Autoimmune Destruction Of Beta Cells Research Articles

Prevention and treatment of type 1 diabetes: in search of the ideal combination therapy targeting multiple immunometabolic pathways

Type 1 diabetes (T1D) represents an autoimmune disease caused by the gradual immune-mediated destruction of the insulin-producing beta cells within the pancreatic islets of Langerhans, resulting in the lifelong need for exogenous insulin therapy. According to recent estimates, T1D currently affects about 8.4 million individuals worldwide. Since a definitive biological cure for this disease is not available yet, there is a great need for novel therapeutic strategies aimed at safely and effectively altering the natural history of the disease during its sequential stages. Ideal therapeutic goals in T1D include the prevention of autoimmune beta-cell destruction, the preservation of residual beta-cell mass and endogenous insulin secretion, the replacement and/or regeneration of beta cells, as well as automated insulin delivery through advanced closed-loop artificial pancreas systems. With this regard, an important research area focused on the identification of a definitive biological cure for T1D is represented by the investigation of immunotherapeutic and beta-cell-protective agents used as disease-modifying therapies to forestall or eliminate insulin dependence. In this commentary, we discuss the reasons why the use of combination therapies targeting the multiple immunometabolic dysfunctions associated with T1D (other than beta-cell autoimmunity) is likely to be more effective in preserving beta cell function in individuals at different stages of T1D, as compared to the use of single therapeutic agents.

Nutritional Management of Athletes with Type 1 Diabetes: A Narrative Review.

Type 1 diabetes mellitus (T1DM) represents a complex clinical challenge for health systems. The autoimmune destruction of pancreatic beta cells leads to a complete lack of insulin production, exposing people to a lifelong risk of acute (DKA, coma) and chronic complications (macro and microvascular). Physical activity (PA) has widely demonstrated its efficacy in helping diabetes treatment. Nutritional management of people living with T1DM is particularly difficult. Balancing macronutrients, their effects on glycemic control, and insulin treatment represents a complex clinical challenge for the diabetologist. The effects of PA on glycemic control are largely unpredictable depending on many individual factors, such as intensity, nutrient co-ingestion, and many others. Due to this clinical complexity, we have reviewed the actual scientific literature in depth to help diabetologists, sport medicine doctors, nutritionists, and all the health figures involved in diabetes care to ameliorate both glycemic control and the nutritional status of T1DM people engaging in PA. Two electronic databases (PubMed and Scopus) were searched from their inception to January 2024. The main recommendations for carbohydrate and protein ingestion before, during, and immediately after PA are explained. Glycemic management during such activity is widely reviewed. Micronutrient needs and nutritional supplement effects are also highlighted in this paper.

Exploring Transcriptional Regulation of Beta Cell SASP by Brd4-Associated Proteins and Cell Cycle Control Protein p21.

Type 1 diabetes (T1D) is a metabolic disease resulting from progressive autoimmune destruction of insulin-producing pancreatic beta cells. Although the majority of beta cells are lost in T1D, a small subset undergoes senescence, a stress response involving growth arrest, DNA damage response, and activation of a senescence-associated secretory phenotype (SASP). SASP in beta cells of the nonobese diabetic (NOD) mouse model of T1D and primary human islets is regulated at the level of transcription by bromodomain extra-terminal (BET) proteins, but the mechanisms remain unclear. To explore how SASP is transcriptionally regulated in beta cells, we used the NOD beta cell line NIT-1 to model beta cell SASP and identified binding partners of BET protein Brd4 and explored the role of the cyclin-dependent kinase inhibitor p21. Brd4 interacted with a variety of proteins in senescent NIT-1 cells including subunits of the Ino80 chromatin remodeling complex, which was expressed in beta cells during T1D progression in NOD mice and in human beta cells of control, autoantibody-positive, and T1D donors as determined from single-cell RNA-seq data. RNAi knockdown of p21 during senescence in NIT-1 cells did not significantly impact viability or SASP. Taken together, these results suggest that Brd4 interacts with several protein partners during senescence in NIT-1 cells, some of which may play roles in SASP gene activation and that p21 is dispensable for the SASP in this beta cell model.

