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Abstract Background Higher cardiac left ventricular (LV) mass (LVM) has independently been associated with cardiovascular risk and mortality. Changes in LV structure have been observed in children with obesity. However, information about the long-term influence of early growth on LV structure is limited. Purpose To explore the associations between early growth patterns, specifically birth weight, age and body mass index (BMI) at infant BMI peak and at childhood BMI rebound, and LV structure at midlife. Methods At the age of 46, a sample of the participants of the Northern Finland Birth Cohort 1966 took part in follow-up examinations. A randomly selected subpopulation was enrolled to echocardiographic examinations (n=1124). BMI at various ages in childhood was calculated from frequent anthropometric measurements collected from child welfare clinical records. Age and BMI at BMI peak (n=541, mean age 9.0 months) and at BMI rebound (n=657, mean age 5.8 years) were derived from random effect models. Results Birth weight (n=1124), BMI at BMI peak and at BMI rebound were directly associated with LVM (beta [standardized]: 0.171, 0.186 and 0.223, respectively, p<0.001 for all) and LVM index (LVMI) (beta: 0.146, 0.120 and 0.120, respectively, p<0.01 for all) at midlife. All the associations, except that between BMI at BMI peak and LVMI, remained significant after adjustments for gender, adult blood pressure, heart rate, antihypertensive medications, heart diseases and diabetes (p<0.05 for all). Significant interaction between gender and age at BMI rebound was observed in LVMI. Age at BMI rebound was inversely associated with LVMI in both genders, the association being stronger in males (beta: −0.212, p<0.001) compared to females (beta: −0.117, p=0.025) and independent of potential confounders. There were direct univariate associations of birth weight and BMI at BMI peak and rebound with LV relative wall thickness (p=0.009–0.019), which were largely explained by potential confounders. However, the association of birth weight with LV relative wall thickness retained its significance even after relevant adjustments (beta: 0.097, p=0.001). After additional adjustments for adult BMI, only associations of birth weight and BMI at BMI peak with LVM remained significant, which, however, did not remain significant after additional adjustment for adult height. Conclusions This study shows that birth weight and early growth patterns are associated with LV structure at midlife, which is largely explained by adult BMI. Therefore, the relationship between early growth patterns to LV structure in the adulthood may be largely explained by their strong tracking to obesity and related cardiovascular risk factors at midlife and to some extent by normal somatic growth.

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Background: Sugar sweetened beverages (SSBs) are the single largest source of calories and added sugars in the US diet and regular consumption has been associated with weight gain and risk of chronic diseases. Artificially sweetened beverages (ASBs) are often suggested as alternatives to SSB but little is known about their long-term health effects. Whether consumption of SSBs or ASBs is associated with risk of mortality is unknown. Methods: We prospectively followed 38,602 men from the Health Professional’s Follow-up study (1986-2010) and 82,592 women from the Nurses’ Health study (1980-2010) who were free from cardiovascular disease (CVD) and cancer at baseline. Diet was assessed using validated food frequency questionnaires every 4 years and Cox Proportional Hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Results: We documented 27,691 deaths (6,631 CVD and 10,447 cancer deaths) during 3.14 million person-years. After adjusting for major dietary and lifestyle risk factors, and BMI, baseline diabetes, hypertension and hypercholesterolemia, consumption of SSBs was associated with an increased risk of total mortality, which was mainly driven by CVD mortality among individuals consuming at least 2 servings per day; pooled HRs (95% CIs) across categories (<1/month, 1-4/month, 2-6/week, 1-<2/day and ≥2/day) were 1.00, 0.95 (0.91, 0.98), 0.96 (0.93, 0.99), 1.02 (0.96, 1.08), and 1.18 (1.04, 1.33), respectively (P-trend= 0.0001) for total mortality, and 1.00, 0.97 (0.90, 1.02), 0.96 (0.90, 1.02), 1.04 (0.93, 1.16) and 1.28 (1.09, 1.51), respectively (P-trend=0.007) for CVD mortality. In contrast, ASBs were not associated with mortality; pooled HR’s (95% CIs) across categories (<1/month, 1-4/month, 2-6/week, 1-<2/day and ≥2/day) were 1.00, 0.92 (0.89, 0.95), 0.91 (0.86, 0.97), 0.91 (0.86, 0.95) and 0.99 (0.85, 1.15), respectively (P-trend=0.50) for total mortality and 1.00, 0.86 (0.80, 0.92), 0.87 (0.81, 0.94), 0.96 (0.88, 1.06) and 0.96 (0.74, 1.25), respectively (P-trend=0.99) for CVD mortality. No associations were observed with cancer mortality for either SSBs or ASBs in multi-variable adjusted models. Conclusion: Regular consumption of SSBs is associated with an increased risk of total and CVD mortality, providing additional support for recommendations and policies to limit intake of these beverages.

