Dance Is More Than Meets the Eye-How Can Dance Performance Be Made Accessible for a Non-sighted Audience?

Dance is regarded as visual art form by common arts and science perspectives. Definitions of dance as means of communication agree that its message is conveyed by the dancer/choreographer via the human body for the observer, leaving no doubt that dance is performed to be watched. Brain activation elicited by the visual perception of dance has also become a topic of interest in cognitive neuroscience, with regards to action observation in the context of learning, expertise and aesthetics. The view that the aesthetic experience of dance is primarily a visual one is still shared by many artists and cultural institutions, yet there is growing interest in making dance performances accessible for individuals with visual impairment / blindness. Means of supporting the non-visual experience of dance include verbal (audio description), auditive (choreographed body sounds, movement sonification), and haptic (touch tour) techniques, applied for different purposes by artists and researchers, with three main objectives: to strengthen the cultural participation of a non-sighted audience in the cultural and aesthetic experience of dance; to expand the scope of dance as an artistic research laboratory toward novel ways of perceiving what dance can convey; and to inspire new lines of (neuro-cognitive) research beyond watching dance. Reviewing literature from different disciplines and drawing on the personal experience of an inclusive performance of Simon Mayer's "Sons of Sissy," we argue that a non-exclusively visual approach can be enriching and promising for all three perspectives and conclude by proposing hypotheses for multidisciplinary lines of research.

Switching to Degludec is Associated with Reduced Hypoglycaemia, Irrespective of Definition Used or Patient Characteristics: Secondary Analysis of the ReFLeCT Prospective, Observational Study.

INTRODUCTION: Hypoglycaemia is a common side effect of insulin therapy; low or high glycated haemoglobin (HbA1c) levels, history of hypoglycaemia or long diabetes duration are known modifiers of hypoglycaemia risk. In randomised clinical trials, lower rates of hypoglycaemia have been observed with the new-generation insulin analogue, long-acting insulin degludec, compared with other basal insulins. METHODS: The ReFLeCT study was a prospective observational study over 12 months. Patient-reported diary data on hypoglycaemia were collected from patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) who were switching from other basal insulins to insulin degludec (degludec) at their physician's discretion in routine clinical care. Two secondary analyses were undertaken to investigate the change in number of hypoglycaemic events: a post hoc analysis using the updated American Diabetes Association (ADA) level 1, 2 and 3 hypoglycaemia definitions, and a pre-specified analysis using patient characteristics (baseline HbA1c, diabetes duration, and physician's rationale for initiating degludec). RESULTS: Switching to degludec was associated with significantly fewer hypoglycaemic events for all definitions in T1D, and level 1 and 2 in T2D (too few level 3 events for statistical comparison). Moreover, patient characteristics did not influence the observed reduction in hypoglycaemia in T1D and T2D. CONCLUSION: These results demonstrate that switching to degludec from other basal insulins was associated with reduced rates of hypoglycaemia, irrespective of the definition used or baseline patient characteristics. TRIAL REGISTRATION: NCT02392117.

Low blood sugar levels (hypoglycaemia) are a common, and sometimes serious, side effect of treatment with insulin in people with diabetes. In the ReFleCT study, adults with type 1 (T1D) and type 2 diabetes (T2D) were asked to complete a diary for 12 months when their doctor changed their previous long-acting insulin treatment to insulin degludec (degludec). The key outcome of the study was whether the frequency of hypoglycaemia changed when a patient's insulin treatment was switched. Here, we used the diary information from the ReFLeCT study to investigate whether the change in the rate of hypoglycaemia was related to the way hypoglycaemia was defined, or to patients' characteristics at the time their insulin was switched. These characteristics included the length of time that patients had had diabetes, their blood sugar control, and their doctor's reason for changing their medication. Our findings showed that the way hypoglycaemia was defined, and patients' characteristics, did not generally influence the frequency of hypoglycaemia for patients with T1D or T2D. However, the most severe hypoglycaemia in patients with T2D occurred too infrequently to be assessed. Patients in all groups had less hypoglycaemia overall after switching compared with their previous treatment, suggesting that degludec may be a treatment option for a broad range of patients with diabetes.

Characteristics of newly diagnosed adults with type 1 diabetes in the UK and evolution of glycaemic control, body mass index and Charlson comorbidity index over the first 5 years after diagnosis.

