John Oldroyd

Diabetes and ethnic minorities

The global prevalence of diabetes for all age groups is estimated to be 2.8%. Type 2 diabetes accounts for at least 90% of diabetes worldwide. Diabetes incidence, prevalence, and disease progression varies by ethnic group. This review highlights unique aspects of the risk of developing diabetes, its overwhelming vascular complications, and their management mainly using data among South Asians and African-Caribbeans in the UK but also using non-UK data. It is concluded that although the origin of the ethnic differences in incidence need further clarification, many factors should be amenable to prevention and treatment in all ethnic groups worldwide.

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.

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.

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

OBJECTIVEnGiven 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.nnnSTUDY DESIGN AND SETTINGnInfants 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.nnnRESULTSnSouth 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.nnnCONCLUSIONnIn 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.

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

CONTEXTnAdiponectin, high-density lipoprotein cholesterol (HDL-C) and insulin concentrations may be important in the pathophysiology of cardiovascular disease.nnnOBJECTIVEnWe 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.nnnDESIGN AND PARTICIPANTSnWe conducted a longitudinal study of 215 British-born children of European (n = 138) and South Asian (n = 77) origin, from birth to 3 yr.nnnMAIN OUTCOME MEASUREnSerum 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.nnnRESULTSnSerum 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).nnnCONCLUSIONSnThese 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.

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.