3-Deoxyfructose concentrations are increased in human plasma and urine in diabetes

3-Deoxyglucosone (3-DG) is a reactive dicarbonyl sugar thought to be a key intermediate in the nonenzymatic polymerization and browning of proteins by glucose. 3-DG may be formed in vivo from fructose, fructose 3-phosphate, or Amadori adducts to protein, such as N epsilon-fructoselysine (FL), all of which are known to be elevated in body fluids or tissues in diabetes. Modification of proteins by 3-DG formed in vivo is thought to be limited by enzymatic reduction of 3-DG to less reactive species, such as 3-deoxyfructose (3-DF). In this study, we have measured 3-DF, as a metabolic fingerprint of 3-DG, in plasma and urine from a group of diabetic patients and control subjects. Plasma and urinary 3-DF concentrations were significantly increased in the diabetic compared with the control population (0.853 +/- 0.189 vs. 0.494 +/- 0.072 microM, P <0.001, and 69.9 +/- 44.2 vs. 38.7 +/- 16.1 nmol/mg creatinine, P <0.001, respectively). Plasma and urinary 3-DF concentrations correlated strongly with one another, with HbA1c (P <0.005 in all cases), and with urinary FL (P <0.02 and P = 0.005, respectively). The overall increase in 3-DF concentrations in plasma and urine in diabetes and their correlation with other indexes of glycemic control suggest that increased amounts of 3-DG are formed in the body during hyperglycemia in diabetes and then metabolized to 3-DF. These observations are consistent with a role for increased formation of the dicarbonyl sugar 3-DG in the accelerated browning of tissue proteins in diabetes.

Predicting the need for insulin therapy in late onset (40-69 years) diabetes mellitus

A six-year prospective study of 144 newly diagnosed, symptomatic diabetic patients aged 40-69 years showed that 21 (15%) required insulin therapy, commencing 1-61 months after diagnosis. The plasma insulin response to oral glucose was assessed at the time of diagnosis. All 12 patients with very low peak insulin response (less than or equal to 6 mU/l) required insulin therapy. Thirty-six patients had an intermediate insulin response (greater than 6 less than or equal to 18 mU/l); of these, 7 with a mean weight 88% (range 73-96%) of average body weight required insulin, while 29 with a mean weight 117% (range 98-158%) of average body weight, did not. Ninety-six patients had a peak insulin response (greater than 18 mU/l); 2 patients whose weights were 96% and 100% of average body weight, required insulin, while the remainder did not. Consideration of initial body weight and peak insulin response provides a useful prediction of the eventual need for insulin.

Secreted Proteins from the Helminth Fasciola hepatica Inhibit the Initiation of Autoreactive T Cell Responses and Prevent Diabetes in the NOD Mouse

Infections with helminth parasites prevent/attenuate auto-inflammatory disease. Here we show that molecules secreted by a helminth parasite could prevent Type 1 Diabetes (T1D) in nonobese diabetic (NOD) mice. When delivered at 4 weeks of age (coincident with the initiation of autoimmunity), the excretory/secretory products of Fasciola hepatica (FhES) prevented the onset of T1D, with 84% of mice remaining normoglycaemic and insulitis-free at 30 weeks of age. Disease protection was associated with suppression of IFN-γ secretion from autoreactive T cells and a switch to the production of a regulatory isotype (from IgG2a to IgG1) of autoantibody. Following FhES injection, peritoneal macrophages converted to a regulatory M2 phenotype, characterised by increased expression levels of Ym1, Arg-1, TGFβ and PD-L1. Expression of these M2 genetic markers increased in the pancreatic lymph nodes and the pancreas of FhES-treated mice. In vitro, FhES-stimulated M2 macrophages induced the differentiation of Tregs from splenocytes isolated from naïve NOD mice. Collectively, our data shows that FhES contains immune-modulatory molecules that mediate protection from autoimmune diabetes via the induction and maintenance of a regulatory immune environment.

The Applicability of Two Strengths-based Systemic Psychotherapy Models for Young People Following Type 1 Trauma

This paper will consider the inter-relationship of a number of overlapping disciplinary theoretical concepts relevant to a strengths-based orientation, including well-being, salutogenesis, sense of coherence, quality of life and resilience. Psychological trauma will be referenced and the current evidence base for interventions with children and young people outlined and critiqued. The relational impact of trauma on family relationships is emphasised, providing a rationale for systemic psychotherapeutic interventions as part of a holistic approach to managing the effects of trauma. The congruence between second-order systemic psychotherapy models and a strengths-based philosophy is noted, with particular reference to solution-focused brief therapy and narrative therapy, and illustrated; via a description of the process of helping someone move from a victim position to a survivor identity using solution-focused brief therapy, and through a case example applying a narrative therapy approach to a teenage boy who suffered a serious assault. The benefits of a strength-based approach to psychological trauma for the clients and therapists will be summarised and a number of potential pitfalls articulated.