A Quick Look at The Present and Immediate Future of Diabetes Mellitus Type 1

Type 1 diabetes (T1DM) is a hyperglycaemic syndrome that results from the autoimmune destruction of pancreatic beta cells. To achieve good metabolic control, for which we have an excellent technological tool, continuous interstitial glucose monitoring (CGM), which should be used in all pediatric patients from diagnosis. Positive results of delay in the diagnosis of DM1 and lengthening of the remission phase have been obtained with the use of monoclonal antibodies. Without a doubt, the greatest current advances in the treatment of DM1 come from the use of technology, together with regulated/structured and continued diabetes education, this being a fundamental piece to improve control, adherence to treatment and quality. of patient’s lives [1,2] . Despite all the advances in general, the objectives advocated by international societies for this age (American Diabetes Association [ADA], International Society for Pediatric and Adolescent Diabetes [ISPAD]) have not been achieved, leading to the search for other systems that lead to greater adherence to treatment.

Deletion of Vβ3+CD4+ T cells by endogenous mouse mammary tumor virus 3 prevents type 1 diabetes induction by autoreactive CD8+ T cells.

In both humans and NOD mice, type 1 diabetes (T1D) develops from the autoimmune destruction of pancreatic beta cells by T cells. Interactions between both helper CD4+ and cytotoxic CD8+ T cells are essential for T1D development in NOD mice. Previous work has indicated that pathogenic T cells arise from deleterious interactions between relatively common genes which regulate aspects of T cell activation/effector function (Ctla4, Tnfrsf9, Il2/Il21), peptide presentation (H2-A g7, B2m), and T cell receptor (TCR) signaling (Ptpn22). Here, we used a combination of subcongenic mapping and a CRISPR/Cas9 screen to identify the NOD-encoded mammary tumor virus (Mtv)3 provirus as a genetic element affecting CD4+/CD8+ T cell interactions through an additional mechanism, altering the TCR repertoire. Mtv3 encodes a superantigen (SAg) that deletes the majority of Vβ3+ thymocytes in NOD mice. Ablating Mtv3 and restoring Vβ3+ T cells has no effect on spontaneous T1D development in NOD mice. However, transferring Mtv3 to C57BL/6 (B6) mice congenic for the NOD H2 g7 MHC haplotype (B6.H2 g7) completely blocks their normal susceptibility to T1D mediated by transferred CD8+ T cells transgenically expressing AI4 or NY8.3 TCRs. The entire genetic effect is manifested by Vβ3+CD4+ T cells, which unless deleted by Mtv3, accumulate in insulitic lesions triggering in B6 background mice the pathogenic activation of diabetogenic CD8+ T cells. Our findings provide evidence that endogenous Mtv SAgs can influence autoimmune responses. Furthermore, since most common mouse strains have gaps in their TCR Vβ repertoire due to Mtvs, it raises questions about the role of Mtvs in other mouse models designed to reflect human immune disorders.

A Review on Latent Autoimmune Diabetes in Adults.

Latent autoimmune diabetes (LADA) is an unique form of diabetes that has characteristics of both type 1 and type 2 diabetes. Type 1.5 diabetes also known as LADA is occasionally confused for type 2 diabetes becausethere isdelayinpresenting featuresand early insulin independence. LADA, on the other hand, is an autoimmune disorder that differs from type 2 diabetes in that autoantibodies against pancreatic beta cells are what characterise it. Insulin production eventually diminishes due to the autoimmune destruction of pancreatic beta cells as a result of the pathophysiology of LADA. Autoantibodies to glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2), and insulin are frequently detected in LADA patients. These autoantibodies have important implications for therapy strategies and are essential in differentiating LADA from type 2 diabetes. LADA clinical management is very challenging. The aim of this article is to view the characteristics, disease presentation, diagnostic challenges, progression and treatment modalities of LADA.

The Current Status of Allogenic Islet Cell Transplantation.

