Low circulating concentrations of citrulline and FGF19 predict chronic cholestasis and poor survival in adult patients with chronic intestinal failure: development of a Model for End-Stage Intestinal Failure (MESIF risk score)

Contains fulltext : 205171.pdf (publisher's version ) (Open Access)BACKGROUND: Patients with chronic intestinal failure (CIF) often develop cholestatic liver injury, which may lead to liver failure and need for organ transplantation. OBJECTIVES: The aim of this study was to investigate whether citrulline (CIT) and the enterokine fibroblast growth factor 19 (FGF19) are associated with chronic cholestasis and survival in adult CIF patients, and to develop a risk score to predict their survival. METHODS: We studied 135 adult CIF patients on intravenous supplementation (>3 mo). Associations of plasma CIT and FGF19 with chronic cholestasis and survival were estimated by logistic and Cox regression models. A predictive risk score was developed and validated internally. RESULTS: Patients with chronic cholestasis (17%) had a reduced 5-y survival rate compared with patients without chronic cholestasis (38% and 62%, respectively). In multivariable analysis, low FGF19, low CIT, and female sex were associated with chronic cholestasis. Patients with low rather than high CIT or FGF19 also had reduced 5-y survival rates (29% compared with 69%; 54% compared with 66%, respectively). Risk factors identified in multivariable analysis of survival were low FGF19 (HR: 3.4), low CIT (HR: 3.3), and number of intravenous infusions per week (HR: 1.4). These 3 predictors were incorporated in a risk model of survival termed Model for End-Stage Intestinal Failure (MESIF) (C-statistic 0.78). The 5-y survival rates for patients with MESIF scores of 0 to 40 (n = 13) were 80%, 58%, and 14%, respectively. CONCLUSIONS: CIT and FGF19 predict chronic cholestasis and survival in this cohort of adult CIF patients, and the derived MESIF score is associated with their survival. Pending external validation, the MESIF score may help to identify patients for closer clinical monitoring or earlier referral to intestinal transplantation centers

The Research on Sino-US Green Building Rating System

AbstractThis paper describes the more commonly used domestic and international green building rating systems and details of the evaluation of U.S. LEED, its old and new versions, the trend of improvement in LEED; Compared Chinese “Evaluation Standard for Green Building” (GB/T 50378-2006)with the LEED2009, the paper points out their shortcomings, and identify the existing differences between them. Then comes out the conclusion that LEED2009 is still target to the U.S. buildings, Chinese engineers should learn from its advantage, make use in our evaluation of green building, which is suitable for China's actual conditions. But we make full use of Chinese buildings of the LEED rating system is not appropriate. Finally, we make a suggestion for “Evaluation Standard for Green Building” that we should add incentives for new energy sources can effectively develop our new energy, give a positive role in environment protection

SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

The evolutionary benefit of insulin resistance

Insulin resistance is perceived as deleterious, associated with conditions as the metabolic syndrome, type 2 diabetes mellitus and critical illness. However, insulin resistance is evolutionarily well preserved and its persistence suggests that it benefits survival. Insulin resistance is important in various states such as starvation, immune activation, growth and cancer, to spare glucose for different biosynthetic purposes such as the production of NADPH, nucleotides in the pentose phosphate pathway and oxaloacetate for anaplerosis. In these conditions, total glucose oxidation by the tricarboxylic acid cycle is actually low and energy demands are largely met by fatty acid and ketone body oxidation. This beneficial role of insulin resistance has consequences for treatment and research. Insulin resistance should be investigated at the cellular, tissue and whole organism level. The metabolic pathways discussed here, should be integrated in the accepted and valid mechanistic events of insulin resistance before interfering with them to promote insulin sensitivity at any cost. (C) 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserve

Adaptive reciprocity of lipid and glucose metabolism in human short-term starvation

