Further studies in NOD mice suggested that there were some decreases in the blood glucose levels during the insulin tolerance test and glucose tolerance test following CNF treatment. However, these small decreases were not considered biologically meaningful as there were no significant changes in either the area under the curve or the first-order rate constant for glucose disappearance. Moreover, serum concentrations of cytokines/chemokines including IL-3, IL-12(p70) and the keratinocyte chemoattractant were increased following chronic exposure to CNF. In addition, behavioral studies suggested that the percentage of immobility time during the tail-suspension test was significantly increased following six months of exposure to CNF in NOD mice, signifying an increase in depression-related behavior.

Collectively, long-term CNF consumption was associated with changes in the ecology of the gut microbiome, immune homeostasis, and possibly energy metabolism and mental health in male NOD mice on a Western diet.

Molecular mimicry is one mechanism by which infectious agents are thought to trigger islet autoimmunity in type 1 diabetes. With a growing number of reported infectious agents and islet antigens, strategies to prioritize the study of infectious agents are critically needed to expedite translational research into the etiology of type 1 diabetes. In this work, we developed an in-silico pipeline for assessing molecular mimicry in type 1 diabetes etiology based on sequence homology, empirical binding affinity to specific MHC molecules, and empirical potential for T-cell immunogenicity. We then assess whether potential molecular mimics were conserved across other pathogens known to infect humans. Overall, we identified 61 potentially high-impact molecular mimics showing sequence homology, strong empirical binding affinity, and empirical immunogenicity linked with specific MHC molecules. We further found that peptide sequences from 32 of these potential molecular mimics were conserved across several human pathogens. These findings facilitate translational evaluation of molecular mimicry in type 1 diabetes etiology by providing a curated and prioritized list of peptides from infectious agents for etiopathologic investigation. These results may also provide evidence for generation of infectious and HLA-specific preclinical models and inform future screening and preventative efforts in genetically susceptible populations.

Diabetes mellitus (DM) is a very serious disease, the incidence of which has been increasing worldwide. The beginning of diabetic research can be traced back to the 17th century. Since then, animals have been experimented on for diabetic research. However, the greatest development of diabetes research occurred in the second half of the last century, along with the development of laboratory techniques. Information obtained by monitoring patients and animal models led to the finding that there are several types of DM that differ significantly from each other in the causes of the onset and course of the disease. Through different types of animal models, researchers have studied the pathophysiology of all types of diabetic conditions and discovered suitable methods for therapy. Interestingly, despite the unquestionable success in understanding DM through animal models, we did not fully succeed in transferring the data obtained from animal models to human clinical research. On the contrary, we have observed that the chances of drug failure in human clinical trials are very high. In this review, we will summarize the history and presence of animal models in the research of DM over the last hundred years. Furthermore, we have summarized the new methodological approaches, such as "organ-on-chip," that have the potential to screen the newly discovered drugs for human clinical trials and advance the level of knowledge about diabetes, as well as its therapy, towards a personalized approach.

Genome wide association studies (GWAS) have identified over 100 signals associated with type 1 diabetes (T1D). However, translating any given T1D GWAS signal into mechanistic insights, including putative causal variants and the context (cell type and cell state) in which they function, has been limited. Here, we present a comprehensive multi-omic integrative analysis of single-cell/nucleus resolution profiles of gene expression and chromatin accessibility in healthy and autoantibody+ (AAB+) human islets, as well as islets under multiple T1D stimulatory conditions. We broadly nominate effector cell types for all T1D GWAS signals. We further nominated higher-resolution contexts, including effector cell types, regulatory elements, and genes for three independent T1D risk variants acting through islet cells within the pancreas at the DLK1/MEG3, RASGRP1, and TOX loci. Subsequently, we created isogenic gene knockouts DLK1-/-, RASGRP1-/-, and TOX-/-, and the corresponding regulatory region knockout, RASGRP1Δ, and DLK1Δ hESCs. Loss of RASGRP1 or DLK1, as well as knockout of the regulatory region of RASGRP1 or DLK1, increased β cell apoptosis. Additionally, pancreatic β cells derived from isogenic hESCs carrying the risk allele of rs3783355A/A exhibited increased β cell death. Finally, RNA-seq and ATAC-seq identified five genes upregulated in both RASGRP1-/- and DLK1-/- β-like cells, four of which are associated with T1D. Together, this work reports an integrative approach for combining single cell multi-omics, GWAS, and isogenic hESC-derived β-like cells to prioritize the T1D associated signals and their underlying context-specific cell types, genes, SNPs, and regulatory elements, to illuminate biological functions and molecular mechanisms.

