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CD8+ T cells are perceived to play a major role in the pathogenesis of type 1 diabetes (T1D). In this study, we characterized the function and phenotype of circulating CD8+ memory T cells in samples from individuals at different stages of T1D progression using flow cytometry and single-cell multiomics. We observed two distinct CD8+ T-cell signatures during progression of T1D within the highly differentiated CD27−CD8+ memory T-cell subset. A proinflammatory signature, with an increased frequency of IFN-γ+TNF-α+ CD27−CD8+ memory T cells, was observed in children with newly diagnosed T1D (stage 3) and correlated with the level of dysglycemia at diagnosis. In contrast, a coinhibitory signature, with an increased frequency of KLRG1+TIGIT+ CD27−CD8+ memory T cells, was observed in islet autoantibody-positive children who later progressed to T1D (stage 1). No alterations within CD27−CD8+ memory T cells were observed in adults with established T1D or in children during the initial seroconversion to islet autoantibody positivity. Single-cell multiomics analyses suggested that CD27−CD8+ T cells expressing the IFNG+TNF+ proinflammatory signature may be distinct from those expressing the KLRG1+TIGIT+ coinhibitory signature at the single-cell level. Collectively, our findings suggest that distinct blood CD8+ T-cell signatures could be employed as potential biomarkers of T1D progression. Article Highlights: Blood CD8+ T-cell signatures have recently been associated with a slower progression of type 1 diabetes (T1D) after diagnosis and with clinical response to immunotherapy. We investigated blood CD8+ T-cell signatures in individuals at different stages of T1D progression. We observed two distinct CD8+ T-cell signatures at different stages of T1D: a proinflammatory signature in children with newly diagnosed T1D (stage 3) and a coinhibitory signature in autoantibody-positive children who later progressed to T1D (stage 1). CD8+ T-cell signatures could potentially be utilized as biomarkers for evaluating the risk of T1D progression. [ABSTRACT FROM AUTHOR]

Background: Mental disorders influence diet and food consumption, but there is a lack of consistent findings. Aims: To investigate food consumption, nutrient intakes and serum metabolic biomarkers in depressive, anxiety and alcohol use disorders in comparison with the remaining from a population-based nationwide sample. Methods: The study was based on the Health 2000 Survey data of which 5504 subjects aged 30 and over (3009 women and 2495 men) were used for the analysis. Depressive disorder, anxiety disorders and alcohol use disorders were diagnosed using the Composite International Diagnostic Interview (M-CIDI). The consumption of food and beverage items, and nutrient intakes were measured with a validated food frequency questionnaire, and the concentrations of biomarkers were determined in blood samples. Results: Overall, no similar differences with both genders were found in the intakes of energy, dietary fibre or macronutrients or in biomarkers in depressive or anxiety disorders. Women suffering from depressed disorder consumed more soft drinks ( P = 0.034) and women suffering from anxiety disorders consumed more oils ( P = 0.001), polyunsaturated fatty acids ( P = 0.001) and less potatoes ( P = 0.002) than the remaining participants. Men suffering from depressive disorder consumed less sweets and chocolate ( P = 0.001) and men with anxiety disorder consumed more tea ( P = 0.033) compared with the remaining participants. In alcohol use disorders, the intake of carbohydrate was lower in both genders ( P = 0.001 for women, P = 0.001 for men). Conclusions: A difference in the usual diet exists between individuals with alcohol use disorders and the remaining participants on a population level. No consistent difference in both genders between those with depressive or anxiety disorders and the remaining was found. [ABSTRACT FROM AUTHOR]

CD8+ T cells are perceived to play a major role in the pathogenesis of type 1 diabetes (T1D). In this study, we characterized the function and phenotype of circulating CD8+ memory T cells in samples from individuals at different stages of T1D progression using flow cytometry and single-cell multiomics. We observed two distinct CD8+ T-cell signatures during progression of T1D within the highly differentiated CD27-CD8+ memory T-cell subset. A proinflammatory signature, with an increased frequency of IFN-γ+TNF-α+ CD27-CD8+ memory T cells, was observed in children with newly diagnosed T1D (stage 3) and correlated with the level of dysglycemia at diagnosis. In contrast, a coinhibitory signature, with an increased frequency of KLRG1+TIGIT+ CD27-CD8+ memory T cells, was observed in islet autoantibody-positive children who later progressed to T1D (stage 1). No alterations within CD27-CD8+ memory T cells were observed in adults with established T1D or in children during the initial seroconversion to islet autoantibody positivity. Single-cell multiomics analyses suggested that CD27-CD8+ T cells expressing the IFNG+TNF+ proinflammatory signature may be distinct from those expressing the KLRG1+TIGIT+ coinhibitory signature at the single-cell level. Collectively, our findings suggest that distinct blood CD8+ T-cell signatures could be employed as potential biomarkers of T1D progression., (© 2024 by the American Diabetes Association.)

Objective: The associations between adrenal histopathology, lateralization studies, and surgical outcomes in primary aldosteronism remain poorly characterized. We examined the value of immunohistochemical analysis of CYP11B2 for evaluation of adrenalectomy outcomes after anatomical versus functional subtyping., Design: A retrospective multicenter study of 277 patients operated for primary aldosteronism who had an adrenalectomy sample available in the Finnish biobanks from 1 January 2000 to 31 December 2019. Adrenal slides from biobanks were analyzed centrally after CYP11B2 and CYP11B1 staining. Clinical data were obtained from patient registries. Histopathological diagnosis and cure after surgery were assessed as outcome measures., Results: Re-evaluation with CYP11B2 staining changed the histopathological diagnosis in 91 patients (33%). The presence of a CYP11B2-positive adenoma and the use of functional subtyping independently predicted clinical cure of primary aldosteronism. CYP11B2-positive <7 mm nodules were more frequent in patients without clinical cure, whereas CYP11B2-positive micronodules were common in all patients and had no impact on adrenalectomy outcomes. Small CYP11B2-positive nodules and micronodules were equally prevalent regardless of the subtyping method applied. Clinical cure rates were lower and CYP11B2-negative adenomas more common after adrenalectomy based on anatomical imaging than functional studies., Conclusions: Incorporating CYP11B2 staining in histopathological diagnosis enhances the prediction of surgical outcomes in primary aldosteronism. A finding of CYP11B2-positive adenoma is indicative of cure of primary aldosteronism, whereas smaller CYP11B2-positive nodules associate with poorer results at postoperative evaluation. Functional subtyping methods decrease the operations of CYP11B2-negative adenomas and are superior to anatomical imaging in identifying unilateral primary aldosteronism.