Structural and functional brain changes in middle-aged type 2 diabetic patients: a cross-sectional study.

BACKGROUND Type 2 diabetes mellitus (T2DM) is an emerging risk factor for cognitive impairment. Whether this impairment is a direct effect of this metabolic disorder on brain function, a consequence of vascular disease, or both, remains unknown. Structural and functional neuroimaging studies in patients with T2DM could help to elucidate this question. OBJECTIVE We designed a cross-sectional study comparing 25 T2DM patients with 25 age- and gender-matched healthy control participants. Clinical information, APOE genotype, lipid and glucose analysis, structural cerebral magnetic resonance imaging including voxel-based morphometry, and F-18 fluorodeoxyglucose positron emission tomography were obtained in all subjects. METHODS Gray matter densities and metabolic differences between groups were analyzed using statistical parametric mapping. In addition to comparing the neuroimaging profiles of both groups, we correlated neuroimaging findings with HbA1c levels, duration of T2DM, and insulin resistance measurement (HOMA-IR) in the diabetic patients group. Results: Patients with T2DM presented reduced gray matter densities and reduced cerebral glucose metabolism in several fronto-temporal brain regions after controlling for various vascular risk factors. Furthermore, within the T2DM group, longer disease duration, and higher HbA1c levels and HOMA-IR were associated with lower gray matter density and reduced cerebral glucose metabolism in fronto-temporal regions. CONCLUSION In agreement with previous reports, our findings indicate that T2DM leads to structural and metabolic abnormalities in fronto-temporal areas. Furthermore, they suggest that these abnormalities are not entirely explained by the role of T2DM as a cardiovascular risk factor.

II Plan Integral de Diabetes de Andalucía : 2009-2013

Publicado en la página web de la Consejería de Igualdad, Salud y Políticas Sociales: www.juntadeandalucia.es/salud (Consejería de Igualdad, Salud y Políticas Sociales / Ciudadanía / Quiénes somos / Planes y Estrategias)

Identification and in vitro reactivity of celiac immunoactive peptides in an apparent gluten-free beer.

Gluten content from barley, rye, wheat and in certain oat varieties, must be avoid in individuals with celiac disease. In most of the Western countries, the level of gluten content in food to be considered as gluten-free products is below 20 parts per million measured by ELISA based on specific anti-gluten peptide antibody. However, in beverages or food suffering complex hydrolytic processes as beers, the relative proportion of reactive peptides for celiac patients and the analytical techniques may differ, because of the diversity of the resulting peptide populations after fermentations. A beer below 20 parts per million of gluten but yet detectable levels of gluten peptides by anti-gliadin 33-mer antibodies (G12 and A1) was analyzed. We identified and characterized the relevant peptides for either antibody recognition or immunoactivity in celiac patients. The beer was fractionated by HPLC. The relative reactivity of the different HPLC fractions to the G12/A1 antibodies correlated to the reactivity of peripheral blood mononuclear cells isolated from 14 celiac individuals. Peptides from representative fractions classified according to the relative reactivity to G12/A1 antibodies were identified by mass spectrometry. The beer peptides containing sequences with similarity to those of previously described G12 and A1 epitopes were synthesized and confirmed significant reactivity for the antibodies. The most reactive peptides for G12/A1 also confirmed the highest immunogenicity by peripheral blood mononuclear cell activation and interferon γ production from celiac patients. We concluded that preparative HPLC combined with anti-gliadin 33-mer G12/A1 antibodies were very sensitive and specific methods to analyze the relevant immunogenic peptides in hydrolyzed gluten.

Plasmapheresis as treatment for hyperlipidemic pancreatitis.

BACKGROUND Severe hypertriglyceridemia with an accumulation of chylomicrons and triglyceride figures >1000 mg/dL can cause acute pancreatitis, a potentially fatal complication. The option of rapid reduction in triglyceride concentrations is attractive and possible with plasmapheresis. METHODS We present the results of an analysis of 11 patients admitted to the intensive care unit with severe hypertriglyceridemic pancreatitis and treated with plasmapheresis. The procedure was repeated until serum triglycerides were below 1000 mg/dL. We recorded anthropometric, clinical data as well as final outcome. RESULTS In eight patients a single plasma exchange was sufficient to reduce triglyceride figures <1000 mg/dL. Only three patients died, all with the worst severity indexes and who experienced the longest delay before the procedure. CONCLUSIONS Our results, together with a review of the literature, confirm the need for a randomized clinical trial to compare conventional treatment vs. plasmapheresis in patients with severe hypertriglyceridemic pancreatitis.

