Long-term risk of incident type 2 diabetes and measures of overall and regional obesity: the EPIC-InterAct case-cohort study

BACKGROUND Waist circumference (WC) is a simple and reliable measure of fat distribution that may add to the prediction of type 2 diabetes (T2D), but previous studies have been too small to reliably quantify the relative and absolute risk of future diabetes by WC at different levels of body mass index (BMI). METHODS AND FINDINGS The prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident T2D cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. We used Prentice-weighted Cox regression and random effects meta-analysis methods to estimate hazard ratios for T2D. Kaplan-Meier estimates of the cumulative incidence of T2D were calculated. BMI and WC were each independently associated with T2D, with WC being a stronger risk factor in women than in men. Risk increased across groups defined by BMI and WC; compared to low normal weight individuals (BMI 18.5-22.4 kg/m(2)) with a low WC (<94/80 cm in men/women), the hazard ratio of T2D was 22.0 (95% confidence interval 14.3; 33.8) in men and 31.8 (25.2; 40.2) in women with grade 2 obesity (BMI≥35 kg/m(2)) and a high WC (>102/88 cm). Among the large group of overweight individuals, WC measurement was highly informative and facilitated the identification of a subgroup of overweight people with high WC whose 10-y T2D cumulative incidence (men, 70 per 1,000 person-years; women, 44 per 1,000 person-years) was comparable to that of the obese group (50-103 per 1,000 person-years in men and 28-74 per 1,000 person-years in women). CONCLUSIONS WC is independently and strongly associated with T2D, particularly in women, and should be more widely measured for risk stratification. If targeted measurement is necessary for reasons of resource scarcity, measuring WC in overweight individuals may be an effective strategy, since it identifies a high-risk subgroup of individuals who could benefit from individualised preventive action.

Residential Exposure to Outdoor Air Pollution during Pregnancy and Anthropometric Measures at Birth in a Multicenter Cohort in Spain

BACKGROUND. A growing body of research suggests that prenatal exposure to air pollution may be harmful to fetal development. We assessed the association between exposure to air pollution during pregnancy and anthropometric measures at birth in four areas within the Spanish Children's Health and Environment (INMA) mother and child cohort study. METHODS. Exposure to ambient nitrogen dioxide (NO2) and benzene was estimated for the residence of each woman (n = 2,337) for each trimester and for the entire pregnancy. Outcomes included birth weight, length, and head circumference. The association between residential outdoor air pollution exposure and birth outcomes was assessed with linear regression models controlled for potential confounders. We also performed sensitivity analyses for the subset of women who spent more time at home during pregnancy. Finally, we performed a combined analysis with meta-analysis techniques. RESULTS. In the combined analysis, an increase of 10 µg/m3 in NO2 exposure during pregnancy was associated with a decrease in birth length of -0.9 mm [95% confidence interval (CI), -1.8 to -0.1 mm]. For the subset of women who spent ≥ 15 hr/day at home, the association was stronger (-0.16 mm; 95% CI, -0.27 to -0.04). For this same subset of women, a reduction of 22 g in birth weight was associated with each 10-µg/m3 increase in NO2 exposure in the second trimester (95% CI, -45.3 to 1.9). We observed no significant relationship between benzene levels and birth outcomes. CONCLUSIONS. NO2 exposure was associated with reductions in both length and weight at birth. This association was clearer for the subset of women who spent more time at home.