Type 1 Diabetes (T1D) is an autoimmune destruction of pancreatic beta cells. The development of the Edmonton Protocol for islet transplantation in 2000 revolutionized T1D treatment and offered a glimpse at a cure for the disease. In 2022, the 20-year follow-up findings of islet cell transplantation demonstrated the long-term safety of islet cell transplantation despite chronic immunosuppression. The Edmonton Protocol, however, remains limited by two obstacles: scarce organ donor availability and risks associated with chronic immunosuppression. To overcome these challenges, the search has begun for an alternative cell source. In 2006, pluripotency genomic factors, coined "Yamanaka Factors," were discovered, which reprogram mature somatic cells back to their embryonic, pluripotent form (iPSC). iPSCs can then be differentiated into specialized cell types, including islet cells. This discovery has opened a gateway to a personalized medicine approach to treating diabetes, circumventing the issues of donor supply and immunosuppression. In this review, we present a brief history of allogenic islet cell transplantation from the early days of pancreatic remnant transplantation to present work on encapsulating stem cell-derived cells. We review data on long-term outcomes and the ongoing challenges of allogenic islet cell and stem cell-derived islet cell transplant.

OR18-05 Interleukin 21 Drives The Development Of Autoimmune Diabetes Mellitus During Immune Checkpoint Inhibitor Cancer Therapy

Abstract Disclosure: J.G. Ortega: None. L.N. Scott: None. S. Wang: None. S. Zhang: None. H. Chen: None. N. Huang: None. M. Lechner: None. Autoimmune diabetes mellitus is a rare but life-threatening side effect of immune checkpoint inhibitor (ICI) cancer therapy. Checkpoint inhibitors increase immune activation by blocking natural regulatory molecules on T cells, including programmed death protein (PD1) and cytotoxic T lymphocyte antigen (CTLA4). As a result of increased immune activation, up to 60% of patients may develop autoimmunity in healthy tissues. Endocrine tissues are among the most often affected by these immune related adverse events (IRAEs). ICI-associated diabetes mellitus (ICI-T1DM) results from autoimmune destruction of insulin-producing pancreatic beta-cells. Patients with ICI-T1DM frequently present in diabetic ketoacidosis and require life-long insulin therapy. Unfortunately, the cause of many IRAEs remains poorly understood. We recently developed a mouse model of IRAEs in which anti-PD1 + anti-CTLA4 antibody treatment of autoimmunity-prone non-obese diabetic mice leads to multi-organ autoimmune infiltrates, including acceleration of insulinitis and DM. ICI-treated mice had increased CD4+ T follicular (Tfh; PD1+ICOS+CXCR5+) and T peripheral helper (Tph; PD1+ICOS+CXCR5-) cells compared to isotype-treated controls. Such Tfh and Tph cells secrete interleukin (IL)-21 and can promote cytotoxic CD8+ T cell function in autoimmunity. Indeed, CD8+ T cells expressing Granzyme B, interferon gamma (IFNγ), and chemokine receptor CXCR6 ("CD8+ autoimmune mediators") were expanded in ICI-treated mice. Furthermore, in vitro, IL21 induced the autoimmune mediator phenotype in CD8+ T cells, with upregulation of IFNγ, cytotoxic and trafficking molecules. Using mice with genetic deletion of T cell receptor alpha (NOD.TCRa-/-), we showed that CD4+ and CD8+ T cells were required for the development of IRAEs in ICI-treated mice. In addition, adoptive transfer of CD4+ and CD8+ T cells into immunodeficient NOD.SCID mice confirmed that these populations were sufficient to cause DM during ICI treatment. Thus, we predicted that IL21 from Tfh and Tph cells contributes to the development of pancreas IRAEs by activating CD8+ autoimmune mediator T cells. Indeed, in our model, mice with genetic blockade of IL21 signaling (IL21R-/-) were protected from developing diabetes. After 4 weeks of ICI treatment, only one of 11 (9.1%) IL21R-/- mice developed DM with onset at day 28, compared to 80% of ICI-treated wild-type (WT) mice, with a median DM-free time of 10 days from start of ICI therapy (p<0.0001, Log Rank test); no isotype-treated WT or IL21R-/- mice developed diabetes. Histologic analyses of pancreatic tissue from ICI-treated mice also showed a significantly lower insulinitis index in IL21R-/- compared to WT mice (mean 0.19±0.06 vs. 0.7±0.14, p<0.01). In summary, we identify IL21+ CD4+ Tfh/Tph cells as drivers of pancreas IRAEs and a potential therapeutic target to prevent ICI-T1DM in cancer patients. Presentation: Saturday, June 17, 2023

