Belavendra Antonisamy

Associations of variants in FTO and Near MC4R with obesity traits in South Asian Indians

Recent genome‐wide association studies show that loci in FTO and melanocortin 4 receptor (MC4R) associate with obesity‐related traits. Outside Western populations the associations between these variants have not always been consistent and in Indians it has been suggested that FTO relates to diabetes without an obvious intermediary obesity phenotype. We investigated the association between genetic variants in FTO (rs9939609) and near MC4R (rs17782313) with obesity‐ and type 2 diabetes (T2DM)‐related traits in a longitudinal birth cohort of 2,151 healthy individuals from the Vellore birth cohort in South India. The FTO locus displayed significant associations with several conventional obesity‐related anthropometric traits. The per allele increase is about 1% for BMI, waist circumference (WC), hip circumference (HC), and waist—hip ratio. Consistent associations were observed for adipose tissue‐specific measurements such as skinfold thickness reinforcing the association with obesity‐related traits. Obesity associations for the MC4R locus were weak or nonsignificant but a signal for height (P < 0.001) was observed. The effect on obesity‐related traits for FTO was seen in adulthood, but not at younger ages. The loci also showed nominal associations with increased blood glucose but these associations were lost on BMI adjustment. The effect of FTO on obesity‐related traits was driven by an urban environmental influence. We conclude that rs9939609 variant in the FTO locus is associated with measures of adiposity and metabolic consequences in South Indians with an enhanced effect associated with urban living. The detection of these associations in Indians is challenging because conventional anthropometric obesity measures work poorly in the Indian “thin‐fat” phenotype.

Glucose tolerance, insulin resistance and insulin secretion in young south Indian adults: Relationships to parental size, neonatal size and childhood body mass index

OBJECTIVE To study the relationship of newborn size and post-natal growth to glucose intolerance in south Indian adults. RESEARCH DESIGN AND METHODS 2218 men and women (mean age 28 years) were studied from a population-based birth cohort born in a large town and adjacent rural villages. The prevalence of adult diabetes mellitus [DM] and impaired glucose tolerance [IGT], and insulin resistance and insulin secretion (calculated) were examined in relation to BMI and height at birth, and in infancy, childhood and adolescence and changes in BMI and height between these stages. RESULTS Sixty-two (2.8%) subjects had Type 2 diabetes (DM) and 362 (16.3%) had impaired glucose tolerance (IGT). IGT and DM combined (IGT/DM) and insulin resistance were associated with low childhood body mass index (BMI) (p<0.001 for both) and above-average BMI gain between childhood or adolescence and adult life (p<0.001 for both). There were no direct associations between birthweight or infant size and IGT/DM; however, after adjusting for adult BMI, lower birthweight was associated with an increased risk. CONCLUSIONS The occurrence of IGT and Type 2 DM is associated with thinness at birth and in childhood followed by accelerated BMI gain through adolescence.

Sample size estimation in prevalence studies.

Estimation of appropriate sample size for prevalence surveys presents many challenges, particularly when the condition is very rare or has a tendency for geographical clustering. Sample size estimate for prevalence studies is a function of expected prevalence and precision for a given level of confidence expressed by the z statistic. Choice of the appropriate values for these variables is sometimes not straight-forward. Certain other situations do not fulfil the assumptions made in the conventional equation and present a special challenge. These situations include, but are not limited to, smaller population size in relation to sample size, sampling technique or missing data. This paper discusses practical issues in sample size estimation for prevalence studies with an objective to help clinicians and healthcare researchers make more informed decisions whether reviewing or conducting such a study.

Patterns of antibiotic use in the community and challenges of antibiotic surveillance in a lower-middle-income country setting: a repeated cross-sectional study in Vellore, South India.

