What’s wrong with us? A patchwork ethnography study of the lived experiences of the clients of a surplus food project in London

Investigating the lived experiences of visitors to a food surplus project in South West London

Processes underlying the nutritional programming of embryonic development by iron deficiency in the rat

Peer reviewedPublisher PD

Diagnosing Type 2 diabetes before patients complain of diabetic symptoms—clinical opportunistic screening in a single general practice

In the UK, patients normally see their general practitioner first and 86% of the health needs of the population are managed in general practice, with 14% being referred to specialist/hospital care. Early diagnosis is the privilege of general practice since general practitioners make most medical diagnoses in the NHS. Their historic aim has been to diagnose as early as possible and if possible before patients are aware of symptoms. Over time, diagnoses are being made earlier in the trajectory of chronic diseases and pre-symptomatic diagnoses through tests like cervical screening. Earlier diagnosis benefits patients and allows earlier treatment. In diabetes, the presence of lower HbA1c levels correlates with fewer complications. Methodologically, single practice research means smaller populations but greater ability to track patients and ask clinicians about missing data. All diagnoses of type 2 diabetes, wherever made, were tracked until death or transfer out. Clinical opportunistic screening has been undervalued and is more cost-effective than population screening. It works best in generalist practice. Over 19 consecutive years, all 429 patients with type 2 diabetes in one NHS general practice were analysed. The prevalence of type 2 diabetes rose from 1.1% to 3.0% of the registered population. Since 2000, 95.9% were diagnosed within the general practice and the majority (70/121 = 57.9%) of diagnoses were made before the patients reported any diabetes-related symptom. These patients had median HbA1c levels 1.1% lower than patients diagnosed after reporting symptoms, a clinically and statistically significant difference (P = 0.01)

Body composition and behaviour in adult rats are influenced by maternal diet, maternal age and high-fat feeding

Fetal exposure to maternal undernutrition has lifelong consequences for physiological and metabolic function. Maternal low-protein diet is associated with an age-related phenotype in rats, characterised by a period of resistance to development of obesity in early adulthood, giving way to an obesity-prone, insulin-resistant state in later adulthood. Offspring of rats fed a control (18 % casein) or low-protein (9 % casein; LP) diet in pregnancy were challenged with a high-fat diet at 9 months of age. To assess whether other maternal factors modulated the programming effects of nutrition, offspring were studied from young (2–4 months old) and older (6–9 months old) mothers. Weight gain with a high-fat diet was attenuated in male offspring of older mothers fed LP (interaction of maternal age and diet; P = 0·011) and adipose tissue deposition was lower with LP feeding in both males and females (P < 0·05). Although the resistance to weight gain and adiposity was partially explained by lower energy intake in offspring of LP mothers (P < 0·001 males only), it was apparent that energy expenditure must be influenced by maternal diet and age. Assessment of locomotor activity indicated that energy expenditure associated with physical activity was unlikely to explain resistance to weight gain, but showed that offspring of older mothers were more anxious than thoseof younger mothers, with more rearing observed in a novel environment and on the elevated plus-maze. The data showed that in addition to maternal undernutrition, greater maternal age may influence development and long-term body composition in the rat

The effect of maternal undernutrition on the rat placental transcriptome: protein restriction up-regulates cholesterol transport

Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life. These effects are present when dietary manipulations target only the first half of pregnancy. It was hypothesised that early gestation protein restriction would impact upon placental gene expression and that this may give clues to the mechanism which links maternal diet to later consequences. Pregnant rats were fed control or a low protein diet from conception to day 13 gestation. Placentas were collected and RNA Sequencing performed using the Illumina platform. Protein restriction down-regulated 67 genes and up-regulated 24 genes in the placenta. Ingenuity pathway analysis showed significant enrichment in pathways related to cholesterol and lipoprotein transport and metabolism, including atherosclerosis signalling, clathrin-mediated endocytosis, LXR/RXR and FXR/RXR activation. Genes at the centre of these processes included the apolipoproteins ApoB, ApoA2 and ApoC2, microsomal triglyceride transfer protein (Mttp), the clathrin-endocytosis receptor cubilin, the transcription factor retinol binding protein 4 (Rbp4) and transerythrin (Ttr; a retinol and thyroid hormone transporter). Real-time PCR measurements largely confirmed the findings of RNASeq and indicated that the impact of protein restriction was often striking (cubilin up-regulated 32-fold, apoC2 up-regulated 17.6-fold). The findings show that gene expression in specific pathways is modulated by maternal protein restriction in the day-13 rat placenta. Changes in cholesterol transport may contribute to altered tissue development in the fetus and hence programme risk of disease in later life

