A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown. METHODS AND FINDINGS The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regression models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01-1.94) participants, but not among metabolically healthy/overweight individuals (OR = 0.96, 95% CI 0.65-1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49-0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the classification of individuals as being hyperinsulinaemic-based on their C-peptide level-was arbitrary. However, when we used quartiles or the median of C-peptide, instead of tertiles, as the cut-point of hyperinsulinaemia, a similar pattern of associations was observed. CONCLUSIONS These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer.

Hábitos y estilos de vida modificables en niños con sobrepeso y obesidad.

INTRODUCTION In the prevention for being overweight and for obesity, much attention is given to the influence of dietary factors, making the joint evaluation with other modifiable factors necessary. OBJECTIVES The aim of this project is to study the association between modifiable factors (physical activity, sedentary lifestyle, and dietary habits) with the prevalence of being overweight or obese in the youth population. METHODS Cross-Sectional study of 1283 school children between the ages of 3 and 16 years old, with measurements of the MBI, dietary habits, physical activity, sedentary lifestyle and family history of being overweight. Physical activity measured in MET was classified according to Pate criteria. RESULTS 22.4% of the boys and 32.9% of the girls were overweight. The presence of a BMI>25 in parents multiplied by 2.4 the risk of being overweight in children (OR CI 95% 1.5-3.7). 63.6% of overweight boys meet physical activity recommendations compared with 52.2% of girls, although in their case, it was greater than the average (45%). Sedentary time was 141 minutes for men and 128 minutes for women, with more sedentary behaviors associated with being overweight, especially in girls over 12 years of age (66.7%). Consuming cereal (OR 0.8) and having five meals per day (OR 0.5) act as protective factors. CONCLUSIONS In subjects with overweight, the levels of physical activity are close to those recommended levels, so which the values of a sedentary lifestyle together with dietary habits (if the parents have overweight) acquire a new relevance in intervention strategies of this problem.

Influencia de la temperatura en la ingesta de pacientes hospitalizados.

BACKGROUND AND OBJECTIVES Prevalence of hyponutrition in hospitalized patients is very high and it has been shown to be an important prognostic factor. Most of admitted patients depend on hospital food to cover their nutritional demands being important to assess the factors influencing their intake, which may be modified in order to improve it and prevent the consequences of inadequate feeding. In previous works, it has been shown that one of the worst scored characteristics of dishes was the temperature. The aim of this study was to assess the influence of temperature on patient's satisfaction and amount eaten depending on whether the food was served in isothermal trolleys keeping proper food temperature or not. MATERIAL AND METHODS We carried out satisfaction surveys to hospitalized patients having regular diets, served with or without isothermal trolleys. The following data were gathered: age, gender, weight, number of visits, mobility, autonomy, amount of orally taken medication, intake of out-of-hospital foods, qualification of food temperature, presentation and smokiness, amount of food eaten, and reasons for not eating all the content of the tray. RESULTS Of the 363 surveys, 134 (37.96%) were done to patients with isothermal trays and 229 (62.04%) to patients without them. Sixty percent of the patients referred having eaten less than the normal amount within the last week, the most frequent reason being decreased appetite. During lunch and dinner, 69.3% and 67.7%, respectively, ate half or less of the tray content, the main reasons being as follows: lack of appetite (42% at lunch time and 40% at dinner), do not like the food (24.3 and 26.2%) or taste (15.3 and 16.8%). Other less common reasons were the odor, the amount of food, having nausea or vomiting, fatigue, and lack of autonomy. There were no significant differences in the amount eaten by gender, weight, number of visits, amount of medication, and level of physical activity. The food temperature was classified as adequate by 62% of the patients, the presentation by 95%, and smokiness by 85%. When comparing the patients served with or without isothermal trays, there were no differences with regards to baseline characteristics analyzed that might have had an influence on amount eaten. Ninety percent of the patients with isothermal trolley rated the food temperature as good, as compared with 57.2% of the patients with conventional trolley, the difference being statistically significant (P = 0.000). Besides, there were differences in the amount of food eaten between patients with and without isothermal trolley, so that 41% and 27.7% ate all the tray content, respectively, difference being statistically significant (P = 0.007). There were no differences in smokiness or presentation rating. CONCLUSIONS Most of the patients (60%) had decreased appetite during hospital admission. The percentage of hospitalized patients rating the food temperature as being good is higher among patients served with isothermal trolleys. The amount of food eaten by the patients served with isothermal trolleys is significantly higher that in those without them.

