Avni Vyas

Effects of early growth on blood pressure of infants of British European and South Asian origin at one year of age: The Manchester children's growth and vascular health study

Objective The objective of this study was to investigate early influences of postnatal growth on blood pressure (BP) in healthy, British-born South Asian and European origin infants. We tested the hypotheses that South Asian infants would be smaller in all body dimensions (length and weight) with higher relative truncal skinfold thickness at birth, and that increased (central) adiposity and accelerated growth up to 1 year would be associated with higher BP in both ethnic groups. Patients and methods Five hundred and sixty infants were followed prospectively from birth to 3 and/or 12 months with measures of anthropometry and resting BP, compared against a UK 1990 growth reference, and analysed using regression methods. Results Marked differences in birth size persisted, as expected, between European and South Asian babies, but with a sexual dichotomy: South Asian boys were smaller in all anthropometric parameters (P < 0.001), including skinfolds (P < 0.05), than European boys, but South Asian girls, although smaller in length and weight, had similar skinfolds to European girls and thus a slightly larger subscapular skinfold thickness relative to birth weight [1.3 versus 1.2, mean difference 0.07, 95% confidence interval (CI) 0.0009–0.14, P = 0.047]. The dichotomy persisted postnatally; South Asian boys showed a striking early increase in weight and length compared with European boys, associated with significant accrual of subscapular fat (6.1 versus 5.3 mm, mean difference 0.8, 95% CI 0.3–1.3, P = 0.003). In gender and ethnicity adjusted regression models, infants with the largest weight standard deviation score (SDS) increases in the first 3 months had the highest 12-month systolic BP (β = 2.4, 95% CI 0.5–4.2, P = 0.01), while those with the greatest birth length (β = 0.7, 95% CI 0.05–1.4, P = 0.04) but the smallest changes in length over 3–12 months (β = −0.57, 95% CI −0.95 to −0.19, P = 0.004) had the highest diastolic BP. Conclusions Ethnic and gender differences in growth and adiposity present in early infancy include truncal fat preservation in South Asian girls from birth, which in boys is related to rapid early weight gain. Weight gain during the first 3 months appears to drive the rise in systolic BP to 1 year, itself a likely driver of later BP.

Dietary intake and the insulin-like growth factor system: effects of migration in two related populations in India and Britain with markedly different dietary intake.

BACKGROUND The insulin-like growth factor (IGF) system is implicated in the pathogenesis of diabetes and cardiovascular disease. OBJECTIVE We report the effects of total energy intake on the IGF system in two populations with markedly different dietary macronutrient intake and cardiovascular event rate. DESIGN, SUBJECTS AND SETTING Dietary macronutrient intake was measured in a specific Gujarati migrant community in Sandwell, UK (n=205) compared with people still resident in the same villages of origin in India (n=246). Fasting IGF-I, IGF-binding protein (IGFBP)-1 and IGFBP-3, insulin and glucose (0 and 2-hour) were measured. RESULTS Total energy and total fat intake were higher in UK migrants, as were IGFBP-3 and IGF-I (mean (95% confidence interval): 145.9 (138.1-153.6) vs. 100.9 (94.6-107.3) ng ml(-1); F=76.6, P<0.001). IGFBP-1 was lower in UK migrants (29.5 (25.9-33.0) vs. 56.5 (50.6-62.5) microg l(-1); F=48.4, P<0.001). At both sites, IGF-I correlated positively with total energy (Spearmans rho=0.45, P<0.001) and total fat (rho=0.44, P<0.001) as did IGFBP-3 with total energy (rho=0.21, P<0.05) and fat (rho=0.26, P<0.001). Conversely, in Indian Gujaratis, IGFBP-1 fell with increasing total energy (rho=-0.27, P<0.001) and fat intake (rho=-0.26, P<0.01) but not in UK Gujaratis. Multiple linear regression modelling showed that increasing quartiles of fat intake were associated with higher IGF-I (beta=0.42, P=0.007) independent of age, body mass index, plasma insulin, fatty acids and 2-hour glucose. CONCLUSION In these genetically similar groups, migration to the UK and adoption of a different diet is associated with marked changes in the IGF system, suggesting that environmental factors profoundly modulate serum concentrations and actions of IGFs.

