Morbidity, Including Fatal Morbidity, throughout Life in Men Entering Adult Life as Obese

Background: The association between obesity in adults and excess morbidity and mortality is well established, but the health impact throughout adult life of being obese in early adulthood needs elucidation. We investigated somatic morbidity, including fatal morbidity, throughout adulthood in men starting adult life as obese. Methods: Among 362,200 Danish young men, examined for military service between 1943 and 1977, all obese (defined as BMI$31.0 kg/m 2), and, as controls, a random 1 % sample of the others was identified. In the age range of 18–25 years, there were 1,862 obese, which encompass the men above the 99.5 percentile, and 3,476 controls. Information on morbidity was obtained via national registers. Cox regression models were used to estimate the relative morbidity assessed as first incidence of disease, occurrence of disease in the year preceding death and prevalent disease at time of death. Results: From age 18 through 80 years the obese had an increased risk of becoming diseased by or die from a broad range of diseases. Generally, the incidence of first event, occurrence in the year prior to death, and prevalence at time of death showed the same pattern. As an example, the relative hazard of type 2 diabetes was constant throughout life at 4.9 (95% confidence intervals [CI]: 4.1–5.9), 5.2 (95 % CI: 3.6–7.5), and 6.8 (95 % CI: 4.6–10.1), respectively. Conclusions: Our findings strongly support the continued need to avoid beginning adult life as obese, as obese young me

Early life factors, childhood cognition and postal questionnaire response rate in middle age: the Aberdeen Children of the 1950s study

BACKGROUND: Little is known about the relationship between early life factors and survey response in epidemiological studies of adults. METHODS: The Children of the 1950s cohort is composed of 12,150 children (boys 51.7%) born in Aberdeen 1950–56 and in primary schools in the city in 1962. Information on birth weight, gestational age, growth, behaviour and socio-economic position at birth and in childhood were obtained from contemporaneous records. Cognitive test scores at ages 7,9 and 11 years were also available from school records. The outcome was response to a postal questionnaire sent (2001–2003) to surviving cohort members in middle age. RESULTS: Of 11,282 potentially mailed subjects, 7,183 (63.7%) returned questionnaires. Response rates were highest among females, and those whose parents were married at birth, were in a non-manual social class at birth or in childhood, had fewer siblings, were taller and heavier in childhood for their age and had lower Rutter B behavioural scores. Childhood cognitive test scores at every age were strongly and positively related to the response rate to a postal questionnaire independently of other early life factors monotonically across the entire range of test scores. Those in the bottom fifth at age 11 had a response rate of 49% while those in the top fifth 75%. CONCLUSION: The strength and consistency of the association of childhood cognition with questionnaire response rate in middle age is surprisingly large. It suggests that childhood cognition across the entire normal range is a powerful influence on the complex set of later behaviours that comprise questionnaire response. The extent of possible response bias in epidemiological studies of the associations between childhood characteristics (particularly those related to cognition) and later health is probably larger than is generally realised, at least in situations where the survey instrument is a postal questionnaire

Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism

Interactions between host and gut microbial communities are modulated by diets and play pivotal roles in immunological homeostasis and health. We show that exchanging the protein source in a high fat, high sugar, westernized diet from casein to whole-cell lysates of the non-commensal bacterium Methylococcus capsulatus Bath is sufficient to reverse western diet-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22 °C) and at thermoneutrality (T30 °C). Concomitant with microbiota changes, mice fed the Methylococcus-based western diet exhibit improved glucose regulation, reduced body and liver fat, and diminished hepatic immune infiltration. Intake of the Methylococcu-based diet markedly boosts Parabacteroides abundances in a manner depending on adaptive immunity, and upregulates triple positive (Foxp3+RORγt+IL-17+) regulatory T cells in the small and large intestine. Collectively, these data point to the potential for leveraging the use of McB lysates to improve immunometabolic homeostasis.publishedVersio

Associations between APOE Variants and Metabolic Traits and the Impact of Psychological Stress

