Osteoarthritis & stroke: a bidirectional mendelian randomization study.

OBJECTIVE: The epidemiological evidence on the link between osteoarthritis (OA) and stroke remains inconclusive. Herein, we adopted a two-sample bidirectional Mendelian randomization (MR) study to determine the causality relationship between OA and stroke. DESIGN: Summary-level data derived from the published genome-wide association studies (GWAS) were employed for analyses. The data for OA at any site (n = 455,211), knee OA (n = 403,124), and hip OA (n = 393,873) were obtained from a meta-analysis of GWAS available in the UK Biobank and Arthritis Research UK Osteoarthritis Genetics resources. The MEGASTROKE consortium provided data for stroke (n = 446,696), ischemic stroke (IS) (n = 440,328) and its subtypes, and intracerebral hemorrhage (ICH) (n = 3,026). The main MR analysis was conducted by the inverse variance weighted (IVW) method. MR-Egger regression, MR pleiotropy residual sum and outlier, weighted median, Cochran Q statistic, and leave-one-out analysis approach were leveraged as supplements. RESULTS: We detected that higher risk of hip OA was significantly associated with overall stroke [IVW odds ratio (OR): 1.12, 95% confidence interval (CI): 1.06-1.20, P = 0.0002], IS (OR: 1.13, 95%CI: 1.06-1.21, P = 0.0003), and small vessel IS (OR: 1.25, 95%CI: 1.10-1.42, P = 0.0006). However, we found no evidence that stroke and subtypes had casual effects on OA in the reverse MR analyses. CONCLUSIONS: The present study provides genetic support that hip OA is a potential risk factor for overall stroke, IS, and small vessel IS. Further studies are warranted to elucidate the underlying mechanisms of causal associations between site-specific OA and stroke subtypes.

Arterial stiffening, insulin resistance and acanthosis nigricans in a community sample of adolescents with obesity.

Acanthosis Nigricans (AN) is a common finding in adolescents with obesity. Little is known about its relevance for cardiovascular (CVS) risk, in particular arterial stiffening. We investigated associations between AN, conventional markers of CVS risk and carotid-radial pulse wave velocity (PWV) in a community sample of adolescents with obesity aged 12-19 recruited to an obesity trial. AN was present in 63% of subjects and 43% had severe grading. Presence of AN and severe AN were associated with z-score of body mass index (BMIz). Presence of AN (but not severity) was associated with abnormal or fasting hyperinsulinaemia but not after adjustment for BMIz. PWV data were available for 147 (84% of participants). Severe-grade AN was associated with PWV (co-efficient 0.51, 95% CI 0.13-0.89, P=0.01) but not when adjusted for BMIz, ethnic grouping and age. In our study presence and severity of AN offered little additional information on CVS risk beyond the degree of obesity itself. The relevance of AN for CVS risk should be interpreted with caution.

Health and happiness is more important than weight': a qualitative investigation of the views of parents receiving written feedback on their child's weight as part of the National Child Measurement Programme.

BACKGROUND: The present study aimed to explore parental perceptions of overweight children and associated health risks after receiving National Child Measurement Programme (NCMP) weight feedback. METHODS: Fifty-two parents of overweight and obese children aged 4-5 years and 10-11 years enrolled in the NCMP programme in England in 2010-2011 participated in qualitative, semi-structured interviews about their perceptions of their child's weight and health risk after receiving weight feedback. Interviews were audio tape recorded and were conducted either by telephone (n = 9) or in the respondents' homes (n = 41). Interviews were transcribed verbatim and analysed using interpretative thematic analysis. RESULTS: Parents who received NCMP written feedback informing them that their child was overweight disregarded the results because they viewed 'health and happiness as being more important than weight'. The feedback was viewed as less credible because it did not consider the individual child's lifestyle.'Broad definitions of healthy' were described that did not include weight,such as reference to the child having good emotional and physical health and a healthy diet. Parents attributed weight to 'inherited/acquired factors' such as genetics or puppy fat, or did not regard their child's 'appearance' as reflecting being overweight. 'Cultural influence' also meant that being overweight was not viewed negatively by some non-white parents. CONCLUSIONS: After receiving written weight feedback, parents use methods other than actual weight when evaluating their child's weight status and health risks. Parents' conceptions of health and weight should be considered when communicating with parents, with the aim of bridging the gap between parental recognition of being overweight and subsequent behaviour change.

