Immunotherapy using short immunogenic peptides of disease-related autoantigens restores immune tolerance in preclinical disease models. We studied safety and mechanistic effects of injecting human leukocyte antigen-DR4()-restricted immunodominant proinsulin peptide intradermally every 2 or 4 weeks for 6 months in newly diagnosed type 1 diabetes patients. Treatment was well tolerated with no systemic or local hypersensitivity. Placebo subjects showed a significant decline in stimulated C-peptide (measuring insulin reserve) at 3, 6, 9, and 12 months versus baseline, whereas no significant change was seen in the 4-weekly peptide group at these time points or the 2-weekly group at 3, 6, and 9 months. The placebo group's daily insulin use increased by 50% over 12 months but remained unchanged in the intervention groups. C-peptide retention in treated subjects was associated with proinsulin-stimulated interleukin-10 production, increased FoxP3 expression by regulatory T cells, low baseline levels of activated β cell-specific CD8 T cells, and favorable β cell stress markers (proinsulin/C-peptide ratio). Thus, proinsulin peptide immunotherapy is safe, does not accelerate decline in β cell function, and is associated with antigen-specific and nonspecific immune modulation.

2014 marks the 20th anniversary of adipokines. Through the identification of leptin, our perceived understanding of adipose tissue was changed instantaneously. From a simple dormant site of energy storage, adipose tissue is now recognized as an integral hub of various hormones known as adipokines. Although great strides have been made in characterizing these hormones in health, research also shows they are significantly implicated in a series of pathologies. One such condition is obesity. Defined as an excess of adipose tissue, obesity remains one of the greatest healthcare epidemics of the 21st century. With no definitive treatment, attention has shifted to understanding the role of adipokines in obesity. This review provides an introduction to the salient obesity-related adipokines and their possible application as a treatment for obesity.

The measurement of FGF-23 by both Immutopics assays is altered in the presence of low circulating concentrations of serum ferritin whereas with the Kainos intact assay this effect was not demonstrated. Serum ferritin should be measured when an elevated FGF-23 is obtained using the Immutopics C-terminal or intact FGF-23 assay to prevent misdiagnosis of the cause of this abnormality.

The aims of this study were to explore women's perceptions and experiences of being pregnant and having pre-existing type 1 diabetes mellitus, and to assess their physical, social, psychological, emotional and educational needs during their transition to motherhood.The qualitative design incorporated a purposive sample of seven women in their first pregnancy, who participated in one-to-one interviews with a researcher at 15-20 and 32-36 weeks gestation, and at 6-8 weeks post-partum.Qualitative analysis identified seven key themes from the data including: knowledge; physical and psychological impact; control and trust; catalyst to action; organisation of care and communication; attendance and intervention; expectations and systems.This study has shown that most women with diabetes who become pregnant are resigned to the fact that their pregnancy is considered high risk, and are willing to play their part to achieve a positive pregnancy outcome. However, they would also like to 'do the normal pregnant bit as well', 'normalise it and make it a nice experience' and make it feel 'less fragmented'. This woman-centred experience of pregnancy care, in women with type 1 diabetes mellitus, may motivate health professionals to revise their approach to care, prompt them to utilise the skills of each individual member of the multidisciplinary team to its full strength and potential, and assist in the provision of a positive, balanced and more holistic approach to care, specific to this client group.

AimsTo identify simple insulin regimens for people with Type 2 diabetes mellitus that can be accepted and implemented earlier in primary and specialist care, taking into consideration each individual's needs and capabilities.MethodsUsing randomized clinical trials identified by a search of the PubMed database, as well as systematic reviews, meta‐analyses and proof‐of‐concept studies, this review addresses topics of interest related to the progressive intensification of a basal insulin regimen to a basal‐plus regimen (one basal insulin injection plus stepwise addition of one to three preprandial short‐acting insulin injections/day) vs a basal‐bolus regimen (basal insulin plus three short‐acting insulin injections per day) in people with Type 2 diabetes. The review explores approaches that can be used to define the meal for first prandial injection with basal‐plus regimens, differences among insulin titration algorithms, and the importance of self‐motivation and autonomy in achieving optimum glycaemic control.ResultsA basal‐plus regimen can provide glycaemic control equivalent to that obtained with a full basal‐bolus regimen, with fewer injections of prandial insulin. The first critical step is to optimize basal insulin dosing to reach a fasting glucose concentration of ~6.7 mmol/l; this allows ~40% of patients with baseline HbA1c >75 mmol/mol (9%) to be controlled with only one basal insulin injection per day.ConclusionsCompared with a basal‐bolus regimen, a basal‐plus insulin regimen is as effective but more practical, and has the best chance of acceptance and success in the real world.