In a previous study, we observed that associations between APOE rs439401 and metabolic traits were moderated by chronic stress. Thus, in a population of stressed and non-stressed Danish men, we examined whether associations between APOE rs439401 and a panel of metabolic quantitative traits, all metabolic traits which may lead to T2D and CVD were moderated by psychological stress.Obese young men (n = 475, BMI ≥ 31.0 kg/m(2)) and a randomly selected control group (n = 709) identified from a population of 141,800 men were re-examined in two surveys (S-46: mean age 46, S-49: mean age 49 years) where anthropometric and biochemical measures were available. Psychological stress factors were assessed by a self-administered 7-item questionnaire. Each item had the possible response categories "yes" and "no" and assessed familial problems and conflicts. Summing positive responses constituted a stress item score, which was then dichotomized into stressed and non-stressed. Logistic regression analysis, applying a recessive genetic model, was used to assess odds ratios (OR) of the associations between APOE rs439401 genotypes and adverse levels of metabolic traits.The APOE rs439401 TT-genotype associated positively with BMI (OR = 1.09 [1.01; 1.17]), waist circumference (OR = 1.09 [1.02; 1.17]) in stressed men at S-46. Positive associations were observed for fasting plasma glucose (OR = 1.42 [1.07; 1.87]), serum triglycerides (OR = 1.41 [1.05; 1.91]) and with fasting plasma insulin (OR = 1.48 [1.05; 2.08]) in stressed men at S-49. Rs439401 TT-genotype also associated positively with surrogate measures of insulin resistance (HOMA-IR; OR = 1.21 [1.03; 1.41]) and inversely with insulin sensitivity (Stumvoll index; OR = 0.90 [0.82; 0.99], BIGTT-S(I); OR = 0.60 [0.43; 0.85]) in stressed men. No significant associations were observed in non-stressed men, albeit the estimates showed similar but weaker trends as in stressed men.The present results suggest that the APOE rs439401 TT-genotype is associated with an adverse metabolic profile in a population of psychologically stressed Danish men

FTO Gene Associated Fatness in Relation to Body Fat Distribution and Metabolic Traits throughout a Broad Range of Fatness

A common single nucleotide polymorphism (SNP) of FTO (rs9939609, T/A) is associated with total body fatness. We investigated the association of this SNP with abdominal and peripheral fatness and obesity-related metabolic traits in middle-aged men through a broad range of fatness present already in adolescence.Obese young Danish men (n = 753, BMI > or = 31.0 kg/m(2)) and a randomly selected group (n = 879) from the same population were examined in three surveys (mean age 35, 46 and 49 years, respectively). The traits included anthropometrics, body composition, oral glucose tolerance test, blood lipids, blood pressure, fibrinogen and aspartate aminotransferase. Logistic regression analysis was used to assess the age-adjusted association between the phenotypes and the odds ratios for the FTO rs9939609 (TT and TA genotype versus the AA genotype), for anthropometrics and body composition estimated per unit z-score. BMI was strongly associated with the AA genotype in all three surveys: OR = 1.17, p = 1.1*10(-6), OR = 1.20, p = 1.7*10(-7), OR = 1.17, p = 3.4*10(-3), respectively. Fat body mass index was also associated with the AA genotype (OR = 1.21, p = 4.6*10(-7) and OR = 1.21, p = 1.0*10(-3)). Increased abdominal fatness was associated with the AA genotype when measured as waist circumference (OR = 1.21, p = 2.2*10(-6) and OR = 1.19, p = 5.9*10(-3)), sagittal abdominal diameter (OR = 1.17, p = 1.3*10(-4) and OR = 1.18, p = 0.011) and intra-abdominal adipose tissue (OR = 1.21, p = 0.005). Increased peripheral fatness measured as hip circumference (OR = 1.19, p = 1.3*10(-5) and OR = 1.18, p = 0.004) and lower body fat mass (OR = 1.26, p = 0.002) was associated with the AA genotype. The AA genotype was significantly associated with decreased Stumvoll insulin sensitivity index (OR = 0.93, p = 0.02) and with decreased non-fasting plasma HDL-cholesterol (OR = 0.57, p = 0.037), but not with any other of the metabolic traits. However, all significant results for both body fat distribution and metabolic traits were explained by a mediating effect of total fat mass.The association of the examined FTO SNP to general fatness throughout the range of fatness was confirmed, and this association explains the relation between the SNP and body fat distribution and decreased insulin sensitivity and HDL-cholesterol. The SNP was not significantly associated with other metabolic traits suggesting that they are not derived from the general accumulation of body fat