Incidence of Type 1 Diabetes Mellitus in Hamadan West Region of Iran2019 - 2020

Objective: Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of insulin-producing beta cells of the pancreas. The objective of the present study was to describe the one year (2019-2020) incidence of T1DM in Hamadan west region of Iran.
 Materials and Methods: All 25 new patients with T1DM resident of Hamadan and its suburbs registered in Besat Hospital, Hamadan, Iran, from March 2019 to 2020 were prospectively reviewed. Information including age, sex, place of residence (urban or rural), season of diagnosis and season of birth were taken from parents through face-to-face interviews.
 Results: During 1 year survey, a total of 57 cases of newly diagnosed T1DM were identified in our center. Among these, 25 patients were residents of Hamadan city and suburbs. Based on this15 per 100 000 per year new cases T1DM occurred in the resident population of Hamadan areas, higher in boys than in girls (18 vs. 11 per 100 000).The mean age of diagnosis was 8.03 yr. The peak incidence was observed at the age group of 10- 14 years. 92% were urban .Most cases were diagnosed in the autumn (44%). 52% had a history of neonatal jaundice and 16% had stressful life events in the family before the onset of diabetes.
 Conclusion: Our study showed a relatively high incidence of T1DM according category of the WHO, being greater in boys and in the age group of 10 to 14 years. The incidence is lower than in some Middle Eastern countries.

Clinical Approach to Immunotherapy-induced Type 1 Diabetes Mellitus: A Case of Pembrolizumab Associated Insulin-dependent Diabetes in a Patient with NSCLC

As the introduction of immune checkpoint inhibitors in the treatment of various cancers is now proven to be already acquired knowledge, so does a new challenge arise for clinicians; the understanding, diagnosis, and management of the rarest adverse effects of immunotherapy. We present a case of type-1 diabetes Mellitus (T1DM) in a patient with non-small cell lung carcinoma (NSCLC) treated with pembrolizumab. Following ten cycles of treatment, our patient was diagnosed with T1DM after being admitted for diabetic ketoacidosis and stayed hospitalized in the ICU. Later, they continued treatment with insulin, having shown disease response to pembrolizumab, and resumed immunotherapy while on insulin. Immunotherapy-induced T1DM can sometimes occur with PD1/PD-L1 blockage therapies. It has a rapid onset, is characterized by insulin deficiency due to the autoimmune destruction of beta-cells, and usually presents itself with diabetic ketoacidosis. Unlike most of the other adverse effects of immunotherapy, glucocorticoids don’t seem to be of therapeutic value, and insulin substitution is required. Regular glucose monitoring can be key to early diagnosis and prevention of hospitalization.

IFNɣ but not IFNα increases recognition of insulin defective ribosomal product-derived antigen to amplify islet autoimmunity.

The inflammatory milieu characteristic of insulitis affects translation fidelity and generates defective ribosomal products (DRiPs) that participate in autoimmune beta cell destruction in type 1 diabetes. Here, we studied the role of early innate cytokines (IFNα) and late immune adaptive events (IFNɣ) in insulin DRiP-derived peptide presentation to diabetogenic CD8+ T cells. Single-cell transcriptomics of human pancreatic islets was used to study the composition of the (immuno)proteasome. Specific inhibition of the immunoproteasome catalytic subunits was achieved using siRNA, and antigenic peptide presentation at the cell surface of the human beta cell line EndoC-βH1 was monitored using peptide-specific CD8 T cells. We found that IFNγ induces the expression of the PSMB10 transcript encoding the β2i catalytic subunit of the immunoproteasome in endocrine beta cells, revealing a critical role in insulin DRiP-derived peptide presentation to T cells. Moreover, we showed that PSMB10 is upregulated in a beta cell subset that is preferentially destroyed in the pancreases of individuals with type 1 diabetes. Our data highlight the role of the degradation machinery in beta cell immunogenicity and emphasise the need for evaluation of targeted immunoproteasome inhibitors to limit beta cell destruction in type 1 diabetes. The single-cell RNA-seq dataset is available from the Gene Expression Omnibus (GEO) using the accession number GSE218316 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE218316 ).

