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Crohn's disease is one of the leading causes of intestinal failure. The term ‘type 2’ intestinal failure is used to describe the relatively rare type of intestinal failure that occurs in association with septic, metabolic and complex nutritional complications, typically following surgical resection and/or laparostomy for intra-abdominal sepsis. A multidisciplinary approach to the management of patients with type 2 intestinal failure is crucial, and it is helpful to approach patient care in a structured manner using the ‘sepsis-nutrition-anatomy-plan’ algorithm: resolution of sepsis is required before adequate nutritional repletion can be achieved, and it is crucial to optimise nutritional status, and define intestinal anatomy before delineating a definitive medical or surgical plan. A structured approach to the management of patients with inflammatory bowel disease, who have developed type 2 intestinal failure, should reduce the likelihood of these patients developing ‘type 3’ intestinal failure, which is characterised by the need for long-term parenteral nutrition. However, Crohn's disease is still the commonest indication for home parenteral nutrition in the UK.
Symposium II: Infant and childhood nutrition and disease
70th Anniversary Conference on ‘Nutrition and health: from conception to adolescence’
The relationship between breast-feeding and later cardiovascular health has been investigated in randomised trials and observational studies. This review focuses on randomised control trials, regarded as the ‘gold standard’ in establishing causal relationships between interventions and outcomes. Since it is not ethical to randomise healthy term infants to be breast- or formula-fed, only two randomised control trials have examined effects of breast-feeding on later health. In one randomised control trial, preterm infants randomised to receive banked donor breast milk had significantly lower blood pressure (BP), more favourable plasma lipid profile and reduced leptin resistance at age of 13–15 years compared with those who were fed preterm formula; with a dose–response relationship between the proportion of human milk and later outcomes. In contrast, a cluster-randomised control trial of a breast-feeding promotion intervention in healthy term infants (Promotion of Breast-feeding Intervention Trial study) found no effect of the intervention on adiposity or BP at 6 years, despite increased incidence, duration and exclusivity of breast-feeding. Potential explanations for the discrepancy between the two studies include: (i) beneficial effects of breast milk on cardiovascular health might be confined to preterm infants; (ii) effects on cardiovascular outcomes may not manifest until adolescence, a concept supported by other studies; (iii) if the underlying mechanism for the effect of breast-feeding on later cardiovascular outcome is slower early growth; a concept supported by data from animal models, human observational studies and now experimental studies in human subjects; it is plausible that differences in early growth between groups in the Promotion of Breast-feeding Intervention Trial were insufficient to produce a detectable effect on these outcomes.
Compelling evidence exists for the cardioprotective benefits resulting from consumption of fatty acids from fish oils, EPA (20:5n-3) and DHA (22:6n-3). EPA and DHA alter membrane fluidity, interact with transcription factors such as PPAR and sterol regulatory element binding protein, and are substrates for enzymes including cyclooxygenase, lipoxygenase and cytochrome P450. As a result, fish oils may improve cardiovascular health by altering lipid metabolism, inducing haemodynamic changes, decreasing arrhythmias, modulating platelet function, improving endothelial function and inhibiting inflammatory pathways. The independent effects of EPA and DHA are poorly understood. While both EPA and DHA decrease TAG levels, only DHA appears to increase HDL and LDL particle size. Evidence to date suggests that DHA is more efficient in decreasing blood pressure, heart rate and platelet aggregation compared to EPA. Fish oil consumption appears to improve arterial compliance and endothelial function; it is not yet clear as to whether differences exist between EPA and DHA in their vascular effects. In contrast, the beneficial effect of fish oils on inflammation and insulin sensitivity observed in vitro and in animal studies has not been confirmed in human subjects. Further investigation to clarify the relative effects of consuming EPA and DHA at a range of doses would enable elaboration of current understanding regarding cardioprotective effects of consuming oily fish and algal sources of long chain n-3 PUFA, and provide clearer evidence for the clinical therapeutic potential of consuming either EPA or DHA-rich oils.
Under- and over-nutrition during pregnancy has been linked to the later development of diseases such as diabetes and obesity. Epigenetic modifications may be one mechanism by which exposure to an altered intrauterine milieu or metabolic perturbation may influence the phenotype of the organism much later in life. Epigenetic modifications of the genome provide a mechanism that allows the stable propagation of gene expression from one generation of cells to the next. This review highlights our current knowledge of epigenetic gene regulation and the evidence that chromatin remodelling and histone modifications play key roles in adipogenesis and the development of obesity. Epigenetic modifications affecting processes important to glucose regulation and insulin secretion have been described in the pancreatic β-cells and muscle of the intrauterine growth-retarded offspring, characteristics essential to the pathophysiology of type-2 diabetes. Epigenetic regulation of gene expression contributes to both adipocyte determination and differentiation in in vitro models. The contributions of histone acetylation, histone methylation and DNA methylation to the process of adipogenesis in vivo remain to be evaluated.