This paper describes experiments that are designed to test the influence of terminal groups incorporating carbon–halogen bonds on the current density (by hole tunneling) across self-assembled monolayer (SAM)-based junctions of the form MTS/S(CH2)9NHCOCHnX3–n//Ga2O3/EGaIn (where M = Ag and Au and X = CH3, F, Cl, Br, I). Within the limits of statistical significance, these rates of tunneling are insensitive to the nature of the terminal group at the interface between the SAM and the Ga2O3. The results are relevant to the origin of an apparent inconsistency in the literature concerning the influence of halogen atoms at the SAM//electrode interface on the tunneling current density.

The pandemic increase in obesity is inversely associated with vitamin D levels. While a higher BMI was causally related to lower 25-hydroxyvitamin D (25(OH)D), no evidence was obtained for a BMI lowering effect by higher 25(OH)D. Some of the physiological functions of 1,25(OH)2D3 (1,25-dihydroxycholecalciferol or calcitriol) via its receptor within the adipose tissue have been investigated such as its effect on energy balance, adipogenesis, adipokine and cytokine secretion. Adipose tissue inflammation has been recognized as the key component of metabolic disorders, e.g. in the metabolic syndrome. The adipose organ secretes more than 260 different proteins/peptides. However, the molecular basis of the interactions of 1,25(OH)2D3, vitamin D binding proteins (VDBPs) and nuclear vitamin D receptor (VDR) after sequestration in adipose tissue and their regulations are still unclear. 1,25(OH)2D3 and its inactive metabolites are known to inhibit the formation of adipocytes in mouse 3T3-L1 cell line. In humans, 1,25(OH)2D3 promotes preadipocyte differentiation under cell culture conditions. Further evidence of its important functions is given by VDR knock out (VDR -/-) and CYP27B1 knock out (CYP27B1 -/-) mouse models: Both VDR -/- and CYP27B1 -/- models are highly resistant to the diet induced weight gain, while the specific overexpression of human VDR in adipose tissue leads to increased adipose tissue mass. The analysis of microarray datasets from human adipocytes treated with macrophage-secreted products up-regulated VDR and CYP27B1 genes indicating the capacity of adipocytes to even produce active 1,25(OH)2D3. Experimental studies demonstrate that 1,25(OH)2D3 has an active role in adipose tissue by modulating inflammation, adipogenesis and adipocyte secretion. Yet, further in vivo studies are needed to address the effects and the effective dosages of vitamin D in human adipose tissue and its relevance in the associated diseases.

AbstractIt is becoming increasingly recognized that early-life nutritional, metabolicand environmental factors can have a long-term impact on the early onsetof obesity, type 2 diabetes and cardiovascular diseases. Numerous experi-mental and epidemiological observations support the concept that an indi-vidual’s response to their adult lifestyle and nutritional environmentdepends not only on their genetic susceptibility but also on their previousearly-life experiences. The current research challenge is to determine theprimary pathways contributing to ‘non- or epi-genetic’ causes of excessadult weight gain and adiposity. Evidence from the fields of genetic epide-miology, life course modelling and diet-induced foetal programming allsupport a role for the FTO gene in this complex biological interaction. Itmay provide a missing link in the developmental regulation of energymetabolism. Our review therefore considers the role of the FTO gene inthe early-life determination of body weight, body composition and energybalance. We will summarize current knowledge on FTO biology combin-ing human genetic epidemiology, molecular models and findings from ani-mal studies. Notably, we will focus on the role of FTO in energy balancein humans, the importance of FTO polymorphisms in childhood growthand the impact of foetal nutrition. Ultimately, we propose a new hypothe-sis for future research designed to understand the role of FTO in settinggene expression in metabolically active tissues.Keywords animal models, early life, foetal programming, FTO, geneticepidemiology, obesity.

Common variation in the FTO gene is associated with BMI and type 2 diabetes. Increased BMI is associated with diabetes risk factors, including raised insulin, glucose, and triglycerides. We aimed to test whether FTO genotype is associated with variation in these metabolic traits.