The association of education with body mass index and waist circumference in the EPIC-PANACEA study

Background To examine the association of education with body mass index (BMI) and waist circumference (WC) in the European Prospective Investigation into Cancer and Nutrition (EPIC). Method This study included 141,230 male and 336,637 female EPIC-participants, who were recruited between 1992 and 2000. Education, which was assessed by questionnaire, was classified into four categories; BMI and WC, measured by trained personnel in most participating centers, were modeled as continuous dependent variables. Associations were estimated using multilevel mixed effects linear regression models. Results Compared with the lowest education level, BMI and WC were significantly lower for all three higher education categories, which was consistent for all countries. Women with university degree had a 2.1 kg/m2 lower BMI compared with women with lowest education level. For men, a statistically significant, but less pronounced difference was observed (1.3 kg/m2). The association between WC and education level was also of greater magnitude for women: compared with the lowest education level, average WC of women was lower by 5.2 cm for women in the highest category. For men the difference was 2.9 cm. Conclusion In this European cohort, there is an inverse association between higher BMI as well as higher WC and lower education level. Public Health Programs that aim to reduce overweight and obesity should primarily focus on the lower educated population.

A comparative study of dyslipidaemia in men and woman with androgenic alopecia

Several studies have analyzed the relationship between androgenetic alopecia and cardiovascular disease (mainly heart disease). However few studies have analyzed lipid values in men and women separately. This case-control study included 300 patients consecutively admitted to an outpatient clinic, 150 with early onset androgenetic alopecia (80 males and 70 females) and 150 controls (80 males and 70 females) with other skin diseases. Female patients with androgenic alopecia showed significant higher triglycerides values (123.8 vs 89.43 mg/dl, p = 0.006), total cholesterol values (196.1 vs 182.3 mg/dl, p = 0.014), LDL-C values (114.1 vs 98.8 mg/dl, p = 0.0006) and lower HDL-C values (56.8 vs 67.7 mg/dl, p <0.0001) versus controls respectively. Men with androgenic alopecia showed significant higher triglycerides values (159.7 vs 128.7 mg/dl, p = 0.04) total cholesterol values (198.3 vs 181.4 mg/dl, p = 0.006) and LDL-C values (124.3 vs 106.2, p = 0.0013) versus non-alopecic men. A higher prevalence of dyslipidemia in women and men with androgenic alopecia has been found. The elevated lipid values in these patients may contribute, alongside other mechanisms, to the development of cardiovascular disease in patient with androgenic alopecia.

A comparative study of the preventative effects exerted by two probiotics, Lactobacillus reuteri and Lactobacillus fermentum, in the trinitrobenzenesulfonic acid model of rat colitis

The intestinal anti-inflammatory effects of two probiotics isolated from breast milk, Lactobacillus reuteri and L. fermentum, were evaluated and compared in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis. Colitis was induced in rats by intracolonic administration of 10 mg TNBS dissolved in 50% ethanol (0.25 ml). Either L. reuteri or L. fermentum was daily administered orally (5 x 10(8) colony-forming units suspended in 0.5 ml skimmed milk) to each group of rats (n 10) for 3 weeks, starting 2 weeks before colitis induction. Colonic damage was evaluated histologically and biochemically, and the colonic luminal contents were used for bacterial studies and for SCFA production. Both probiotics showed intestinal anti-inflammatory effects in this model of experimental colitis, as evidenced histologically and by a significant reduction of colonic myeloperoxidase activity (P<0.05). L. fermentum significantly counteracted the colonic glutathione depletion induced by the inflammatory process. In addition, both probiotics lowered colonic TNFalpha levels (P<0.01) and inducible NO synthase expression when compared with non-treated rats; however, the decrease in colonic cyclo-oxygenase-2 expression was only achieved with L.fermentum administration. Finally, the two probiotics induced the growth of Lactobacilli species in comparison with control colitic rats, but the production of SCFA in colonic contents was only increased when L. fermentum was given. In conclusion, L. fermentum can exert beneficial immunomodulatory properties in inflammatory bowel disease, being more effective than L. reuteri, a probiotic with reputed efficacy in promoting beneficial effects on human health.