Type 1 diabetes mellitus (T1DM) is an autoimmune condition with a genetic predisposition. It has underlying autoimmune destruction of the pancreatic cells that produce insulin. It is often accompanied by other autoimmune conditions. This article focuses on celiac disease (CD), also an autoimmune disease. It is caused by gluten exposure. Both these conditions have genetic predisposing factors. Apart from the genetic background, aberrant small intestine immune response, inflammation, and different grades of enteropathy present in T1DM and CD are the same. With a mean frequency of 8%, the CD frequency of T1DM ranges from 3 to 16%. All T1DM patients should undergo serological testing for CD using antibodies to tissue transglutaminase at the time of T1DM onset. Individuals with T1DM and those accompanied by CD must follow a diet with no gluten. To outline the steps that can avert the development of these disorders and reduce the morbidity of the affected people, a complete understanding of the intricate pathophysiology of T1DM and its connection to CD has been undertaken in this review. The use of resources, such as PubMed and Google Scholar, has made this possible.

To describe the incidence of new onset paediatric diabetes mellitus, clinical characteristics and patterns of presentation to emergency departments (ED) during the COVID-19 pandemic, and to assess whether this increase was associated with SARS-CoV-2 infection.

Retrospective medical record review.

Forty nine paediatric EDs across the UK and Ireland.

All children aged 6 months to 16 years presenting to EDs with (1) new onset diabetes or (2) pre-existing diabetes with diabetic ketoacidosis (DKA), during the COVID-19 pandemic (1 March 2020-28 February 2021) and the preceding year (1 March 2019-28 February 2020).

There were increases in new onset diabetes (1015 to 1183, 17%), compared with background incidence of 3%-5% in the UK over the past 5 years. There were increases in children presenting with new onset diabetes in DKA (395 to 566, 43%), severe DKA (141 to 252, 79%) and admissions to intensive care (38 to 72, 89%). Increased severity was reflected in biochemical and physiological parameters and administration of fluid boluses. Time to presentation from symptom onset for children presenting with new onset diabetes and DKA were similar across both years; healthcare seeking delay did not appear to be the sole contributing factor to DKA during the pandemic. Patterns of presentation changed in the pandemic year and seasonal variation was lost. Children with pre-existing diabetes presented with fewer episodes of decompensation.

There were increases in new onset diabetes in children and a higher risk of DKA in the first COVID pandemic year.

The coronavirus disease (COVID-19) pandemic affected the management and follow-up of several chronic ailments, including pediatric type 1 diabetes mellitus (T1DM). Restricted access to healthcare and fear of contracting the virus during medical facility visits resulted in poor compliance, irregular follow-up visits, treatment, and delayed diagnosis of complications in pediatric diabetes such as diabetic ketoacidosis (DKA). As such, the incidence of complicated DKA in resource-limited settings is high due to delayed presentation, poor compliance with therapy, and associated comorbidities such as malnutrition and sepsis. The pandemic had only added to the woes. The increased surge in DKA, in the face of limited resources, prompted clinicians to find alternative solutions to manage these children effectively. In this narrative review, we discuss the key challenges faced globally while caring for children with T1DM and DKA during the COVID-19 pandemic, and the lessons learned thereof.

Autoimmunity is defined by the presence of antibodies and/or T cells directed against self-components. Although of unknown etiology, autoimmunity commonly is associated with environmental factors such as infections, which have been reported to increase the risk of developing autoimmune diseases. Occasionally, similarities between infectious non-self and self-tissue antigens may contribute to immunological cross-reactivity in autoimmune diseases. These reactions may be interpreted as molecular mimicry, which describes cross-reactivity between foreign pathogens and self-antigens that have been reported to cause tissue damage and to contribute to the development of autoimmunity. By focusing on the nature of antibodies, cross-reactivity in general, and antibody-antigen interactions, this review aims to characterize the nature of potential cross-reactive immune reactions between infectious non-self and self-tissue antigens which may be associated with autoimmunity but may not actually be the cause of disease onset.