This paper describes an analytical system that uses magnetic levitation to measure densities of solids and water-immiscible organic liquids with accuracies ranging from ±0.0002 to ±0.02 g/cm3, depending on the type of experiment. The technique is compatible with densities of 0.8−3 g/cm3 and is applicable to samples with volumes of 1 pL to 1 mL; the samples can be either spherical or irregular in shape. The method employs two permanent NdFeB magnets positioned with like poles facing one another—with the axis between the poles aligned with the gravitational field—and a container filled with paramagnetic medium (e.g., MnCl2 dissolved in water) placed between these magnets. Density measurements are obtained by placing the sample into the container and measuring the position of the sample relative to the bottom magnet. The balance of magnetic and gravitational forces determines the vertical position of the sample within the device; knowing this position makes it possible to calculate the density of the sample.

Thyroid dysfunction and antibodies are increasingly recognized as risk factors during pregnancy. Thyroid function changes during pregnancy and there is a need for gestational age-specific reference intervals for thyroid hormones. The aim of this study was to calculate gestational age-specific thyrotropin (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) reference intervals in an iodine-sufficient thyroid antibody-negative population.The study population consisted of a large, prospective population-based cohort, the Northern Finland Birth Cohort 1986 (singleton births, n = 9362), with extensive data throughout gestation. The subjects underwent serum sampling in early pregnancy. Samples were assayed for TSH, fT4, fT3, thyroid-peroxidase, and thyroglobulin antibodies (n = 5805). All mothers with thyroid antibodies or previous thyroid diseases were excluded when calculating gestational age-specific percentile categories for TSH, fT4, and fT3. Also, associations between body mass index (BMI) and thyroid hormones were established.The upper reference limit for TSH was 2.5 multiples of median (2.7-3.5 mU/L, depending on gestational week). The lower reference limit was as low as 0.07 mU/L. Reference intervals for fT4 rose during early pregnancy and decreased thereafter, ranging between 11-22 pmol/L. Reference intervals for fT3 were uniform throughout gestation, ranging between 3.4 and 7.0 pmol/L. BMI was associated positively with early pregnancy TSH and fT3 concentrations and negatively with fT4 concentrations.These gestational age-specific reference intervals for thyroid hormones provide a framework for clinical decision making. Overweight and obesity are increasing problems among fertile women and they are associated with possibility of thyroid dysfunction during pregnancy.

OBJECTIVES: DNA methylation may play a role in the development of type 2 diabetes (T2D). DNA methylation can be influenced by methyl donor nutrients such as vitamins B2, B6, B12, folate, and methionine, which are all central to one carbon metabolism. Using 3 large cohorts of US health professionals, we examined whether intake of these nutrients from food or supplements is associated with T2D risk. METHODS: We included 69,949 women from the Nurses’ Health Study (1984–2012), 90,239 women from the Nurses’ Health Study II (1991–2011), and 40,539 men from the Health Professionals Follow-Up Study (1986–2010). Dietary data were collected every 2–4 years using a validated semi-quantitative FFQ, from which dietary intakes of vitamin B2, vitamin B6, vitamin B12, folate, and methionine were calculated. We used Cox proportional hazards model with time-varying covariates and adjusted for several sociodemographic and lifestyle variables. We also adjusted for cereal fiber, animal protein, polyunsaturated and saturated fatty acids ratio. Food sources of vitamins were additionally adjusted for multivitamin use while supplemental sources of vitamins were adjusted for a measure of overall diet quality. RESULTS: During 1763,428 years of follow-up, we documented 8141 T2D cases. In pooled multivariable-adjusted analyses, compared to those in the lowest quintile, those in the highest quintile of vitamins B2 and B6 had a 10% (95% CI 3%–16%) and 11% (95% CI 3%–16%) lower T2D risk, respectively. Total vitamin B12 intake was not associated with T2D. However, when analyses were stratified by source, vitamin B12 from food sources was associated with a higher T2D risk (HR [95% CI] = 1.11 [1.02–1.19]). On the other hand, supplemental vitamin B12 was associated with lower T2D risk (HR [95% CI] for Q5 vs Q1 = 0.92 [0.85–0.98]). We found no evidence for an association between intakes of folate and methionine and T2D risk. CONCLUSIONS: Our study suggests that higher intakes of vitamin B2 and vitamin B6 are associated with a lower T2D risk. A higher vitamin B12 intake from food seems to be associated with a higher T2D risk, which may be due to consumption of animal products. FUNDING SOURCES: The analysis was supported by grants from the National Institutes of Health.

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV1 and FEV1/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest PJMA = 5.00×10−11), HLA-DQB1 and HLA-DQA2 (smallest PJMA = 4.35×10−9), and KCNJ2 and SOX9 (smallest PJMA = 1.28×10−8) were associated with FEV1/FVC or FEV1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.