Siddharth Ramji

Adult Metabolic Syndrome and Impaired Glucose Tolerance Are Associated With Different Patterns of BMI Gain During Infancy: Data from the New Delhi birth cohort

OBJECTIVE—The purpose of this study was to describe patterns of infant, childhood, and adolescent BMI and weight associated with adult metabolic risk factors for cardiovascular disease. RESEARCH DESIGN AND METHODS—We measured waist circumference, blood pressure, glucose, insulin and lipid concentrations, and the prevalence of metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel III definition) in 1,492 men and women aged 26–32 years in Delhi, India, whose weight and height were recorded every 6 months throughout infancy (0–2 years), childhood (2–11 years), and adolescence (11 years–adult). RESULTS—Men and women with metabolic syndrome (29% overall), any of its component features, or higher (greater than upper quartile) insulin resistance (homeostasis model assessment) had more rapid BMI or weight gain than the rest of the cohort throughout infancy, childhood, and adolescence. Glucose intolerance (impaired glucose tolerance or diabetes) was, like metabolic syndrome, associated with rapid BMI gain in childhood and adolescence but with lower BMI in infancy. CONCLUSIONS—In this Indian population, patterns of infant BMI and weight gain differed for individuals who developed metabolic syndrome (rapid gain) compared with those who developed glucose intolerance (low infant BMI). Rapid BMI gain during childhood and adolescence was a risk factor for both disorders.

Adult metabolic syndrome abd impaired glucose tolerance are associated with different patterns of BMI from the New Delhi birth cohort

OBJECTIVE—The purpose of this study was to describe patterns of infant, childhood, and adolescent BMI and weight associated with adult metabolic risk factors for cardiovascular disease. RESEARCH DESIGN AND METHODS—We measured waist circumference, blood pressure, glucose, insulin and lipid concentrations, and the prevalence of metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel III definition) in 1,492 men and women aged 26–32 years in Delhi, India, whose weight and height were recorded every 6 months throughout infancy (0–2 years), childhood (2–11 years), and adolescence (11 years–adult). RESULTS—Men and women with metabolic syndrome (29% overall), any of its component features, or higher (greater than upper quartile) insulin resistance (homeostasis model assessment) had more rapid BMI or weight gain than the rest of the cohort throughout infancy, childhood, and adolescence. Glucose intolerance (impaired glucose tolerance or diabetes) was, like metabolic syndrome, associated with rapid BMI gain in childhood and adolescence but with lower BMI in infancy. CONCLUSIONS—In this Indian population, patterns of infant BMI and weight gain differed for individuals who developed metabolic syndrome (rapid gain) compared with those who developed glucose intolerance (low infant BMI). Rapid BMI gain during childhood and adolescence was a risk factor for both disorders.

Predicting adult metabolic syndrome from childhood body mass index: follow-up of the New Delhi birth cohort

Objectives: To assess whether serial measurements of childhood body mass index (BMI) give clinically useful predictions of the risk of developing adult metabolic syndrome and impaired glucose tolerance or type 2 diabetes. Design/setting: Follow-up of a community-based birth cohort in Delhi, India. Participants: 1492 men and women aged 26–32 years whose BMI was recorded 6-monthly throughout childhood. Main outcome measures: The predictive value of childhood BMI for adult metabolic syndrome and impaired glucose tolerance (IGT) and diabetes mellitus. Results: 25% of subjects had metabolic syndrome and 15% had IGT/diabetes mellitus. Both outcomes were associated with greater childhood BMI gain (metabolic syndrome: OR 1.63 (95% CI 1.44 to 1.85); IGT/diabetes mellitus: 1.39 (1.20 to 1.60) per unit increase in within-cohort BMI SD score between 5 and 14 years). The best predictions of adult disease were obtained using a combined test comprising (i) any increase in BMI SD score between 5 and 14 years and (ii) a BMI SD score >0 at 14 years (metabolic syndrome: sensitivity 45%, specificity 78%; IGT/diabetes mellitus: 37%, 73%). Likelihood ratios were low (metabolic syndrome: 1.4–2.0; IGT/diabetes mellitus: 1.2–1.4). A single high BMI measurement at 14 years (overweight or obese, according to International Obesity Task Force criteria) was highly specific but insensitive (metabolic syndrome: sensitivity 7%, specificity 97%; IGT/diabetes mellitus: 8%, 97%). Charts for plotting BMI SD scores through childhood were produced. Conclusions: Serial measurements of childhood BMI give useful predictions of adult risk and could guide advice to children and parents on preventing later disease.