Most postprandial studies have investigated the response of a single meal, yet the ingestion of sequential meals is more typical in a Western society. The aim of this review is to explain how natural and stable isotope tracers of fatty acids have been used to investigate the metabolism of dietary fat after single and multiple meals, with a focus on in vivo measurements of adipose tissue metabolism. When stable isotope tracers are combined with arteriovenous difference measurements, very specific measurements of metabolic flux across tissues can be made. We have found that adipose tissue is a net importer of dietary fat for 5 h following a single test meal and for most of the day during a typical three-meal eating pattern. When dietary fat is cleared from plasma, some fatty acids ‘spillover’ into the plasma and contribute up to 50% of postprandial plasma NEFA concentrations. Therefore, plasma NEFA concentrations after a meal reflect the balance between intracellular and extracellular lipolysis in adipose tissue. This balance is altered after the acute ingestion of fructose. The enzyme lipoprotein lipase is a key modulator of fatty acid flux in adipose tissue and its rate of action is severely diminished in obese men. In conclusion, in vivo studies of human metabolism can quantify the way that adipose tissue fatty acid trafficking modulates plasma lipid concentrations. This has implications for the flux of fatty acids to tissues that are susceptible to ectopic fat deposition such as the liver and muscle.
This paper considers the body of observational evidence examining the association of being breast-fed to cardiovascular risk factors and outcomes in later life, and whether any potentially advantageous findings are causal. Early cardiovascular consequences/correlates of breast-feeding, compared to being formula fed, include markedly higher levels of total blood cholesterol, lower levels of pre-prandial blood glucose and insulin and lower levels of adiposity. However, a key issue is whether these early differences at a period of rapid development programme/influence cardiovascular risk factors and outcomes in later life. Evidence of long-term effects of early feeding, largely from observational studies, has shown that those breast-fed have lower levels of blood total cholesterol, lower risk of type-2 diabetes and marginally lower levels of adiposity and blood pressure in adult life. There is no strong evidence to suggest effects of early feeding on adult levels of blood glucose, blood insulin and CHD outcomes, although further data are needed. However, the influence of confounding factors, such as maternal body size, maternal smoking and socio-demographic factors, and exclusivity of early feeding on these potentially beneficial associations needs to be considered before inferring any causal effects. Moreover, fewer studies have examined whether duration of exclusive breast-feeding has a graded influence on these risk factors and outcomes; such data would help further in deciding upon causal associations. While strong observational evidence suggests nutritional programming of adult cholesterol levels, associations with other markers of cardiometabolic risk and their consequences in later life need to be confirmed in well-conducted observational and experimental studies.
Rank Prize Lecture
Conference on ‘Nutrition and health: cell to community’
The world has experienced a marked shift in the global BMI distribution towards reduced undernutrition and increased obesity. The collision between human biology, shaped over the millennia and modern technology, globalization, government policies and food industry practices have worked to create far-reaching energy imbalance across the globe. A prime example is the clash between our drinking habits and our biology. The shift from water and breast milk as the only beverages available, to a vast array of caloric beverages was very rapid, shaped both by our tastes and aggressive marketing of the beverage industry. Our biology, shaped over millennia by daily consumption of water and seasonal availability of food, was not ready to compensate for the liquid energies. Other dietary changes were similarly significant, particularly the shift towards increased frequency of eating and larger portions. The roles of the food and beverage production, distribution and marketing sectors in not only shaping our diet but also accelerating these changes must be understood. Apart from the role of beverages, there is much less consensus about the role of various components of our diet in energy imbalance. Understanding the determinants of change in the key components of our diet through an array of research provides insights into some of the options we face in attempting to attain a great balance between energy intake and expenditures while creating an overall healthier dietary pattern. A few countries are systematically addressing the causes of poor dietary and physical activity patterns and high energy imbalance.
Nutrition Society Silver Medal Lecture
Conference on ‘Nutrition and health: cell to community’
In nutritional epidemiology, development of valid dietary assessment instruments specific to populations in diverse settings is of paramount importance. Such instruments are essential when trying to characterise dietary patterns and intake, investigate diet–disease associations, inform and evaluate nutrition interventions, assess nutrient–gene interactions, conduct cross-country comparison studies and monitor nutrition transitions. The FFQ is a relatively inexpensive tool for measuring long-term dietary intake for large populations and for allowing researchers to track dietary changes over time. However, FFQ must be population specific to capture the local diet and available foods. Collecting 24-h dietary recalls and utilising community feedback to build the FFQ ensures that a culturally appropriate instrument is developed. This article presents several examples describing FFQ development and utilisation in different settings globally. In the Canadian Arctic, FFQ were developed and utilised to inform and evaluate a community-based intervention programme, characterise the diet and track dietary changes occurring among Inuit and Inuvialuit, populations experiencing rising rates of chronic disease and likely to be extremely vulnerable to the potential effects of climate change. Another example is an FFQ developed to assess sodium intake and evaluate a sodium reduction trial in a high-risk population in Barbados. An example is provided from Brazil, where an FFQ was developed to assess associations between diet, heterocyclic aromatic amines and colorectal adenoma among Japanese Brazilians and to conduct cross-country comparisons. These and other case studies highlight the diversity in dietary intake between populations and the need for FFQ to be developed to capture this diversity.