The human organism has tools to cope with metabolic challenges like starvation that are crucial for survival. Lipolysis, lipid oxidation, ketone body synthesis, tailored endogenous glucose production and uptake, and decreased glucose oxidation serve to protect against excessive erosion of protein mass, which is the predominant supplier of carbon chains for synthesis of newly formed glucose. The starvation response shows that the adaptation to energy deficit is very effective and coordinated with different adaptations in different organs. From an evolutionary perspective, this lipid-induced effect on glucose oxidation and uptake is very strong and may therefore help to understand why insulin resistance in obesity and type 2 diabetes mellitus is difficult to treat. The importance of reciprocity in lipid and glucose metabolism during human starvation should be taken into account when studying lipid and glucose metabolism in general and in pathophysiological conditions in particular

Leerboek Voeding

Dit leerboek helpt kennis over voeding toe te passen in preventie en behandeling. Het richt zich vooral op praktiserende en aankomende artsen, diëtisten, verpleegkundigen en fysiotherapeuten. Voeding speelt op velerlei manieren een belangrijke rol tijdens ziekte. De epidemiologie van ziekten en de rol van voeding, zowel in preventie als behandeling, is verschoven en de daarbij behorende voedingsadviezen zijn meebewogen. Zo komen suikerziekte, hart- en vaatziekten en kanker meer voor in een zwaarder en ouder wordende populatie. Behandelingen zijn verbeterd, ziekenhuisopnames werden korter en de poliklinische zorg is veel belangrijker geworden. Ondanks het feit dat voeding steeds relevanter wordt in de moderne geneeskunde, zijn er lacunes in de voedingskennis van de dokters van vandaag én de dokters van morgen. Vooraanstaande artsen, wetenschappers, diëtisten, paramedici en andere experts werkten mee aan deze uitgave. Tevens is dit boek niet alleen geschreven voor, maar ook door studenten geneeskunde. Het is onze nadrukkelijke bedoeling om het boek in de toekomst actueel te houden en aantrekkelijk voor hen die hun kennis wat betreft voeding willen vergroten. Leerboek voeding is opgebouwd uit zes thema’s. Achtereenvolgens zijn dat de fysiologie van voeding, nutritional assessment, aan voeding gerelateerde aandoeningen, klinische voeding, voeding en preventie, voeding en ziekte, en voedingsonderzoek. In totaal telt het boek 52 hoofdstukken. Die zijn in het algemeen kort en vatten de kern van elk onderwerp samen. Bij verschillende onderwerpen krijgt de lezer verdieping in tekst, boxen en figuren. Ook is er een online omgeving met extra informatie. De redactie was in handen van internist-endocrinoloog Maarten Soeters, diëtist-onderzoekers Nicolette Wierdsma en Hinke Kruizenga, en maag-darm-leverarts Gerd Bouma

Muscle acylcarnitines during short-term fasting in lean healthy men

The transition from the fed to the fasted resting state is characterized by, among other things, changes in lipid metabolism and peripheral insulin resistance. Acylcarnitines have been suggested to play a role in insulin resistance, as well as other long-chain fatty acid metabolites. Plasma levels of long-chain acylcarnitines increase during fasting, but this is unknown for muscle long-chain acylcarnitines. In the present study we investigated whether muscle long-chain acylcarnitines increase during fasting and we investigated their relationship with glucose/fat oxidation and insulin sensitivity in lean healthy humans. After 14 h and 62 h of fasting, glucose fluxes, substrate oxidation, and plasma and muscle acylcarnitines were measured before and during a hyperinsulinaemic-euglycaemic clamp. Hyperinsulinaemia decreased long-chain muscle acylcarnitines after 14 h of fasting, but not after 62 h of fasting. In both the basal state and during the clamp, glucose oxidation was lower and fatty acid oxidation was higher after 62 h compared with 14 h of fasting. Absolute changes in glucose and fatty acid oxidation in the basal compared with hyperinsulinaemic state were not different. Muscle long-chain acylcarnitines did not correlate with glucose oxidation, fatty acid oxidation or insulin-mediated peripheral glucose uptake. After 62 h of fasting, the suppression of muscle long-chain acylcarnitines by insulin was attenuated compared with 14 h of fasting. Muscle long-chain acylcarnitines do not unconditionally reflect fatty acid oxidation. The higher fatty acid oxidation during hyperinsulinaemia after 62 h compared with 14 h of fasting, although the absolute decrease in fatty acid oxidation was not different, suggests a different set point