Management of adults with diabetes on the haemodialysis unit: summary of guidance from the Joint British Diabetes Societies and the Renal Association.

Diabetic nephropathy remains the principal cause of end-stage renal failure in the UK and its prevalence is set to increase. People with diabetes and end-stage renal failure on maintenance haemodialysis are highly vulnerable, with complex comorbidities, and are at high risk of adverse cardiovascular outcomes, the leading cause of mortality in this population. The management of people with diabetes receiving maintenance haemodialysis is shared between diabetes and renal specialist teams and the primary care team, with input from additional healthcare professionals providing foot care, dietary support and other aspects of multidisciplinary care. In this setting, one specialty may assume that key aspects of care are being provided elsewhere, which can lead to important components of care being overlooked. People with diabetes and end-stage renal failure require improved delivery of care to overcome organizational difficulties and barriers to communication between healthcare teams. No comprehensive guidance on the management of this population has previously been produced. These national guidelines, the first in this area, bring together in one document the disparate needs of people with diabetes on maintenance haemodialysis. The guidelines are based on the best available evidence, or on expert opinion where there is no clear evidence to inform practice. We aim to provide clear advice to clinicians caring for this vulnerable population and to encourage and improve education for clinicians and people with diabetes to promote empowerment and self-management.

Serum resistin in older patients with hip fracture: Relationship with comorbidity and biochemical determinants of bone metabolism.

OBJECTIVES: To determine the relationship of serum resistin concentrations to biochemical determinants of bone metabolism, comorbidity and outcomes in patients with hip fracture (HF). METHODS: In 256 consecutive patients (mean age 81.9±7.8 years; 71.1% women) serum levels of resistin (determined by ELISA), biochemical parameters of bone turnover and mineral metabolism as well as routine haematological and biochemical parameters were measured. Clinical data were recorded prospectively. RESULTS: In multivariate analysis cervical HF (OR=1.81; 95% CI 1.05-3.11), diabetes (OR=2.60; 95% CI 1.23-5.51) and history of stroke (OR=2.67; 95% CI 1.17-6.13) were significant independent predictors of higher resistin levels (≥16.26 ng/ml, median value). The independent correlates of serum resistin levels in patients with cervical HF were serum osteocalcin and magnesium (both negatively associated) and in patients with trochanteric HF, serum PTH, calcium and age (all positively associated). Resistin and glomerular filtration rate were the only independent (inverse) predictors of serum osteocalcin. Resistin levels on admission did not predict short-term outcomes. CONCLUSIONS: In older patients with HF there is a significant association of higher resistin levels with cervical fracture, type 2 diabetes and history of stroke, which is partly influenced by the reciprocal interaction between resistin and osteocalcin. However, the design of the study does not prove causality and further prospective studies are needed to clarify these relationships.

Serum leptin levels in older patients with hip fracture--impact on peri-operative myocardial injury.

To evaluate whether there is a relationship between admission serum leptin concentrations and peri-operative myocardial injury, 238 consecutive older patients (mean age 81.9+/-7.9 years; 172 women) with low-trauma hip fracture were assessed. Myocardial injury as defined by elevated serum cardiac troponin I was associated with lower leptin levels analyzed as continuous or categorical variables. Patients with serum leptin concentrations <12ng/ml (medium value) had a two-fold greater increased risk for such complications compared with those with higher leptin levels (odd ratio 2.13, 95% confidence interval 1.06-4.28; p=0.033). This association remained significant after adjustments for age, gender, clinical (history of coronary artery disease [CAD], stroke, hypertension, diabetes, dementia), hematological (red, white, and lymphocyte count, hemoglobin, hematocrit), metabolic (parathyroid hormone [PTH], albumin), renal(creatinine, urea, glomerular filtration rate [GFR]), and inflammatory (C-reactive protein [CRP], ferritin) factors. The predictive value of lower leptin levels increased significantly when used in combination with traditional risk factors for myocardial injury.

Prognostic efficacy of cardiac biomarkers for mortality in dialysis patients.

BACKGROUND: The high prevalence of cardiovascular mortality in the end-stage renal disease population is well established. The aim of this current study was to document the relative prognostic significance of established cardiac biomarkers troponin T (TnT), troponin I (TnI), B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro-BNP) in this population. METHODS: A prospective cohort study of dialysis patients undertaken in a single tertiary centre in Australia. Relevant clinical and biochemical information was collected at entry and all patients followed up prospectively without any loss to follow up. End-point of interest was all-cause mortality. Statistical analysis using Cox proportional hazards was used to study relationship between competing covariates and outcome. A total of 143 patients with a mean age of 59.67 +/- 15.49 years was followed up for a median duration of 30 months. Of these patients, 89.3% were white Australians of European ancestry. Twenty-seven per cent had an established diagnosis of diabetes mellitus. The mean concentrations (+/-SD) of TnT, TnI, BNP and N-terminal peptide pro-BNP (NT-pro-BNP) were 0.08 +/- 0.04 microg/L, 0.09 +/- 0.2 microg/L, 270 +/- 117 ng/L and 1434 +/- 591 ng/L respectively. RESULTS: Twenty-eight subjects died during the period of follow up. By univariate analysis, all cardiac markers (TnT, TnI, BNP, NT-pro-BNP and C-reactive protein) were significantly associated with an increase in mortality. On Cox proportionate hazards analysis, only albumin and NT-pro-BNP showed a significant association with mortality, with hazard ratios of 0.834, 95% confidence interval (CI) 0.779-0.893, P < 0.001, and 1.585, 95%CI 1.160-20165, P = 0.004 respectively. CONCLUSION: In patients with end-stage renal failure on dialysis NT-pro-BNP provides greater prognostic information compared with TnT and TnI.