Prevention of overweight and obesity: a Spanish approach

Background. Obesity is considered a major public health issue in most developed countries nowadays. This paper provides an overview of current population data available in Spain and the approach to develop preventive strategies in the country. Methods. Review of population data available is based on individually measured weight and height as well as determinants. On this basis, the approach used in the country to develop preventive strategies is discussed. Results. According to the DORICA study, the prevalence of obesity (BMI ≥30 kg m−2) is 15.5% in Spanish adults aged 25–60 years (13.2% in men and 17.5% in women). Obesity rates are higher among women aged 45 years and older, low social class, living in semi-urban places. Population estimates for the prevalence of obesity in Spanish children and young people based on the enKid study are 13.9% for the whole group. In this study, overweight and obesity is related to absence of breastfeeding, low consumption of fruit and vegetables, high consumption of cakes, buns, softdrinks and butchery products, low physical activity levels and a positive association with time spent watching TV. In 2005, the Spanish Ministry of Health jointly with the Spanish Agency for Food Safety and Nutrition launched the multifaceted NAOS strategy for nutrition, physical activity and the prevention of obesity. The important role of the family and the school setting as well as the responsibility of the Health Administration and Pediatric Care in the prevention of obesity is highlighted in the document. The need for environmental actions is recognised. The PERSEO programme, a multicomponent school-based intervention project is part of the strategy currently in place. Conclusion. Obesity is a public health issue in Spain. A national multifaceted strategy was launched to counteract the problem. Environmental and policy actions are a priority. Young children and their families are among the main target groups.

Structured intermittent interruption of chronic HIV infection treatment with highly active antiretroviral therapy: Effects on leptin and TNF-alpha.

The changes in nutritional parameters and adipocytokines after structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the beginning of structured interruptions <50 copies/ml; median time of previous treatment: 60 months) were evaluated during three cycles of intermittent interruptions of therapy (8 weeks on/4 weeks off). CD4+ T cell count, HIV viral load, anthropometric measures, and serum concentrations of triglycerides, cholesterol, leptin, and tumor necrosis factor and its soluble receptors I and II were determined. After the three cycles of intermittent interruptions of therapy, no significant differences in CD4+ T cell count/microl, viral load, or serum concentrations of cholesterol or triglycerides with reference to baseline values were found. A near-significant higher fatty mass (skinfold thicknesses, at the end, 121 mm, at the beginning, 100 mm, p = 0.100), combined with a significant increase of concentration of leptin (1.5 vs. 4.7 ng/ml, p = 0,044), as well as a decrease in serum concentrations of soluble receptors of tumor necrosis factor (TNFRI, 104 vs. 73 pg/ml, p = 0.022; TNFRII 253 vs. 195 pg/ml, p = 0.098) were detected. Structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection induces a valuable positive modification in markers of lipid turnover and adipose tissue mass.

Cerebral perfusion pressure and risk of brain hypoxia in severe head injury: a prospective observational study

INTRODUCTION Higher and lower cerebral perfusion pressure (CPP) thresholds have been proposed to improve brain tissue oxygen pressure (PtiO2) and outcome. We study the distribution of hypoxic PtiO2 samples at different CPP thresholds, using prospective multimodality monitoring in patients with severe traumatic brain injury. METHODS This is a prospective observational study of 22 severely head injured patients admitted to a neurosurgical critical care unit from whom multimodality data was collected during standard management directed at improving intracranial pressure, CPP and PtiO2. Local PtiO2 was continuously measured in uninjured areas and snapshot samples were collected hourly and analyzed in relation to simultaneous CPP. Other variables that influence tissue oxygen availability, mainly arterial oxygen saturation, end tidal carbon dioxide, body temperature and effective hemoglobin, were also monitored to keep them stable in order to avoid non-ischemic hypoxia. RESULTS Our main results indicate that half of PtiO2 samples were at risk of hypoxia (defined by a PtiO2 equal to or less than 15 mmHg) when CPP was below 60 mmHg, and that this percentage decreased to 25% and 10% when CPP was between 60 and 70 mmHg and above 70 mmHg, respectively (p < 0.01). CONCLUSION Our study indicates that the risk of brain tissue hypoxia in severely head injured patients could be really high when CPP is below the normally recommended threshold of 60 mmHg, is still elevated when CPP is slightly over it, but decreases at CPP values above it.

