OBJECTIVE: We examined associations of birth weight and weight gain in infancy and early childhood with type 2 diabetes (DM) risk in five cohorts from low- and middle-income countries. RESEARCH DESIGN AND METHODS: Participants were 6,511 young adults from Brazil, Guatemala, India, the Philippines, and South Africa. Exposures were weight at birth, at 24 and 48 months, and adult weight, and conditional weight gain (CWG, deviation from expected weight gain) between these ages. Outcomes were adult fasting glucose, impaired fasting glucose or DM (IFG/DM), and insulin resistance homeostasis model assessment (IR-HOMA, three cohorts). RESULTS: Birth weight was inversely associated with adult glucose and risk of IFG/DM (odds ratio 0.91[95% CI 0.84-0.99] per SD). Weight at 24 and 48 months and CWG 0-24 and 24-48 months were unrelated to glucose and IFG/DM; however, CWG 48 months-adulthood was positively related to IFG/DM (1.32 [1.22-1.43] per SD). After adjusting for adult waist circumference, birth weight, weight at 24 and 48 months and CWG 0-24 months were inversely associated with glucose and IFG/DM. Birth weight was unrelated to IR-HOMA, whereas greater CWG at 0-24 and 24-48 months and 48 months-adulthood predicted higher IR-HOMA (all P < 0.001). After adjusting for adult waist circumference, birth weight was inversely related to IR-HOMA. CONCLUSIONS: Lower birth weight and accelerated weight gain after 48 months are risk factors for adult glucose intolerance. Accelerated weight gain between 0 and 24 months did not predict glucose intolerance but did predict higher insulin resistance.

Both the early environment and genetic variation may affect DNA methylation, which is one of the major molecular marks of the epigenome. The combined effect of these factors on a well-defined locus has not been studied to date. We evaluated the association of periconceptional exposure to the Dutch Famine of 1944-45, as an example of an early environmental exposure, and single nucleotide polymorphisms covering the genetic variation (tagging SNPs) with DNA methylation at the imprinted IGF2/H19 region, a model for an epigenetically regulated genomic region. DNA methylation was measured at five differentially methylated regions (DMRs) that regulate the imprinted status of the IGF2/H19 region. Small but consistent differences in DNA methylation were observed comparing 60 individuals with periconceptional famine exposure with unexposed same-sex siblings at all IGF2 DMRs (P BH < 0.05 after adjustment for multiple testing), but not at the H19 DMR. IGF2 DMR0 methylation was associated with IGF2 SNP rs2239681 (P BH = 0.027) and INS promoter methylation with INS SNPs, including rs689, which tags the INS VNTR, suggesting a mechanism for the reported effect of the VNTR on INS expression (P BH = 3.4×10 -3 ). Prenatal famine and genetic variation showed similar associations with IGF2/H19 methylation and their contributions were additive. They were small in absolute terms ( < 3%), but on average 0.5 standard deviations relative to the variation in the population. Our analyses suggest that environmental and genetic factors could have independent and additive similarly sized effects on DNA methylation at the same regulatory site. © 2012 Tobi et al.

The prevalence of overweight and obesity is rapidly increasing among Latin American children, posing challenges for current healthcare systems and increasing the risk for a wide range of diseases. To understand the factors contributing to childhood obesity in Latin America, this paper reviews the current nutrition status and physical activity situation, the disparities between and within countries and the potential challenges for ensuring adequate nutrition and physical activity. Across the region, children face a dual burden of undernutrition and excess weight. While efforts to address undernutrition have made marked improvements, childhood obesity is on the rise as a result of diets that favour energy-dense, nutrient-poor foods and the adoption of a sedentary lifestyle. Over the last decade, changes in socioeconomic conditions, urbanization, retail foods and public transportation have all contributed to childhood obesity in the region. Additional research and research capacity are needed to address this growing epidemic, particularly with respect to designing, implementing and evaluating the impact of evidence-based obesity prevention interventions.

