1.
B cells in type 1 diabetes mellitus and diabetic kidney disease.
Smith, MJ, Simmons, KM, Cambier, JC
Nature reviews. Nephrology. 2017;(11):712-720
-
-
Free full text
-
Abstract
Type 1 diabetes mellitus (T1DM) is an autoimmune disorder that affects an estimated 30 million people worldwide. It is characterized by the destruction of pancreatic β cells by the immune system, which leads to lifelong dependency on exogenous insulin and imposes an enormous burden on patients and health-care resources. T1DM is also associated with an increased risk of comorbidities, such as cardiovascular disease, retinopathy, and diabetic kidney disease (DKD), further contributing to the burden of this disease. Although T cells are largely considered to be responsible for β-cell destruction in T1DM, increasing evidence points towards a role for B cells in disease pathogenesis. B cell-depletion, for example, delays disease progression in patients with newly diagnosed T1DM. Loss of tolerance of islet antigen-reactive B cells occurs early in disease and numbers of pancreatic CD20+ B cells correlate with β-cell loss. Although the importance of B cells in T1DM is increasingly apparent, exactly how these cells contribute to disease and its comorbidities, such as DKD, is not well understood. Here we discuss the role of B cells in the pathogenesis of T1DM and how these cells are activated during disease development. Finally, we speculate on how B cells might contribute to the development of DKD.
2.
New Insights and Biomarkers for Type 1 Diabetes: Review for Scandinavian Journal of Immunology.
Heinonen, MT, Moulder, R, Lahesmaa, R
Scandinavian journal of immunology. 2015;(3):244-53
-
-
Free full text
-
Abstract
The increasing incidence of type 1 diabetes observed in the past 60 years has spawned massive efforts in multiple research fields to elucidate the aetiology of this disease. While GWAS studies provide a good genetic basis for the current knowledge, it is clear that environmental triggers and their influence in disease prevalence and origin are highly important. The realization of disease heterogeneity has created a requirement for better biomarkers to complement the known autoantibody markers and to more successfully predict the severity and onset time of the disease. Such biomarkers would be needed both for prevention as well as for monitoring disease activity and response to preventive and therapeutic measures. Systematic holistic approaches concentrating on the triggering molecular mechanisms, pancreatic beta cells, immune response, as well as the influence of diet and environment, are necessary to understand the disease pathogenesis and find a cure. The current genomic knowledge is being broadened with accompanying studies in epigenetics and transcriptomic regulation, metabolomics, proteomics and lipidomics, covering the whole system from beta cells, the profile and cellular balance of the infiltrating lymphocytes, to gut microbiota and viral infections. Here we highlight interesting recent findings in type 1 diabetes research.
3.
Impact of fetal and neonatal environment on beta cell function and development of diabetes.
Nielsen, JH, Haase, TN, Jaksch, C, Nalla, A, Søstrup, B, Nalla, AA, Larsen, L, Rasmussen, M, Dalgaard, LT, Gaarn, LW, et al
Acta obstetricia et gynecologica Scandinavica. 2014;(11):1109-22
-
-
Free full text
-
Abstract
The global epidemic of diabetes is a serious threat against health and healthcare expenses. Although genetics is important it does not explain the dramatic increase in incidence, which must involve environmental factors. Two decades ago the concept of the thrifty phenotype was introduced, stating that the intrauterine environment during pregnancy has an impact on the gene expression that may persist until adulthood and cause metabolic diseases like obesity and type 2 diabetes. As the pancreatic beta cells are crucial in the regulation of metabolism this article will describe the influence of normal pregnancy on the beta cells in both the mother and the fetus and how various conditions like diabetes, obesity, overnutrition and undernutrition during and after pregnancy may influence the ability of the offspring to adapt to changes in insulin demand later in life. The influence of environmental factors including nutrients and gut microbiota on appetite regulation, mitochondrial activity and the immune system that may affect beta cell growth and function directly and indirectly is discussed. The possible role of epigenetic changes in the transgenerational transmission of the adverse programming may be the most threatening aspect with regard to the global diabetes epidemics. Finally, some suggestions for intervention are presented.