AIMS: This retrospective, longitudinal study characterised 2430 adults (mean age 40.8±16.1years) with newly diagnosed type 1 diabetes (T1D) over the first 5years of insulin treatment. METHODS: Data from 1year pre- and up to 5 years post-insulin initiation were extracted from the UK Clinical Practice Research Datalink (1990-2013). Baseline HbA1c, BMI and Charlson comorbidity index (CCI) score were compared with data at 1, 2, 3 and 5 years. RESULTS: Mean HbA1c decreased significantly from baseline 95±32.8mmol/mol (10.8±3.0%) to 61±21.9mmol/mol (7.7±2.0%) at 1year, remaining significantly lower at 2, 3 and 5 years (p<0.0001). One year after initiating insulin, only 6.3% of patients had HbA1c <48mmol/mol (<6.5%). There was no further improvement in HbA1c after 1year. Mean BMI increased significantly from baseline 25.3±5.5kg/m2 to 27.2±5.8kg/m2 at 1year; p<0.0001), remaining significantly higher thereafter, with over two-thirds having overweight/obesity by year 5. Mean CCI score increased significantly (1.32, baseline; 1.46, year 1; 1.75, year 5). CCI patterns were similar within BMI and HbA1c strata. CONCLUSIONS: More intensive support to reach and maintain glycaemic targets soon post-diagnosis, while avoiding weight gain, and prevention and optimal management of comorbidities are warranted.

Switching to Degludec From Other Basal Insulins Is Associated With Reduced Hypoglycemia Rates: A Prospective Study.

CONTEXT: Observational studies of insulin degludec (degludec) with hypoglycemia events prospectively recorded are lacking. OBJECTIVE: To evaluate the safety and effectiveness of degludec in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) switching from other basal insulins in routine care. DESIGN: Results From Real-World Clinical Treatment With Tresiba® was a multinational, multicenter, prospective, observational, single-arm study comprising a 4-week baseline period (preswitch basal insulin) and 12-month follow-up (degludec). SETTING: Routine clinical practice. PATIENTS OR OTHER PARTICIPANTS: Insulin-treated patients (≥18 years) with T1D (n = 556) or T2D (n = 611) with treatment plans to initiate degludec. INTERVENTIONS: Switching to degludec from other basal insulins. MAIN OUTCOME MEASURE: Change from baseline in number of overall hypoglycemic events recorded in patient diaries. RESULTS: In T1D, the 12-month follow-up/baseline rate ratios (95% CI) of overall [0.80 (0.74 to 0.88)], nonsevere [0.83 (0.76 to 0.91)], severe [0.28 (0.14 to 0.56)], and nocturnal [0.61 (0.50 to 0.73)] hypoglycemia suggested significantly lower hypoglycemia rates with degludec (all Ps < 0.001). At 12 months, HbA1c, fasting plasma glucose (FPG), and basal insulin dosage decreased significantly. Body weight increased, and treatment satisfaction improved significantly. In T2D, the hypoglycemia rate ratios were overall [0.46 (0.38 to 0.56)], nonsevere [0.53 (0.44 to 0.64)], and nocturnal [0.35 (0.20 to 0.62)] (all Ps < 0.001; too few events for analysis of severe hypoglycemia). At 12 months, HbA1c and FPG decreased significantly. Body weight and insulin dosages remained unchanged, and treatment satisfaction was significantly improved. CONCLUSIONS: In a routine clinical care setting, switching to degludec from other basal insulins was associated with significantly lower rates of hypoglycemia, improved glycemic control, and treatment satisfaction in patients with T1D or T2D.

Childhood body mass index and development of type 2 diabetes throughout adult life-A large-scale danish cohort study.

OBJECTIVE: This study investigated how a wide spectrum of body mass index (BMI) values at ages 7 to 13 years are associated with type 2 diabetes throughout adulthood, including potential modifying effects of sex and birth weight. METHODS: From the Copenhagen School Health Records Register, 292,827 individuals, born between 1930 and 1989, were followed in national registers for type 2 diabetes (women, n = 7,472; men, n = 11,548). Heights and weights were measured at ages 7 to 13 years. RESULTS: Below-average BMIs, with few exceptions, were not associated with type 2 diabetes. Above-average BMIs had positive associations that were stronger in women than men, stronger in younger birth cohorts, and weaker with older age at diagnosis. Women born 1930-1947, 1948-1965, and 1966-1983 with above-average BMIs at 13 years (≥18.2 kg/m2 ) had hazard ratios (95% confidence intervals) ranging from 2.12 (1.91-2.36) to 2.84 (2.31-3.49) per z score when diagnosed at 30 to 47 years. Birth weight did not modify these associations. CONCLUSIONS: Childhood BMIs below average are not associated with type 2 diabetes, whereas childhood BMIs above average are strongly associated with type 2 diabetes in adulthood, corresponding to excess risks even at levels below international definitions of overweight. The associations are stronger in women than men but are not affected by birth weight.

