RESUMO
This review offers a comprehensive analysis of the intricate relationship between the gut virome and diabetes, elucidating the mechanisms by which the virome engages with both human cells and the intestinal bacteriome. By examining a decade of scientific literature, we provide a detailed account of the distinct viral variations observed in type 1 diabetes (T1D) and type 2 diabetes (T2D). Our synthesis reveals that the gut virome significantly influences the development of both diabetes types through its interactions, which indirectly modulate immune and inflammatory responses. In T1D, the focus is on eukaryotic viruses that stimulate the host's immune system, whereas T2D is characterized by a broader spectrum of altered phage diversities. Promisingly, in vitro and animal studies suggest fecal virome transplantation as a potential therapeutic strategy to alleviate symptoms of T2D and obesity. This study pioneers a holistic overview of the gut virome's role in T1D and T2D, its interplay with host immunity, and the innovative potential of fecal transplantation therapy in clinical diabetes management.
Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Viroma , Humanos , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/virologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/virologia , Animais , Bacteriófagos/genética , Bacteriófagos/fisiologia , Vírus/genética , Vírus/classificaçãoRESUMO
Endogenous retroviruses (ERVs) are involved in autoimmune diseases such as type 1 diabetes (T1D). ERV gene products homologous to murine leukemia retroviruses are expressed in the pancreatic islets of NOD mice, a model of T1D. One ERV gene, Gag, with partial or complete open reading frames (ORFs), is detected in the islets, and it contains many sequence variants. An amplicon deep sequencing analysis was established by targeting a conserved region within the Gag gene to compare NOD with T1D-resistant mice or different ages of prediabetic NOD mice. We observed that the numbers of different Gag variants and ORFs are linked to T1D susceptibility. More importantly, these numbers change during the course of diabetes development and can be quantified to calculate the levels of disease progression. Sequence alignment analysis led to identification of additional markers, including nucleotide mismatching and amino acid consensus at specific positions that can distinguish the early and late stages, before diabetes onset. Therefore, the expression of sequence variants and ORFs of ERV genes, particularly Gag, can be quantified as biomarkers to estimate T1D susceptibility and disease progression.
Assuntos
Diabetes Mellitus Tipo 1 , Retrovirus Endógenos , Produtos do Gene gag , Sequenciamento de Nucleotídeos em Larga Escala , Camundongos Endogâmicos NOD , Fases de Leitura Aberta , Animais , Camundongos , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/virologia , Diabetes Mellitus Tipo 1/imunologia , Fases de Leitura Aberta/genética , Retrovirus Endógenos/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Produtos do Gene gag/genética , Feminino , Ilhotas PancreáticasRESUMO
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 ß-cells, and type 2 (T2DM), accounting for approximately 95 % of cases globally and characterized by the inability of pancreatic ß-cells to meet the demand for insulin due to a relative ß-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.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/complicações , SARS-CoV-2/patogenicidade , Diabetes Mellitus/etiologia , Diabetes Mellitus/virologia , Diabetes Mellitus Tipo 1/virologia , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/complicações , Viroses/complicações , Células Secretoras de Insulina/virologia , Células Secretoras de Insulina/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/virologia , Diabetes Mellitus Tipo 2/metabolismoRESUMO
OBJECTIVES: It has been hypothesized that SARS-CoV-2 may play a role in the development of different forms of diabetes mellitus (DM). The Canary Islands have the highest incidence of type 1 DM (T1DM) reported in Spain (30-35/100,000 children under 14 years/year). In 2020-2021 we observed the highest incidence so far on the island of Gran Canaria, as a result of which we decided to evaluate the possible role of COVID-19 in the increased number of onsets. METHODS: We examined the presence of IgG antibodies against SARS-CoV-2 in children with new onset T1DM between October 2020 and August 2021. We compared recent T1DM incidence with that of the previous 10 years. RESULTS: Forty-two patients were diagnosed with T1DM (48.1/100,000 patients/year), representing a nonsignificant 25.7% increase from the expected incidence. Of the 33 patients who consented to the study, 32 presented negative IgG values, with only one patient reflecting undiagnosed past infection. Forty-four percent of patients presented with ketoacidosis at onset, which was similar to previous years. CONCLUSIONS: We conclude that there is no direct relationship between the increased incidence of T1DM and SARS-CoV-2 in the region. The COVID-19 pandemic did not result in an increased severity of T1DM presentation.