Elevated glucose metabolism driving pro-inflammatory response in B cells contributes to the progression of type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease characterized by the immune system's failure to maintain self-tolerance, resulting in the autoimmune destruction of pancreatic beta cells. Although T1D has conventionally been viewed as a T-cell-dominant disease, recent research has emphasized the contribution of B cells in the onset of the disease. However, the mechanism underlying aberrant B cell responses remains unknown. B cell metabolism is a crucial prerequisite for B cell function and the development of adaptive immune responses. Here, we investigated the metabolic features of B cells, first in a cross-sectional cohort and subsequently in non-obese diabetic (NOD) mice, and revealed that there is an increased frequency of high-glucose-avidity (2-NBDGhigh) B cell population that may contribute to T1D progression. Further characterization of the metabolic, transcriptional and functional phenotype of B cells in NOD mice found that elevated glucose avidity is associated with a greater capacity for co-stimulation, proliferation and inflammatory cytokine production. Mechanistically, elevated Myc signaling orchestrated the glucose metabolism and the pro-inflammatory response of B cells in T1D. In vitro experiments demonstrated that pharmacological inhibition of glucose metabolism using metformin and 2-DG reduced pro-inflammatory cytokine production and B cell proliferation. Moreover, the combination of these inhibitors successfully delayed insulitis development, onset of diabetes, and improved high blood glucose levels in streptozotocin (STZ)-induced diabetic mice model. Taken together, our work has uncovered these high-glucose-avidity B cells as novel adjuvant diagnostic and therapeutic targets for T1D.

Frequency of Celiac Disease among Children with Type I Diabetes Mellitus

Background: Type 1 diabetes mellitus (T1DM) is a metabolic condition of chronic hyperglycemia due to a lack of insulin resulting from the autoimmune destruction of pancreatic beta cells. T1DM is associated with many autoimmune conditions, especially hypothyroidism and celiac disease (CD). Objective: To determine the frequency of celiac disease among children and adolescents with type 1 diabetes mellitus. Study Design: Prospective cross-sectional study. Settings: Department of Pediatric Gastroenterology, Hepatology, and Nutrition, University of Child Health Sciences, The Children’s Hospital, Lahore Pakistan. Duration: October 2019 to January 2022. Methods: A total of 150 children and adolescents with T1DM were included in this study. Patients already diagnosed with CD, patients with concomitant autoimmune disease, patients with Down syndrome, and patients who refused to participate and who lost follow-up were excluded from the study. All patients underwent a celiac screen, and those with positive or borderline serology had an endoscopic biopsy of the distal duodenum. Biopsy reporting was done as per Modified Marsh Classification. The patient's data and laboratory findings were recorded through a predesigned proforma and analyzed using SPSS version 20. Results: The mean age of participants was 8.08 ± 2.95 years, including 79 (52.7%) male and 71 (47.3%) female patients. A total of 19 (12.7%) had positive serology for celiac disease, and 8 (5.3%) had biopsy findings confirming celiac disease. Conclusion: Children and adolescents with T1DM have an increased tendency for CD, warranting earlier screening for timely detection and management.

1332-P: Comparison of Clinical Characteristics of People Living with Latent Autoimmune Diabetes of the Adult (LADA) and Type 1 Diabetes (T1D) in the Canadian BETTER Registry