Maternal and Neonatal Influences on, and Reproducibility of, Neonatal Aortic Pulse Wave Velocity

Aortic pulse wave velocity (aPWV), a noninvasive measure of vascular stiffness, is an independent predictor of cardiovascular disease both before and in overt vascular disease. Its characteristics in early life and its relationship to maternal factors have hardly been studied. To test the hypothesis that infant aPWV was positively related to maternal anthropometry and blood pressure (BP) at 28 weeks gestation, after adjusting for neonatal anthropometry and BP, 148 babies born in Manchester were measured 1 to 3 days after birth. A high reproducibility of aPWV, assessed in 30 babies within 3 days of birth, was found with a mean difference between occasions of −0.04 m/s (95% CI: −0.08 to 0.16 m/s). Contrary to our hypothesis, a significant inverse relation was found between neonatal aPWV (mean: 4.6 m/s) and maternal systolic BP (mean: 108.9 mm Hg; r=−0.57; 95% CI: −0.67 to −0.45) but not maternal height nor weight. Neonatal aPWV was positively correlated with birth length, birth weight, and systolic BP. In multiple regression, neonatal aPWV remained significantly inversely associated with maternal systolic BP (adjusted β coefficient: −0.032; 95% CI: −0.040 to −0.024; P<0.001), after adjustment for maternal age, birth weight, length, and neonatal BP (all independently and positively related to aPWV) and for gestational age, maternal weight, and height (unrelated). These results suggest that infant aPWV may be a useful index of infant vascular status, is less disturbing to measure than infant BP, and is sensitive to the gestational environment marked by maternal BP.

Triglycerides and small dense low density lipoprotein in the discrimination of coronary heart disease risk in South Asian populations.

INTRODUCTION Coronary heart disease (CHD) is exceptionally prevalent amongst globally dispersed migrant groups originating from the Indian subcontinent, but the contribution of dyslipidaemia to their increased risk remains poorly defined. METHODS Fasting lipids and lipoproteins, apolipoproteins (Apo), low density lipoprotein (LDL) diameter and oxidised LDL were measured amongst rural Indians in India (n=294) and their migrant contemporaries in the UK (n=242). The performance of qualitative and quantitative measures of lipid metabolism were compared in the discrimination of WHO defined metabolic risk and raised Framingham CHD risk scores (>15%) using Receiver Operating Characteristic (ROC) curves. RESULTS LDL diameter was correlated with triglycerides (R(2)=0.12, P<0.001) and with high density lipoprotein (HDL) cholesterol levels (R(2)=0.15, P<0.001) in both groups. Migrants had less small dense LDL (95% CI: 12.5-14.2%) vs. rural Indians (15.7-17.2, P<0.05). On ROC analysis, triglycerides were the only consistent discriminators of metabolic and CHD risk scores (all P< or =0.001). Apo B was also a strong indicator of raised CHD risk scores. Irrespective of site, individuals with raised triglycerides also had higher total cholesterol and Apo B, denser LDL, lower HDL and more oxidised LDL (all P< or =0.01). DISCUSSION Fasting triglycerides reflect both qualitative and quantitative aspects of lipid metabolism, and are a comprehensive discriminator of CHD risk in this South Asian population.

Inflammatory markers and growth in South Asian and European origin infants in Britain: the Manchester Children's Growth and Vascular Health Study.

OBJECTIVE Given the high risk of cardiovascular disease in South Asians and the importance of inflammation in coronary heart disease we tested the hypothesis that circulating C-reactive protein (CRP) and interleukin 6 (IL-6) would be higher in healthy British born infants of South Asian origin than in infants of European origin in the first 2 years of life. STUDY DESIGN AND SETTING Infants of South Asian (n=74) and European (n=129) origin were followed prospectively from birth. Anthropometry and fasting CRP and IL-6 concentrations were measured at one or more of 3, 6, 12 and 24 months of age. RESULTS South Asian infants had a significantly lower circulating CRP compared with European infants (beta=0.63, 95% CI 0.41-0.98 mg/l, P=0.040). There was no significant change in CRP from birth to 2 years in either ethnic group so that neither infant weight nor weight gain were associated with CRP during follow-up. IL-6 concentrations were low or undetectable during follow-up in all participants. CONCLUSION In our cohort, South Asian origin infants had significantly lower markers of inflammation compared with European infants. Infant growth to age 2 years was not associated with CRP or IL-6. Inflammatory markers are not useful indices of CVD risk at this age, with such markers not being elevated as expected in South Asian infants. The timing of the rise of such markers to the levels found in adult South Asian populations needs longer prospective study.

Migration is associated with lower total, but not free testosterone levels in South Asian men

Objective  Serum testosterone measurement is an integral part of the endocrine assessment of men. Little is known about its variation in relation to migration. We examined within a South Asian group the effect of migration to the UK on androgen levels.