Protocolo de tratamiento de la deficiencia de vitamina D.

Vitamin D deficiency is highly prevalent worldwide and in our country estimated un 60% in the adult population and closer to 80% in the elderly population and the fractured hip.

The rise of soluble TWEAK levels in severely obese subjects after bariatric surgery may affect adipocyte-cytokine production induced by TNFα.

CONTEXT Soluble TNF-like weak inducer of apoptosis (sTWEAK) is generated by the intracellular proteolytic cleavage of full-length membrane-bound TNF-like weak inducer of apoptosis (mTWEAK). sTWEAK levels are reduced in diseases with an inflammatory component. Additionally, sTWEAK hampers TNFα activity in human cells. OBJECTIVES The objectives of the study were as follows: 1) to determine circulating sTWEAK in severe obesity and after bariatric surgery; 2) to study m/sTWEAK and its receptor fibroblast growth factor-inducible 14 (Fn14) protein expression in sc adipose tissue (SAT) of severely obese subjects, in SAT stromal vascular fraction (SVF), and isolated adipocytes and in human monocyte-derived macrophages; and 3) to explore, on human adipocytes, the sTWEAK effect on TNFα proinflammatory activity. DESIGN sTWEAK levels were measured in cohort 1: severely obese subjects (n = 23) and a control group (n = 35); and in cohort 2: (n = 23) severely obese subjects before and after surgery. The m/sTWEAK and Fn14 expressions were determined in SAT biopsies, SVF, and isolated adipocytes from severely obese and control subjects and in human monocyte-derived macrophages. In human primary cultured adipocytes, sTWEAK pretreated and TNFα challenged, IL-6, IL-8, and adiponectin protein and gene expressions were determined and nuclear factor-κ B and MAPK signaling analyzed. RESULTS sTWEAK levels were reduced in severely obese subjects. After surgery, sTWEAK levels rose in 69% of patients. mTWEAK protein expression was increased in SAT and SVF of severely obese subjects, whereas Fn14 was up-regulated in isolated adipocytes. M2 human monocyte-derived macrophages overexpress mTWEAK. In human adipocytes, sTWEAK down-regulates TNFα cytokine production by hampering TNFα intracellular signaling events. CONCLUSION The decrease of sTWEAK in severely obese patients may favor the proinflammatory activity elicited by TNFα.

Infornut® Process; improves accessibility to diagnosis and nutritional support for the malnourished hospitalized patient; impact on management indicators; two-year assessment.

Introduction: The high prevalence of disease-related hospital malnutrition justifies the need for screening tools and early detection in patients at risk for malnutrition, followed by an assessment targeted towards diagnosis and treatment. At the same time there is clear undercoding of malnutrition diagnoses and the procedures to correct it Objectives: To describe the INFORNUT program/ process and its development as an information system. To quantify performance in its different phases. To cite other tools used as a coding source. To calculate the coding rates for malnutrition diagnoses and related procedures. To show the relationship to Mean Stay, Mortality Rate and Urgent Readmission; as well as to quantify its impact on the hospital Complexity Index and its effect on the justification of Hospitalization Costs. Material and methods: The INFORNUT® process is based on an automated screening program of systematic detection and early identification of malnourished patients on hospital admission, as well as their assessment, diagnoses, documentation and reporting. Of total readmissions with stays longer than three days incurred in 2008 and 2010, we recorded patients who underwent analytical screening with an alert for a medium or high risk of malnutrition, as well as the subgroup of patients in whom we were able to administer the complete INFORNUT® process, generating a report for each.

Peripheral arterial disease, type 2 diabetes and postprandial lipidaemia: Is there a link?

Peripheral arterial disease, manifested as intermittent claudication or critical ischaemia, or identified by an ankle/brachial index < 0.9, is present in at least one in every four patients with type 2 diabetes mellitus. Several reasons exist for peripheral arterial disease in diabetes. In addition to hyperglycaemia, smoking and hypertension, the dyslipidaemia that accompanies type 2 diabetes and is characterised by increased triglyceride levels and reduced high-density lipoprotein cholesterol concentrations also seems to contribute to this association. Recent years have witnessed an increased interest in postprandial lipidaemia, as a result of various prospective studies showing that non-fasting triglycerides predict the onset of arteriosclerotic cardiovascular disease better than fasting measurements do. Additionally, the use of certain specific postprandial particle markers, such as apolipoprotein B-48, makes it easier and more simple to approach the postprandial phenomenon. Despite this, only a few studies have evaluated the role of postprandial triglycerides in the development of peripheral arterial disease and type 2 diabetes. The purpose of this review is to examine the epidemiology and risk factors of peripheral arterial disease in type 2 diabetes, focusing on the role of postprandial triglycerides and particles.

