This article summarizes the Diabetes UK evidence-based guidelines for the prevention of Type 2 diabetes and nutritional management of diabetes. It describes the development of the recommendations and highlights the key changes from previous guidelines. The nutrition guidelines include a series of recommendations for the prevention of Type 2 diabetes, nutritional management of Type 1 and Type 2 diabetes, weight management, management of microvascular and macrovascular disease, hypoglycaemia management, and additional considerations such as nutrition support, end-of-life care, disorders of the pancreas, care of the older person with diabetes, nutrition provided by external agencies and fasting. The evidence-based recommendations were graded using the Scottish Intercollegiate Guidelines Network methodology and, in a small number of topic areas, where strong evidence was lacking, the recommendations were reached by consensus. The Diabetes UK 2011 guidelines place an emphasis on carbohydrate management and a more flexible approach to weight loss, unlike previous guidelines which were expressed in terms of recommendations for individual nutrient intakes. Additionally, the guidelines for alcohol have been aligned to national recommendations. The full evidence-based nutrition guidelines for the prevention and management of diabetes are available from: http://www.diabetes.org.uk/nutrition-guidelines.

A summary of the latest evidence-based nutrition guidelines for the prevention and management of diabetes is presented. These guidelines are based on existing recommendations last published in 2011, and were formulated by an expert panel of specialist dietitians after a literature review of recent evidence. Recommendations have been made in terms of foods rather than nutrients wherever possible. Guidelines for education and care delivery, prevention of Type 2 diabetes, glycaemic control for Type 1 and Type 2 diabetes, cardiovascular disease risk management, management of diabetes-related complications, other considerations including comorbidities, nutrition support, pregnancy and lactation, eating disorders, micronutrients, food supplements, functional foods, commercial diabetic foods and nutritive and non-nutritive sweeteners are included. The sections on pregnancy and prevention of Type 2 diabetes have been enlarged and the weight management section modified to include considerations of remission of Type 2 diabetes. A section evaluating detailed considerations in ethnic minorities has been included as a new topic. The guidelines were graded using adapted 'GRADE' methodology and, where strong evidence was lacking, grading was not allocated. These 2018 guidelines emphasize a flexible, individualized approach to diabetes management and weight loss and highlight the emerging evidence for remission of Type 2 diabetes. The full guideline document is available at www.diabetes.org.uk/nutrition-guidelines.

The T-cell receptor (TCR) repertoire is selected in the thymus after rearrangement of genes encoding TCR alpha and beta chains. Selection is based on the recognition by newly emergent T cells of self-ligands associated with molecules of the major histocompatibility complex: some combinations result in positive selection, others in negative selection. Negative selection, or clonal deletion, is an important mechanism for eliminating autoreactive T cells. A group of self-ligands involved in clonal deletion was identified because they, like exogenous superantigens, were recognized by almost all T cells expressing particular TCR V beta genes. V beta 17a T cells are deleted by a tissue-specific ligand; V beta 6, V beta 7, V beta 8.1 and V beta 9 T cells are deleted by the minor lymphocyte-stimulating (Mls) determinant Mls-1a; V beta 3 T cells by Mls-2a and Mls-3a; V beta 11 T cells by ligands encoded by independently segregating genes; and V beta 5 T cells by ligands encoded by two genes. Chromosome mapping using recombinant inbred strains of mice and classic backcrosses show that Mls-1a in DBA/2 mice is encoded on chromosome 1, that one of the two ligand genes for deletion of V beta 5 T cells maps to chromosome 12 and that a ligand gene for V beta 11 deletion is linked to the CD8 locus on chromosome 6. Here we present evidence from three sets of backcross mice for concordance between V beta 11 deletion ligand genes on chromosomes 6, 12 and 14 and endogenous mouse mammary tumour virus integrant (Mtv) genomes.(ABSTRACT TRUNCATED AT 250 WORDS)

FGF21 does not play a major role in regulating the fasting response or ketosis in man. However, plasma FGF21 is elevated in response to pharmacological activation of PPAR alpha and PPAR delta and may contribute to the beneficial metabolic effects observed in response to pharmacotherapy with these compounds.

The diet was equally effective in those with and without diabetes.

We have applied MHC class I tetramers representing the two H2b MHC class I-restricted epitopes of the mouse male-specific minor transplantation Ag, HY, to directly determine the extent of expansion and immunodominance within the CD8+ T cell compartment following exposure to male tissue. Immunization with male bone marrow (BM), spleen, dendritic cells (DCs) and by skin graft led to rapid expansion of both specificities occupying up to >20% of the CD8+ T cell pool. At a high dose, whole BM or spleen were found to be more effective at stimulating the response than BM-derived DCs. In vivo, immunodominance within the responding cell population was only observed following chronic Ag stimulation, whereas epitope immunodominance was established rapidly following in vitro restimulation. Peptide affinity for the restricting MHC molecule was greater for the immunodominant epitope, suggesting that this might be a factor in the emergence of immunodominance. Using tetramers, we were able to directly visualize the cross-primed CD8+ HY response, but we did not find it to be the principal route for MHC class I presentation. Immunization with female spleen or DCs coated with the full complement of defined HY peptides, including the Ab-restricted CD4+ Th cell determinant, failed to induce tetramer-reactive cells.

In cellular immunology the critical balance between effector and regulatory mechanisms is highlighted by serious immunopathologies attributable to mutations in Foxp3, a transcription factor required for a major subset of regulatory T (Tr) cells. Thus, many studies have focused on the developmental origin of Tr cells, with the prevailing view that they emerge in the thymus from late-stage T-cell progenitors whose T-cell receptors (TCRs) engage high affinity (agonist) ligands. This study questions the completeness of that interpretation. Here we show that without any obvious effect on TCR-mediated selection, the normal differentiation of mouse gammabeta T cells into potent cytolytic and interferon-gamma-secreting effector cells is switched towards an aggregate regulatory phenotype by limiting the capacity of CD4+CD8+ T-cell progenitors to influence in trans early gammabeta cell progenitors. Unexpectedly, we found that the propensity of early TCR-alphabeta+ progenitors to differentiate into Foxp3+ Tr cells is also regulated in trans by CD4+CD8+ T-cell progenitor cells, before agonist selection.

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