Ceruloplasmina y su importancia clínica como factor indicador del riesgo cardiovascular en una población de escolares de Granada.

Also known as ferroxidase ceruloplasmin, belongs to the family of inflammation-sensitive proteins, and its main function to transport copper in the blood. Although, in addition to this transport function, at present, there are numerous studies that have attempted to use the determination of serum concentrations as a predictive indicator of cardiovascular risk in patients who are overweight or obese. The results of this study confirm the existence of a significant correlation between serum ceruloplasmin and nutritional status of the subjects, which means that for the population of students assessed, serum levels of this protein are an important predictor the risk of cardiovascular disease.

Acute oxygen sensing in heme oxygenase-2 null mice.

Hemeoxygenase-2 (HO-2) is an antioxidant enzyme that can modulate recombinant maxi-K(+) channels and has been proposed to be the acute O(2) sensor in the carotid body (CB). We have tested the physiological contribution of this enzyme to O(2) sensing using HO-2 null mice. HO-2 deficiency leads to a CB phenotype characterized by organ growth and alteration in the expression of stress-dependent genes, including the maxi-K(+) channel alpha-subunit. However, sensitivity to hypoxia of CB is remarkably similar in HO-2 null animals and their control littermates. Moreover, the response to hypoxia in mouse and rat CB cells was maintained after blockade of maxi-K(+) channels with iberiotoxin. Hypoxia responsiveness of the adrenal medulla (AM) (another acutely responding O(2)-sensitive organ) was also unaltered by HO-2 deficiency. Our data suggest that redox disregulation resulting from HO-2 deficiency affects maxi-K(+) channel gene expression but it does not alter the intrinsic O(2) sensitivity of CB or AM cells. Therefore, HO-2 is not a universally used acute O(2) sensor.

Resultados materno-fetales de la gestación tras cirugía bariátrica.

BACKGROUND Obesity is the most frequent metabolic disease in the World, and is associated with several comorbidities. Bariatric procedures arise as a promising treatment when classical approach is ineffective. Half of the operated patients are reproductive-aged women and there is evidence that obesity is related to worse maternal and fetal outcomes. Because nutritional status is affected by bariatric surgery and is a vital component during pregnancy, the aim of our study is to asses the impact of bariatric surgery on pregnancy in these patients. MATERIAL AND METHODS We studied 10 women and 15 pregnancies following bariatric surgery between 2003 and 2009. The visits took place every three months by an obstetrician and an endocrinologist with experience in nutrition, recording clinical features and lab work. RESULTS We found iron deficiency in 80% of the pregnancies, vitamin D in 46,7%, vitamin A in 20%, vitamin E in 13,3% and vitamin B12 in 26,7%. There were no complications during pregnancy, except one case of gravidic hiperemesis. There were nine deliveries without malformations, three of them were small for gestational age newborns and one suffered aspiration pneumonia. There were three stillbirths and one preterm delivery with fetal death. CONCLUSIONS our results show fewer complications during pregnancy in these women than obese women and similar to general population.

Analysis of CXCL12 3 ' UTR G > A polymorphism in colorectal cancer

Colorectal cancer is one of the most prevalent cancers in developed countries. However, the genetic factors influencing its appearance remain far from being fully characterized. Recently, a G>A functional transition mapping the 3' untranslated region of the CXCL12 gene (rs1801157) has been found to be under-represented among rectal cancer patients when compared to colon cancer patients from a Swedish series. Here we present the results from an independent analysis of CXCL12 rs1801157 in a larger CRC series of Spanish origin in order to analyse the robustness of this association within a different European population. No significant difference was observed between controls and colon or rectal cancer patients. We were also unable to find a correlation between rs1801157 and different prognostic markers such as metastasis development or disease-free survival time. The epidemiologic data involving CXCL12 rs1801157 in colorectal cancer risk are discussed.

Breast cancer prognostic classification in the molecular era: the role of histological grade.

