Suboptimal vitamin D levels during critical periods of immune development have emerged as an explanation for higher rates of allergic diseases associated with industrialization and residing at higher ...latitudes.
We sought to determine the effects of early postnatal vitamin D supplementation on infant eczema and immune development.
By using a double-blind randomized controlled trial, newborn infants were randomized to receive vitamin D supplementation (400 IU/d) or a placebo until 6 months of age. Some infants also wore personal UV dosimeters to measure direct UV light (290-380 nm) exposure. Infant vitamin D levels were measured at 3 and 6 months of age. Eczema, wheeze, and immune function outcomes were assessed at 6 months of age.
At 3 (P < .01) and 6 (P = .02) months of age, vitamin D levels were greater for the vitamin D–supplemented group than the placebo group, but there was no difference in eczema incidence between groups. Infants with eczema were found to have had less UV light exposure (median, 555 Joules per square meter J/m2; interquartile range, 322-1210 J/m2) compared with those without eczema (median, 998 J/m2 interquartile range, 676-1577 J/m2; P = .02). UV light exposure was also inversely correlated with IL-2, GM-CSF, and eotaxin production to Toll-like receptor ligands.
This study is the first to demonstrate an association between greater direct UV light exposures in early infancy with lower incidence of eczema and proinflammatory immune markers by 6 months of age. Our findings indicate that UV light exposure appears more beneficial than vitamin D supplementation as an allergy prevention strategy in early life.
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Background
Low vitamin D levels have been associated with allergic diseases. Vitamin D has potent immunomodulatory properties, but the mechanisms remain unclear. We have investigated the effect of ...oral vitamin D supplementation on circulating immune cell phenotypes in infants.
Method
A double‐blinded randomised controlled trial was conducted to investigate the effect of oral vitamin D supplementation (400 IU/d) on eczema and immune development. A subset of 78 infants was included in this analysis. Phenotypic analysis of immune cell subsets was performed using flow cytometry.
Results
Vitamin D supplementation resulted in median 25(OH)D levels of 80.5 vs 59.5 nmol/L in the placebo group at 3 months of age (P = .002) and 87.5 vs 77 nmol/L at 6 months of age (P = .08). We observed significant changes in immune cell composition from birth (cord blood) to 6 months of age. Vitamin D supplementation did not impact these changes, nor did immune cell composition correlate with plasma 25(OH)D levels. Through exploratory analysis, we identified possible associations with eczema development and increased abundance of naïve CD4‐ T cells at birth, as well as associations with basophils, iNKT and central memory CD4+ T cells, and altered expression patterns of IgE receptor (FcεR1) on monocytes and dendritic cells with eczema at 6 months.
Conclusions
Vitamin D supplementation in infants who were vitamin D sufficient at birth did not affect developmental changes in immune cells during the first 6 months of life. However, immune cell profiles at birth and at 6 months of age were associated with early life eczema.
Context:
In cross-sectional studies, serum TSH concentrations increase with age. This has not been examined longitudinally, and it is uncertain whether the TSH increase reflects healthy aging or ...occult thyroid failure.
Methods:
We measured serum TSH, free T4, thyroid peroxidase, and thyroglobulin antibodies in 1100 participants in the 1981 and 1994 Busselton Health Surveys and derived a reference group of 908 individuals without thyroid disease or thyroid antibodies. We examined changes in thyroid function longitudinally and, in 781 participants, explored associations with the CAPZB polymorphism rs10917469.
Results:
At 13 yr follow-up, mean serum TSH increased from 1.49 to 1.81 mU/liter, a change in mean TSH (ΔTSH) of 0.32 mU/liter 95% confidence interval (CI) 0.27, 0.38, P < 0.001, whereas mean free T4 concentration was unchanged (16.6 vs. 16.6 pmol/liter, P = 0.7). The TSH increase was most marked in the elderly, such that gender-adjusted ΔTSH increased by 0.08 mU/liter (95% CI 0.04, 0.11) for each decade of baseline age. People with higher baseline TSH values had proportionally smaller increases in TSH, with each additional 1.0 mU/liter of baseline TSH associated with a 0.13 mU/liter decrease (age and gender adjusted) in ΔTSH (95% CI 0.09, 0.16). The ΔTSH did not differ significantly by CAPZB genotype.
Conclusions:
Aging is associated with increased serum TSH concentrations, with no change in free T4 concentrations. The largest TSH increase is in people with the lowest TSH at baseline. This suggests that the TSH increase arises from age-related alteration in the TSH set point or reduced TSH bioactivity rather than occult thyroid disease.