Socio-economic position and cardiovascular risk in rural Indian adolescents: evidence from the Andhra Pradesh children and parents study (APCAPS).

OBJECTIVES: This study examined association between socio-economic position and cardiovascular risk factors in adolescents to investigate whether childhood socio-economic position is a risk factor for future cardiovascular disease, independently of adult behaviours. STUDY DESIGN AND METHODS: Participants (n = 1128, 46% girls, aged 13-18 years) were members of a birth cohort (Andhra Pradesh Children and Parents Study or APCAPS) established to investigate long-term effects of a pregnancy and childhood nutritional supplementation trial conducted in 29 villages near Hyderabad in South India. Cross-sectional associations between socio-economic position and cardiovascular risk factors were examined using linear regression models. RESULTS: The mean BMI was 16.7 kg/m(2) for boys and 17.8 kg/m(2) for girls. Socio-economic position was positively associated with fat mass index (0.15 kg/m(2); 95% CI: 0.05-0.25) and inversely associated with central-peripheral skinfold ratio (-0.04; 95% CI: -0.06 to -0.01) and, in boys, fasting triglycerides (-0.05; 95% CI: -0.09 to -0.01). Association of socio-economic position with other risk factors (blood pressure, arterial stiffness, fasting glucose, insulin and cholesterol) was weak and inconsistent, and did not persist after adjustment for potential confounders, including age, sex, pubertal stage, height, adiposity and nutrition supplementation. CONCLUSIONS: The study thus showed that lower socio-economic position may be associated with greater central adiposity and higher triglyceride levels in these settings. Socio-economic gradient in cardiovascular risk may strengthen in future with later economic and lifestyle changes. Cardiovascular disease prevention strategies should therefore focus on the youth from the low income group.

Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs.

AIMS/HYPOTHESIS: Evaluation of the association of 31 common single nucleotide polymorphisms (SNPs) with fasting glucose, fasting insulin, HOMA-beta cell function (HOMA-ß), HOMA-insulin resistance (HOMA-IR) and type 2 diabetes in the Indian population. METHODS: We genotyped 3,089 sib pairs recruited in the Indian Migration Study from four cities in India (Lucknow, Nagpur, Hyderabad and Bangalore) for 31 SNPs in 24 genes previously associated with type 2 diabetes in European populations. We conducted within-sib-pair analysis for type 2 diabetes and its related quantitative traits. RESULTS: The risk-allele frequencies of all the SNPs were comparable with those reported in western populations. We demonstrated significant associations of CXCR4 (rs932206), CDKAL1 (rs7756992) and TCF7L2 (rs7903146, rs12255372) with fasting glucose, with ß values of 0.007 (p = 0.05), 0.01 (p = 0.01), 0.007 (p = 0.05), 0.01 (p = 0.003) and 0.08 (p = 0.01), respectively. Variants in NOTCH2 (rs10923931), TCF-2 (also known as HNF1B) (rs757210), ADAM30 (rs2641348) and CDKN2A/B (rs10811661) significantly predicted fasting insulin, with ß values of -0.06 (p = 0.04), 0.05 (p = 0.05), -0.08 (p = 0.01) and -0.08 (p = 0.02), respectively. For HOMA-IR, we detected associations with TCF-2, ADAM30 and CDKN2A/B, with ß values of 0.05 (p = 0.04), -0.07 (p = 0.03) and -0.08 (p = 0.02), respectively. We also found significant associations of ADAM30 (ß = -0.05; p = 0.01) and CDKN2A/B (ß = -0.05; p = 0.03) with HOMA-ß. THADA variant (rs7578597) was associated with type 2 diabetes (OR 1.5; 95% CI 1.04, 2.22; p = 0.03). CONCLUSIONS/INTERPRETATION: We validated the association of seven established loci with intermediate traits related to type 2 diabetes in an Indian population using a design resistant to population stratification.

