Finney S. Geethanjali

Low apolipoprotein A-IV plasma concentrations in men with coronary artery disease

OBJECTIVESnThe objective of this study was to evaluate the relation between apolipoprotein A-IV (apoA-IV) plasma concentrations and coronary artery disease (CAD).nnnBACKGROUNDnExperimental in vitro and in vivo studies favor apoA-IV to be protective against the development of atherosclerosis. Mice that overexpress either human or mouse apoA-IV demonstrated a significant reduction of aortic atherosclerotic lesions compared with control mice. Data on apoA-IV plasma concentrations and CAD in humans are lacking.nnnMETHODSnWe determined in two independent case-control studies of a Caucasian and an Asian Indian population whether apoA-IV plasma concentrations are related to the presence of angiographically assessed CAD.nnnRESULTSnPlasma apoA-IV levels were significantly lower in 114 male Caucasian subjects with angiographically defined CAD when compared with 114 age-adjusted male controls (10.2 +/-3.8 mg/dL vs. 15.1 +/- 4.0 mg/dL, p < 0.001). Logistic regression analysis indicated that the association between apoA-IV levels and CAD was independent of the high-density lipoprotein cholesterol and triglyceride concentrations. The inverse relationship between plasma levels of apoA-IV and the presence of CAD was confirmed in an independent sample of 68 male Asian Indians with angiographically documented CAD and 68 age-matched controls.nnnCONCLUSIONSnThe results of this cross-sectional study demonstrate for the first time an association between low apoA-IV concentrations and CAD in humans and suggest that apoA-IV may play an antiatherogenic role in humans.

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

OBJECTIVEnTo study the relationship of newborn size and post-natal growth to glucose intolerance in south Indian adults.nnnRESEARCH DESIGN AND METHODSn2218 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.nnnRESULTSnSixty-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.nnnCONCLUSIONSnThe occurrence of IGT and Type 2 DM is associated with thinness at birth and in childhood followed by accelerated BMI gain through adolescence.

Born With Low Birth Weight in Rural Southern India - What Are the Metabolic Consequences 20 Years Later?

OBJECTIVEnLow birth weight (LBW) is common in the Indian population and may represent an important predisposing factor for type 2 diabetes (T2D) and the metabolic syndrome. Intensive metabolic examinations in ethnic LBW Asian Indians have been almost exclusively performed in immigrants living outside India. Therefore, we aimed to study the metabolic impact of being born with LBW in a rural non-migrant Indian population.nnnSUBJECTS AND METHODSnOne hundred and seventeen non-migrant, young healthy men were recruited from a birth cohort in a rural part of south India. The subjects comprised 61 LBW and 56 normal birth weight (NBW) men, with NBW men acting as controls. Subjects underwent a hyperinsulinaemic euglycaemic clamp, i.v. and oral glucose tolerance tests and a dual-energy X-ray absorptiometry scan. The parents anthropometric status and metabolic parameters were assessed.nnnRESULTSnMen with LBW were shorter (167±6.4 vs 172±6.0 cm, P<0.0001), lighter (51.9±9 vs 55.4±7 kg, P=0.02) and had a reduced lean body mass (42.1±5.4 vs 45.0±4.5u200akg, P=0.002) compared with NBW controls. After adjustment for height and weight, the LBW subjects had increased diastolic blood pressure (77±6 vs 75±6 mmHg, P=0.01). Five LBW subjects had impaired glucose tolerance. In vivo insulin secretion and peripheral insulin action were similar in both the groups. Mothers of the LBW subjects were 3 cm shorter than the control mothers.nnnCONCLUSIONnOnly subtle features of the metabolic syndrome and changes in body composition among LBW rural Indians were found. Whether other factors such as urbanisation and ageing may unmask more severe metabolic abnormalities may require a long-term follow-up.