Lower vitamin D status at birth and during infancy has been associated with increased incidence of eczema and food allergies. The aim of this study was to investigate the effect of early infancy ...vitamin D supplementation on allergic disease outcomes in infants at "hereditary risk" of allergic disease, but who had sufficient vitamin D levels at birth. Here, we report the early childhood follow-up to 2.5 years of age of "high-risk" infants who participated in a double-blinded, randomized controlled trial. For inclusion in this trial, late gestation (36-40 weeks) maternal 25-hydroxyvitamin D levels needed to be ≥50 nmol/L. Infants were randomized to either oral vitamin D supplementation of 400 IU/day (
= 97) or a placebo (
= 98) for the first six months of life. Vitamin D levels and allergic disease outcomes were followed up. There were no statistically significant differences in incidence of any medically diagnosed allergic disease outcomes or allergen sensitization rates between the vitamin D-supplemented and placebo groups at either 1 year or at 2.5 years of age. In conclusion, for "allergy high-risk" infants who had sufficient vitamin D status at birth, early infancy oral vitamin D supplementation does not appear to reduce the development of early childhood allergic disease.
IMPORTANCE Hypoglycemia is a critical obstacle to the care of patients with type 1 diabetes. Sensor-augmented insulin pump with automated low-glucose insulin suspension has the potential to reduce ...the incidence of major hypoglycemic events. OBJECTIVE To determine the incidence of severe and moderate hypoglycemia with sensor-augmented pump with low-glucose suspension compared with standard insulin pump therapy. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial involving 95 patients with type 1 diabetes, recruited from December 2009 to January 2012 in Australia. INTERVENTIONS Patients were randomized to insulin pump only or automated insulin suspension for 6 months. MAIN OUTCOMES AND MEASURES The primary outcome was the combined incidence of severe (hypoglycemic seizure or coma) and moderate hypoglycemia (an event requiring assistance for treatment). In a subgroup, counterregulatory hormone responses to hypoglycemia were assessed using the hypoglycemic clamp technique. RESULTS Of the 95 patients randomized, 49 were assigned to the standard-pump (pump-only) therapy and 46 to the low-glucose suspension group. The mean (SD) age was 18.6 (11.8) years; duration of diabetes, 11.0 (8.9) years; and duration of pump therapy, 4.1 (3.4) years. The baseline rate of severe and moderate hypoglycemic events in the pump-only group was 20.7 vs 129.6 events per 100 patient months in the low-glucose suspension group. After 6 months of treatment, the event rates decreased from 28 to 16 in the pump-only group vs 175 to 35 in the low-glucose suspension group. The adjusted incidence rate per 100 patient-months was 34.2 (95% CI, 22.0-53.3) for the pump-only group vs 9.5 (95% CI, 5.2-17.4) for the low-glucose suspension group. The incidence rate ratio was 3.6 (95% CI, 1.7-7.5; P <.001). There was no change in glycated hemoglobin in either group: mean, 7.4 (95% CI, 7.2-7.6) to 7.4 (95% CI, 7.2-7.7) in the pump-only group vs mean, 7.6 (95%, CI, 7.4-7.9) to 7.5 (95% CI, 7.3-7.7) in the low-glucose suspension group. Counterregulatory hormone responses to hypoglycemia were not changed. There were no episodes of diabetic ketoacidosis or hyperglycemia with ketosis. CONCLUSIONS AND RELEVANCE Sensor-augmented pump therapy with automated insulin suspension reduced the combined rate of severe and moderate hypoglycemia in patients with type 1 diabetes. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12610000024044
Chrononutrition, an emerging body of evidence on the relationship between biological rhythms and metabolism, has been established to be associated with glycemic responses. However, the available ...evidence is inconsistent, due to protocol variations. Therefore, this review aims to summarize the findings on chrononutrition characteristics and their association with glycemic responses among adults. Systematic searches were conducted across six databases (PubMed, EBSCO Host, ProQuest Central, MEDLINE & Ovid, Scopus and Web of Science) to identify all relevant studies published from January 2012. Two reviewers independently screened the abstracts and full-text articles based on the inclusion and exclusion criteria. Details about population characteristics, study methods and key findings were extracted following the PRISMA-ScR guideline. The quality of selected studies was evaluated using the mixed methods appraisal tool. The searchers identified 49 studies eligible for analysis. The results showed that meal timing, particularly night-time eating and snacking were associated with glycemic responses. Regarding meal regularity, skipping breakfast may affect glycemic responses, but no clear conclusion was drawn about its effect on insulin. The association between meal frequency and glycemic responses was inconclusive. Night fasting duration and restricted eating window are potentially associated with glycemic responses. The current review extensively investigates the association between chrononutrition factors and glycemic responses in adults. However, more prospective cohort and interventional studies are needed to better understand this causal-effect relationship.
Abstract
Objective
There are no large, longitudinal studies of thyroid function across adolescence. The aims of this study were to examine longitudinal trends in thyrotropin (TSH), free ...triiodothyronine (fT3) and free thyroxine (fT4) and determine age-specific reference ranges.
Methods
Thyroid function was assessed in 3415 participants in the Brisbane Longitudinal Twin Study at ages 12, 14, and 16, using the Abbott ARCHITECT immunoassay. Longitudinal analyses were adjusted for body mass index and puberty.