Characteristics and effectiveness of diabetes self-management educational programs targeted to racial/ethnic minority groups: a systematic review, meta-analysis and meta-regression.

BACKGROUND It is not clear to what extent educational programs aimed at promoting diabetes self-management in ethnic minority groups are effective. The aim of this work was to systematically review the effectiveness of educational programs to promote the self-management of racial/ethnic minority groups with type 2 diabetes, and to identify programs' characteristics associated with greater success. METHODS We undertook a systematic literature review. Specific searches were designed and implemented for Medline, EMBASE, CINAHL, ISI Web of Knowledge, Scirus, Current Contents and nine additional sources (from inception to October 2012). We included experimental and quasi-experimental studies assessing the impact of educational programs targeted to racial/ethnic minority groups with type 2 diabetes. We only included interventions conducted in countries members of the OECD. Two reviewers independently screened citations. Structured forms were used to extract information on intervention characteristics, effectiveness, and cost-effectiveness. When possible, we conducted random-effects meta-analyses using standardized mean differences to obtain aggregate estimates of effect size with 95% confidence intervals. Two reviewers independently extracted all the information and critically appraised the studies. RESULTS We identified thirty-seven studies reporting on thirty-nine educational programs. Most of them were conducted in the US, with African American or Latino participants. Most programs obtained some benefits over standard care in improving diabetes knowledge, self-management behaviors and clinical outcomes. A meta-analysis of 20 randomized controlled trials (3,094 patients) indicated that the programs produced a reduction in glycated hemoglobin of -0.31% (95% CI -0.48% to -0.14%). Diabetes knowledge and self-management measures were too heterogeneous to pool. Meta-regressions showed larger reduction in glycated hemoglobin in individual and face to face delivered interventions, as well as in those involving peer educators, including cognitive reframing techniques, and a lower number of teaching methods. The long-term effects remain unknown and cost-effectiveness was rarely estimated. CONCLUSIONS Diabetes self-management educational programs targeted to racial/ethnic minority groups can produce a positive effect on diabetes knowledge and on self-management behavior, ultimately improving glycemic control. Future programs should take into account the key characteristics identified in this review.

Gene-lifestyle interaction and type 2 diabetes: the EPIC interact case-cohort study.

BACKGROUND Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention. METHODS AND FINDINGS The InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction  = 1.20×10-4). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction  = 1.50×10-3) and waist circumference (p for interaction  = 7.49×10-9). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score. CONCLUSIONS The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this sub-group is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.

Algoritmo para el diagnóstico precoz de la deficiencia de vitamina b12 en ancianos

BACKGROUND: The elderly population is particularly at risk for developing vitamin B12-deficiency. Serum cobalamin does not necessarily reflect a normal B12 status. The determination of methylmalonic acid is not available in all laboratories. Issues of sensitivity for holotranscobalamin and the low specificity of total homocysteine limit their utility. The aim of the present study is to establish a diagnostic algorithm by using a combination of these markers in place of a single measurement. METHODS: We compared the diagnostic efficiency of these markers for detection of vitamin B12 deficiency in a population (n = 218) of institutionalized elderly (median age 80 years). Biochemical, haematological and morphological data were used to categorize people with or without vitamin B12 deficiency. RESULTS: In receiver operating curves characteristics for detection on vitamin B12 deficiency using single measurements, serum folate has the greatest area under the curve (0.87) and homocysteine the lowest (0.67). The best specificity was observed for erythrocyte folate and methylmalonic acid (100% for both) but their sensitivity was very low (17% and 53%, respectively). The highest sensitivity was observed for homocysteine (81%) and serum folate (74%). When we combined these markers, starting with serum and erythrocyte folate, followed by holotranscobalamin and ending by methylmalonic acid measurements, the overall sensitivity and specificity of the algorithm were 100% and 90%, respectively. CONCLUSION: The proposed algorithm, which combines erythrocyte folate, serum folate, holotranscobalamin and methylmalonic acid, but eliminate B12 and tHcy measurements, is a useful alternative for vitamin B12 deficiency screening in an elderly institutionalized cohort.

Temsirolimus in overtreated metastatic renal cancer with subsequent use of sunitinib: A case report.