A children's nurse's role in the global development of a child with diabetes mellitus.

The nursing care of a six year old with type 1 diabetes reveals the importance of accurate control of the condition for normal physical, emotional and cognitive development. Clearly the children's nurse can educate and support the child, parents and extended family towards achieving independence and self-care. Theoretical knowledge of normal child maturation can guide nurses to constantly adapt their modes of communication and nursing skills, so as to promote every aspect and stage of the child's growth. Prevalence of type 1 diabetes is increasing, and nurses should use their close professional involvement with patients to assist research at every opportunity.

Type 2 diabetes: a case study

Increased prevalence of diabetes in the community has been accompanied by an increase in diabetes in hospitalised patients. About a quarter of these patients experience a hypoglycaemic episode during their admission, which is associated with increased risk of mortality and length of stay. This article examines the aetiology, pathophysiology, diagnosis and treatment of type 2 diabetes using a case study approach. The psychosocial implications for the patient are also discussed. The case study is based on a patient with diabetes who was admitted to hospital following a hypoglycaemic episode and cared for during a practice placement. The importance of early diagnosis of diabetes and the adverse effects of delayed diagnosis are discussed.

A study protocol for a pilot randomised trial of a structured education programme for the self-management of type 2 diabetes for adults with intellectual disabilities

BACKGROUND: The need for structured education programmes for type 2 diabetes is a high priority for many governments around the world. One such national education programme in the United Kingdom is the DESMOND Programme, which has been shown to be robust and effective for patients in general. However, these programmes are not generally targeted to people with intellectual disabilities (ID), and robust evidence on their effects for this population is lacking. We have adapted the DESMOND Programme for people with ID and type 2 diabetes to produce an amended programme known as DESMOND-ID. This protocol is for a pilot trial to determine whether a large-scale randomised trial is feasible, to test if DESMOND-ID is more effective than usual care in adults with ID for self-management of their type 2 diabetes, in particular as a means to reduce glycated haemoglobin (Hb1Ac), improve psychological wellbeing and quality of life and promote a healthier lifestyle. This protocol describes the rationale, methods, proposed analysis plan and organisational and administrative details.

METHODS/DESIGN: This trial is a two arm, individually randomised, pilot trial for adults with ID and type 2 diabetes, and their family and/or paid carers. It compares the DESMOND-ID programme with usual care. Approximately 36 adults with mild to moderate ID will be recruited from three countries in the United Kingdom. Family and/or paid carers may also participate in the study. Participants will be randomly assigned to one of two conditions using a secure computerised system with robust allocation concealment. A range of data will be collected from the adults with ID (biomedical, psychosocial and self-management strategies) and from their carers. Focus groups with all the participants will assess the acceptability of the intervention and the trial.

DISCUSSION: The lack of appropriate structured education programmes and educational materials for this population leads to secondary health conditions and may lead to premature deaths. There are significant benefits to be gained globally, if structured education programmes are adapted and shown to be successful for people with ID and other cognitive impairments.

TRIAL REGISTRATION: Registered with International Standard Randomised Controlled Trial (identifier: ISRCTN93185560 ) on 10 November 2014.

Infection of donor lymphocytes with human T lymphotrophic virus type 1 (HTLV-I) following allogeneic bone marrow transplantation for HTLV-I positive adult T-cell leukaemia

Human T lymphotrophic virus type 1 (HTLV-I) associated leukaemia has a poor prognosis even with chemotherapy. We describe a patient with adult T-cell leukaemia treated with allogeneic bone marrow transplantation from an HTLV-I negative identical sibling donor. During follow-up after bone marrow transplantation, HTLV-I could be repeatedly isolated inspite of anti-viral prophylaxis. The patient died of an acute encephalitis and HTLV-I could be detected in autopsy material from the brain. By a PCR-based technique using short tandem repeats (STRs) it was shown that the patient's haemopoiesis was of donor origin. This shows the infection of donor cells in vivo by an aetiological agent which has been implicated in the leukaemogenic process for adult T-cell leukaemia.

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity.