Comment on the consensus report on the management of hyperglycaemia in Type 2 diabetes by the American Diabetes Association and the European Association for the Study of Diabetes

Letter to the edito

Patients' Experience of therapeutic footwear whilst living at risk of neuropathic diabetic foot ulceration: an interpretative phenomenological analysis (IPA).

BACKGROUND: Previous work has found that people with diabetes do not wear their therapeutic footwear as directed, but the thinking behind this behaviour is unclear. Adherence to therapeutic footwear advice must improve in order to reduce foot ulceration and amputation risk in people with diabetes and neuropathy. Therefore this study aimed to explore the psychological influences and personal experiences behind the daily footwear selection of individuals with diabetes and neuropathy. METHODS: An interpretative phenomenological analysis (IPA) approach was used to explore the understanding and experience of therapeutic footwear use in people living at risk of diabetic neuropathic foot ulceration. This study benefited from the purposive selection of a small sample of four people and used in-depth semi structured interviews because it facilitated the deep and detailed examination of personal thoughts and feelings behind footwear selection. FINDINGS: Four overlapping themes that interact to regulate footwear choice emerged from the analyses: a) Self-perception dilemma; resolving the balance of risk experienced by people with diabetes and neuropathy day to day, between choosing to wear footwear to look and feel normal and choosing footwear to protect their feet from foot ulceration; b) Reflective adaption; The modification and individualisation of a set of values about footwear usage created in the minds of people with diabetes and neuropathy; c) Adherence response; The realignment of footwear choice with personal values, to reinforce the decision not to change behaviour or bring about increased footwear adherence, with or without appearance management; d) Reality appraisal; A here and now appraisal of the personal benefit of footwear choice on emotional and physical wellbeing, with additional consideration to the preservation of therapeutic footwear. CONCLUSION: For some people living at risk of diabetic neuropathic foot ulceration, the decision whether or not to wear therapeutic footwear is driven by the individual 'here and now', risks and benefits, of footwear choice on emotional and physical well-being for a given social context

White-to-brown metabolic conversion of human adipocytes by JAK inhibition

The rising incidence of obesity and related disorders such as diabetes and heart disease has focused considerable attention on the discovery of novel therapeutics. One promising approach has been to increase the number or activity of brown-like adipocytes in white adipose depots, as this has been shown to prevent diet-induced obesity and reduce the incidence and severity of type 2 diabetes. Thus, the conversion of fat-storing cells into metabolically active thermogenic cells has become an appealing therapeutic strategy to combat obesity. Here, we report a screening platform for the identification of small molecules capable of promoting a white-to-brown metabolic conversion in human adipocytes. We identified two inhibitors of Janus Kinase (JAK) activity with no precedent in adipose tissue biology that stably confer brown-like metabolic activity to white adipocytes. Importantly, these metabolically converted adipocytes exhibit elevated UCP1 expression and increased mitochondrial activity. We further found that repression of interferon signalling and activation of hedgehog signalling in JAK-inactivated adipocytes contributes to the metabolic conversion observed in these cells. Our findings highlight a novel role for the JAK/STAT pathway in the control of adipocyte function and establish a platform to identify compounds for the treatment of obesity

Supporting shared decision making for older people with multiple health and social care needs: a realist synthesis

Background: Health care systems are increasingly moving towards more integrated approaches. Shared decision making (SDM) is central to these models but may be complicated by the need to negotiate and communicate decisions between multiple providers, as well as patients and their family carers; particularly for older people with complex needs. The aim of this review was to provide a context relevant understanding of how interventions to facilitate SDM might work for older people with multiple health and care needs, and how they might be applied in integrated care models. Methods: Iterative, stakeholder driven, realist synthesis following RAMESES publication standards. It involved: 1) scoping literature and stakeholder interviews (n-13) to develop initial programme theory/ies, 2) systematic searches for evidence to test and develop the theories, and 3) validation of programme theory/ies with stakeholders (n=11). We searched PubMed, The Cochrane Library, Scopus, Google, Google Scholar, and undertook lateral searches. All types of evidence were included. Results: We included 88 papers; 29 focused on older people or people with complex needs. We identified four context-mechanism-outcome configurations that together provide an account of what needs to be in place for SDM to work for older people with complex needs. This includes: understanding and assessing patient and carer values and capacity to access and use care, organising systems to support and prioritise SDM, supporting and preparing patients and family carers to engage in SDM and a person-centred culture of which SDM is a part. Programmes likely to be successful in promoting SDM are those that allow older people to feel that they are respected and understood, and that engender confidence to engage in SDM. Conclusions: To embed SDM in practice requires a radical shift from a biomedical focus to a more person-centred ethos. Service providers will need support to change their professional behaviour and to better organise and deliver services. Face to face interactions, permission and space to discuss options, and continuity of patient-professional relationships are key in supporting older people with complex needs to engage in SDM. Future research needs to focus on inter-professional approaches to SDM and how families and carers are involved

Synthesis and characterization of fluorescent and photoactivatable MIP-1alpha ligands and interactions with chemokine receptors CCR1 and CCR5

Photoaffinity and fluorescent analogues of the 70-amino acid chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) were designed, synthesized, characterized, and applied to probe MIP-1alpha interactions with the chemokine receptors CCR1 and CCR5. The photoactivatable MIP-1alpha ligand, BP-MIP-1alpha, and the fluorescent ligand, Flu-MIP-1alpha were prepared by selective chemical coupling of p-benzoylphenylthiocarbamyl or fluoresceinthiocarbamyl, respectively, at the N-terminus of MIP-1alpha. Both ligands BP-MIP-1alpha and Flu-MIP-1alpha retained high binding affinity and agonist potency at CCR1 and CCR5. Photoaffinity labeling of CCR1 and CCR5 receptors stably expressed in CHO cells resulted in specific covalent attachment of [125I]BP-MIP-1alpha and production of protein complexes of 54 and 48 kDa, respectively, on SDS-PAGE. This represents the first photo-cross-linking between a chemokine and its receptor. Flu-MIP-1alpha selectively labeled CCR1 or CCR5 receptors expressed in CHO cells and was used to characterize receptor binding domains. When bound to CCR1 or CCR5 receptors, the fluorescence signal of Flu-MIP-1alpha was quenched by collision with iodide indicating that the N-terminal end of MIP-1alpha is accessible to the solvent. These data strongly suggest that the N-terminal end of MIP-1alpha interacts with domains of CCR1 or CCR5 receptors located at the extracellular surface. The photoactivatable BP-MIP-1alpha described here should prove valuable for the identification of contact sites on receptors by photoaffinity labeling experiments