Co-morbid Gestational Diabetes and PCOS: Risks and Management

Diabetes is emerging global burden and is defined as chronic metabolic disorder that results in elevated level of blood glucose and is due to beta cell destruction. Gestational diabetes is the type of diabetes that occurs in women during pregnancy or first recognized at the Gestational period. The prevalence of Gestational diabetes is increasing tremendously in developing countries. Approximately 2 to 14% of pregnancy is diagnosed with Gestational diabetes and 90% of all Gestational diabetes is reported from low- and middleincome countries. Of these North Africa has the highest prevalence followed by South Asia. The chance of developing type 2 diabetes is 7 times higher in women with previous history of Gestational diabetes and also it involves in increasing the risk of cardio metabolic disorders in later life. Gestational diabetes results from various complex interactions of environmental, genetic and maternal factors. Polycystic ovarian syndrome (PCOS), a major cause of infertility in women causes hormonal abnormalities and is also associated with insulin resistance. There exists a relationship between Gestational diabetes and PCOS stating that PCOS increase the risk of Gestational diabetes since insulin resistance is common factor in both. It is observed that the risk of Gestational diabetes is threefold higher n women with PCOS. Both PCOS as well as Gestational diabetes affects the quality of life of women due to many pathological changes. Life style modification is essential for management of PCOS and Gestational diabetes. Insulin therapy is recommended to treat hyperglycemic condition during pregnancy.

The MicroRNA Landscape of Acute Beta Cell Destruction in Type 1 Diabetic Recipients of Intraportal Islet Grafts

Ongoing beta cell death in type 1 diabetes (T1D) can be detected using biomarkers selectively discharged by dying beta cells into plasma. microRNA-375 (miR-375) ranks among the top biomarkers based on studies in animal models and human islet transplantation. Our objective was to identify additional microRNAs that are co-released with miR-375 proportionate to the amount of beta cell destruction. RT-PCR profiling of 733 microRNAs in a discovery cohort of T1D patients 1 h before/after islet transplantation indicated increased plasma levels of 22 microRNAs. Sub-selection for beta cell selectivity resulted in 15 microRNAs that were subjected to double-blinded multicenter analysis. This led to the identification of eight microRNAs that were consistently increased during early graft destruction: besides miR-375, these included miR-132/204/410/200a/429/125b, microRNAs with known function and enrichment in beta cells. Their potential clinical translation was investigated in a third independent cohort of 46 transplant patients by correlating post-transplant microRNA levels to C-peptide levels 2 months later. Only miR-375 and miR-132 had prognostic potential for graft outcome, and none of the newly identified microRNAs outperformed miR-375 in multiple regression. In conclusion, this study reveals multiple beta cell-enriched microRNAs that are co-released with miR-375 and can be used as complementary biomarkers of beta cell death.

Enhanced Characterization of Beta Cell Mass in a Tg(Pdx1-GFP) Mouse Model of Beta Cell Destruction

IntroductionMeasurement of pancreatic beta cell mass in animal models is a common assay in diabetes researches. Novel whole-organ clearance methods in conjunction with transgenic mouse models hold tremendous promise to improve methods for beta cell mass measurement. Here, we propose a refined method to estimate the beta cell mass using a new transgenic Tg(Pdx1-GFP) mouse model and a recently developed free-of-acrylamide clearing tissue (FACT) protocol. MethodsFirst, we generated and evaluated a Tg(Pdx1-GFP) transgenic mouse model. By using the FACT protocol in this model, we could quantify the beta cell mass and alloxan-induced beta cell destruction in whole pancreas specimens.ResultsTg(Pdx1-GFP) transgenic mice expressed green fluorescent protein (GFP) only in the beta cells of the pancreas and limited to the beta cells. This GFP expression enabled us to accurately measure beta cell loss in a beta cell destruction model. The results suggest that our proposed method can be used as a simple, rapid assay for beta cell mass measurement in studies of islet biology and diabetes.ConclusionThe Tg(Pdx1-GFP) transgenic mouse in conjunction with the FACT protocol can enhance large-scale screening studies in the field of diabetes.

The microRNA Landscape of Acute Beta Cell Destruction in Type 1 Diabetic Recipients of Intraportal Islet Grafts

Ongoing beta cell death in type 1 diabetes (T1D) can be detected using biomarkers selectively discharged by dying beta cells into plasma. MicroRNA-375 (miR-375) ranks among top biomarkers based on studies in animal models and human islet transplantation. Our objective was to identify additional microRNAs that are co-released with miR-375 proportionate to the amount of beta cell destruction. RT-PCR profiling of 733 microRNAs in a discovery cohort of T1D patients 1 hour before/after islet transplantation indicated increased plasma levels of 22 microRNAs. Sub-selection for beta cell selectivity resulted in 15 microRNAs that were subjected to double-blinded multicenter analysis. This led to identification of 8 microRNAs that were consistently increased during early graft destruction: besides miR-375, these included miR-132/204/410/200a/429/125b, microRNAs with known function and enrichment in beta cells. Their potential clinical translation was investigated in a third independent cohort of 46 transplant patients, by correlating post-transplant microRNA levels to C-peptide levels 2 months later. Only miR-375 and miR-132 had prognostic potential for graft outcome and none of the newly identified microRNAs outperformed miR-375 in multiple regression. In conclusion, this study reveals multiple beta cell-enriched microRNAs that are co-released with miR-375 and can be used as complementary biomarkers of beta cell death.