Introduction: LADA is known for a slow progression of autoimmune destruction of beta-cells with cases that span a spectrum between classic T1D and T2D phenotypes. To date, lacking a good understanding of LADA has prohibited the release of specific clinical practice guidelines and subsequently an optimal management. Methodology: Cross-sectional analysis of online clinical questionnaires in the Canadian BETTER registry; participants can specify having received a diagnosis of LADA or T1D. Data was analyzed for the first 1464 participants; 131 (9%) reported LADA and 1333 (91%) T1D. Results: At registration; LADA vs T1D were 49 ± 13 y.o. vs 42 ± 15 y.o; 61% vs. 62% females; diabetes duration 10 ± 9 vs. 24 ± 15 years. LADA vs. T1D were older at diagnosis (39 ± 12 vs. 18 ± 12 years old; p<0.001), only half started insulin in first year of diagnosis (52 vs. 97%; p<0.001), more often reported a family history of T1D (46 vs. 32%; p=0.001). For comparable glycemic control (HbA1c < 8.6 mmol/l, <7%, 38 vs. 32%), fewer cases with LADA reported at least an episode in last month of level II hypoglycemia <54 mg/dL (3.0mmol/L) 63% vs. 77%; p= 0.004, severe hypoglycemia rates were 8% vs. 12%, p=0.15. Diabetes related hospitalizations were 10% in LADA vs. 6%, p=0.11, insulin pumps and glucagon were less used in LADA. In a matched analysis for diabetes duration and gender (1:1), glycemic control was still statistically comparable in LADA vs. T1D (HbA1c <7%: 38 vs 35%, p=0.12) as well as rates of nephropathy (6% vs. 11%, p=0.22), neuropathy (12% vs. 7%, p=0.23) and retinopathy (6% vs. 9%, p=0.07) yet with more cardiovascular disease (5% vs. 2%; p=0.02) and less coeliac disease (3 vs. 5%; p=0.001). Data analysis of 3000 participants is ongoing in early 2023. Conclusion: Reported differences may impact LADA management. This study sets the stage for building a prospective Canadian cohort of LADA to undergo deep phenotyping, genotyping and interventional trials. Disclosure M.Issa: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé. S.Haag: Other Relationship; Omnipod. A.Roy-fleming: None. V.Messier: None. N.Taleb: Consultant; Viatris Inc.

Deletion of Vβ3 +CD4 +T-cells by endogenous mouse mammary tumor virus 3 prevents type 1 diabetes induction by autoreactive CD8 +T-cells

Abstract In both humans and NOD mice, type 1 diabetes (T1D) develops from the autoimmune destruction of pancreatic beta cells by T-cells. Interactions between both helper CD4 +and cytotoxic CD8 +T-cells are essential for T1D development in NOD mice. Previous work has indicated that pathogenic T-cells arise from deleterious interactions between relatively common genes which regulate aspects of T-cell activation/effector function (Ctla-4, Tnfrsf9, Il2/Il21), peptide presentation (H2-A g7, B2m), and T-cell receptor signaling (Ptpn22). In this study, we used a combination of subcongenic mapping and a CRISPR/Cas9 screen to identify the NOD-encoded Mtv3 provirus as a genetic element affecting CD4 +/CD8 +T-cell interactions through an additional mechanism, altering the T-cell receptor (TCR) repertoire. Mtv3 encodes a superantigen that deletes the majority of Vβ3 +thymocytes in NOD mice. Ablating Mtv3 and restoring Vβ3 +T-cells has no effect on spontaneous T1D development in NOD mice. However, transferring Mtv3 to C57BL/6 (B6) mice congenic for the NOD H2 g7MHC haplotype (B6.H2 g7) completely blocks their normal susceptibility to T1D mediated by transferred CD8 +T-cells transgenically expressing AI4 or NY8.3 TCRs. The entire genetic effect is manifest by Vβ3 +CD4 +T-cells, which unless deleted by Mtv3, accumulate in insulitic lesions and trigger in B6 background mice the pathogenic activation of diabetogenic CD8 +T-cells. Our findings provide evidence that endogenous Mtv superantigens can influence autoimmune responses. Furthermore, since most common mouse strains have gaps in their TCR Vβ repertoire due to Mtvs, it raises questions about the role of Mtvs in other mouse models designed to reflect human disorders. Supported by grants from the American Diabetes Association (1-14-BS-051) and NIH (AI130656)

Type 1 Diabetes Mellitus and Autoimmune Diseases: A Critical Review of the Association and the Application of Personalized Medicine.