Differences in consumption of food items between obese and normal-weight people in India.

BACKGROUND: There is a rising prevalence of obesity in India, and diet may be a major determinant of this. We aimed to assess differences in types and quantities of food items consumed by obese and normal-weight people in India. METHODS: Cross-sectional data of 7067 factory workers and their families were used from the Indian Migration Study, conducted in four cities across northern, central and southern India. Food frequency questionnaire data were used to compare the quantities of consumption of 184 food items between 287 obese (body mass index>30 kg/m2) and 1871 normalweight (body mass index 18.50-22.99 kg/m2) individuals, using t tests and ANCOVAs. Individuals with diabetes,hypertension and cardio-vascular disease were excluded. SPSS 16.0 was used for analysis. RESULTS: After adjusting for age, sex, location and socioeconomic status, obese individuals were found to eat significantly larger quantities of 11 food items compared with normalweight individuals. These included phulkas, chapatis/parathas/naan, plain dosa, mutton/chicken pulao/biryani, chicken fried/grilled, rasam, mixed vegetable sagu, vegetable raitha, honey,beetroot and bottlegourd (p< 0.01). Consumption of plain milk was higher among normal-weight than among obese individuals (p< 0.05). Consumption of some of these food items was also found to increase by socioeconomic status, decrease by age, and be higher among men relative to women. CONCLUSION: Obese individuals were found to consume larger quantities of certain food items compared with normal weight individuals. Interventions should aim at limiting overall food consumption among obese individuals.

Drivers of food acquisition practices in the food environment of peri-urban Hyderabad, India: A qualitative investigation.

This study investigates drivers of food acquisition practices in the food environment of peri-urban Hyderabad, India. We used a multi-method qualitative methodology that included in-depth interviews (n = 18) and an innovative qualitative geographical information systems (Q-GIS) approach, featuring participatory photo mapping and follow-up graphic-elicitation interviews (n = 22). Secondary data from eight focus group discussions (n = 94) was used to corroborate findings related to fruits and vegetables. Thematic analysis identified three primary drivers of food acquisition practices among adults: 1) Food prices and affordability; 2) Vendor and product properties, including (a) quality and freshness, and (b) adulteration and contamination; and 3) Social capital. Drivers of food acquisition and consumption among children and adolescents were a key concern for our participants, and included food availability and accessibility, desirability, and convenience. Findings reveal a need for targeted interventions in external and personal food environments to improve diets, nutrition, and health in this setting.

Insufficient evidence to support separate BMI definitions for obesity in children and adolescents from south Asian ethnic groups in the UK.

Re-evaluation of adult obesity thresholds in some ethnic groups has led to the questioning of childhood obesity thresholds. An expert group was convened to examine the representativeness of childhood obesity definitions, evidence for ethnic differences in body composition in UK children and the extent of misclassification of adiposity by current body mass index (BMI) thresholds in south Asian and black groups. The group concluded that the current International Obesity Task Force (IOTF) definitions remained the most appropriate for use in the United Kingdom, but further research was needed on the relationship of body shape, fat mass, metabolic markers and ethnicity in children and adolescents.

The Development and Implementation of a Commissioned Pathway for the Identification and Stratification of Liver Disease in the Community.