Cell Cycle Regulation and Cytoskeletal Remodelling Are Critical Processes in the Nutritional Programming of Embryonic Development

Many mechanisms purport to explain how nutritional signals during early development are manifested as disease in the adult offspring. While these describe processes leading from nutritional insult to development of the actual pathology, the initial underlying cause of the programming effect remains elusive. To establish the primary drivers of programming, this study aimed to capture embryonic gene and protein changes in the whole embryo at the time of nutritional insult rather than downstream phenotypic effects. By using a cross-over design of two well established models of maternal protein and iron restriction we aimed to identify putative common “gatekeepers” which may drive nutritional programming

Gatekeeping and delayed diagnosis - Delayed diagnosis: longer and improved GP training and more GPs are the answer

This is the final version. Available from BMJ Publishing Group via the DOI in this record

Early life programming of health and disease: The long-term consequences of obesity in pregnancy

The prevalence of overweight and obesity is rising in all parts of the world and, among young women, it presents a very clear danger during pregnancy. Women who are overweight or who gain excessive weight during pregnancy are at greater risk of complications in pregnancy and labour, and are more likely to lose their child to stillbirth or die themselves during pregnancy. This narrative review considers the evidence that, in addition to increasing risk of poor pregnancy outcomes, obesity has the capacity to programme foetuses to be at greater risk of cardiometabolic disorders later in life. An extensive body of evidence from prospective and retrospective cohorts, as well as record linkage studies, demonstrates associations of maternal obesity and/or gestational diabetes with cardiovascular disease, as well as type 1 and type 2 diabetes. Studies in animals suggest that these associations are underpinned by adaptations that occur in foetal life, which remodel the structures of major organs, including the brain, kidney and pancreas

The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins

<p>Abstract</p> <p>Background</p> <p>Maternal protein restriction during rat pregnancy is known to impact upon fetal development, growth and risk of disease in later life. It is of interest to understand how protein undernutrition influences the normal maternal adaptation to pregnancy. Here we investigated the mechanisms regulating renal haemodynamics and plasma volume during pregnancy, in the context of both normal and reduced plasma volume expansion. The study focused on expression of renal angiotensin receptors (ATR) and vasopressin-related aquaporins (AQP), hypothesising that an alteration in the balance of these proteins would be associated with pregnancy <it>per se </it>and with compromised plasma volume expansion in rats fed a low-protein diet.</p> <p>Methods</p> <p>Female Wistar rats were mated and fed a control (18% casein) or low-protein (9% casein) diet during pregnancy. Animals were anaesthetised on days 5, 10, 15 and 20 of gestation (n = 8/group/time-point) for determination of plasma volume using Evans Blue dye, prior to euthanasia and collection of tissues. Expression of the ATR subtypes and AQP2, 3 and 4 were assessed in maternal kidneys by PCR and western blotting. 24 non-pregnant Wistar rats underwent the same procedure at defined points of the oestrous cycle.</p> <p>Results</p> <p>As expected, pregnancy was associated with an increase in blood volume and haemodilution impacted upon red blood cell counts and haemoglobin concentrations. Expression of angiotensin II receptors and aquaporins 2, 3 and 4 was stable across all stages of the oestrus cycle. Interesting patterns of intra-renal protein expression were observed in response to pregnancy, including a significant down-regulation of AQP2. In contrast to previous literature and despite an apparent delay in blood volume expansion in low-protein fed rats, blood volume did not differ significantly between groups of pregnant animals. However, a significant down-regulation of AT₂R protein expression was observed in low-protein fed animals alongside a decrease in creatinine clearance.</p> <p>Conclusion</p> <p>Regulatory systems involved in the pregnancy-induced plasma volume expansion are susceptible to the effects of maternal protein restriction.</p