The U-shaped association of body mass index with mortality: Influence of the traits height, intelligence, and education.

OBJECTIVE: The U-shaped association between body mass index (BMI) and mortality may depend on other traits with permanent health effects. Whether the association between BMI and mortality depends on levels of health-related traits known to be inversely associated with mortality throughout adult life such as height, intelligence, and education was investigated. METHODS: The study was based on a cohort of young men with data on weight, height, intelligence test score, and education from the Danish Conscription Database. In total, 346,500 men born 1939 to 1959 were followed until December 2013. The association between BMI and mortality was analyzed using Cox-regression models including interactions between BMI and height, intelligence, and education, respectively. RESULTS: BMI and mortality showed the U-shaped association from the start of the follow-up period, and it persisted through the subsequent 56 years. As expected, the mortality was inversely associated with height, intelligence, and education, but the U shape of the association between BMI and mortality was unaffected by the levels of these traits except at higher BMI values, where the slopes were steeper for men with higher levels of height, intelligence, and education. CONCLUSIONS: High and low BMI was associated with higher mortality throughout life regardless of the levels of height, intelligence, and education.

Associations between birth weight and colon and rectal cancer risk in adulthood.

BACKGROUND: Birth weight has inconsistent associations with colorectal cancer, possibly due to different anatomic features of the colon versus the rectum. The aim of this study was to investigate the association between birth weight and colon and rectal cancers separately. METHODS: 193,306 children, born from 1936 to 1972, from the Copenhagen School Health Record Register were followed prospectively in Danish health registers. Colon and rectal cancer cases were defined using the International Classification of Disease version 10 (colon: C18.0-18.9, rectal: 19.9 and 20.9). Only cancers classified as adenocarcinomas were included in the analyses. Cox regressions were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Analyses were stratified by birth cohort and sex. RESULTS: During 3.8 million person-years of follow-up, 1465 colon and 961 rectal adenocarcinomas were identified. No significant sex differences were observed; therefore combined results are presented. Birth weight was positively associated with colon cancers with a HR of 1.14 (95% CI, 1.04-1.26) per kilogram of birth weight. For rectal cancer a significant association was not observed for birth weights below 3.5kg. Above 3.5kg an inverse association was observed (at 4.5kg, HR=0.77 [95% CI, 0.61-0.96]). Further, the associations between birth weight and colon and rectal cancer differed significantly from each other (p=0.006). CONCLUSIONS: Birth weight is positively associated with the risk of adult colon cancer, whereas the results for rectal cancer were inverse only above values of 3.5kg. The results underline the importance of investigating colon and rectal cancer as two different entities.

Sex-specific associations between birth weight and adult primary liver cancer in a large cohort of Danish children.

Whether the prenatal period is critical for the development of adult primary liver cancer (PLC) is sparsely investigated. Recently, attention has been drawn to potential sex-differences in the early origins of adult disease. The association between birth weight and adult PLC, separately in men and women was investigated, using a large cohort of 217,227 children (51% boys), born from 1936 to 1980, from the Copenhagen School Health Records Register, and followed them until 2010 in national registers. Hazard ratios (95% confidence intervals) of PLC (30 years or older) were estimated by Cox regression models stratified by birth cohort. During 5.1 million person-years of follow-up, 185 men and 65 women developed PLC. Sex modified the association between birth weight and adult PLC (p values for interaction = 0.0005). Compared with a sex-specific reference group of birth weights between 3.25 and 3.75 kg, men with birth weights between 2.00 and 3.25 kg and 3.75-5.50 kg, had HRs of 1.48 (1.06-2.05) and 0.85 (0.56-1.28), respectively. Among women the corresponding HRs were 1.71 (0.90-3.29) and 3.43 (1.73-6.82). Associations were similar for hepatocellular carcinoma only, across year of birth, and after accounting for diagnoses of alcohol-related disorders, viral hepatitis and biliary cirrhosis. Prenatal exposures influenced the risk of adult PLC, and the effects at the high birth weight levels appeared to be sex-specific. These findings underscore the importance of considering sex-specific mechanisms in the early origins of adult PLC.