OBJECTIVE: To describe the development of the Nottingham liver disease stratification pathway, present a 12-month evaluation of uptake, stratification results and compare the pathway to current British Society of Gastroenterology (BSG) guidelines. DESIGN: A referral pathway between primary and secondary care for the detection and risk stratification of liver disease. SETTING: Four Nottinghamshire Clinical Commissioning Groups (700,000 population). PATIENTS: Patients are referred to the pathway with i) raised AST/ALT ratio ii) harmful alcohol use or iii) risk or presence of non-alcoholic fatty liver disease (NAFLD). INTERVENTIONS: Clinic attendance within secondary care for transient elastography (TE) and brief lifestyle intervention. The TE result is reported back to the GP with advice on interpretation and referral guidance. MAIN OUTCOME MEASURES: Pathway uptake, patient characteristics, liver disease stratification results and stakeholder feedback. RESULTS: Over the first 12 months 968 patients attended a TE clinic appointment, with raised AST/ALT ratio being the most common single reason for referral (36.9%). Of the total, 222 (22.9%) patients had an elevated liver stiffness (≥8kPa) and in 60 (27.0%) liver stiffness was indicative of advanced chronic liver disease. If a traditional approach based on raised liver enzymes (BSG guidance) had been followed, 38.7% of those with significant liver disease (≥8kPa) would have gone undetected among those referred for either NAFLD or raised AST:ALT. CONCLUSIONS: Targeting patients with risk factors for chronic liver disease and stratifying them using TE can detect significant chronic liver disease above and beyond the approach based on liver enzyme elevation.

Non-communicable diseases in low- and middle-income countries: context, determinants and health policy.

The rise of non-communicable diseases and their impact in low- and middle-income countries has gained increased attention in recent years. However, the explanation for this rise is mostly an extrapolation from the history of high-income countries whose experience differed from the development processes affecting today's low- and middle-income countries. This review appraises these differences in context to gain a better understanding of the epidemic of non-communicable diseases in low- and middle-income countries. Theories of developmental and degenerative determinants of non-communicable diseases are discussed to provide strong evidence for a causally informed approach to prevention. Health policies for non-communicable diseases are considered in terms of interventions to reduce population risk and individual susceptibility and the research needs for low- and middle-income countries are discussed. Finally, the need for health system reform to strengthen primary care is highlighted as a major policy to reduce the toll of this rising epidemic.

Cost-effectiveness of bariatric surgery in adolescents with severe obesity in the UK.

Evidence shows that surgery for severe obesity in adults improves health and psychological functioning, and is cost-effective. Data on bariatric surgery for adolescents with severe obesity are extremely limited, with no evidence on cost-effectiveness. We evaluated the lifetime cost-effectiveness of bariatric surgery compared with no surgery in adolescents with severe obesity from the UK's National Health Service perspective. Eighteen adolescents with body mass index ≥40 kg m-2 who underwent bariatric surgery (laparoscopic Roux en Y Gastric Bypass [RYGB] [N = 9], and laparoscopic Sleeve Gastrectomy [SG] [N = 9]) at University College London Hospitals between January 2008 and December 2013 were included. We used a Markov cohort model to compare the lifetime expected costs and quality-adjusted life years (QALYs) between bariatric surgery and no surgery. Mean cost of RYGB and SG procedures were £7100 and £7312, respectively. For RYGB vs. no surgery, the incremental cost/QALY was £2018 (95% CI £1942 - £2042) for males and £2005 (95% CI £1974 - £2031) for females. For SG vs. no surgery, the incremental cost/QALY was £1978 (95% CI £1954 - £2002) for males and £1941 (95% CI £1915 - £1969) for females. Bariatric surgery in adolescents with severe obesity is cost-effective; it is more costly than no surgery however it markedly improved quality of life.

Socioeconomic differences in prevalence of biochemical, physiological, and metabolic risk factors for non-communicable diseases among urban youth in Delhi, India.