Assuntos
Anticorpos Antivirais/sangue , COVID-19/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/virologia , SARS-CoV-2/imunologia , Adolescente , Autoanticorpos/sangue , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/imunologia , Cetoacidose Diabética/epidemiologia , Humanos , Imunoglobulina G/sangue , Lactente , Recém-Nascido , Ilhotas Pancreáticas/imunologia , Espanha/epidemiologiaRESUMO
Objective: The association between enterovirus infection and type 1 diabetes (T1D) is controversial, and this meta-analysis aimed to explore the correlation. Methods: PubMed, Embase, Web of Science, and Cochrane Database were searched from inception to April 2020. Studies were included if they could provide sufficient information to calculate odds ratios and 95% confidence intervals. All analyses were performed using STATA 15.1. Results: Thirty-eight studies, encompassing 5921 subjects (2841 T1D patients and 3080 controls), were included. The pooled analysis showed that enterovirus infection was associated with T1D (P < 0.001). Enterovirus infection was correlated with T1D in the European (P < 0.001), African (P = 0.002), Asian (P = 0.001), Australian (P = 0.011), and Latin American (P = 0.002) populations, but no conclusion could be reached for North America. The association between enterovirus infection and T1D was detected in blood and tissue samples (both P < 0.001); no association was found in stool samples. Conclusion: Our findings suggest that enterovirus infection is associated with T1D.
Assuntos
Diabetes Mellitus Tipo 1/virologia , Infecções por Enterovirus/complicações , Enterovirus/fisiologia , Predisposição Genética para Doença , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patologia , Infecções por Enterovirus/virologia , Humanos , PrognósticoRESUMO
Type 1 diabetes (T1D) is a proinflammatory pathology that leads to the specific destruction of insulin producing ß-cells and hyperglycaemia. Much of the knowledge about type 1 diabetes (T1D) has focused on mechanisms of disease progression such as adaptive immune cells and the cytokines that control their function, whereas mechanisms linked with the initiation of the disease remain unknown. It has been hypothesized that in addition to genetics, environmental factors play a pivotal role in triggering ß-cell autoimmunity. The BioBreeding Diabetes Resistant (BBDR) and LEW1.WR1 rats have been used to decipher the mechanisms that lead to virus-induced T1D. Both animals develop ß-cell inflammation and hyperglycemia upon infection with the parvovirus Kilham Rat Virus (KRV). Our earlier in vitro and in vivo studies indicated that KRV-induced innate immune upregulation early in the disease course plays a causal role in triggering ß-cell inflammation and destruction. Furthermore, we recently found for the first time that infection with KRV induces inflammation in visceral adipose tissue (VAT) detectable as early as day 1 post-infection prior to insulitis and hyperglycemia. The proinflammatory response in VAT is associated with macrophage recruitment, proinflammatory cytokine and chemokine upregulation, endoplasmic reticulum (ER) and oxidative stress responses, apoptosis, and downregulation of adipokines and molecules that mediate insulin signaling. Downregulation of inflammation suppresses VAT inflammation and T1D development. These observations are strikingly reminiscent of data from obesity and type 2 diabetes (T2D) in which VAT inflammation is believed to play a causal role in disease mechanisms. We propose that VAT inflammation and dysfunction may be linked with the mechanism of T1D progression.