Parental socioeconomic position and development of overweight in adolescence: longitudinal study of Danish adolescents

<p>Abstract</p> <p>Background</p> <p>An inverse social gradient in overweight among adolescents has been shown in developed countries, but few studies have examined whether weight gain and the development of overweight differs among adolescents from different socioeconomic groups in a longitudinal study. The objective was to identify the possible association between parental socioeconomic position, weight change and the risk of developing overweight among adolescents between the ages 15 to 21.</p> <p>Methods</p> <p>Prospective cohort study conducted in Denmark with baseline examination in 1996 and follow-up questionnaire in 2003 with a mean follow-up time of 6.4 years. A sample of 1,656 adolescents participated in both baseline (mean age 14.8) and follow-up (mean age 21.3). Of these, 1,402 had a body mass index (BMI = weight/height²kg/m²) corresponding to a value below 25 at baseline when adjusted for age and gender according to guidelines from International Obesity Taskforce, and were at risk of developing overweight during the study period. The exposure was parental occupational status. The main outcome measures were change in BMI and development of overweight (from BMI < 25 to BMI > = 25).</p> <p>Results</p> <p>Average BMI increased from 21.3 to 22.7 for girls and from 20.6 to 23.6 in boys during follow-up. An inverse social gradient in overweight was seen for girls at baseline and follow-up and for boys at follow-up. In the full population there was a tendency to an inverse social gradient in the overall increase in BMI for girls, but not for boys. A total of 13.4% developed overweight during the follow-up period. Girls of lower parental socioeconomic position had a higher risk of developing overweight (OR's between 4.72; CI 1.31 to 17.04 and 2.03; CI 1.10-3.74) when compared to girls of high parental socioeconomic position. A tendency for an inverse social gradient in the development of overweight for boys was seen, but it did not meet the significance criteria</p> <p>Conclusions</p> <p>The levels of overweight and obesity among adolescents are high and continue to rise. Results from this study suggest that the inverse social gradient in overweight becomes steeper for girls and emerges for boys in late adolescence (age span 15 to 21 years). Late adolescence seems to be an important window of opportunity in reducing the social inequality in overweight among Danish adolescents.</p

Polymorphisms of Serotonin Receptor 2A and 2C Genes and COMT in Relation to Obesity and Type 2 Diabetes

BACKGROUND:Candidate genes of psychological importance include 5HT2A, 5HT2C, and COMT, implicated in the serotonin, noradrenaline and dopamine pathways, which also may be involved in regulation of energy balance. We investigated the associations of single nucleotide polymorphisms (SNPs) of these genes with obesity and metabolic traits. METHODOLOGY/PRINCIPAL FINDINGS:In a population of 166 200 young men examined at the draft boards, obese men (n = 726, BMI> or =31.0 kg/m(2)) and a randomly selected group (n = 831) were re-examined at two surveys at mean ages 46 and 49 years (S-46, S-49). Anthropometric, physiological and biochemical measures were available. Logistic regression analyses were used to assess age-adjusted odds ratios. No significant associations were observed of 5HT2A rs6311, 5HT2C rs3813929 and COMT rs4680 with obesity, except that COMT rs4680 GG-genotype was associated with fat-BMI (OR = 1.08, CI = 1.01-1.16). The SNPs were associated with a number of physiological variables; most importantly 5HT2C rs3813929 T-allele was associated with glucose (OR = 4.56, CI = 1.13-18.4) and acute insulin response (OR = 0.65, CI = 0.44-0.94) in S-49. COMT rs4680 GG-genotype was associated with glucose (OR = 1.04, CI = 1.00-1.09). Except for an association between 5HT2A rs6311 and total-cholesterol at both surveys, significant in S-46 (OR = 2.66, CI = 1.11-6.40), no significant associations were observed for the other phenotypes. Significant associations were obtained when combined genotype of 5HT2C rs3813929 and COMT rs4680 were examined in relation to BMI (OR = 1.12, CI = 1.03-1.21), fat-BMI (OR = 1.22, CI = 1.08-1.38), waist (OR = 1.13, CI = 1.04-1.22), and cholesterol (OR = 5.60, CI = 0.99-31.4). Analyses of impaired glucose tolerance (IGT) and type 2 diabetes (T2D) revealed, a 12.3% increased frequency of 5HT2C rs3813929 T-allele and an 11.6% increased frequency of COMT rs4680 GG-genotype in individuals with IGT or T2D (chi(2), p = 0.05 and p = 0.06, respectively). Examination of the combined genotypes of 5HT2C and COMT showed a 34.0% increased frequency of IGT or T2D (chi(2), p = 0.01). CONCLUSIONS:The findings lend further support to the involvement of serotonin, noradrenaline and dopamine pathways on obesity and glucose homeostasis, in particular when combined genotype associations are explored