Yoghurts containing probiotics reduce disruption of the small intestinal barrier in methotrexate-treated rats.

Small intestinal permeability was employed to assess the efficacy of commercially available yoghurts containing probiotics in a rat model of methotrexate (MTX)-induced mucositis. Male Sprague-Dawley rats were allocated to four groups (n = 8): MTX + water, MTX + cow's milk yoghurt (CY; fermented with Lactobacillus johnsonii), MTX + sheep's milk yoghurt (SY; containing Lactobacillus bulgaricus and Streptococcus thermophilus), and saline. Treatment gavage occurred twice daily for 7 days pre-MTX and 5 days post-MTX. Intestinal permeability was assessed on days -7, -1, 2, and 5 of the trial. Intestinal sections were collected at sacrifice for histological and biochemical analyses. Histology revealed that rats receiving CY and SY did not have a significantly damaged duodenum compared to controls. However, an improved small intestinal barrier function was evident, determined by a decreased lactulose/mannitol ratio. Probiotics containing SY and CY may be useful in preventing disruption to intestinal barrier function in MTX-induced mucositis.

Elevated serum cardiac troponin I in older patients with hip fracture: incidence and prognostic significance.

INTRODUCTION: Cardiovascular complications are the main causes of morbidity and mortality in patients with osteoporotic hip fracture (HF). The aim of this prospective study was to evaluate the incidence and prognostic significance of elevated cardiac troponin I (cTnI) in the early peri-operative period in older patients with HF. MATERIALS AND METHODS: A blind evaluation of myocardial injury as detected by cTnI elevation in 238 consecutive older patients with low-trauma HF (mean age 81.9 +/- 7.8 (SD) years; 72% females). Data on demographic and clinical characteristics, in-hospital mortality, hospital length of stay and discharge destination were collected prospectively. Serum cTnI level was analysed from blood collected routinely in the first 72 h of hospital admission. RESULTS: Sixty-nine (29%) patients had elevated cTnI (>0.06 microg/l) but myocardial injury was clinically recognised in only 23 (33%) and only 24 (34.8%) had a history of coronary artery disease (CAD). Patients with elevated cTnI were significantly older, more often had American Society of Anaesthesiologist status score >or=3, a history of CAD or stroke and more often were current smokers than the patients without cTnI elevation. In multivariate regression analysis only age was an independent predictor of cTnI elevation. Patients with cTnI release were twice as likely to have a length of stay >or=20 days (P = 0.047) and 2.7 times more likely to be discharged to a long-term residential care facility (RCF) (P = 0.013). cTnI level >or=1 microg/l was a strong independent predictor of all-cause mortality with 98.3% specificity and 89.1% negative predictive value. CONCLUSION: Peri-operative myocardial injury is common in older HF patients but is frequently unrecognised clinically. Elevated blood cTnI level is an independent predictor of prolonged length of hospital stay (>or=20 days), need for long-term RCF and mortality (if cTnI >or=1 microg/l).

Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease.

It is often difficult to assess small bowel recovery in adults with coeliac disease on a gluten-free diet (GFD). This prospective study compares changes in intestinal permeability with changes in intestinal biopsy at various intervals after commencing a GFD. Intestinal permeability was measured by lactulose/rhamnose absorption from 1 week to 24 months after commencing a GFD. Intestinal morphometry was measured by villus area, crypt length and mitotic count per crypt at diagnosis and after commencing a GFD. Median intestinal permeability values decreased from 0.47 (n = 35) at diagnosis to 0.25 (n = 17) after 1 week and to 0.16 (n = 18) after 2 months of a GFD. Rhamnose absorption improved significantly at an early stage, from 6.6% (untreated) to 15.4% at 3 months of a GFD, whereas the decrease in lactulose permeation took longer: from 3.4% (untreated) to 0.8% after 12 months of a GFD. Mean villus area (n = 29) was reduced to 16% of control values at diagnosis, and improved to a maximum of 48% after 6 months on a GFD, but did not change thereafter. Mean crypt length and mitotic count per crypt were increased by 222% and 356% respectively at diagnosis, and these parameters remained elevated at 172% and 216% above control values after 6 months of a GFD. We conclude that intestinal permeability improves within 2 months after starting a GFD, but that measurable intestinal biopsy improvement requires ingestion of a GFD for at least 3-6 months, and even then remains incomplete.

The sugar permeability test reflects disease activity in children and adolescents with inflammatory bowel disease.

OBJECTIVES: To investigate the relationship of intestinal permeability in children and adolescents with inflammatory bowel disease (IBD) to disease activity, disease extent, and response to therapy. STUDY DESIGN: Patients with new and established diagnoses of IBD (12 Crohn's disease [CD] and 18 ulcerative colitis [UC]) were studied. Intestinal permeability was evaluated by measuring with high-performance liquid chromatography 5-hour urinary excretion ratio of lactulose/L-rhamnose (L/Rh). RESULTS: In 8 of 9 patients with active CD, the L/Rh ratio was higher than the reference range (0.006 to 0.074, n = 36). In inactive CD (n = 3) the L/Rh ratio was within the reference range. In 6 of 7 patients with active extensive UC, the L/Rh ratio was elevated. In inactive extensive UC (n = 6) the normal permeability ratio was shown. In both active CD and active extensive UC, the frequency of elevated intestinal permeability was significantly greater than values in both inactive forms. The permeability ratio was normal in 4 of 5 patients with active left-sided colitis. In 5 of 7 patients (3 CD, 4 UC), repeat permeability values entered the reference range after acute phase therapy. Two patients with persistently elevated intestinal permeability (1 CD, 1 UC) had a disease flare-up within 6 months. CONCLUSIONS: Intestinal permeability is a marker of disease activity in CD and extensive UC. Serial permeability test may be useful in monitoring disease activity.