Assuntos
Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/virologia , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/virologia , Infecções por Parvoviridae/imunologia , Animais , Humanos , Parvovirus/imunologia , RatosRESUMO
AIMS/HYPOTHESIS: The Diabetes Virus Detection (DiViD) study is the first study to laparoscopically collect pancreatic tissue and purified pancreatic islets together with duodenal mucosa, serum, peripheral blood mononuclear cells (PBMCs) and stools from six live adult patients (age 24-35 years) with newly diagnosed type 1 diabetes. The presence of enterovirus (EV) in the pancreatic islets of these patients has previously been reported. METHODS: In the present study we used reverse transcription quantitative real-time PCR (RT-qPCR) and sequencing to characterise EV genomes present in different tissues to understand the nature of infection in these individuals. RESULTS: All six patients were found to be EV-positive by RT-qPCR in at least one of the tested sample types. Four patients were EV-positive in purified islet culture medium, three in PBMCs, one in duodenal biopsy and two in stool, while serum was EV-negative in all individuals. Sequencing the 5' untranslated region of these EVs suggested that all but one belonged to enterovirus B species. One patient was EV-positive in all these sample types except for serum. Sequence analysis revealed that the virus strain present in the isolated islets of this patient was different from the strain found in other sample types. None of the islet-resident viruses could be isolated using EV-permissive cell lines. CONCLUSIONS/INTERPRETATION: EV RNA can be frequently detected in various tissues of patients with type 1 diabetes. At least in some patients, the EV strain in the pancreatic islets may represent a slowly replicating persisting virus.
Assuntos
Diabetes Mellitus Tipo 1/virologia , Infecções por Enterovirus/virologia , Enterovirus/isolamento & purificação , Ilhotas Pancreáticas/virologia , RNA Viral/genética , Adulto , Linhagem Celular , Diabetes Mellitus Tipo 1/diagnóstico , Enterovirus/genética , Fezes/virologia , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Adulto JovemRESUMO
BACKGROUND AND AIMS: We aimed to assess patient perception toward the rapid implementation of virtual phone clinics among Saudi adult patients with type 1 diabetes mellitus (T1DM) during the coronavirus disease (COVID-19) pandemic. METHODS: This cross-sectional, web-based study included Saudi adult patients with T1DM who attended at least one virtual phone visit with the diabetes clinic at King Abdulaziz Medical City, Jeddah, Saudi Arabia, between August 1 and December 31, 2020. Patients anonymously answered a Google form-created Arabic questionnaire. Information about patient characteristics, outcome, and perception of the virtual phone visit were obtained. Data were presented using descriptive statistics, chi-square, one-way ANOVA, independent t-, and Welch's t-tests. RESULTS: The questionnaire was sent to 281 patients, of whom 201 completed it. 59.2% patients were satisfied with their overall virtual phone clinic experience, and 75.6% preferred to continue attending the virtual phone clinics in the future. The average perception value of patients toward virtual phone clinics was 67.76 ± 19.9, suggesting good perception among the majority. Negative or neutral views of current health, asking to be physically seen, and missing a virtual appointment were associated with significantly lower average patient perception value (p < 0.001). CONCLUSIONS: Most Saudi patients with T1DM have adapted to virtual phone consultations, exhibiting good satisfaction and perception, and high preference to continue using this system in the future. The utilization of the service to assist patients with diabetes is highly encouraged, especially during the COVID-19 pandemic. Strategies need to be developed to further enhance the patient experience.
Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , COVID-19/complicações , Diabetes Mellitus Tipo 1/prevenção & controle , Hospitalização/estatística & dados numéricos , Consulta Remota/estatística & dados numéricos , SARS-CoV-2/isolamento & purificação , Adolescente , Adulto , COVID-19/transmissão , COVID-19/virologia , Estudos Transversais , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 1/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Encaminhamento e Consulta , Arábia Saudita/epidemiologia , Inquéritos e Questionários , Adulto JovemRESUMO
AIMS/HYPOTHESIS: The incidence of type 1 diabetes is increasing more rapidly than can be explained by genetic drift. Viruses may play an important role in the disease, as they seem to activate the 2'-5'-linked oligoadenylate (2'-5'A) pathway of the innate antiviral immune system. Our aim was to investigate this possibility. METHODS: Innate antiviral immune pathways were searched for type 1 diabetes-associated polymorphisms using genome-wide association study data. SNPs within ±250kb flanking regions of the transcription start site of 64 genes were examined. These pathways were also investigated for type 1 diabetes-associated RNA expression profiles using laser-dissected islets from two to five tissue sections per donor from the Diabetes Virus Detection (DiViD) study and the network of Pancreatic Organ Donors (nPOD). RESULTS: We found 27 novel SNPs in genes nominally associated with type 1 diabetes. Three of those SNPs were located upstream of the 2'-5'A pathway, namely SNP rs4767000 (p = 1.03 × 10-9, OR 1.123), rs1034687 (p = 2.16 × 10-7, OR 0.869) and rs739744 (p = 1.03 × 10-9, OR 1.123). We also identified a large group of dysregulated islet genes in relation to type 1 diabetes, of which two were novel. The most aberrant genes were a group of IFN-stimulated genes. Of those, the following distinct pathways were targeted by the dysregulation (compared with the non-diabetic control group): OAS1 increased by 111% (p < 1.00 × 10-4, 95% CI -0.43, -0.15); MX1 increased by 142% (p < 1.00 × 10-4, 95% CI -0.52, -0.22); and ISG15 increased by 197% (p = 2.00 × 10-4, 95% CI -0.68, -0.18). CONCLUSIONS/INTERPRETATION: We identified a genetic predisposition in the 2'-5'A pathway that potentially contributes to dysregulation of the innate antiviral immune system in type 1 diabetes. This study describes a potential role for the 2'-5'A pathway and other components of the innate antiviral immune system in beta cell autoimmunity.
Assuntos
Nucleotídeos de Adenina/genética , Diabetes Mellitus Tipo 1/genética , Regulação da Expressão Gênica/fisiologia , Predisposição Genética para Doença , Imunidade Inata/genética , Oligorribonucleotídeos/genética , Polimorfismo de Nucleotídeo Único/genética , Viroses/imunologia , Adulto , Antivirais/uso terapêutico , Diabetes Mellitus Tipo 1/virologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Viroses/tratamento farmacológico , Adulto JovemRESUMO
In the last decade, the widespread application of shotgun metagenomics provided extensive characterization of the bacterial "dark matter" of the gut microbiome, propelling the development of dedicated, standardized bioinformatic pipelines and the systematic collection of metagenomic data into comprehensive databases. The advent of next-generation sequencing also unravels a previously underestimated viral population (virome) present in the human gut. Despite extensive efforts to characterize the human gut virome, to date, little is known about the childhood gut virome. However, alterations of the gut virome in children have been linked to pathological conditions such as inflammatory bowel disease, type 1 diabetes, malnutrition, diarrhea and celiac disease.
Assuntos
Doença Celíaca/virologia , Diabetes Mellitus Tipo 1/virologia , Diarreia/virologia , Doenças Inflamatórias Intestinais/virologia , Mucosa Intestinal/virologia , Viroma , Doença Celíaca/microbiologia , Criança , Diabetes Mellitus Tipo 1/microbiologia , Diarreia/microbiologia , Humanos , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/microbiologia , MetagenomaRESUMO
Rotaviruses, double-stranded, non-enveloped RNA viruses, are a global health concern, associated with acute gastroenteritis and secretory-driven watery diarrhoea, especially in infants and young children. Conventionally, rotavirus is primarily viewed as a pathogen for intestinal enterocytes. This notion is challenged, however, by data from patients and animal models documenting extra-intestinal clinical manifestations and viral replication following rotavirus infection. In addition to acute gastroenteritis, rotavirus infection has been linked to various neurological disorders, hepatitis and cholestasis, type 1 diabetes, respiratory illness, myocarditis, renal failure and thrombocytopenia. Concomitantly, molecular studies have provided insight into potential mechanisms by which rotavirus can enter and replicate in non-enterocyte cell types and evade host immune responses. Nevertheless, it is fair to say that the extra-intestinal aspect of the rotavirus infectious process is largely being overlooked by biomedical professionals, and there are gaps in the understanding of mechanisms of pathogenesis. Thus with the aim of increasing public and professional awareness we here provide a description of our current understanding of rotavirus-related extra-intestinal clinical manifestations and associated molecular pathogenesis. Further understanding of the processes involved should prove exceedingly useful for future diagnosis, treatment and prevention of rotavirus-associated disease.