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 (nu200a=u200a2,151) 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 (pu200a=u200a0.87) or ADCY5 (pu200a=u200a0.54). 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, pu200a=u200a0.027), 2-hours glucose (β 0.127, pu200a=u200a0.019), and reduced insulinogenic index (β -0.106, pu200a=u200a0.050) and 2-hour insulin (β -0.058, pu200a=u200a0.010). 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.

Anthropometric measurements for the prediction of the metabolic syndrome: a cross-sectional study on adolescents and young adults from southern india

Objectives To determine which anthropometric measurement correlates best with the metabolic abnormalities associated with the metabolic syndrome in adolescents and young adults. Design Cross-sectional study. Setting Schools, high schools and universities. Participants 1359 adolescents and young adults aged 14–25u2005years. Main outcome measures Anthropometric predictors of metabolic abnormalities as classified by International Diabetes Federation definition. Results The waist circumference (OR 1.56, 95% CI 1.0 to 2.43: p≤0.01) and the abdominal skin fold thickness (OR 1.44, 95% CI 1.02 to 2.04, p≤0.01) above the third quintile cut-offs were found to be significantly associated with metabolic abnormalities. The sensitivity of either one of these measurements in predicting metabolic abnormalities was 66.1% with a negative predictive value of 82.8%. Hyperglycaemia was significantly associated with an abdominal skin fold thickness over the fourth quintile alone (OR 1.63, 95% CI 1.24 to 2.1). All the anthropometric measurements correlated well with elevated triglycerides and hypertension. Conclusions In a large community-based cross-sectional survey of subjects aged 14–25u2005years, the waist circumference and the abdominal skin fold thickness are important predictors of the metabolic abnormalities associated with metabolic syndrome. This simple clinical tool may help in a primary care setting to identify subjects who require a further biochemical evaluation and would considerably reduce the cost of unwarranted testing.

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

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.

Parental determinants of metabolic syndrome among adolescent Asian Indians: A cross‐sectional analysis of parent–offspring trios

The aim of the present study was to investigate the relationship between parental metabolic syndrome (MS) and the risk of MS and associated abnormalities in adolescent offspring.

IndEcho study: cohort study investigating birth size, childhood growth and young adult cardiovascular risk factors as predictors of midlife myocardial structure and function in South Asians.

Introduction South Asians have high rates of cardiovascular disease (CVD) and its risk factors (hypertension, diabetes, dyslipidaemia and central obesity). Left ventricular (LV) hypertrophy and dysfunction are features of these disorders and important predictors of CVD mortality. Lower birth and infant weight and greater childhood weight gain are associated with increased adult CVD mortality, but there are few data on their relationship to LV function. The IndEcho study will examine associations of birth size, growth during infancy, childhood and adolescence and CVD risk factors in young adulthood with midlife cardiac structure and function in South Asian Indians. Methods and analysis We propose to study approximately 3000 men and women aged 43–50 years from two birth cohorts established in 1969–1973: the New Delhi Birth Cohort (n=1508) and Vellore Birth Cohort (n=2156). They had serial measurements of weight and height from birth to early adulthood. CVD risk markers (body composition, blood pressure, glucose tolerance and lipids) and lifestyle characteristics (tobacco and alcohol consumption, physical activity, socioeconomic status) were assessed at age ~30 years. Clinical measurements in IndEcho will include anthropometry, blood pressure, biochemistry (glucose, fasting insulin and lipids, urinary albumin/creatinine ratio) and body composition by dual energy X-ray absorptiometry and bioelectrical impedance. Outcomes are LV mass and indices of LV systolic and diastolic function assessed by two-dimensional and Doppler echocardiography, carotid intimal-media thickness and ECG indicators of ischaemia. Regression and conditional growth models, adjusted for potential confounders, will be used to study associations of childhood and young adult exposures with these cardiovascular outcomes. Ethics and dissemination The study has been approved by the Health Ministry Steering Committee, Government of India and institutional ethics committees of participating centres in India and the University of Southampton, UK. Results will be disseminated through scientific meetings and peer-reviewed journals. nTrial registration numbern ISRCTN13432279; Pre-results.