This study examined whether the distribution of biochemical, physiological, and metabolic risk factors for non-communicable diseases (NCDs) among children and youth in urban India vary by socioeconomic status (SES). Data were derived from a cross-sectional survey of students enrolled in the 2nd and 11th grades in 19 randomly selected schools in Delhi (N = 1329) in 2014-15. Mixed-effect regression models were used to determine the prevalence of risk factors for NCDs among private (higher SES) and government (lower SES) school students. After adjusting for age, gender, and grade we found the percentage of overweight (13.16% vs. 3.1%, p value < 0.01) and obese (8.7% vs. 0.3%, p value < 0.01) students was significantly higher among private relative to government school students. Similarly, significantly higher percentage of private school students had higher waist circumference values (7.72% vs. 0.58%, p value < 0.01) than government school students. Furthermore, similar trend was observed across schools in the distribution of other NCD risk factors: raised blood pressure, raised total cholesterol, and low-density lipoprotein. Surprisingly, despite a higher prevalence of all risk factors, significantly higher percentage of private school students had adequate/ideal levels of high-density lipoprotein. Overall, the risk profile of private school students suggests they are more vulnerable to future NCDs.

The co-occurrence of anemia and cardiometabolic disease risk demonstrates sex-specific sociodemographic patterning in an urbanizing rural region of southern India.

BACKGROUND/OBJECTIVES: To determine the extent and sociodemographic determinants of anemia, overweight, metabolic syndrome (MetS) and the co-occurrence of anemia with cardiometabolic disease risk factors among a cohort of Indian adults. SUBJECT/METHODS: Cross-sectional survey of adult men (n=3322) and nonpregnant women (n=2895) aged 18 years and older from the third wave of the Andhra Pradesh Children and Parents Study that assessed anemia, overweight based on body mass index, and prevalence of MetS based on abdominal obesity, hypertension and blood lipid and fasting glucose measures. We examined associations of education, wealth and urbanicity with these outcomes and their co-occurrence. RESULTS: The prevalence of anemia and overweight was 40% and 29% among women, respectively, and 10% and 25% among men (P<0.001), respectively, whereas the prevalence of MetS was the same across sexes (15%; P=0.55). The prevalence of concurrent anemia and overweight (9%), and anemia and MetS (4.5%) was highest among women. Household wealth was positively associated with overweight and MetS across sexes (P<0.05). Independent of household wealth, higher education was positively correlated with MetS among men (odds ratio (95% confidence interval): MetS: 1.4 (0.99, 2.0)) and negatively correlated with MetS among women (MetS: 0.54 (0.29, 0.99)). Similar sex-specific associations were observed for the co-occurrence of anemia with overweight and MetS. CONCLUSIONS: Women in this region of India may be particularly vulnerable to co-occurring anemia and cardiometabolic risk, and associated adverse health outcomes as the nutrition transition advances in India.

Deprivation and childhood obesity: a cross sectional study of 20,973 children in Plymouth, United Kingdom.

OBJECTIVE: To study the association between socioeconomic deprivation and childhood obesity. DESIGN: Cross sectional study. SETTING: All state primary schools in Plymouth. Plymouth is a relatively deprived city in the United Kingdom, ranking 338th of 366 local authorities on the Department of the Environment Index of Local Conditions. SUBJECTS: 20 973 children between the ages of 5 and 14 years, 1994-96. MAIN OUTCOME MEASURE: Numbers of obese children (body mass index (BMI) above the 98th centile) by quarters of Townsend score. RESULTS: Plymouth had a rate of childhood obesity two and half times that expected nationally (5% v 2%). The obesity prevalence increased with age, being almost double in the oldest age quarter (boys 6.2%; girls 7.0%), compared with the youngest age quarter. Within Plymouth, there was a significant trend for higher rates of obesity related to increasing deprivation in both boys (p=0. 017) and girls (p=0.018). The odds ratio (OR) for childhood obesity (highest-lowest quarter of Townsend scores) had borderline significance in boys (OR 1.29, 95% confidence intervals (CI) 1.00 to 1.65, p=0.049) but was larger and more significant in the girls (OR 1.39, 95% CI 1.08 to 1.80, p=0.011). Unlike boys, the association between obesity in girls and Townsend scores became stronger with age such that in the oldest age quarter (over 11.7 years), girls in the highest quarter of Townsend scores were nearly twice as likely be obese, as compared with the lowest quarter (OR 1.95, 95% CI 1.23 to 3.08, p=0.005). State of pubertal development could not be accounted for as this information was not available. CONCLUSIONS: This study provides evidence for an association between deprivation and childhood obesity in this English population. The health of children from deprived households is affected by a number of adverse influences. The high prevalence of obesity in these children is yet another factor that could predispose to greater morbidity in adult life.