Inflammation affects trace nutrient concentrations, but research on copper and particularly in children is limited. We assessed associations between serum C-reactive protein (CRP) and zinc, iron, copper, and other biomarkers (alkaline phosphatase, hemoglobin, and albumin), in 634 healthy 6- to 11-year-old Guatemalan schoolchildren. CRP was measured by a standardized, high-sensitive method. For significant associations with CRP, we stratified nutrient concentrations across categories of CRP and compared concentrations above and below several CRP cutoff points (0.5, 1, 3, 5, and 10 mg/L), and then adjusted values using correction factors (ratios of geometric means of the nutrients in the low and high groups). Prevalence of serum zinc (<65 μg/dL0, ferritin (<15 μg/L), and copper (<90 μg/dL) deficiency were 21%, 2.1%, and 23.8%, respectively. Median (25th and 75th percentiles) CRP was 0.56 (0.26 and 1.54) mg/L. CRP concentration was positively associated with ferritin and copper concentrations (r=0.23 and 0.29, respectively; P<0.0001) but not with zinc and other bio-markers (P>0.05). Regardless of CRP cutoffs, high (> cutoff) vs. low (≤ cutoff) CRP levels had higher ferritin and copper concentrations and lower prevalence of copper deficiency of <90 μg/dL (P<0.05). Adjustment for inflammation had the greatest influence on recalculated prevalence for the CRP 0.5 mg/L cutoff. The low ferritin prevalence hardly changed (from 2.1% to 2.5%) while the low copper prevalence changed appreciably (from 23.8% to 31.2%). In conclusion, CRP was positively associated with ferritin and copper but not with zinc concentrations. Adjustment for inflammation had little effect on low ferritin prevalence, low to begin with, and a large impact on low copper prevalence. High-sensitive CRP methods and the use of very low CRP cutoffs may be more accurate than traditional CRP methods in the adjustment of serum copper concentrations for inflammation in healthy school children.

Background: The associations among dietary zinc intakes and biomarkers of zinc status are unknown in apparently healthy children at high risk for zinc deficiency. Objective: To assess associations among zinc-related parameters in a sample of Guatemalan school-aged children. Methods: We assessed total dietary intakes and biomarkers of zinc status before and after receiving 6 months of zinc supplementation or placebo in 691 Guatemalan schoolchildren aged 6 to 11 years. Most of the children also received zinc-fortified milk from a government program that started shortly after the trial began. We assessed associations between zinc intakes and serum zinc, alkaline phosphatase (ALP), and albumin. Results: At baseline, the prevalence of serum zinc < 65 μg/dL and dietary zinc intake below Estimated Average Requirements (EAR) (< 4 and < 7 mg/day for children < 9 and ≥ 9 years, respectively) were 21.6% and 39.4%, respectively. Pearson correlations between serum zinc concentration and dietary zinc intake, serum ALP, and serum albumin were r = 0.07, 0.15, and 0.07, respectively. At the 6-month follow-up, low serum zinc and low total (diet plus fortified milk) zinc intakes were observed in 1.2% and 0.0% of children in the zinc-supplemented group and 4.0% and 34.1% in the placebo group, respectively. Pearson correlations between serum zinc concentration and total zinc intake, serum ALP, and serum albumin were 0.10, 0.06, and −0.11 in the zinc-supplemented group and −0.04, 0.05, and 0.01 in the placebo group, respectively. Conclusions: Zinc intake was inconsistently associated with markers of serum zinc concentration. Zinc fortification or supplementation attenuated the associations.

To evaluate the sustainability of market-based community distribution of micronutrient powders (Sprinkles®, Hexagon Nutrition, Mumbai, India.) among pre-school children in Kenya, we conducted in August 2010 a follow-up survey, 18 months after study-related marketing and household monitoring ended. We surveyed 849 children aged 6-35 months randomly selected from 60 study villages. Nutritional biomarkers were measured by fingerstick; demographic characteristics, Sprinkles purchases and use were assessed through household questionnaires. We compared Sprinkles use, marketing efforts and biomarker levels with the data from surveys conducted in March 2007, March 2008 and March 2009. We used logistic regression to evaluate associations between marketing activities and Sprinkles use in the 2010 survey. At the 2010 follow-up, 21.9% of children used Sprinkles in the previous 7 days, compared with 64.9% in 2008 (P<0.001). Average intake was 3.2 sachetsweek-1 in 2008, 1.6 sachetsweek-1 in 2009 and 1.1 sachetsweek-1 in 2010 (P<0.001). Factors associated with recent Sprinkles use in 2010 included young age [6-23 months vs. 24-35 months, adjusted odds ratio (aOR)=1.5, P=0.02], lowest 2 quintiles of socio-economic status (aOR=1.7, P=0.004), household attendance at trainings or launches (aOR=2.8, P<0.001) and ever receiving promotional items including free Sprinkles, calendars, cups and t-shirts (aOR=1.7, P=0.04). In 2010, there was increased prevalence of anaemia and malaria (P<0.001), but not iron deficiency (P=0.44), compared with that in 2008. Sprinkles use in 2010 was associated with decreased iron deficiency (P=0.03). Sprinkles coverage reduced after stopping household monitoring and reducing marketing activities. Continued promotion and monitoring of Sprinkles usage may be important components to sustain the programme.

