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Treatment of type 2 diabetes includes lifestyle and pharmacological interventions. Drugs are marginally effective in achieving glycemic targets and reducing cardiovascular (CV) events, whereas intervention on lipids, blood pressure, and lifestyle is more effective. Rethink Organisation to iMprove Education and Outcomes (ROMEO) (ISRCTN19509463), a 4-year multicenter randomized trial, showed that patients with type 2 diabetes on group care (GC), a previously described systemic self-management education model, improved body weight, HbA1c, HDL and LDL cholesterol, blood pressure, quality of life, and health behaviors, compared with patients on usual care and similar pharmacological treatment (1). The ROMEO data set was fed into three risk engines, Framingham (2), UK Prospective Diabetes Study (UKPDS) (3), and CUORE (4), to verify if GC modifies CV risk scores. A total of 815 non-insulin–treated patients aged

Posted: 5 Jan 2022 This EU3D Research Paper tentatively explores ways of applying the differentiation lens from the EU to the global level of inter-state cooperation. Given the wide scope of this research agenda, its only ambition is to offer a few building blocks for further research on the basis of a relational view of differentiated cooperation, which starts with characterising the relations between actors rather than the actors themselves. The research paper is divided in four sections. (1) Whether differentiation is desirable and for whom if we seek to maximise democratic congruence, including vertical and horizontal non domination. (2) What types of differentiated relations constitute the landscape of forms of differentiation, presenting a relational typology consisting of selection, recognition, distinction and discretion. (3) Why delves into the many categories of causes or factors explaining why states engage in differentiation at the EU and the global level – reading functional and political drivers as indicators of patterns of relations, distinguishing in particular between states that are un-able, unwilling or unamenable when considering joining integration schemes. And finally the last section (4) How offers a few preliminary thoughts on how or under what conditions, DI/DC can pass the democratic congruence test.

PURPOSE: We examined the expression of a panel of epigenetic enzymes catalyzing histone tails post-transcriptional modifications, together with effectors of metabolic and inflammatory alterations, in type 2 diabetes. METHODS: Cross-sectional, case-control study of 21 people with type 2 diabetes and 21 matched controls. Total RNA was extracted from white cells and reverse transcribed. PCR primer assays for 84 key genes encoding enzymes known to modify genomic DNA and histones were performed. Western blot was performed on lysates using primary antibodies for abnormally expressed enzymes. Hormones and cytokines were measured by multiplex kits. A Bayesian network was built to investigate the relationships between epigenetic, cytokine, and endocrine variables. RESULTS: Co-activator-associated aRginine Methyltransferase 1 (CARM1) expression showed a five-fold higher median value, matched by higher protein levels, among patients who also had increased GIP, IL-4, IL-7, IL-13, IL-17, FGF basic, G-CSF, IFN-γ, and TNFα and decreased IP-10. In a Bayesian network approach, CARM1 expression showed a conditional dependence on diabetes, but was independent of all other variables nor appeared to influence any. CONCLUSIONS: Increased CARM1 expression in type 2 diabetes suggests that epigenetic mechanisms are altered in human diabetes. The impact of lifestyle and pharmacological treatment on regulation of this enzyme should be further investigated.