Sex Differences in the Association Between Birth Weight and Adult Type 2 Diabetes.

Low birth weight is a well-established risk factor for type 2 diabetes, but the risk at high birth weight levels remains uncertain. Potential sex differences in the associations are unexplored. We investigated whether sex influences the association of birth weight and adult type 2 diabetes, using a cohort of 113,801 men and 109,298 women, born 1936-1983, from the Copenhagen School Health Records Register, Denmark. During 5.6 million person-years of follow-up, 7,750 men and 4,736 women had a diagnosis of adult type 2 diabetes (30 years of age or older) obtained from national registers. When birth weights between 3.251 and 3.750 kg were used as the reference group for each sex separately, women with birth weights in the categories of 2.000 to 2.750 kg and 4.751 to 5.500 kg had hazard ratios [HRs] of type 2 diabetes of 1.46 (95% CI, 1.34-1.59) and 1.56 (1.20-2.04), respectively, whereas men had HRs of 1.20 (1.12-1.30) and 0.93 (0.76-1.15). Thus, sex modified the association, with stronger risk estimates of type 2 diabetes in women at both low and high birth weights compared with men (P = 0.001). In conclusion, birth weight is more strongly associated with type 2 diabetes in women than in men. Future search for sex-specific causal mechanisms may provide new insights into the early origins of type 2 diabetes.

No evidence of seasonality of birth in adult type 2 diabetes in Denmark.

AIMS/HYPOTHESIS: The season of birth might influence prenatal circumstances, which may influence the risk of developing type 2 diabetes. The aim of this study was to determine whether the diagnosis of type 2 diabetes in Denmark changed with the season of birth. METHODS: This study used data from the population-based Copenhagen School Health Records Register (CSHRR) that includes schoolchildren born between 1930 and 1989. Via a personal identification number, the CSHRR was linked to the National Patient Register containing hospital discharge diagnoses since 1977. The effect of seasonal variation in birth on the risk of type 2 diabetes was assessed using Cox regression, with month or season of birth as the predictor. The underlying time variable was age, and follow-up started in 1977 or at age 30 years. RESULTS: The study population consisted of 223,099 people, of whom 12,486 developed adult type 2 diabetes. Using January as the reference month, the risk of type 2 diabetes by month of birth was not statistically different for any of the 11 comparative birth months. Grouping month of birth into seasons (spring was the reference) gave essentially similar results, showing no difference in the risk of type 2 diabetes for any season. Repeating the analysis by sex, birth cohort and birthweight categories revealed no associations. CONCLUSIONS/INTERPRETATION: The risk of adult type 2 diabetes was not associated with month of birth in a large Danish population-based study. The results suggest that the causes of seasonality in birthweight are not causes of type 2 diabetes.

Body mass index in school-aged children and the risk of routinely diagnosed non-alcoholic fatty liver disease in adulthood: a prospective study based on the Copenhagen School Health Records Register.

OBJECTIVE: The relation between childhood overweight and adult non-alcoholic fatty liver disease (NAFLD) is largely unknown. We investigated if weight and weight gain in childhood increases the risk of being diagnosed with NAFLD in routine clinical settings in adulthood. PARTICIPANTS: We studied 244,464 boys and girls, born between 1930 and 1989, who attended school in Copenhagen, Denmark. Their heights and weights were measured by physicians or nurses at mandatory school health examinations at ages 7-13 years. Body mass index (BMI) z-scores were calculated from an internal age-specific and sex-specific reference. OUTCOME MEASURES: NAFLD reported in the National Patient Register and the National Register of Pathology at 18 years of age or older. HRs with 95% CIs were estimated. RESULTS: During follow-up, 1264 and 1106 NAFLD cases, respectively, occurred in men and women. In both sexes, childhood BMI z-score was not consistently associated with adult NAFLD. Change in BMI z-score between 7 and 13 years of age was positively associated with NAFLD in both sexes. When adjusted for BMI z-score at age 7 years, the HRs of adult NAFLD were 1.15 (95% CI 1.05 to 1.26) and 1.12 (95% CI 1.02 to 1.23) per 1-unit gain in BMI z-score in men and women, respectively. Associations were similar when adjusted for BMI z-score at age 13 years, and were consistent across birth years. CONCLUSIONS: A BMI gain in school-aged children is associated with adult NAFLD. Intriguingly, BMI gain appears to have an effect on adult NAFLD irrespective of either the initial or the attained BMI. Taken together, our results suggest that BMI gain in childhood, rather than the level of BMI per se, is important in the development of adult NAFLD.