ObjectivesThe Royal College of Physician’s (RCP) Future Hospital Programme (FHP) set out a blueprint for a radical new model of care that put patient experience centre stage. This paper reports on the results of an independent evaluation of the FHP and focuses on the role public patient involvement (PPI) played in these projects. The paper explores the perceptions and experiences of those involved in the FHP of how PPI was operationalised in this context, and develops an ‘ex-post’ programme theory of PPI in the FHP. We conclude by assessing the benefits and challenges of this work.SettingSecondary care. The FHP consisted of eight clinician-led healthcare improvement hospital development sites with two phases.ParticipantsDevelopment site clinical teams, patient representatives, the RCP’s Patient and Carer Network, members of the FHP team, and fellows and members of the RCP.Design/methodsWe conducted an independent evaluation of the FHP using FHP documentation and data collected specifically for the evaluation: qualitative interviews, focus groups and a web-based survey.ResultsThe PPI initiatives set out to develop more patient-centred care and improve the patient experience. The mechanisms designed to meet these goals were (1) a programme of PPI in the development site’s projects, (2) a better understanding of patient experience and (3) evaluation of patient experience.ConclusionThis evaluation of the FHP identifies some key elements that need to be considered when attempting to more closely integrate PPI and co-production in service re-design. The structure of FHP over two phases enabled learning from phase I to be incorporated into phase II. Having the PPI representatives closely involved, developing communities of practice, and the oversight and measuring activities acted as ‘disciplinary structures’ that contributed to embedding PPI in the FHP and kept the patient experience at the forefront of the improvement initiatives.

Introduction: An oral glucose tolerance test (OGTT) six weeks after delivery is considered the gold standard test to identify persistently abnormal glucose metabolism in women with gestational diabetes mellitus (GDM) but the National Institute for Health and Clinical Excellence (NICE) recommends fasting plasma glucose (FPG) alone. This however, cannot be used to diagnose those with persisting impaired glucose tolerance and will also fail to identify some women with persisting diabetes mellitus (DM). This study aims to identify the percentage of women with DM and impaired glucose tolerance (IGT) that would be missed using this strategy. Methods: Data from 147 women from two sites were analysed. Fishers’ exact test was used to demonstrate differences between OGTT and FPG and a receiver operating characteristic curve was used to try and identify a FPG concentration that would predict a post-glucose load abnormality. Results: Fifty-two of the 147 women had a persistent abnormality in glucose metabolism. Twenty-three had impaired fasting glycaemia (IFG), 21 had IGT and eight women had DM. Only seven of the eight women with DM had a FPG ≥ 7.0 mmol/L and hence one out of eight women with DM (12.5%) and all 21 women with IGT would have been missed if FPG alone were used (p<0.001). Conclusion: Postnatal FPG alone is inadequate to identify all women with DM and would miss a significant number of women with IGT. An OGTT in all women with diagnosed GDM remains the gold standard test to identify persistent abnormal glucose metabolism in these women.

Both hospital-based care and physician training have undergone significant changes within the past decade. Current physician training in the UK is failing to meet the needs of patients, with significant numbers of acute and general medicine posts unfilled. Building on the themes of the 2013 Shape of Training review, we propose a model that places an alternative model of generalist-the 'future hospitalist'-at the centre of patient care and medical training. The reinstatement of the general physician at the heart of hospital care will increase flexibility in both training and workforce planning, and embed active leadership, patient safety and quality improvement in care delivery.