Relationship of Maternal Serum Ferritin with Foetal Serum Ferritin, Birth Weight and Gestation

Haemoglobin and ferritin estimations employing the micro-ELISA technique were done in 308 random selected mothers in labour and their newborns. The values of haemoglobin and serum ferritin as well as birth weight and gestation of babies born to iron depleted, and mildly and moderately anaemic mothers were no different from those of newborns of non-anaemic women. However, the values of serum ferritin per se in all these newborns were much lower than what are generally reported from the western countries. Babies born to severely anaemic women, on the other hand, showed elevated levels of haemoglobin and serum ferritin, and lower birth weights and gestation. Thus, mild to moderate iron deficiency in the mother does contribute to lower iron reserves in the foetus, if not frank iron depletion, and severe iron deficiency anaemia to lower birth weight and gestation.

Incidence of cardiovascular risk factors in an Indian urban cohort results from the New Delhi birth cohort.

India has one of the highest burdens of cardiovascular disease (CVD) worldwide. The annual number of deaths from CVD in India is projected to rise from 2.26 million (1990) to 4.77 million (2020) ([1][1]). Coronary heart disease prevalence rates in India have been estimated over the past several

Childhood body mass index and adult pro-inflammatory and pro-thrombotic risk factors: data from the New Delhi birth cohort

OBJECTIVE Weight gain and growth in early life may influence adult pro-inflammatory and pro-thrombotic cardiovascular risk factors. METHODS Follow-up of a birth cohort in New Delhi, India, whose weight and height were measured every 6 months until age 21 years. Body mass index (BMI) at birth, during infancy (2 years), childhood (11 years) and adulthood (26-32 years) and BMI gain between these ages were analysed in 886 men and 640 women with respect to adult fibrinogen, high-sensitivity C-reactive protein (hsCRP) and plasminogen activator inhibitor-1 (PAI-1) concentrations. RESULTS All the pro-inflammatory/pro-thrombotic risk factors were higher in participants with higher adiposity. In women, BMI at birth and age 2 years was inversely related to fibrinogen (P = 0.002 and 0.05) and, after adjusting for adult adiposity, to hsCRP (P = 0.02 and 0.009). After adjusting for adult adiposity, BMI at 2 years was inversely related to hsCRP and PAI-1 concentrations (P < 0.001 and 0.02) in men. BMI gain between 2 and 11 years and/or 11 years to adulthood was positively associated with fibrinogen and hsCRP in women and with hsCRP and PAI-1 in men. CONCLUSIONS Thinness at birth or during infancy, and accelerated BMI gain during childhood/adolescence are associated with a pro-inflammatory/pro-thrombotic state in adult life. An altered inflammatory state could be one link between small newborn/infant size and adult cardiovascular disease. Associations between pro-inflammatory markers and childhood/adolescent BMI gain are probably mediated through adult adiposity.

Predictors of carotid intima-media thickness and carotid plaque in young Indian adults: the New Delhi birth cohort.