Adiponectin and Lipid Profiles Compared with Insulins in Relation to Early Growth of British South Asian and European Children: The Manchester Children's Growth and Vascular Health Study

CONTEXT Adiponectin, high-density lipoprotein cholesterol (HDL-C) and insulin concentrations may be important in the pathophysiology of cardiovascular disease. OBJECTIVE We tested the hypothesis that serum adiponectin rather than insulin differs from early life, between South Asians and Europeans, with a potentially key role in excess cardiovascular risk characteristic of adult South Asians. DESIGN AND PARTICIPANTS We conducted a longitudinal study of 215 British-born children of European (n = 138) and South Asian (n = 77) origin, from birth to 3 yr. MAIN OUTCOME MEASURE Serum adiponectin, insulin, proinsulin and HDL-C concentrations were assessed in relation to ethnic group and growth in anthropometric variables from 0-3 yr of age. RESULTS Serum adiponectin was lower in South Asian children, despite their smaller size, notable at age 3-6 months (9.5 vs. 11.8 mg/liter; P = 0.04), with no ethnic differences in serum lipids or insulin or proinsulin. In mixed-effects longitudinal models for HDL-C, determinants were adiponectin (P = 0.034), age (P < 0.001), and body mass index (P < 0.001) but not ethnicity. None of these or growth variables affected either insulin or proinsulin. In a fully adjusted mixed-effects longitudinal model including age, sex, insulin, and proinsulin, the independent determinants of serum adiponectin were height [21.3 (95% confidence interval = 31.7-10.8 cm lower, for every 1 mmol/liter increase in adiponectin, P < 0.001], HDL-C [2.8 (1.3-4.2) mmol/liter higher, P < 0.0001], body mass index (lower, P = 0.03), and South Asian ethnicity (lower, P = 0.01). CONCLUSIONS These British South Asian-origin infants have lower serum adiponectin but no differences in HDL-C or insulin molecules. In South Asians, factors affecting adiponectin metabolism in early life, rather than insulin resistance, likely determine later excess cardiovascular risk.

Change in pancreatic B-cell function (HOMA-B) varies in different populations with similar genetic backgrounds but different environments.

Objective  To determine whether pancreatic B‐cell function varies in different populations with similar genetic backgrounds but different environments.

Circulating insulin-like growth factor-binding protein 3 levels, independent of insulin-like growth factor 1, associate with truncal fat and systolic blood pressure in South asian and white European preschool children.

Aims: To study the effect of the insulin-like growth factor (IGF) system on growth, adiposity and systolic blood pressure (SBP) in early life in British-born South Asian (SA) and White European (WE) children. Methods: The effect of IGF-1 and insulin-like growth factor-binding protein 3 (IGFBP-3) over the first 4 years in 204 healthy SA and WE children was investigated by mixed linear regression modelling. This enabled inclusion of all follow-up observations and adjustment for repeated measures. Results: At birth, SA babies were shorter and lighter than WE babies. Over 4 years, SA ethnicity was associated with lower height, weight and body mass index (BMI) standard deviation score (SDS), higher subscapular/triceps skinfold thickness (Ss/Tr SFT) and lower SBP (all p < 0.01). IGF-1 was associated with greater height (p = 0.03), weight (p < 0.001) and BMI SDS (p < 0.001), and IGFBP-3 with greater weight SDS (p < 0.001), BMI SDS (p = 0.001), Ss/Tr SFT (p = 0.003) and SBP (p = 0.023). Conclusions: Over this first 4-year period of life, SA ethnicity was associated with being shorter, lighter, having more superficial truncal adiposity and lower SBP. IGFBP-3 (and not IGF-1) was independently associated with both superficial truncal adiposity and SBP, suggesting that IGFBP-3 is a potential metabolic and cardiovascular marker in healthy children in the early years of life.

79 INFLUENCE OF EARLY BODY COMPOSITION AND TRUNCAL FAT ON RISE OF BLOOD PRESSURE IN EARLY CHILDHOOD; SOUTH ASIANS COMPARED WITH EUROPEANS

Background: South Asian (SA) adults, often born at lower birth weights in western society, have excess Cardiovascular Disease (CVD) compared with European-origin (WE) counterparts, in part related to increased truncal/visceral adiposity. When in early life the latter emerges and its effects on blood pressure (BP) are unclear. Aim: To test if fat proportions by skinfolds or weight/height indices (eg: BMI) determine BPs later and whether ethnicity or fat remain as risk factors at ages 0-9years. Method: In a cohort of 586 children (373 WE, 213 SA), we took standardised growth measures and BP at birth and >1 subsequent time point from 3 months to 9 years. Measurements were age-banded as <2y (n = ∼580), 2-4y (∼160), 4-6y (∼40) and >6 y (∼30). Growth was standardized against 1990 UK standard deviation scores (SDS). Results: Despite significantly lower mean BMI SDS from birth to 6y (-0.4, 95%CI -0.6to-0.1, vs WE +0.45, 0.15to0.75, p<0.01), young SA had elevated Subscapular/ Triceps ratios (>5%, in age bands <2y to 4y), suggesting relative increased truncal fat. Both systolic (S) and diastolic (D) BPs were comparable between ethnic groups and gender. However, if adjusted for BMI, SA had significantly higher mean SBP/BMI ratios upto 4y and significantly higher DBP/BMI ratios at 2-6y (Anova; F 3.6, P<0.01). Conclusions: SA children had increased BP/BMI ratios and greater central fat, from birth. Early-life differences in body composition and size adjusted BP may increase CVD risk in later life.