Double or hybrid diabetes: A systematic review on disease prevalence, characteristics and risk factors

Diabetes mellitus is a worldwide epidemic affecting the health of millions of people. While type 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing beta cells of the pancreas, type 2 diabetes (T2D) results from a combination of insulin resistance and beta cell insulin secretory defect. Clear definition and diagnosis of these two types of diabetes has been increasing more and more difficult, leading to the inclusion of a new category, namely double or hybrid diabetes (DD) that demonstrates symptoms of both T1D and T2D via the accelerator hypothesis. In this review, we discuss the worldwide prevalence of DD, its main physiological characteristics, including beta-cell autoimmunity, insulin resistance, and cardiovascular disease, the main risk factors of developing DD, mainly genetics, obesity and lifestyle choices, as well as potential treatments, such as insulin titration, metformin and behavioural modifications. Increasing awareness of DD among the general population and primary care practitioners is necessary for successfully treating this complex, hybrid disease in the future.

Az 1-es típusú diabetes genetikája: jelen és jövő

Over the past decades the majority of genetic research focused on common diseases, and remarkable results were obtained for exploring the genetic background of type 1 diabetes. The classic linkage analyses and the modern genome-wide association studies demonstrated that the genetic background is the primary risk factor for beta-cell autoimmunity while the progression to clinical onset could be triggered by the genetic factors, epigenetic modifications of gene expression and environmental factors together. The new system biology concept can help to understand the mechanisms underlying the immune-mediated beta-cell destruction by generating networks based on data from whole genome scans, fine mapping and gene expression studies to develop targeted prevention and therapeutic strategies. In this paper, we discuss the present understanding of genetic factors which could initiate beta-cell autoimmunity (i.e. define the aetiology) and the genetic and epigenetic factors which might contribute to the progression to clinical disease in individuals with autoantibodies (i.e. define the pathogenesis). Orv Hetil. 2017; 158(44): 1731–1740.

Peripherally-induced regulatory T cells contribute to the control of autoimmune diabetes

Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic beta cells and is partly caused by deficiencies in the Foxp3+ regulatory T cell (Treg) compartment. Conversely, therapies that increase Treg function can prevent autoimmune diabetes in animal models. The majority of Tregs develop in the thymus (tTregs), but a proportion of Foxp3+ Tregs is generated in the periphery (pTregs) from Foxp3-CD4+ T cell precursors. Whether pTregs play a distinct role in T1D has not yet been explored. We report here that pTregs are a key modifier of disease in the nonobesed diabetic (NOD) mouse model for T1D. We generated NOD mice deficient for the Foxp3 enhancer CNS1 involved in pTreg induction. We show that CNS1 knockout decreased the frequency of pTregs and increased the risk of diabetes. Our results show that pTregs fulfill an important non-redundant function in the prevention of beta cell autoimmunity that causes T1D.