Ethnic variations in overweight and obesity among children over time: findings from analyses of the Health Surveys for England 1998-2009.

BACKGROUND: The increase in the prevalence of obesity among children and adolescents in England since the mid-1990s has been dramatic. Cross-sectional evidence suggests ethnic variations in childhood obesity prevalence. OBJECTIVES: The objective of the study was to examine whether and how ethnic variations in childhood overweight/obesity have changed over time, and are affected by socioeconomic factors. METHOD: This study uses logistic regression to analyse ethnic differences in the relative likelihood of being at or above the age- and gender-specific thresholds for overweight and obesity developed by the International Obesity Task Force among children aged between 2 and 15 from 11 ethnic groups included in the Health Surveys for England between 1998 and 2009, adjusting for age, gender, year of data collection and equivalized household income. We separately analyse the likelihood of being at or above the thresholds for overweight (but below those for obesity) and obesity. RESULTS: Trends in overweight/obesity over time among ethnic minority groups do not follow those of white English children. Black African children had higher rates of overweight and obesity, which appear to have peaked, and black Caribbean children had higher rates of obesity than other groups examined, which appear to continue rising. These differences were not explained by socioeconomic variations between groups. CONCLUSION: Policies are required that encourage healthy lifestyles among ethnic minority young people, while engaging with the complexities associated with these choices during childhood and adolescence.

The impact of childhood obesity on morbidity and mortality in adulthood: a systematic review.

The objective of this study was to evaluate the evidence on whether childhood obesity is a risk factor for adult disease, independent of adult body mass index (BMI). Ovid MEDLINE (1948-May 2011), EMBASE (1980-2011 week 18) and the Cochrane Library (1990-2011) were searched for published studies of BMI from directly measured weight and height in childhood (2-19 years) and disease outcomes in adulthood. Data were synthesized in a narrative fashion. Thirty-nine studies (n 181-1.1 million) were included in the review. There was evidence for associations between childhood BMI and type 2 diabetes, hypertension and coronary heart disease. Few studies examined associations independent of adult BMI; these showed that effect sizes were attenuated after adjustment for adult BMI in standard regression analyses. Although there is a consistent body of evidence for associations between childhood BMI and cardiovascular outcomes, there is a lack of evidence for effects independent of adult BMI. Studies have attempted to examine independent effects using standard adjustment for adult BMI, which is subject to over-adjustment and problems with interpretation. Studies that use more robust designs and analytical techniques are needed to establish whether childhood obesity is an independent risk factor for adult disease.

Associations of FTO and MC4R Variants with Obesity Traits in Indians and the Role of Rural/Urban Environment as a Possible Effect Modifier.

Few studies have investigated the association between genetic variation and obesity traits in Indian populations or the role of environmental factors as modifiers of these relationships. In the context of rapid urbanisation, resulting in significant lifestyle changes, understanding the aetiology of obesity is important. We investigated associations of FTO and MC4R variants with obesity traits in 3390 sibling pairs from four Indian cities, most of whom were discordant for current dwelling (rural or urban). The FTO variant rs9939609 predicted increased weight (0.09 Z-scores, 95% CI: 0.03, 0.15) and BMI (0.08 Z-scores, 95% CI: 0.02, 0.14). The MC4R variant rs17782313 was weakly associated with weight and hip circumference (P < .05). There was some indication that the association between FTO and weight was stronger in urban than that in rural dwellers (P for interaction = .03), but no evidence for effect modification by diet or physical activity. Further studies are needed to investigate ways in which urban environment may modify genetic risk of obesity.