OBJECTIVES There is considerable evidence linking antibiotic usage to bacterial resistance. Intervention strategies are needed to contain antibiotic use and thereby resistance. To plan appropriate strategies, it is imperative to undertake surveillance in the community to monitor antibiotic encounters and drivers of specific antibiotic misuse. Such surveillance is rarely in place in lower-middle-income countries (LMICs). This study describes antibiotic patterns and challenges faced while developing such surveillance systems in an LMIC. PATIENTS AND METHODS Surveillance of antibiotic encounters (prescriptions and dispensations) was carried out using a repeated cross-sectional design for 2 years in Vellore, south India. Every month, patients attending 30 health facilities (small hospitals, general practitioner clinics and pharmacy shops) were observed until 30 antibiotic encounters were attained in each. Antibiotic use was expressed as the percentage of encounters containing specific antibiotics and defined daily doses (DDDs)/100 patients. Bulk antibiotic sales data were also collected. RESULTS Over 2 years, a total of 52,788 patients were observed and 21,600 antibiotic encounters (40.9%) were accrued. Fluoroquinolones and penicillins were widely used. Rural hospitals used co-trimoxazole more often and urban private hospitals used cephalosporins more often; 41.1% of antibiotic prescriptions were for respiratory infections. The main challenges in surveillance included issues regarding sampling, data collection, denominator calculation and sustainability. CONCLUSIONS Patterns of antibiotic use varied across health facilities, suggesting that interventions should involve all types of health facilities. Although challenges were encountered, our study shows that it is possible to develop surveillance systems in LMICs and the data generated may be used to plan feasible interventions, assess impact and thereby contain resistance.

Cohort profile: The 1969-73 Vellore Birth Cohort Study in South India

This report summarizes a longitudinal study of maternal health and pregnancy outcomes including mothers from urban and rural areas of the North Arcot district in India. It describes the study sample the follow up attrition measurements the findings and the strengths and weaknesses of the study.

Absence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians.

Background A feature of the Asian Indian phenotype is low birth weight with increased adult type 2 diabetes risk. Most populations show consistent associations between low birth weight and adult type 2 diabetes. Recently, two birth weight-lowering loci on chromosome 3 (near CCNL1 and ADCY5) were identified in a genome-wide association study, the latter of which is also a type 2 diabetes locus. We therefore tested the impact of these genetic variants on birth weight and adult glucose/insulin homeostasis in a large Indian birth cohort. Methodology/Principal Findings Adults (n = 2,151) enrolled in a birth cohort (established 1969-73) were genotyped for rs900400 (near CCNL1) and rs9883204 (ADCY5). Associations were tested for birth weight, anthropometry from infancy to adulthood, and type 2 diabetes related glycemic traits. The average birth weight in this population was 2.79±0.47 kg and was not associated with genetic variation in CCNL1 (p = 0.87) or ADCY5 (p = 0.54). Allele frequencies for the ‘birth weight-lowering’ variants were similar compared with Western populations. There were no significant associations with growth or adult weight. However, the ‘birth weight-lowering’ variant of ADCY5 was associated with modest increase in fasting glucose (β 0.041, p = 0.027), 2-hours glucose (β 0.127, p = 0.019), and reduced insulinogenic index (β -0.106, p = 0.050) and 2-hour insulin (β -0.058, p = 0.010). Conclusions The low birth weight in Asian Indians is not even partly explained by genetic variants near CCNL1 and ADCY5 which implies that non-genetic factors may predominate. However, the ‘birth-weight-lowering’ variant of ADCY5 was associated with elevated glucose and decreased insulin response in early adulthood which argues for a common genetic cause of low birth weight and risk of type 2 diabetes.

Transmission dynamics of methicillin-resistant Staphylococcus aureus in a medical intensive care unit in India.

Background Methicillin-resistant Staphylococcus aureus (MRSA) is a global pathogen and an important but seldom investigated cause of morbidity and mortality in lower and middle-income countries where it can place a major burden on limited resources. Quantifying nosocomial transmission in resource-poor settings is difficult because molecular typing methods are prohibitively expensive. Mechanistic statistical models can overcome this problem with minimal cost. We analyse the transmission dynamics of MRSA in a hospital in south India using one such approach and provide conservative estimates of the organisms economic burden. Methods and Findings Fifty months of MRSA infection data were collected retrospectively from a Medical Intensive Care Unit (MICU) in a tertiary hospital in Vellore, south India. Data were analysed using a previously described structured hidden Markov model. Seventy-two patients developed MRSA infections and, of these, 49 (68%) died in the MICU. We estimated that 4.2% (95%CI 1.0, 19.0) of patients were MRSA-positive when admitted, that there were 0.39 MRSA infections per colonized patient month (0.06, 0.73), and that the ward-level reproduction number for MRSA was 0.42 (0.08, 2.04). Anti-MRSA antibiotic treatment costs alone averaged

Weight Gain and Height Growth during Infancy, Childhood, and Adolescence as Predictors of Adult Cardiovascular Risk

124/patient, over three times the monthly income of more than 40% of the Indian population. Conclusions Our analysis of routine data provides the first estimate of the nosocomial transmission potential of MRSA in India. The high levels of transmission estimated underline the need for cost-effective interventions to reduce MRSA transmission in hospital settings in low and middle income countries.