Using Polarized Spectroscopy to Investigate Order in Thin-Films of Ionic Self-Assembled Materials Based on Azo-Dyes

Three series of ionic self-assembled materials based on anionic azo-dyes and cationic benzalkonium surfactants were synthesized and thin films were prepared by spin-casting. These thin films appear isotropic when investigated with polarized optical microscopy, although they are highly anisotropic. Here, three series of homologous materials were studied to rationalize this observation. Investigating thin films of ordered molecular materials relies to a large extent on advanced experimental methods and large research infrastructure. A statement that in particular is true for thin films with nanoscopic order, where X-ray reflectometry, X-ray and neutron scattering, electron microscopy and atom force microscopy (AFM) has to be used to elucidate film morphology and the underlying molecular structure. Here, the thin films were investigated using AFM, optical microscopy and polarized absorption spectroscopy. It was shown that by using numerical method for treating the polarized absorption spectroscopy data, the molecular structure can be elucidated. Further, it was shown that polarized optical spectroscopy is a general tool that allows determination of the molecular order in thin films. Finally, it was found that full control of thermal history and rigorous control of the ionic self-assembly conditions are required to reproducibly make these materials of high nanoscopic order. Similarly, the conditions for spin-casting are shown to be determining for the overall thin film morphology, while molecular order is maintained

The effect of type of femoral component fixation on mortality and morbidity after hip hemiarthroplasty:A systematic review and meta-analysis

Background: Hip hemiarthroplasty is a well-established treatment of displaced femoral neck fracture, although debate exists over whether cemented or uncemented fixation is superior. Uncemented prostheses have typically been used in younger, healthier patients and cemented prostheses in older patients with less-stable bone. Also, earlier research has suggested that bone cement has cytotoxic effects and may trigger cardiovascular and respiratory adverse events. Questions/Purposes: The aim of this systematic review and meta-analysis was to compare morbidity and mortality rates after cemented and uncemented hemiarthroplasty for the treatment of displaced femoral neck fractures in elderly patients. Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched seven medical databases for randomized clinical trials and observational studies. We compared cemented and uncemented hemiarthroplasty using the Harris Hip Score (HHS), as well as measures of postoperative pain, mortality, and complications. Data were extracted and pooled as risk ratios or standardized mean difference with their corresponding 95% confidence intervals in a meta-analysis model. Results: The meta-analysis included 34 studies (12 randomized trials and 22 observational studies), with a total of 42,411 patients. In the pooled estimate, cemented hemiarthroplasty was associated with less risk of postoperative pain than uncemented hemiarthroplasty. There were no significant differences between groups regarding HHS or rates of postoperative mortality, pulmonary embolism, cardiac arrest, myocardial infarction, acute cardiac arrhythmia, or deep venous thrombosis. Conclusions: While we found that cemented hemiarthroplasty results in less postoperative pain than uncemented hemiarthroplasty in older patients with femoral neck fracture, the lack of significant differences in functional hip scores, mortality, and complications was surprising. Further high-level research is needed