BACKGROUND Carotid intima-media thickness (CIMT) and carotid plaques represent preclinical markers of atherosclerosis. We sought to describe predictors of CIMT and carotid plaques, including early life growth, in a young urban Indian cohort free of clinical cardiovascular disease (CVD). METHODS In 2006-2009, we performed B-mode carotid ultrasound on 600 participants (mean [SD] age 36 [1.1] years; 45% women) from the New Delhi Birth Cohort to evaluate CIMT and carotid plaques (>1mm). Height and weight were recorded at birth, 2 and 11 years of age. Data on CVD risk factors, anthropometry, medical history, socio-economic position, and lifestyle habits were collected in 1998-2002. RESULTS Mean (SD) CIMT for men and women was 0.91 (0.12) and 0.86 (0.13) mm, respectively. Carotid plaque was present in 33% of men and 26% of women. Waist circumference in 1998-2002 was positively associated with CIMT (β coefficient 0.26 mm [0.17, 0.36] per SD) and carotid plaque (OR 1.27 [1.06,1.52] per SD) in 2006-2009. Higher triglycerides, PAI-1, insulin resistance, and diastolic blood pressure, metabolic syndrome, and lower HDL-cholesterol and physical activity predicted higher CIMT and/or plaque (p<0.05). Longer length at 2 years was associated with higher CIMT (p<0.05). These associations were attenuated after adjusting for adult waist circumference. CONCLUSIONS These are the first prospective data from India showing that early life growth, adult socio-demographics, and CVD risk factors predict future CIMT and/or carotid plaque. These relationships appear primarily mediated through central adiposity, highlighting the importance of maintaining a healthy weight in early adulthood to prevent CVD.

Effect of Maternal Anaemia and Iron Depletion on Foetal Iron Stores, Birthweight and Gestation

India is considered to have the highest prevalence of nutritional anaemia in women. Between 6040% of pregnant women have been found to be anaemic, mainly due to iron deficiency (1). There are also reports on the development of iron deficiency anaemia in Indian infants already at 6 months of age (2). In view of this, it was considered pertinent to study the effect not only of anaemia but also of iron depletion in the mother on fetal iron stores. The influence of these factors on birth weight and gestation was also determined.

Comparison of Human Neonatal and Adult Blood Leukocyte Subset Composition Phenotypes

The human peripheral leukocyte subset composition depends on genotype variation and pre-natal and post-natal environmental influence diversity. We quantified this composition in adults and neonates, and compared the median values and dispersal ranges of various subsets in them. We confirmed higher frequencies of monocytes and regulatory T cells (Tregs), similar frequencies of neutrophils, and lower frequencies of CD8 T cells, NKT cells, B1 B cells and gamma-delta T cells in neonatal umbilical cord blood. Unlike previous reports, we found higher frequencies of eosinophils and B cells, higher CD4:CD8 ratios, lower frequencies of T cells and iNKT cells, and similar frequencies of CD4 T cells and NK cells in neonates. We characterized monocyte subsets and dendritic cell (DC) subsets in far greater detail than previously reported, using recently described surface markers and gating strategies and observed that neonates had lower frequencies of patrolling monocytes and lower myeloid dendritic cell (mDC):plasmacytoid DC (pDC) ratios. Our data contribute to South Asian reference values for these parameters. We found that dispersal ranges differ between different leukocyte subsets, suggesting differential determination of variation. Further, some subsets were more dispersed in adults than in neonates suggesting influences of postnatal sources of variation, while some show the opposite pattern suggesting influences of developmental process variation. Together, these data and analyses provide interesting biological possibilities for future exploration.

Newborn screening for G6PD deficiency: A 2-year data from North India

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common erythrocyte enzymopathy, being present in more than 400 million people worldwide that may lead to neonatal jaundice or hemolytic crisis due to drugs or infections. In our study, we aimed to study the frequency of G6PD deficiency in neonates and the proportion of deficient neonates, who developed neonatal hyperbilirubinemia in the study population. The study was an observational one, conducted at the Division of Genetics of Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, over a 2-year period from January 2011 to December 2012. A total of 6,000 newborns delivered during that period underwent newborn screening on 24-72 h of birth. Neonatal hyperbilirubinemia was presented in 13.3% of the study population. Of female neonates, 16% demonstrated G6PD deficiency. This is worth noting for an X-linked recessive trait. Thus, in view of a high gene frequency for a disorder that is manageable with just elimination of few drugs and foodstuff, we stress the need for a newborn screening program for G6PD deficiency.