Endoplasmic Reticulum-Mitochondria Crosstalk and Beta-Cell Destruction in Type 1 Diabetes

Beta-cell destruction in type 1 diabetes (T1D) results from the combined effect of inflammation and recurrent autoimmunity. In response to inflammatory signals, beta-cells engage adaptive mechanisms where the endoplasmic reticulum (ER) and mitochondria act in concert to restore cellular homeostasis. In the recent years it has become clear that this adaptive phase may trigger the development of autoimmunity by the generation of autoantigens recognized by autoreactive CD8 T cells. The participation of the ER stress and the unfolded protein response to the increased visibility of beta-cells to the immune system has been largely described. However, the role of the other cellular organelles, and in particular the mitochondria that are central mediator for beta-cell survival and function, remains poorly investigated. In this review we will dissect the crosstalk between the ER and mitochondria in the context of T1D, highlighting the key role played by this interaction in beta-cell dysfunctions and immune activation, especially through regulation of calcium homeostasis, oxidative stress and generation of mitochondrial-derived factors.

Non-Genetically Encoded Epitopes Are Relevant Targets in Autoimmune Diabetes

Islet antigen reactive T cells play a key role in promoting beta cell destruction in type 1 diabetes (T1D). Self-reactive T cells are typically deleted through negative selection in the thymus or deviated to a regulatory phenotype. Nevertheless, those processes are imperfect such that even healthy individuals have a reservoir of potentially autoreactive T cells. What remains less clear is how tolerance is lost to insulin and other beta cell specific antigens. Islet autoantibodies, the best predictor of disease risk, are known to recognize classical antigens such as proinsulin, GAD65, IA-2, and ZnT8. These antibodies are thought to be supported by the expansion of autoreactive CD4+ T cells that recognize these same antigenic targets. However, recent studies have identified new classes of non-genetically encoded epitopes that may reflect crucial gaps in central and peripheral tolerance. Notably, some of these specificities, including epitopes from enzymatically post-translationally modified antigens and hybrid insulin peptides, are present at relatively high frequencies in the peripheral blood of patients with T1D. We conclude that CD4+ T cells that recognize non-genetically encoded epitopes are likely to make an important contribution to the progression of islet autoimmunity in T1D. We further propose that these classes of neo-epitopes should be considered as possible targets for strategies to induce antigen specific tolerance.

Innate Immunity Mediated Inflammation and Beta Cell Function: Neighbors or Enemies?

Type 1 diabetes (T1D) is still considered a huge burden because the available treatments are not effective in preventing the onset or progression of the disease. Recently, the idea that diabetes is an autoimmune disease mediated exclusively by T cells has been reshaped. In fact, T cells are not the only players with an active role in beta cell destruction. Macrophages and neutrophils, which physiologically reside in pancreatic tissue, can also participate in tissue homeostasis and damage by promoting innate immune responses and modulating inflammation. During the development of the pancreatic islet inflammation there is a strong interplay of both adaptive and innate immune cells, and the presence of innate immune cells has been demonstrated both in exocrine and endocrine pancreatic compartments during the earliest stages of insulitis. Innate immune cell populations secrete cytokines, which must be considered both as physiological and pathological mediators. In fact, it has been demonstrated that cytokines could regulate directly and indirectly insulin secretion and, simultaneously, trigger inflammatory reaction. Indeed, cytokines pathways could represent targets both to improve glucose metabolism and to prevent autoimmune damage. Concordantly, the combination of immunomodulatory strategies against both innate and adaptive immunity should be tested in the next future, as they can be more efficient to prevent or delay islet damage and T1D onset.

Integrative analyses of TEDDY Omics data reveal lipid metabolism abnormalities, increased intracellular ROS and heightened inflammation prior to autoimmunity for type 1 diabetes

Background The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective birth cohort designed to study type 1 diabetes (T1D) by following children with high genetic risk. An integrative multi-omics approach was used to evaluate islet autoimmunity etiology, identify disease biomarkers, and understand progression over time. Results We identify a multi-omics signature that was predictive of islet autoimmunity (IA) as early as 1 year before seroconversion. At this time, abnormalities in lipid metabolism, decreased capacity for nutrient absorption, and intracellular ROS accumulation are detected in children progressing towards IA. Additionally, extracellular matrix remodeling, inflammation, cytotoxicity, angiogenesis, and increased activity of antigen-presenting cells are observed, which may contribute to beta cell destruction. Our results indicate that altered molecular homeostasis is present in IA-developing children months before the actual detection of islet autoantibodies, which opens an interesting window of opportunity for therapeutic intervention. Conclusions The approach employed herein for assessment of the TEDDY cohort showcases the utilization of multi-omics data for the modeling of complex, multifactorial diseases, like T1D.

A Comprehensive Review on Recently Detected Herbal Phytoactives Having Anti-Diabetic Potential for Various Diabetes Related Complications

Background: Diabetes is a metabolic, endocrine disorder which is featured by hyperglycemia and glucose intolerance, primarily due to beta cell destruction, with Insulin Resistance playing a secondary role. It is treated with the help of many chemical based drugs as well as natural derivatives. Objective: There is urgent need to develop new efficacious, cheaper and more available drugs to face this growing public health challenge. Many anti-diabetic drugs are often often associated with many adverse effects. Materials & Methods: Literature was reviewed in a narrative manner in order to pertain the information about active phytoactives present in the different plants. Anti-diabetic drugs are often loaded with side effects; therefore, review is being done for the selection of effective natural therapeutic moieties with less or no adverse effects. Results: In this review article, we described the detailed review of recently detected bioactive compounds present in different natural substances; which can be used effectively for diabetes related adversities. Conclusion: Natural products based bioactive molecules have been proven to improve insulin resistance and other related complications through suppression of inflammatory signaling pathways.