Nutritional demands for docosahexaenoic acid (DHA) are high during pregnancy. Diets low in DHA and long-chain polyunsaturated fatty-acids (LC-PUFA) in pregnancy are associated with poorer DHA status and slower reestablishment of maternal stores. To assess intakes of LC-PUFA among urban pregnant women in Central Mexico, we conducted a cross-sectional survey in Prenatal Clinic at the General Hospital No. 1 of the Mexican Society Security Institute, Cuernavaca, Morelos, Mexico. We ascertained intakes over past three months of 110 food items using a food frequency questionnaire developed for this population. Among 1364 pregnant women 18-35 years of age (mean age 26.2±4.7 years) who were interviewed at 18-22 weeks gestation, median (inter-quartile range) daily intakes of linoleic acid, alpha-linolenic acid (LA), arachidonic acid, eicosapentaenoic acid and DHA were 17.6 (13.6; 22.2) g, 1.4 (1.0; 2.0) g, 137 (102; 174) mg, 18 (10; 38) mg, and 55 (37; 99) mg respectively. The median ratio of n-6 to n-3 PUFA was 11.8:1. The main dietary contributions to DHA intake were eggs, chicken, and fresh canned fish. Intakes of PUFAs were higher among women who had completed high school (p<0.01). We conclude that intakes of DHA were much lower than recommended values; the high n-6 to n-3 ratio suggests a suboptimal balance of these PUFAs. Very few sources of DHA are commonly eaten.

Evidence is accumulating that the pattern of growth in childhood is associated with development of cardiovascular disease in adulthood, but such evidence comes mostly from developed countries. We conducted a review of studies from countries undergoing the nutrition transition. Five birth cohorts with measures of child growth and outcomes through adolescence were identified, from China, India, Guatemala, Brazil and the Philippines. Across studies there are major differences in data availability and in statistical approaches to modelling child growth and its effects. Nevertheless, generally consistent associations of growth failure in early childhood and development of overweight in later childhood with the risk of elevated blood pressure, glucose, and serum lipids in adulthood were observed. As these cohorts mature they will provide a wealth of critical information on the relation between early life factors and later disease risk, and efforts should be made to ensure ongoing follow-up using standardized approaches and more comprehensive assessments.

Balkan Endemic Nephropathy (BEN), first described in 1956 in Vratza region, Bulgaria, may result from prolonged, chronic exposure to environmental toxicants, but the underlying etiologic factors remain elusive. There has been no recent systematic characterization of the epidemiology of this disease. Recently, it has been suggested that the incidence of the disease is decreasing. We therefore abstracted data from registers of patients in 21 affected villages and the town of Vratza, Bulgaria maintained from 1964 through 1987. In 1964, the prevalence of BEN was 6.0 per 1000 inhabitants; among residents of the affected villages, the prevalence was 12.3 per 1000. From 1965 to 1975 the incidence rate was 0.7 per 1000 person-years, and from 1976 to 1987 the incidence rate was 0.3 per 1000 person-years (rate ratio 0.43; p < 0.001). Incidence was much lower in Vratza town; among residents of affected villages, the period-specific rates were 1.7 and 0.8 per 1000 per year, respectively (rate ratio 0.47; p < 0.01). These trends were consistent across all villages for which registers were maintained. Median survival following registration increased from 2.0 to 5.0 years over the same period (p < 0.001). BEN appears to be decreasing in incidence in this region.

While birth weight and weight gain have been associated with hypertension (HT), the association of linear growth, independently of weight gains, has been less well studied. We assessed the independent association of body mass index (BMI) and length at birth and changes in BMI and height during the first two decades of life with adult blood pressure (BP). A birth cohort (n = 1141) was assembled in 1978-79, and followed up at school-age and adulthood. We used conditional length and BMI measures. BMI at birth was inversely associated with HT; c-BMI from school age to adulthood and c-height from birth to school age were positively associated with hypertension. Early adiposity accretion from birth to 9 years and late linear growth from 9 to 24 years were not associated with increased HT. Regarding BP, systolic and diastolic BP presented similar partterns: The lower the BMI at birth the higher the adult BP; the higher the BMI gains in the first 2 decades of life the higher the adult BP; linear accretion only in the first decade of life was associated with adult BP. Linear growth in the first decade of life and fat accretion in the second decade are associated with adults HT.