Type 1 Diabetes Mellitus (T1DM) is a common hyperglycemic disease characterized by the autoimmune destruction of insulin-producing beta cells of the pancreas. Various attempts have been made to understand the complex interplay of genetic and environmental factors which lead to the development of the autoimmune response in an individual. T1DM is frequently associated with other autoimmune illnesses, the most common being autoimmune thyroid disorders affecting more than 90% of people with T1D and autoimmune disorders. Antithyroid antibodies are present in around 20% of children with T1D at the start of the illness and are more frequent in girls. Patients with T1DM often have various other co-existing multi-system autoimmune disorders including but not limited to thyroid diseases, parathyroid diseases, celiac disease, vitiligo, gastritis, skin diseases, and rheumatic diseases. It is a consistent observation in clinics that T1DM patients have other autoimmune disorders which in turn affect their prognosis. Concomitant autoimmune illness might affect diabetes care and manifest itself clinically in a variety of ways. A thorough understanding of the complex pathogenesis of this modern-day epidemic and its association with other autoimmune disorders has been attempted in this review in order to delineate the measures to prevent the development of these conditions and limit the morbidity of the afflicted individuals as well. The measures including antibody screening in susceptible individuals, early identification and management of other autoimmune disorders, and adoption of personalized medicine can significantly enhance the quality of life of these patients. Personalized medicine has recently gained favor in the scientific, medical, and public domains, and is frequently heralded as the future paradigm of healthcare delivery. With the evolution of the 'omics', the individualization of therapy is not only closer to reality but also the need of the hour.

The effect of pregnant serum, cord blood serum and hCG on jurkat T-cell IL-2 secretion

Type 1 diabetes mellitus (T1DM) results in autoimmune destruction of insulin producing pancreatic beta cells. Although thought to be terminally differentiated, beta cells may undergo expansion during pregnancy. As pregnancy creates a state of immune tolerance, exploring this finding may offer insights to possible therapies for T1DM. We investigated whether circulating factors in serum from pregnant women could reduce the degree of immune activation of human T cells specific for beta cell antigens by measuring interleukin-2 (IL-2).

Monogenic diabetes : a pioneer in precision medicine management

Diabetes mellitus in children is subdivided into several categories depending on the underlying pathological mechanism. Type 1 diabetes is due to the autoimmune destruction of pancreatic beta-cells, type 2 diabetes to progressive impairment in insulin secretion or insulin sensitivity, and monogenic diabetes due to genetic abnormalities, impairing insulin secretion. In monogenic diabetes, genetic defects result in pancreatic or beta-cell defects (abnormal function or destruction), resulting in neonatal or MODY (Maturity-Onset Diabetes of the Young) diabetes, depending on the age of onset. The identification of monogenic diabetes is crucial as it allows the initiation of targeted and personalized treatment.

PSYCHOSOCIAL ISSUES IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS

ABSTRACT: Type 1 diabetes mellitus (T1DM) is a form of DM that results from autoimmune destruction of insulin producing beta cells of the pancreas. There is enough discussion about the pharmacological management of the disease but its psycho-sociological aspect has not been explored much. Patient with T1DM often experience psychological stress during the first year of diagnosis. , Approximately 36% of patients have some sort of psychiatric disorder in the first year, which may be related to both stress and treatment side effects. The lifelong administration of insulin, a restricted diet and complications from diabetes can cause great difficulties in living a normal life for patients. For optimum survival, psychological monitoring must be done along with medical treatment beginning from the diagnosis. A multidisciplinary team should be involved to assess newly diagnosed type 1 diabetes mellitus. The team should include a pediatric endocrinologist, nurse educator, dietician and mental health professional to provide specific education and support for patients. Interaction between parents, nurses, doctors and the school authority must be ensured to monitor the child\'s progress closely. Above all, proper education of self-care must be given so that the child can cope with his/her existing disease and maintain self-confidence while ensuring self-management. In addition, it is important that he/she adapts to life at large. KEYWORDS: Type 1 Diabetes mellitus, Adolescence, Psychological stress, Psychosocial issues, Self management

Perinatal Stem Cell Therapy to Treat Type 1 Diabetes Mellitus: A Never-Say-Die Story of Differentiation and Immunomodulation

Human term placenta and other postpartum-derived biological tissues are promising sources of perinatal cells with unique stem cell properties. Among the massive current research on stem cells, one medical focus on easily available stem cells is to exploit them in the design of immunotherapy protocols, in particular for the treatment of chronic non-curable human diseases. Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells and perinatal cells can be harnessed both to generate insulin-producing cells for beta cell replenishment and to regulate autoimmune mechanisms via immunomodulation capacity. In this study, the strong points of cells derived from amniotic epithelial cells and from umbilical cord matrix are outlined and their potential for supporting cell therapy development. From a basic research and expert stem cell point of view, the aim of this review is to summarize information regarding the regenerative medicine field, as well as describe the state of the art on possible cell therapy approaches for diabetes.