Pre-term birth and low birth weight following preimplantation genetic diagnosis: analysis of 88 010 singleton live births following PGD and IVF cycles.

Objectives To investigate independent relationships of childhood linear growth (height gain) and relative weight gain to adult cardiovascular disease (CVD) risk traits in Asian Indians. Study design Data from 2218 adults from the Vellore Birth Cohort were examined for associations of cross‐sectional height and body mass index (BMI) and longitudinal growth (independent conditional measures of height and weight gain) in infancy, childhood, adolescence, and adulthood with adult waist circumference (WC), blood pressure (BP), insulin resistance (homeostatic model assessment‐insulin resistance [HOMA‐IR]), and plasma glucose and lipid concentrations. Results Higher BMI/greater conditional relative weight gain at all ages was associated with higher adult WC, after 3 months with higher adult BP, HOMA‐IR, and lipids, and after 15 years with higher glucose concentrations. Taller adult height was associated with higher WC (men &bgr; = 2.32 cm per SD, women &bgr; = 1.63, both P < .001), BP (men &bgr; = 2.10 mm Hg per SD, women &bgr; = 1.21, both P ≤ .001), and HOMA‐IR (men &bgr; = 0.08 log units per SD, women &bgr; = 0.12, both P ≤ .05) but lower glucose concentrations (women &bgr; = −0.03 log mmol/L per SD P = .003). Greater height or height gain at all earlier ages were associated with higher adult CVD risk traits. These positive associations were attenuated when adjusted for adult BMI and height. Shorter length and lower BMI at birth were associated with higher glucose concentration in women. Conclusions Greater height or weight gain relative to height during childhood or adolescence was associated with a more adverse adult CVD risk marker profile, and this was mostly attributable to larger adult size.

South Indian calcaneal talar facet configurations and osteoarthritic changes

STUDY QUESTION Is PGD associated with the risk of adverse perinatal outcomes such as pre-term birth (PTB) and low birth weight (LBW)? SUMMARY ANSWER There was no increase in the risk of adverse perinatal outcomes of PTB, and LBW following PGD compared with autologous IVF. WHAT IS KNOWN ALREADY Pregnancies resulting from ART are associated with a higher risk of pregnancy complications compared with spontaneously conceived pregnancies. The possible reason of adverse obstetric outcomes following ART has been attributed to the underlying infertility itself and embryo specific epigenetic modifications due to the IVF techniques. It is of interest whether interventions such as embryo biopsy as performed in PGD affect perinatal outcomes. STUDY DESIGN, SIZE, DURATION Anonymous data were obtained from the Human Fertilization and Embryology Authority (HFEA), the statutory regulator of ART in the UK. The HFEA has collected data prospectively on all ART performed in the UK since 1991. Data from 1996 to 2011 involving a total of 88 010 singleton live births were analysed including 87 571 following autologous stimulated IVF ± ICSI and 439 following PGD cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS Data on all women undergoing either a stimulated fresh IVF ± ICSI treatment cycle or a PGD cycle during the period from 1996 to 2011 were analysed to compare perinatal outcomes of PTB and LBW among singleton live births. Logistic regression analysis was performed adjusting for female age category, year of treatment, previous IVF cycles, infertility diagnosis, number of oocytes retrieved, whether IVF or ICSI was used and day of embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE There was no increase in the risk of PTB and LBW following PGD versus autologous stimulated IVF ± ICSI treatment, unadjusted odds of PTB (odds ratio (OR) 0.68, 95% CI: 0.46–0.99) and LBW (OR 0.56, 95% CI: 0.37–0.85). After adjusting for the potential confounders, there was again no increase in the risk of the adverse perinatal outcomes following PGD: PTB (adjusted odds ratio (aOR) 0.66, 95% CI: 0.45–0.98) and LBW (aOR 0.58, 95% CI: 0.38–0.88). LIMITATIONS, REASONS FOR CAUTION Although the analysis was adjusted for a number of important confounders, the data set had no information on confounders such as smoking, body mass index and the medical history of women during pregnancy to allow adjustment. There was no information on the stage of embryo at biopsy, whether blastomere or trophectoderm biopsy. WIDER IMPLICATIONS FOR THE FINDINGS The demonstration that PGD is not associated with higher risk of PTB and LBW provides reassurance towards its current expanding application. STUDY FUNDING/COMPETING INTEREST(S) No funding was obtained. There are no competing interests to declare.