Type 1 diabetes (T1D) is a complex autoimmune disease that develops in genetically susceptible individuals. Most T1D-associated single nucleotide polymorphisms (SNPs) are located in non-coding regions of the human genome. Interestingly, SNPs in long non-coding RNAs (lncRNAs) may result in the disruption of their secondary structure, affecting their function, and in turn, the expression of potentially pathogenic pathways. In the present work, the function of a virus-induced T1D-associated lncRNA named ARGI (Antiviral Response Gene Inducer) is characterized. Upon a viral insult, ARGI is upregulated in the nuclei of pancreatic β cells and binds to CTCF to interact with the promoter and enhancer regions of IFNβ and interferon-stimulated genes, promoting their transcriptional activation in an allele-specific manner. The presence of the T1D risk allele in ARGI induces a change in its secondary structure. Interestingly, the T1D risk genotype induces hyperactivation of type I IFN response in pancreatic β cells, an expression signature that is present in the pancreas of T1D patients. These data shed light on the molecular mechanisms by which T1D-related SNPs in lncRNAs influence pathogenesis at the pancreatic β cell level and opens the door for the development of therapeutic strategies based on lncRNA modulation to delay or avoid pancreatic β cell inflammation in T1D.

Reports around the world indicate that COVID-19 pandemic may be contributing to an increase in the incidence of new onset diabetic ketoacidosis (DKA). This has yet to be studied in Africa. We aimed to compare the incidence trend of new onset DKA before and during the COVID-19 pandemic, with a focus on the type of diabetes mellitus (DM).Materials and methodsThis was a cross sectional analytical study, over a 4-year period, between March 2018 until February 2022 conducted in the referral center: diabetology department of university hospital Farhat Hached Sousse, Tunisia. The study population included patients hospitalized for new onset DKA divided in two groups: G1: before COVID-19 pandemic and G2: during COVID-19 pandemic. Patients younger than 14, new onset DM not presenting with DKA, other types of diabetes (monogenic, secondary or pancreatic diabetes) were not included. A statistical analysis of the monthly incidence trend was conducted using the Jointpoint software providing the average monthly percentage of change (AMPC).

a total of 340 patients were included:137 registered before the pandemic and 203 during the pandemic, representing a 48.17% increase. The mean monthly incidence of new onset DKA during COVID-19 pandemic was statistically higher than that before COVID-19 pandemic (8.42 ± 4.87 vs 5.75 ± 4.29 DKA per month) (p=0.049). The temporal trend of DKA during the 4-year study showed a significant upward trend with a change in AMPC of +0.2% (p=0.037). The incidence of type 1 diabetes (T1D) and type 2 diabetes (T2D) increased by 50% and 44% respectively during COVID-19 pandemic. Anti-glutamic acid decarboxylase (anti-GAD) antibodies' titers significantly increased in G2 compared with G1 (median of 330[Q1-Q3]=[58.5-1795]vs 92.5[Q1-Q3]=[22.5-1074] respectively)(p=0.021).

The incidence trend of DKA showed an increase during the COVID-19 pandemic along with an increase of T1D and T2D implying that the pandemic may have been the underlying factor of this upward trend.

Coronavirus disease 2019 (COVID-19) is a complex infectious disease caused by the SARS-CoV-2 virus, and it currently represents a worldwide public health emergency. The pediatric population is less prone to develop severe COVID-19 infection, but children presenting underlying medical conditions, such as diabetes mellitus, are thought to be at increased risk of developing more severe forms of COVID-19. Diabetic children face new challenges when infected with SARS-CoV-2. On one hand, the glycemic values become substantially more difficult to manage as COVID-19 is a predisposing factor for hyperglycemia. On the other hand, alongside other risk factors, high glycemic values are incriminated in modulating immune and inflammatory responses, leading to potentially severe COVID-19 cases in the pediatric population. Also, there are hypotheses of SARS-CoV-2 being diabetogenic itself, but this information is still to be confirmed. Furthermore, it is reported that there was a noticeable increase in the number of cases of new-onset type 2 diabetes among the pediatric population, and the complications in these patients with COVID-19 include the risk of developing autoimmune diseases under the influence of stress. Additionally, children with diabetes mellitus are confronted with lifestyle changes dictated by the pandemic, which can potentially lead to the onset or exacerbation of a potential underlying anxiety disorder or depression. Since the literature contains a series of unknowns related to the impact of COVID-19 in both types of diabetes in children, the purpose of our work is to bring together the data obtained so far and to identify potential knowledge gaps and areas for future investigation regarding COVID-19 and the onset of diabetes type 1 or type 2 among the pediatric population.