Assuntos
Viroses do Sistema Nervoso Central/virologia , Diabetes Mellitus Tipo 1/virologia , Doenças do Sistema Digestório/virologia , Gastroenterite/virologia , Infecções Respiratórias/virologia , Infecções por Rotavirus/virologia , Animais , Pré-Escolar , Humanos , Lactente , Rotavirus/patogenicidade , Rotavirus/fisiologia , Infecções por Rotavirus/complicaçõesRESUMO
OBJECTIVES: Studies of the fecal virome in type 1 diabetes (T1D) have been limited to populations of Europe and the United States. We therefore sought to characterize the stool virome in children after onset of T1D and in matched control subjects from four geographically distant African and Asian countries. METHODS: Samples of stool were collected from 73 children and adolescents shortly after T1D onset (Azerbaijan 19, Jordan 20, Nigeria 14, Sudan 20) and 105 matched control subjects of similar age and locale. Metagenomic sequencing of the DNA and RNA virome was performed, and virus positivity was defined as more than 0.001% of reads of the sample. Selected viruses were also quantified using real-time PCR. Conditional logistic regression was used to model associations with eukaryotic virus positivity. RESULTS: Signals of 387 different viral species were detected; at least one eukaryotic virus was detected in 71% case and 65% control samples. Neither of observed eukaryotic virus species or genera differed in frequency between children with T1D and controls. There was a suggestive association of the total count of different viral genera per sample between cases (1.45 genera) and controls (1.10 genera, OR 1.24, 95%CI 0.98-1.57), and an unplanned subanalysis suggested marginally more frequent endogenous retrovirus signal in cases (in 28.8% vs. in 8.6% controls, OR = 4.55, 95%CI 1.72-12). CONCLUSIONS: No clear and consistent association with T1D was observed in the fecal viromes from four distant non-European populations. The finding of borderline associations of human endogenous retroviruses merits further exploration.
Assuntos
Diabetes Mellitus Tipo 1/virologia , Fezes/virologia , Adolescente , Azerbaijão , Estudos de Casos e Controles , Criança , Diabetes Mellitus Tipo 1/diagnóstico , Feminino , Microbioma Gastrointestinal , Humanos , Jordânia , Masculino , Nigéria , Sudão , ViromaRESUMO
This study aimed to assess the psychological impact of the COVID-19 pandemic on guardians of children and adolescents with type 1 diabetes. An online survey was performed to assess the prevalence of pandemic-related emotional burden, mental health disorders and diabetes-specific emotional burden related to diabetes care during the COVID-19 pandemic. Caregivers of children and adolescents with diabetes under the age of 18 and caregivers of youth without diabetes for the non-diabetes group were invited to participate. For the primary outcome, mental health disorders were evaluated using the Self-Reporting Questionnaire (SRQ-20), while pandemic-related emotional burden and diabetes-specific emotional burden related to diabetes care were evaluated in different domains with specific questions. For analyses, a hierarchical testing strategy was performed. A total of 764 participants were included in the study. Regarding the pandemic period, caregivers of youth with type 1 diabetes endorsed significantly more pandemic-related emotional burden for both themselves (OR 1.67; 95% CI, 1.10 to 2.53) and for their child (OR 2.28; 95% CI, 1.54 to 3.38) when compared to the non-diabetes group. The emotional burden evaluation on different age ranges showed that the two groups were similar when the dependent youth was younger than 6 years. Moreover, a positive screening for mental health disorders during social distancing was higher in the diabetes group compared to the non-diabetes group (OR 2.43; 95% CI, 1.70 to 3.47), particularly in those aged under 12 years old. There was no difference between groups in mental health disorders among caregivers of adolescents older than 12 years. Our results allow to conclude that concern, burden and mental health disorders can be present in caregivers of youth with diabetes, and behavioral changes during the COVID-19 pandemic may enhance this situation.