Breast cancer is a heterogeneous disease with varied morphological appearances, molecular features, behavior, and response to therapy. Current routine clinical management of breast cancer relies on the availability of robust clinical and pathological prognostic and predictive factors to support clinical and patient decision making in which potentially suitable treatment options are increasingly available. One of the best-established prognostic factors in breast cancer is histological grade, which represents the morphological assessment of tumor biological characteristics and has been shown to be able to generate important information related to the clinical behavior of breast cancers. Genome-wide microarray-based expression profiling studies have unraveled several characteristics of breast cancer biology and have provided further evidence that the biological features captured by histological grade are important in determining tumor behavior. Also, expression profiling studies have generated clinically useful data that have significantly improved our understanding of the biology of breast cancer, and these studies are undergoing evaluation as improved prognostic and predictive tools in clinical practice. Clinical acceptance of these molecular assays will require them to be more than expensive surrogates of established traditional factors such as histological grade. It is essential that they provide additional prognostic or predictive information above and beyond that offered by current parameters. Here, we present an analysis of the validity of histological grade as a prognostic factor and a consensus view on the significance of histological grade and its role in breast cancer classification and staging systems in this era of emerging clinical use of molecular classifiers.

Estudio longitudinal del Índice de masa corporal (IMC) en pacientes en diálisis

Chronic renal failure is commonly related to hyponutrition, affecting approximately on third of patients with advanced renal failure. We carried out a longitudinal study to assess nutritional evolution of 73 patients on a regular hemodialysis program, assessing changes in the anthropometrical parameter body mass index (BMI) and its correspondence to biochemical nutritional parameters such as total protein (TP) levels and serum albumin (Alb). Every three months plasma TP and albumin levels were collected and BMI was calculated by the standard formula: post-dialysis weight in kg/height in m2. For classifying by BMI categories, overweight and low weight were defined according to the WHO Expert Committee. Studied patients had a mean age of 53 years, 43 were male and 30 were female patients. BMI in women was lower than that in men (p < 0.001), as well as TP (p < 0.001) and Alb (p < 0.001) levels. Mean BMI was 29.3 kg/m2. Three point two percent of the determinations showed low weight, 12.16% overweight, and 83.97% normal BMI. TP were normal in 90.76% and decreased in 9.24%. Alb was normal in 82.2% and low in 17.78%. After the follow-up time (21.6 months, minimum 18 months, maximum 53 months), the Kruskal-Wallis test did not show a statistically significant change for BMI but it did show a change for the biochemical parameters albumin and total proteins (p < 0.05): nutritional impairment in CRF patients is manifested on biochemical parameters (TP and Alb) with no reflection on anthropometrical data.

Nutrición, fibrosis quística y aparato digestivo

The prevalence of hyponutrition in cystic fibrosis is high although it may vary according to the different studies. Detection of hyponutrition should be done by combining different methods, depending on their availability. However, the simplest and most validated criterion is to measure at each visit the weight (and height in children) in order to calculate the body mass index and categorizing hyponutrition according to absolute criteria: in adults < 18.5 kg/m(2), and in children as percentiles of the body mass index. Worsening of the nutritional status is directly related with the decrease in lung function parameters and it has been proposed as a morbidity (and even mortality) predictive factor in people with cystic fibrosis, independently of the level of pulmonary dysfunction. Exocrine pancreatic insufficiency is present is approximately 70-90% of the patients with cystic fibrosis and the genotype-phenotype correlation is high. Most of the patients with exocrine pancreatic insufficiency tolerate a high-fat diet provided that they are treated with pancreatic enzymes at appropriate doses. The prevalence of diabetes increases with age, reaching up 40% of the cases in patients older than 30 years. Clinical liver involvement is less prevalent (it approximately affects 1/3 of the patients). Other intestinal complications such as meconial ileus, gastroesophageal reflux, obstruction of the distal intestine, or fibrosing colon disease may also condition malnourishment. In patients with cystic fibrosis, a usual high-fat diet providing 120%-150% of the recommended calories is advised. If the nutritional goals are not achieved or maintained with diet modifications, artificial supplements may be added, although the recommendation for their use has not been endorsed by solid scientific evidences. The most frequently used preparations usually are polymeric or hypercaloric. The indications for enteral (through a tube, especially gastrostomy) or parenteral nutritional support are similar to those used in other pathologies. Dietary and nutritional control should be included in a multidisciplinary program allowing the improvement of the functional capacity and the quality of life and reducing, at least from a theoretical viewpoint, the morbimortality associated to malnourishment in these patients.