Do rapid BMI growth in childhood and early-onset obesity offer cardiometabolic protection to obese adults in mid-life? Analysis of a longitudinal cohort study of Danish men.

OBJECTIVE: Some obese individuals have no cardiometabolic abnormalities; they are 'metabolically healthy, but obese' (MHO). Similarly, some non-obese individuals have cardiometabolic abnormalities, that is, 'metabolically at risk, normal weight' (MANW). Previous studies have suggested that early-onset obesity may be associated with MHO. We aimed to assess whether body mass index (BMI) in childhood and early-onset obesity are associated with MHO. SETTING: General population longitudinal cohort study, Denmark. PARTICIPANTS: From 362 200 young men (mean age 20) examined for Danish national service between 1943 and 1977, all obese men (BMI ≥31 kg/m(2), N=1930) were identified along with a random 1% sample of the others (N=3601). Our analysis includes 2392 of these men attending a research clinic in mid-life (mean age 42). For 613 of these men, data on childhood BMI are available. We summarised childhood BMI growth (7-13 years) using a multilevel model. Early-onset obesity was defined as obesity at examination for national service. OUTCOME MEASUREMENT: We defined metabolic health at the mid-life clinic as non-fasting serum cholesterol <6.6 mmol/L, non-fasting glucose <8.39 mmol/L and pulse pressure <48 mm Hg. Participants were categorised into four groups according to their obesity (BMI ≥30 kg/m(2)) and metabolic health in mid-life. RESULTS: 297 of 1097 (27.1%) of obese men were metabolically healthy; 826 of 1295 (63.8%) non-obese men had at least one metabolic abnormality. There was no evidence that rapid BMI growth in childhood or early-onset obesity was associated with either MHO or the MANW phenotype, for example, among obese men in mid-life, the OR for MHO comparing early-onset obesity with non-early-onset obesity was 0.97 (95% CI 0.85 to 1.10). CONCLUSIONS: We found no robust evidence that early-onset obesity or rapid BMI growth in childhood is protective for cardiometabolic health.

Being an only or last-born child increases later risk of obesity.

BACKGROUND: Studies have suggested that number of siblings and birth order is associated with obesity. However, studies combining these exposures are needed. This study aimed at investigating obesity in children and young adults in regard to different combinations of family size and birth order. METHODS: Two cohorts selected from the general population were investigated: The Copenhagen School Health Records Register (CSHRR) and a Draft Board (DB) sample with measured heights and weights in childhood (age 13 years) and young adulthood (age 19 years), respectively. Information on birth order, number of siblings, and relevant covariates were available on 29 327 children, as well as on 323 obese young men and 575 randomly selected controls of young men representing approximately 58 000. The relation between number of siblings and birth order, respectively, and having a Body Mass Index (BMI) z-score above or equal to the 95(th) percentile in childhood or having a BMI of at least 31.00 kg/m(2) in young adulthood was analysed using logistic regression analyses adjusted for relevant confounders. RESULTS: Only children had significantly higher odds of obesity both in childhood and in young adulthood compared with children with siblings, odds ratio (OR) =1.44 (95% Confidence Interval (CI): 1.26-1.66) and OR=1.76 (95% CI: 1.18-2.61), respectively. No association between first-born status and obesity was found. The OR of last-born children being obese was also significantly increased in childhood, e.g. OR=1.93 (95% CI: 1.09-3.43) of obesity if last-born in a family of four children. This was not found in young adulthood. Additionally, higher spacing to previous sibling (average 1872 vs. 1303 days; p=0.026 in four children families) was observed in obese last-born compared to non-obese last-born children. CONCLUSION: Being an only or last-born child is associated with obesity. These associations may provide leads to targeted prevention of obesity in children.

Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.

BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268). METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction)  = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio  = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio  = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.

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 men experience an increased morbidity, including fatal morbidity, from many diseases throughout life.