Assuntos
COVID-19/psicologia , Cuidadores/psicologia , Adulto , Ansiedade/psicologia , COVID-19/epidemiologia , COVID-19/virologia , Depressão/psicologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/virologia , Família , Feminino , Humanos , Masculino , Transtornos Mentais/epidemiologia , Saúde Mental , Pessoa de Meia-Idade , Pandemias , Prevalência , SARS-CoV-2/isolamento & purificação , Inquéritos e QuestionáriosAssuntos
COVID-19/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Hiperpigmentação/diagnóstico , Prurigo/diagnóstico , Adolescente , Negro ou Afro-Americano , Anticorpos Antivirais/sangue , Biópsia , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/virologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/virologia , Feminino , Humanos , Hiperpigmentação/imunologia , Hiperpigmentação/patologia , Hiperpigmentação/virologia , Imunoglobulina G/sangue , Prurigo/imunologia , Prurigo/patologia , Prurigo/virologia , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Pele/patologiaRESUMO
AIMS: To analyse the effects of confinement among people with type 1 diabetes (T1D) and their caregivers over the course of the COVID-19 crisis and to evaluate contemporary changes in medical assistance and patient preferences. METHODS: An observational cross-sectional study designed as a self-reported web-based survey was conducted over the course of the COVID-19 pandemic. RESULTS: A total of 769 subjects participated in the survey (603 people with T1D and 166 caregivers). Changes in glycaemic control were reported in 66% of cases, weight gain in 40.4% of cases and decreased exercise levels in 65.4% of cases. Of the cohort, 53% maintained contact with the healthcare team, and 23% received specific information related to COVID-19. Emotional support was requested by 17% of respondents. Regarding telemedicine, 97.9% agreed with its use with the following preferences regarding the future: telephone call (84.5%), video-call (60.6%) and platform devices (39.7%). CONCLUSIONS: Over the course of the COVID-19 pandemic, at least two-thirds of people with T1D underwent changes in the management of their condition. Almost all participants agreed with the concept of telemedicine, favouring telephone and video calls as their preferred means of communication.
Assuntos
COVID-19/complicações , Cuidadores/psicologia , Diabetes Mellitus Tipo 1/terapia , SARS-CoV-2/isolamento & purificação , Telemedicina/métodos , Adolescente , Adulto , Idoso , COVID-19/virologia , Estudos Transversais , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/virologia , Gerenciamento Clínico , Feminino , Humanos , Masculino , Assistência Médica , Pessoa de Meia-Idade , Espanha/epidemiologia , Inquéritos e Questionários , Adulto JovemRESUMO
Type 1 diabetes (T1D) is an auto-immune disorder characterized by a complex interaction between the host immune system and various environmental factors in genetically susceptible individuals. Genome-wide association studies (GWAS) identified different T1D risk and protection alleles, however, little is known about the environmental factors that can be linked to these alleles. Recent evidence indicated that, among those environmental factors, dysbiosis (imbalance) in the gut microbiota may play a role in the pathogenesis of T1D, affecting the integrity of the gut and leading to systemic inflammation and auto-destruction of the pancreatic ß cells. Several studies have identified changes in the gut microbiome composition in humans and animal models comparing T1D subjects with controls. Those changes were characterized by a higher abundance of Bacteroides and a lower abundance of the butyrate-producing bacteria such as Clostridium clusters IV and XIVa. The mechanisms by which the dysbiotic bacteria and/or their metabolites interact with the genome and/or the epigenome of the host leading to destructive autoimmunity is still not clear. As T1D is a multifactorial disease, understanding the interaction between different environmental factors such as the gut microbiome, the genetic and the epigenetic determinants that are linked with the early appearance of autoantibodies can expand our knowledge about the disease pathogenesis. This review aims to provide insights into the interaction between the gut microbiome, susceptibility genes, epigenetic factors, and the immune system in the pathogenesis of T1D.
Assuntos
Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/microbiologia , Diabetes Mellitus Tipo 1/virologia , Epigenoma , Microbioma Gastrointestinal , Predisposição Genética para Doença , Genoma Humano , Alelos , Animais , Bacteroides , Clostridium , Metilação de DNA , Estudo de Associação Genômica Ampla , Antígenos HLA , Humanos , Sistema Imunitário , Intestinos/microbiologia , Intestinos/virologia , Camundongos , Camundongos Endogâmicos NOD , Polimorfismo de Nucleotídeo Único , RNA não Traduzido/metabolismoRESUMO
BACKGROUND: The recent COVID-19 pandemic has accelerated the treatment process through IT/technological supports, useful in the management of chronic patients such as those affected by type 1 Diabetes Mellitus (T1DM). Specific routes for fragile patients such as those with micro-infusers have been created thanks to the application of "Diabetes Technology," which allows patients to monitor blood glucose quickly and easily. The present pilot study aimed to assess the quality of care provided to patients with micro-infusers in a delicate phase such as a pandemic lockdown. MATERIALS AND METHODS: A mixed-methods approach was used. In the first part, with prior written consent, patients with insulin pumps enrolled voluntarily. In the second part, the focus group discussion (FGD) was carried out with the voluntarily enrolled participants. The FGD data were organized and analyzed by the thematic areas. RESULTS: The number of patients with afferent insulin pumps at the center was 50 individuals. Among them, 20 patients voluntarily joined the first part of the study by completing the PACIC questionnaire, which gave an average result of 3.34 (min. 2.2 and max. 4.2). In the second part, the application of the focus group technique demonstrated that technology is decisive in the management of diabetic pathology, not only in the emergency phase. CONCLUSIONS: At the time of public health crises, alternative strategies such as Tele-Nursing or Telemedicine could be crucial for the management of patients with micro-infuser not only in critical moments, such as lockdown, but also in ordinary health management.