Standardisation of the waist circumference (WC) for each range of body mass index (BMI) in adult outpatients attended to in Endocrinology and Nutrition departments

By this study we seek the expectable range of waist circumference (WC) for every degree of body mass index (BMI), which will serve to studies targeting ascertaining the health risk. We studied 2,932 patients (39.6% men and 60.4% women, between 18 and 96 years ) of the same ethnic group who consecutively attended outpatient departments of our clinics between 2000 and 2004. BMI correlated linearly with the WC (cc: 0.85; p < 0.001). The men, the obese, and diabetics were older (p < 0.001). BMI was greater in women and WC in men. The women had a greater WC if they had diabetes (p < 0.01), being equal to diabetic males. The men had greater WC when they had diabetes (p < 0.001). Waist at risk was detected (men > or = 102 cm and women > or = 88 cm) in 94.3% of the obese, in 32.3% of overweight patients, in 3.8% of patients with BMI < 25, in 84.3% of diabetics, and in 72.6% of patients without diabetes. We made graphic standardisation of WC with regard to BMI, and we calculated the percentiles 10, 25, 50, 75 and 90, grouping in ranges of 2 kg/m(2) of BMI. The diabetic patients are grouped in ranges of 4 kg/m(2). As conclusion we present a standardisation of the WC measurement of patients attended to in our Endocrinology and Nutrition practices distributed in percentiles as a clinically usable tool to define the ranges of WC for every BMI value.

Improvement in growth after two years of growth hormone therapy in very young children born small for gestational age and without spontaneous catch-up growth: results of a multicenter, controlled, randomized, open clinical trial.

CONTEXT GH treatment is effective in children born small for gestational age (SGA); however, its effectiveness and safety in very young SGA children is unknown. OBJECTIVE The aim was to analyze the outcome of very young SGA children treated with GH and followed for 2 yr. The results after 24 months of treatment, compared with a control group without treatment during 12 months followed by 12 months of treatment, are shown. DESIGN We performed a multicenter, controlled, randomized, open trial. SETTINGS The pediatric endocrinology departments of 14 public hospitals in Spain participated in the study. PATIENTS Seventy-six children, aged 2-5 yr born SGA and without catch-up growth, were studied. INTERVENTION Children received GH at 0.06 mg/kg.d for 2 yr (group I) or were followed for 12 months with no treatment and then treated for 12 months (group II). MAIN OUTCOME MEASURES Age, general health status, pubertal stage, bone age, height, weight, biochemical and hormonal analyses, and adverse side effects were determined at biannual check-ups. RESULTS The mean height sd score gain for chronological age in children treated for 24 months (group I) was 2.10, whereas in those treated only during the last 12 months (group II) was 1.43. In both groups, children under 4 yr of age had the greatest gain in growth velocity. No significant acceleration of bone age or side effects related to treatment was seen. CONCLUSION Very young SGA children without spontaneous catch-up growth could benefit from GH treatment because growth was accelerated and no negative side effects were observed.

Prevalence and Clinical Features of Isolated Clinical Hypertension and Dipping Profile in a Large Cohort of Untreated Hypertensive Subjects

Aim: To examine the prevalence and clinical features of isolated clinical hypertension (ICH) and the dipping patterns in a large cohort of untreated hypertensive subjects form the Spanish ABPM registry

Influence of physical activity and dietary habits on lipid profile, blood pressure and BMI in subjects with metabolic syndrome