Thin healthy women have a similar low bone mass to women with anorexia nervosa.

An association between anorexia nerviosa (AN) and low bone mass has been demonstrated. Bone loss associated with AN involves hormonal and nutritional impairments, though their exact contribution is not clearly established. We compared bone mass in AN patients with women of similar weight with no criteria for AN, and a third group of healthy, normal-weight, age-matched women. The study included forty-eight patients with AN, twenty-two healthy eumenorrhoeic women with low weight (LW group; BMI < 18.5 kg/m2) and twenty healthy women with BMI >18.5 kg/m2 (control group), all of similar age. We measured lean body mass, percentage fat mass, total bone mineral content (BMC) and bone mineral density in lumbar spine (BMD LS) and in total (tBMD). We measured anthropometric parameters, leptin and growth hormone. The control group had greater tBMD and BMD LS than the other groups, with no differences between the AN and LW groups. No differences were found in tBMD, BMD LS and total BMC between the restrictive (n 25) and binge-purge type (n 23) in AN patients. In AN, minimum weight (P = 0.002) and percentage fat mass (P = 0.02) explained BMD LS variation (r2 0.48) and minimum weight (r2 0.42; P = 0.002) for tBMD in stepwise regression analyses. In the LW group, BMI explained BMD LS (r2 0.72; P = 0.01) and tBMD (r2 0.57; P = 0.04). We concluded that patients with AN had similar BMD to healthy thin women. Anthropometric parameters could contribute more significantly than oestrogen deficiency in the achievement of peak bone mass in AN patients.

Adipose tissue gene expression of factors related to lipid processing in obesity.

BACKGROUND Adipose tissue lipid storage and processing capacity can be a key factor for obesity-related metabolic disorders such as insulin resistance and diabetes. Lipid uptake is the first step to adipose tissue lipid storage. The aim of this study was to analyze the gene expression of factors involved in lipid uptake and processing in subcutaneous (SAT) and visceral (VAT) adipose tissue according to body mass index (BMI) and the degree of insulin resistance (IR). METHODS AND PRINCIPAL FINDINGS VLDL receptor (VLDLR), lipoprotein lipase (LPL), acylation stimulating protein (ASP), LDL receptor-related protein 1 (LRP1) and fatty acid binding protein 4 (FABP4) gene expression was measured in VAT and SAT from 28 morbidly obese patients with Type 2 Diabetes Mellitus (T2DM) or high IR, 10 morbidly obese patients with low IR, 10 obese patients with low IR and 12 lean healthy controls. LPL, FABP4, LRP1 and ASP expression in VAT was higher in lean controls. In SAT, LPL and FABP4 expression were also higher in lean controls. BMI, plasma insulin levels and HOMA-IR correlated negatively with LPL expression in both VAT and SAT as well as with FABP4 expression in VAT. FABP4 gene expression in SAT correlated inversely with BMI and HOMA-IR. However, multiple regression analysis showed that BMI was the main variable contributing to LPL and FABP4 gene expression in both VAT and SAT. CONCLUSIONS Morbidly obese patients have a lower gene expression of factors related with lipid uptake and processing in comparison with healthy lean persons.

Sources of pre-analytical variations in yield of DNA extracted from blood samples: analysis of 50,000 DNA samples in EPIC.