Assuntos
COVID-19/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Sistemas de Infusão de Insulina/estatística & dados numéricos , Insulina/administração & dosagem , SARS-CoV-2/isolamento & purificação , Telemedicina , Adulto , Glicemia/análise , COVID-19/transmissão , COVID-19/virologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/virologia , Gerenciamento Clínico , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Masculino , Monitorização Fisiológica , Projetos Piloto , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND AIMS: Type 1 diabetes (T1D) is a multifactorial autoimmune disease that combines genetics and environmental factors. The aim of this study is to determine the environmental risk factors and to investigate how virals infections are risks factors for type 1 diabetics whom have HLA DR3/DR4 predisposition in our population. METHODS: This study includes 233 subjects, 145 diabetics and 88 controls from regions of the extreme western of Algeria. All the informations related to the disease were collected using predesigned questionnaire. Using in silico approach, we attempt to improve the understanding of this analytical result by molecular mimicry, which is associated with the breakdown of several autoimmune pathologies. RESULTS: The statistical study showed that history of varicella and measles infection and T1D related inheritance and type 2 diabetes are risk factors for T1D in the population of Tlemcen. We have determined the homologous antigenic regions between the glycoprotein "gE" of the varicella virus, the "hemagglutinin" of measles and the human protein "HSP60" at the level of their sequence and 3D structure. These cross-reactive epitopes bind to MHC class II molecules (HLA DR3/DR4) that predispose to T1D but not to MHC class II molecules (HLA DR2) that protect against T1D. This epitopes induce Th2 cells but only "hemagglutinin" and "Hsp60" can activate Th1 differentiation. This indicates their potential to destroy pancreatic cells ß. CONCLUSION: Our study can allow us to adapt biological markers to genetically predisposed T1D and to establish a preventive strategy for healthy genetic predisposed individuals in Tlemcen population.
Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Antígeno HLA-DR3/metabolismo , Antígeno HLA-DR4/metabolismo , Sarampo/complicações , Mimetismo Molecular , Infecção pelo Vírus da Varicela-Zoster/complicações , Argélia/epidemiologia , Biomarcadores/análise , Glicemia/análise , Estudos de Casos e Controles , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/virologia , Seguimentos , Antígeno HLA-DR3/imunologia , Herpesvirus Humano 3/fisiologia , Humanos , Morbillivirus/fisiologia , PrognósticoRESUMO
AIMS: This study aims at evaluating the metrics of glycemic control in people with type 1 diabetes using the hybrid closed loop (HCL) system during the COVID-19 lockdown. METHODS: This is a retrospective study of thirty adults with type 1 diabetes using HCL and followed with telemedicine at an Italian University Hospital. Data on metrics of glucose control were collected at different times: two weeks before the lockdown (Time 0), first two weeks of lockdown (Time 1), last two weeks of lockdown (Time 2) and first two weeks after the lockdown (Time 3). The primary endpoint was the change in glucose management indicator (GMI) across the different time points. RESULTS: GMI did not worsen over time (Time 1 vs Time 3, 7% vs 6.9%, P < 0.05), whereas a reduction of mean glucose (P = 0.004) and indices of glucose variability was observed. Time in range (TIR) significantly increased (68.5% vs 73.5%, P = 0.012), and time above range (TAR) level 2 (251-400 mg/dL) significantly decreased (P = 0.002). The improvement of TIR and glucose variability was mainly observed in participants < 35 years. CONCLUSIONS: Adults with type 1 diabetes using HCL showed a significant improvement of most of the metrics of glucose control during the COVID-19 lockdown.