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.

Inflammasome molecules make up a family of receptors that typically function to initiate a proinflammatory response upon infection by microbial pathogens. Dysregulation of inflammasome activity has been linked to unwanted chronic inflammation, which has also been implicated in certain autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes, systemic lupus erythematosus, and related animal models. Classical inflammasome activation-dependent events have intrinsic and extrinsic effects on both innate and adaptive immune effectors, as well as resident cells in the target tissue, which all can contribute to an autoimmune response. Recently, inflammasome molecules have also been found to regulate the differentiation and function of immune effector cells independent of classical inflammasome-activated inflammation. These alternative functions for inflammasome molecules shape the nature of the adaptive immune response, that in turn can either promote or suppress the progression of autoimmunity. In this review we will summarize the roles of inflammasome molecules in regulating self-tolerance and the development of autoimmunity.

Autoimmune and autoinflammatory diseases (AIIDs) involve a deficit in an individual's immune system function, whereby the immune reaction is directed against self-antigens. Many AIIDs have a strong genetic component, but they can also be triggered by environmental factors. AIIDs often have a highly negative impact on the individual's physical and mental wellbeing. Understanding the genetic underpinning of AIIDs is thus crucial both for diagnosis and for identifying individuals at high risk of an AIID and mental illness as a result thereof. The aim of the present study was to perform systematic statistical and genetic analyses to assess the role of human leukocyte antigen (HLA) alleles in 30 AIIDs and to study the links between AIIDs and psychiatric disorders. We leveraged the Danish iPSYCH Consortium sample comprising 65 534 individuals diagnosed with psychiatric disorders or selected as part of a random population sample, for whom we also had genetic data and diagnoses of AIIDs. We employed regression analysis to examine comorbidities between AIIDs and psychiatric disorders and associations between AIIDs and HLA alleles across seven HLA genes. Our comorbidity analyses showed that overall AIID and five specific AIIDs were associated with having a psychiatric diagnosis. Our genetic analyses found 81 significant associations between HLA alleles and AIIDs. Lastly, we show connections across AIIDs, psychiatric disorders and infection susceptibility through network analysis of significant HLA associations in these disease classes. Combined, our results include both novel associations as well as replications of previously reported associations in a large sample, and highlight the genetic and epidemiological links between AIIDs and psychiatric disorders.

Autoimmune diseases (AIDs) are the consequence of a breach in immune tolerance, leading to the inability to sufficiently differentiate between self and non-self. Immune reactions that are targeted towards self-antigens can ultimately lead to the destruction of the host's cells and the development of autoimmune diseases. Although autoimmune disorders are comparatively rare, the worldwide incidence and prevalence is increasing, and they have major adverse implications for mortality and morbidity. Genetic and environmental factors are thought to be the major factors contributing to the development of autoimmunity. Viral infections are one of the environmental triggers that can lead to autoimmunity. Current research suggests that several mechanisms, such as molecular mimicry, epitope spreading, and bystander activation, can cause viral-induced autoimmunity. Here we describe the latest insights into the pathomechanisms of viral-induced autoimmune diseases and discuss recent findings on COVID-19 infections and the development of AIDs.

The group B coxsackieviruses (CVBs) exist in six serotypes (CVB1 to CVB6). Disease associations have been reported for most serotypes, and multiple serotypes can cause similar diseases. For example, CVB1, CVB3, and CVB5 are generally implicated in the causation of myocarditis, whereas CVB1 and CVB4 could accelerate the development of type 1 diabetes (T1D). Yet, no vaccines against these viruses are currently available. In this review, we have analyzed the attributes of experimentally tested vaccines and discussed their merits and demerits or limitations, as well as their impact in preventing infections, most importantly myocarditis and T1D.