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Senthil K Vasan,
Tove Fall,
Matthew J Neville, Belavendra Antonisamy,
Caroline H Fall,
Finney S Geethanjali,
Harvest F Gu,
Palany Raghupathy,
Prasanna Samuel,
Nihal Thomas,
Kerstin Brismar,
Erik Ingelsson,
Fredrik Karpe
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ABSTRACT: 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.
Obesity 03/2012; · 4.28 Impact Factor
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ABSTRACT: We examined associations between socio-economic status (SES) indicators and cardiovascular disease (CVD) risk factors among urban and rural South Indians.
Data from a population-based birth cohort of 2218 men and women aged 26-32 years from Vellore, Tamilnadu were used. SES indicators included a household possessions score, attained education and paternal education. CVD risk factors included obesity, hypertension, impaired glucose tolerance or diabetes, plasma total cholesterol to high density lipoprotein (HDL) ratio and triglyceride levels and consumption of tobacco and alcohol. Multiple logistic regression analysis was used to assess associations between SES indicators and risk factors.
Most risk factors were positively associated with possessions score in urban and rural men and women, except for tobacco use, which was negatively associated. Trends were similar with the participants' own education and paternal education, though weaker and less consistent. In a concurrent analysis of all the three SES indicators, adjusted for gender and urban/rural residence, independent associations were observed only for the possessions score. Compared with those in the lowest fifth of the score, participants in the highest fifth had a higher risk of abdominal obesity [odds ratio (OR) = 6.4, 95% CI 3.4-11.6], high total cholesterol to HDL ratio (OR = 2.4, 95% CI 1.6-3.5) and glucose intolerance (OR = 2.8, 95% CI 1.9-4.1). Their tobacco use (OR = 0.4, 95% CI 0.2-0.6) was lower. Except for hypertension and glucose intolerance, risk factors were higher in urban than rural participants independently of SES.
In this young cohort of rural and urban south Indians, higher SES was associated with a more adverse CVD risk factor profile but lower tobacco use.
International Journal of Epidemiology 02/2012; 41(5):1315-27. · 6.41 Impact Factor
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ABSTRACT: 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 organism's economic burden.
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 $124/patient, over three times the monthly income of more than 40% of the Indian population.
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.
PLoS ONE 01/2011; 6(7):e20604. · 4.09 Impact Factor
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ABSTRACT: 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.
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).
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.
PLoS ONE 01/2011; 6(6):e21331. · 4.09 Impact Factor
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ABSTRACT: To study the relationship of newborn size and post-natal growth to glucose intolerance in south Indian adults.
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.
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.
The occurrence of IGT and Type 2 DM is associated with thinness at birth and in childhood followed by accelerated BMI gain through adolescence.
Diabetes research and clinical practice 02/2010; 87(2):283-92. · 2.16 Impact Factor
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ABSTRACT: India is experiencing an epidemic of Type 2 diabetes mellitus (DM) in young adults. This study reports the prevalence of glucose intolerance, and insulin profiles, and their relationship to lifestyle factors in 2218 young adults (aged 26-32 years; 997 urban, 1221 rural) in south India. They were drawn from a cohort of 10,691 individuals born during 1969-1973 in Vellore and nearby villages. Family history, socio-economic status, physical activity and tobacco and alcohol use were recorded. Oral glucose tolerance tests were performed for diagnosis (WHO recommendations). Insulin resistance and secretion were derived from plasma insulin concentrations. Median BMI was 20.0kg/m(2). The prevalence of Type 2 DM and impaired glucose tolerance (IGT) was higher in urban than in rural subjects (3.7% versus 2.1%, p=0.02; 18.9% versus 14.3%, p=0.002, respectively), while prevalence of impaired fasting glycaemia (IFG) was similar in urban and rural populations (3.8% versus 3.4%, p=0.04). Type 2 DM, IGT, IFG or higher insulin resistance and increment were associated with higher socio-economic status (more household possessions) and higher percentage body fat, body mass index and waist/hip ratio. Insulin increment was lower in men with higher alcohol consumption. Our data suggest high levels of glucose intolerance in young rural and urban adults highlighting an urgent need for preventive action to avert a public health catastrophe in India.
Diabetes Research and Clinical Practice 09/2007; 77(2):269-79. · 2.75 Impact Factor
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ABSTRACT: We evaluated the effect of the alpha-blocker tamsulosin on stone clearance, analgesic requirements and steinstrasse in shock wave lithotripsy for solitary renal and ureteral calculus.
A prospective, double-blind, randomized placebo controlled study was performed during 1 year involving 60 patients with a solitary renal or ureteral calculus undergoing shock wave lithotripsy. The control group (30) received 0.4 mg tamsulosin and the study group (30) received placebo daily until stone clearance or for a maximum of 30 days. An oral preparation of dextropropoxyphene hydrochloride and acetaminophen was the analgesic used on an on-demand basis. The parameters assessed were stone size, position, clearance time, effect on steinstrasse and analgesic requirement.
The overall clearance rate was 96.6% (28 of 29) in the study group and 79.3% (23 of 29) in the control group (p = 0.04). With larger stones 11 to 24 mm the difference in the clearance rate was significant (p = 0.03) but not so with the smaller stones 6 to 10 mm (p = 0.35). The average dose of analgesic used was lower with tamsulosin than with controls, without statistical significance. Steinstrasse resolved spontaneously in the tamsulosin group whereas 25% (2 of 8) required intervention in the placebo group. There was no difference between the 2 groups with regard to age, stone size or location.
The alpha-blocker tamsulosin seemed to facilitate stone clearance, particularly with larger stones during shock wave lithotripsy for renal and ureteral calculus. It also appeared to improve the outcome of steinstrasse. Tamsulosin may have a potential role in routine shock wave lithotripsy.
The Journal of Urology 07/2007; 177(6):2185-8. · 3.75 Impact Factor