BACKGROUND The present study was determined the influence of physical activity and dietary habits on lipid profile, blood pressure (BP) and body mass index (BMI) in subjects with metabolic syndrome (MS). AIMS Identify the relationship between physical activity and proper nutrition and the probability of suffering from myocardial infarction (MI). METHODS Hundred chronically ill with MS who were active and followed a healthy diet were classified as compliant, while the remaining subjects were classified as non-compliant. RESULTS The compliant subjects show lower BMI values (30.8±4.9 vs 32.5±4.6), as well as lower levels of triacylglycerol (130.4±48.2 vs 242.1±90.1), total cholesterol (193.5±39 vs 220.2±52.3) and low-density lipoprotein cholesterol (105.2±38.3 vs 139.2±45). They show higher values in terms of high-density lipoprotein cholesterol levels (62.2±20.1 vs 36.6±15.3), with statistically significant differences. In terms of both systolic and diastolic pressure, no differences were revealed between the groups; however, those who maintain proper dietary habits show lower systolic blood pressure levels than the inactive subjects. The probability of suffering from MI greatly increases among the group of non-compliant subjects. CONCLUSIONS Our results demonstrate how performing aerobic physical activity and following an individualized, Mediterranean diet significantly reduces MS indicators and the chances of suffering from MI.

Inverse relation between FASN expression in human adipose tissue and the insulin resistance level.

BACKGROUND Adipose tissue is a key regulator of energy balance playing an active role in lipid storage and may be a dynamic buffer to control fatty acid flux. Just like PPARgamma, fatty acid synthesis enzymes such as FASN have been implicated in almost all aspects of human metabolic alterations such as obesity, insulin resistance or dyslipemia. The aim of this work is to investigate how FASN and PPARgamma expression in human adipose tissue is related to carbohydrate metabolism dysfunction and obesity. METHODS The study included eighty-seven patients which were classified according to their BMI and to their glycaemia levels in order to study FASN and PPARgamma gene expression levels, anthropometric and biochemical variables. RESULTS The main result of this work is the close relation between FASN expression level and the factors that lead to hyperglycemic state (increased values of glucose levels, HOMA-IR, HbA1c, BMI and triglycerides). The correlation of the enzyme with these parameters is inversely proportional. On the other hand, PPARgamma is not related to carbohydrate metabolism. CONCLUSIONS We can demonstrate that FASN expression is a good candidate to study the pathophysiology of type II diabetes and obesity in humans.

Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study.

INTRODUCTION Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use. METHODS Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed. RESULTS For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime. CONCLUSIONS An elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors.

Compliance with dietary and nutrient recommendations in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Granada cohort at recruitment

BACKGROUND: The overall intake of energy and nutrients in the Granada EPIC-cohort (European Prospective Investigation into Cancer and Nutrition) is examined in order to assess compliance with the Spanish Nutritional Objectives (NO) and the Recommended Intakes (RI). METHODS: During recruitment (1992-1996), 7,789 participants, aged 35-69, were asked about diet through a validated diet history questionnaire. Nutrient intake is compared to the NO and RI that were valid at that time. Risk of inadequate intake is estimated as the percentage of the sample with intakes: ≤ 1/3 RI (high risk), ≤ 2/3 RI- > 1/3 RI (moderate risk), ≤ RI- > 2/3 RI, > RI. Differences in intakes have been analyzed by sex and age, and by smoking status and BMI. RESULTS: The daily intake of nutrients did not meet the NO as the total contribution of energy from proteins and fats exceeded these guidelines. Whilst intake of most nutrients was above the RI, the amount of iron, magnesium and vitamins D and E provided by the diet was not enough to meet the RI: in women aged 20-49 years, about 55% were at moderate risk for iron inadequacy, and a 20% of women for magnesium. Both sexes were at high risk of inadequacy for vitamin D, although sunlight exposure may supply adequate amounts. Never smokers showed a higher compliance to the NO. CONCLUSION: At recruitment, the nutrient profile of the diet was unbalanced. The observed nutrient inadequacy for iron, magnesium and vitamin E might be attributed to inappropriate dietary habits, and may have implications for future disease risk.