C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patients.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a major hepatic consequence of obesity. It has been suggested that the high sensitivity C-reactive protein (hs-CRP) is an obesity-independent surrogate marker of severity of NAFLD, especially development of non-alcoholic steato-hepatitis (NASH), but this remains controversial. We aimed to investigate whether associations between various features of NAFLD and hs-CRP are independent of body mass index (BMI) in its broad range among obese patients. METHODS: A total of 627 obese adults (80% females), representing three cohorts from France and Belgium, had information on liver histology obtained from liver biopsies and measures of hs-CRP and BMI. We investigated whether the different features of NAFLD and BMI were associated with hs-CRP, with and without mutual adjustments using linear regression. RESULTS: BMI and hs-CRP were strongly associated. Per every 10% increase in BMI the hs-CRP level increased by 19-20% (p<0.001), and adjustment for NAFLD-stage (including no-NAFLD) did not influence the association. We found no BMI-independent association between NASH and hs-CRP. However, a positive association between degree of steatosis and hs-CRP was observed (p<0.05) and this effect remained significant after adjusting for BMI, lobular inflammation, hepatocyte ballooning, and fibrosis. We found no significant associations between the other features of NAFLD and hs-CRP. CONCLUSIONS: This study indicates that it is the accumulation of fat -both in the adipose tissue and in liver steatosis- that leads to increased hs-CRP levels among obese patients. Thus, hs-CRP may be a marker of steatosis, but not of severity of NAFLD, in obese patients.

Influences of the common FTO rs9939609 variant on inflammatory markers throughout a broad range of body mass index.

BACKGROUND: A recent study reported that the fatness associated A-allele of FTO rs9939609 increased plasma high sensitivity C-reactive protein (hs-CRP) levels independent of fatness. We aimed to investigate if this gene variant had fatness-independent effects on plasma hs-CRP and 10 additional circulating obesity-related adipokines throughout a broad range of body mass index (BMI) among Danish men. METHODOLOGY/PRINCIPAL FINDINGS: In a population of 362,200 young men, examined for military service between 1943 and 1977, two groups were identified: 1) a random 1% sample and 2) all obese men (BMI = 31.0 kg/m(2), all of whom were above the 99(th) percentile of this population). At an average age of 49 years (range: 39 through 65 years), 551 men, hereof 231 of the obese, were re-examined, including genotyping and measurement of the fasting circulating inflammatory markers hs-CRP, IL-1ß, IL-6, IL-10, IL-18, mip1α, mip1ß, sTNFα-R1, TGF-ß, TNF-α and leptin. Men with known disease were excluded from the examination. All the inflammatory markers were log-transformed to approximate a normal distribution. Genotype-phenotype relationships were studied using linear regression analyses with the inflammatory markers as the response variable. Significant positive associations between hs-CRP, leptin and a broad range of BMI were observed, but the associations did not significantly differ across FTO rs9939609 genotype. There were no significant associations between the other inflammatory markers, FTO rs9939609 genotype or BMI, respectively. CONCLUSION: No fatness-independent effects of the FTO rs9939609 A-allele on a series of inflammatory markers were observed in this cohort of healthy middle-aged men representing a broad range of fatness.

Fatness-associated FTO gene variant increases mortality independent of fatness--in cohorts of Danish men.

BACKGROUND: The A-allele of the single nucleotide polymorphism (SNP), rs9939609, in the FTO gene is associated with increased fatness. We hypothesized that the SNP is associated with morbidity and mortality through the effect on fatness. METHODOLOGY/PRINCIPAL FINDINGS: In a population of 362,200 Danish young men, examined for military service between 1943 and 1977, all obese (BMI>or=31.0 kg/m(2)) and a random 1% sample of the others were identified. In 1992-94, at an average age of 46 years, 752 of the obese and 876 of the others were re-examined, including measurements of weight, fat mass, height, and waist circumference, and DNA sampling. Hospitalization and death occurring during the following median 13.5 years were ascertained by linkage to national registers. Cox regression analyses were performed using a dominant effect model (TT vs. TA or AA). In total 205 men died. Mortality was 42% lower (p = 0.001) with the TT genotype than in A-allele carriers. This phenomenon was observed in both the obese and the randomly sampled cohort when analysed separately. Adjustment for fatness covariates attenuated the association only slightly. Exploratory analyses of cause-specific mortality and morbidity prior to death suggested a general protective effect of the TT genotype, whereas there were only weak associations with disease incidence, except for diseases of the nervous system. CONCLUSION: Independent of fatness, the A-allele of the FTO SNP appears to increase mortality of a magnitude similar to smoking, but without a particular underlying disease pattern barring an increase in the risk of diseases of the nervous system.

FTO gene associated fatness in relation to body fat distribution and metabolic traits throughout a broad range of fatness.

BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION: 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.