Results
In girls, mean fT4 (± SE) increased between age 12 and 14 (by 0.30 ± 0.08 pmol/L; P < 0.001), while remaining unchanged in boys; from age 14 to 16, fT4 increased in both girls (by 0.42 ± 0.07 pmol/L; P < 0.001) and boys (0.64 ± 0.07 pmol/L, P < 0.001). There was a slight increase in fT3 from age 12 to 14 years in girls (by 0.07 ± 0.03 pmol/L; P = 0.042), with a more marked increase in boys (0.29 ± 0.03 pmol/L; P < 0.001), followed by a decrease from age 14 to 16 in both sexes (girls, by 0.53 ± 0.02 pmol/L; P < 0.001; boys, by 0.62 ± 0.03 pmol/L; P < 0.001). From age 12 to 14, TSH showed no significant change in girls or boys, then levels increased from age 14 to 16 in both sexes (in girls, by 4.9%, 95% CI: 2.4%-10.3%, P = 0.020; in boys, by 7.2%, 95% CI: 3.0%-11.6%, P = 0.001). Reference ranges differed substantially from adults, particularly for fT4 and fT3.
Conclusions
Thyroid function tests in adolescents display complex, sexually dimorphic patterns. Implementation of adolescence-specific reference ranges may be appropriate.
Human ageing is a complex, multifactorial process and early developmental factors affect health outcomes in old age.
Metabolomic profiling on fasting blood was carried out in 6055 individuals from ...the UK. Stepwise regression was performed to identify a panel of independent metabolites which could be used as a surrogate for age. We also investigated the association with birthweight overall and within identical discordant twins and with genome-wide methylation levels.
We identified a panel of 22 metabolites which combined are strongly correlated with age (R(2) = 59%) and with age-related clinical traits independently of age. One particular metabolite, C-glycosyl tryptophan (C-glyTrp), correlated strongly with age (beta = 0.03, SE = 0.001, P = 7.0 × 10(-157)) and lung function (FEV1 beta = -0.04, SE = 0.008, P = 1.8 × 10(-8) adjusted for age and confounders) and was replicated in an independent population (n = 887). C-glyTrp was also associated with bone mineral density (beta = -0.01, SE = 0.002, P = 1.9 × 10(-6)) and birthweight (beta = -0.06, SE = 0.01, P = 2.5 × 10(-9)). The difference in C-glyTrp levels explained 9.4% of the variance in the difference in birthweight between monozygotic twins. An epigenome-wide association study in 172 individuals identified three CpG-sites, associated with levels of C-glyTrp (P < 2 × 10(-6)). We replicated one CpG site in the promoter of the WDR85 gene in an independent sample of 350 individuals (beta = -0.20, SE = 0.04, P = 2.9 × 10(-8)). WDR85 is a regulator of translation elongation factor 2, essential for protein synthesis in eukaryotes.
Our data illustrate how metabolomic profiling linked with epigenetic studies can identify some key molecular mechanisms potentially determined in early development that produce long-term physiological changes influencing human health and ageing.
Objective
ED chest pain assessments can be challenging, lengthy and contribute to overcrowding. Rapid accurate risk stratification strategies should improve ED length of stay (EDLOS). Emergency, ...Biochemistry and Cardiology implemented new guidelines using paired (<3 h) multiple cardiac markers to stratify patients. The intervention would reduce chest pain EDLOS. We observed for safety and disposition effects.
Methods
This is a single‐site, prospective observational, before and after intervention study. In December 2009, paired multiple cardiac markers, the second at least 4 h from pain, replaced late troponins. The 4 h rule (ED flow improvement) started in April 2009 (unplanned confounder). Demographics, clinical features, risk assessment and disposition; preferably prospective. Administrative datasets provided disposition outcomes, 4 months pre‐/post‐intervention. Follow up with partially blinded adjudications assessed for 45 day major adverse cardiac events (MACE). Before intervention, consecutive patients were enrolled with mixed prospective/retrospective data. After, sampling occurred whenever prospective data were collected.
Results
Adjudicated patients were n = 1029 (14.2% MI, 14.9% MACE), 426 before, 603 after. EDLOS reduced 87 min (416–329; P < 0.001), similar to triage 2 patients without chest pain. Possibly, avoidable MACE occurred in five of 598 discharges (0.8%, CI 0.3–1.8%) with non‐significant decreases (0.5%, CI 0.1–1.8%) post‐intervention. Disposition changes included greater observation ward use (3.8–12.3%; P < 0.001), more discharges (47.4–52.9%, P = 0.002), less transfers (9.3–6.9%, P = 0.014) and less late inpatient discharge decisions (15.2–8.7%, P = 0.001).
Conclusion
Paired cardiac markers performed adequately for avoidable MACE, and disposition improved significantly. A confounding system change meant the reduced EDLOS (primary outcome) was unable to be associated with the intervention.
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