The European Prospective Investigation into Cancer and nutrition (EPIC) is a long-term, multi-centric prospective study in Europe investigating the relationships between cancer and nutrition. This study has served as a basis for a number of Genome-Wide Association Studies (GWAS) and other types of genetic analyses. Over a period of 5 years, 52,256 EPIC DNA samples have been extracted using an automated DNA extraction platform. Here we have evaluated the pre-analytical factors affecting DNA yield, including anthropometric, epidemiological and technical factors such as center of subject recruitment, age, gender, body-mass index, disease case or control status, tobacco consumption, number of aliquots of buffy coat used for DNA extraction, extraction machine or procedure, DNA quantification method, degree of haemolysis and variations in the timing of sample processing. We show that the largest significant variations in DNA yield were observed with degree of haemolysis and with center of subject recruitment. Age, gender, body-mass index, cancer case or control status and tobacco consumption also significantly impacted DNA yield. Feedback from laboratories which have analyzed DNA with different SNP genotyping technologies demonstrate that the vast majority of samples (approximately 88%) performed adequately in different types of assays. To our knowledge this study is the largest to date to evaluate the sources of pre-analytical variations in DNA extracted from peripheral leucocytes. The results provide a strong evidence-based rationale for standardized recommendations on blood collection and processing protocols for large-scale genetic studies.

Estudio comparativo del estatus clínico-nutricional en mujeres obesas posmenopáusicas incluídas en un programa de pérdida de peso basado en platos preparados.

INTRODUCTION Few studies have evaluated the efficacy and reliability of weight loss-focussed prepared food dishes in obese post-menopausal women. OBJECTIVE To compare the efficacy of a weight loss programme based on a balanced hypocaloric diet using prepared dishes* with that of a similar programme based on standard commercially available foods and with a non-intervened control group. A further aim was to evaluate the subjectivity of participants in the preparation of the diet-adjusted dishes based on usually consumed products. SUBJECTS Obese post-menopausal women aged between 55 and 65 years. DESIGN Controlled longitudinal interventional study. METHOD The sample of 75 female volunteers were divided into three groups of 25 women: a control group, who continued to consume their usual non-dietary adjusted meals (CG), an intervened group, treated with a diet adjusted to their individual requirements and based on standard commercially available food (SG), and another intervened group, treated with a similarly adjusted diet but based on prepared dishes (PG). Data were gathered on anthropometric variables, consumption habits and physical activity levels, and clinical-nutritional controls were conducted at the start and every two weeks to the end of the 8-week study in order to evaluate biochemical changes. RESULTS The weight loss was slightly higher in the prepared-dishes group (PG) than in the standard food diet group (SG), but the difference was not statistically significant, whereas it was considerably higher in both groups than in the non-dietary adjusted control group (CG) and this difference was highly significant (losses of 7.60 kg in PG and 7.01 kg in SG versus 2.10 kg in CG (p < 0.01). However, the PG showed a significantly higher (p < 0.01) loss of fatty mass and abdominal circumference versus the SG women. CONCLUSION More weight was lost by the two groups treated with a diet based on prepared dishes or usual food items in comparison to untreated controls, but the diet based on prepared dishes obtained more reliable and higher quality outcomes, achieving a positive change at fatty compartment level and in the abdominal circumference.

Implementation of a nutrition education program in a handball team; consequences on nutritional status.

OBJECTIVE: To evaluate nutritional status and dietary habits after implementation of a nutritional education program in professional handball players. RESEARCH METHODS AND PROCEDURES: Longitudinal study of 14 handball players evaluated with 72-h recall, a questionnaire on food consumption and anthropometric measures during 4 months. The intervention consisted of a nutrition education program. RESULTS: Energy intake was consistently below the recommended allowances. Macronutrient intakes as a percentage of total energy intake were below the recommended allowances for carbohydrates, and above recommended allowances for fats. Nutritional education was followed by a significant increase (p < 0.01) in total energy and macronutrient intakes, with no significant changes in macronutrient or micronutrient intakes after adjustment for energy intake. DISCUSSION: The imbalance in nutrient intake in handball players suggests that detailed re-analysis is needed to determine specific recommendations for this population. Nutritional education with continuous follow-up to monitor athletes' dietary habits may lead them to adopt appropriate nutritional habits to optimize dietary intakes. The lack of specific recommendations for micronutrient intakes in athletes leads to confusion regarding appropriate intakes; biochemical tests that yield normal values (albeit approaching cut-off values for deficiency) may disguise deficient status for some nutrients when strenuous exercise is involved. CONCLUSION: In-depth studies with nutrition education programs that include long-term follow-up are advisable to avoid deficiencies that can lead to irreversible damage in competitive athletes.