During the last decade, we have been developing new therapeutic strategies for the treatment of renal cancer, based on knowledge derived from molecular biology. We report a case of long-term renal metastatic cancer progression despite therapy with sunitinib and interleukin, which are the most active drugs in renal cancer. Disease stabilization for 58 weeks was achieved upon sequential use of temsirolimus, following the occurrence of disease progression during angiogenic therapy. The patient demonstrated excellent tolerance without marked symptoms for 10 months. Hypothyroidism and mumps-related adverse events were present. The survival time from diagnosis to lung metastasis was 8 years. Thus, this case demonstrates promising therapeutic effects of the sequential use of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors during different stages of the disease.

Evaluación del estado nutricional en pacientes trasplantados renales durante 5 años de seguimiento.

INTRODUCTION: Weight gain and malnutrition after kidney transplantation is common and the resulting overweight and obesity is associated with serious health complications. By contrast, the prevalence of malnutrition in patients with renal transplantation and its impact on the outcome of kidney transplantation is underestimated. OBJECTIVES: The aim of this study was to evaluate the nutritional status of renal transplant patients and determine if the five-year follow-up, these patients undergo alterations that suggest nutritional deterioration. METHODS: The sample consisted of 119 renal transplant patients who attended for five years post-transplant consultation. All patients measurements of total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides and ferritin (Ft) were performed. and anthropometric measurements were made of weight, height and BMI. Patients were divided into three groups according to GFR Group 1: <60 mL/min, Group 2: 89-60 mL/min Group 3: ≥ 90 mL/min. RESULTS: The weight and BMI tended to decrease in group 3 while increasing in the other groups. A decrease in total cholesterol, HDL, LDL, Triglycerides and Ferritin less pronounced in group 3 occurs. CONCLUSIONS: After five years you can see a significant reduction in nutritional biochemical parameters in general, likewise the nutritional status is closely related, and is directly proportional to the function of the graft.

Estudio y prevalencia de la diabetes mellitus postrasplante; análisis en un grupo de pacientes trasplantados renales.

INTRODUCTION: The onset of post-transplant diabetes mellitus (PTDM) among kidney recipients is associated with an increased risk of graft failure and high rates of morbidity and mortality. Minimize the risk of PTDM is a priority for improving long-term survival rates. Aims. This study aims to assess the prevalence of PTDM in a renal transplant patient population, to identify risk factors and assess the graft and patient survival. METHODS: The sample consisted of 112 renal transplant patients , 69 men and 43 women , renal transplant , who attended for five years post-transplant consultation. Were analyzed as potential risk factors for PTDM : age , sex, body mass index (BMI ) , obesity , VHC , hypertension, dyslipidemia , total cholesterol (TC) , serum triglyceride and immunosuppressive therapy ( cyclosporine , tacrolimus , mycophenolate mofetil and sirolimus ), also the prevalence of acute rejection episodes was evaluated. RESULTS: The prevalence of PTDM was 24.2 %, compared with 85 patients (75.8%) with standard glucose (PGN) . PTDM patients showed a higher BMI , a higher percentage of overweight , dyslipidemia , total cholesterol levels , triglycerides and performed a greater percentage of patients with PDMPT including Mycophenolate mofetil was administered. CONCLUSIONS: There is a high incidence of PTDM in kidney recipients , the importance of weight control and strict adherence to all identified risk factors , as well as in minimizing the doses of immunosuppressive therapies to prevent the onset of PTDM.

Estudio longitudinal del peso e índice de masa corporal tras el trasplante renal durante 5 años de evolución.

INTRODUCTION: Gain weight after transplantation is relatively common, also tends to be multifactorial and can be influenced by glucocorticoids and immunosuppressive medications, delayed graft function and cause serious health complications. OBJECTIVES: Assess changes in weight, degree of obesity and body mass index as well as the effect of immunosuppressive treatment over these 5 years after kidney transplantation. METHODS: The samples were 119 kidney transplant recipients, 70 men and 49 women, that attended the query post for five years. All patients were measured Pretransplant and post (from 1st year to the 5th year) weight, height and body mass index calculated by the formula weight/size2 relating it to immunosuppressive treatment taking. RESULTS: There is a considerable increase of body mass index, weight and degree of obesity in the first year after transplantation to increase more slowly in the next four years. The type of immunosuppressive treatment influence the weight and degree of obesity that occurs in this period of time. CONCLUSIONS: A high prevalence there are overweight and obesity after the transplant especially during the first year. A year patients earn an average of 6.6 kg in weight and an average of 2.5 kg/m2 in their BMI. During treatment should minimize doses of steroids and include dietary treatment and adequate physical exercise