Seasonal periodicity of serum vitamin D and parathyroid hormone, bone resorption, and fractures : the Geelong Osteoporosis Study

In this population-based study, seasonal periodicity was seen with reduced serum vitamin D, increased serum PTH, and increased bone resorption in winter. This was associated with an increased proportion of falls resulting in fracture and an increased risk of wrist and hip fractures.

Introduction: In a population of women who reside in a temperate climate and do not generally receive dietary vitamin D supplementation, we investigated whether seasonal vitamin D insufficiency is associated with increased risk of fracture.

Materials and Methods: An observational, cross-sectional, population-based study set in southeastern Australia (latitude 38–39° S). Participants were drawn from a well-defined community of 27,203 women ≥55 years old: 287 randomly selected from electoral rolls, 1635 with incident fractures, and 1358 presenting to a university hospital with falls. The main outcome measures were annual periodicities of ultraviolet radiation, serum 25-hydroxyvitamin D [25(OH)D], serum parathyroid hormone (PTH), serum C-telopeptide (CTx), BMD, falls, and fractures.

Results: Cyclic variations in serum 25(OH)D lagged 1 month behind ultraviolet radiation, peaking in summer and dipping in winter (p < 0.001). Periodicity of serum PTH was the inverse of serum 25(OH)D, with a phase shift delay of 1 month (p = 0.004). Peak serum CTx lagged peak serum PTH by 1–2 months. In late winter, a greater proportion of falls resulted in fracture (p < 0.001). Seasonal periodicity in 439 hip and 307 wrist fractures also followed a simple harmonic model (p = 0.078 and 0.002, respectively), peaking 1.5–3 months after the trough in 25(OH)D.

Conclusions: A fall in 25(OH)D in winter is accompanied by increases in (1) PTH levels, (2) bone resorption, (3) the proportion of falls resulting in fracture, and (4) the frequency of hip and wrist fracture. Whether vitamin D supplementation in winter can reduce the population burden of fractures requires further investigation.

How does perceived risk mediate associations between perceived safety and parental restriction of adolescents' physical activity in their neighborhood?

Background
There is evidence that adolescence is a critical period of decline in physical activity. However, adolescents may have limited opportunities to be physically active outdoors if their parents are concerned about neighborhood safety and restrict their adolescent’s physical activity within their neighborhood. Pathways that lead to parental restriction of adolescents’ physical activity (constrained behavior) are under-researched. This study aimed to examine perceived risk as a potential mediator of associations between perceived safety/victimization and constrained behavior.
Methods
Cross-sectional study of adolescents (43% boys) aged 15–17 years (n = 270) in Melbourne, Australia. Parents reported perceived safety (road safety, incivilities and personal safety) and prior victimization in their neighborhood, perceived risk of their children being harmed and whether they constrained their adolescent’s physical activity. Constrained behavior was categorized as ‘avoidance’ or ‘defensive’ behavior depending on a whether physical activity was avoided or modified, respectively, due to perceived risk. MacKinnon’s product-of-coefficients test of mediation was used to assess potential mediating pathways between perceived safety/victimization and constrained behavior.
Results
For girls only, perceived risk was a significant mediator of associations between perceived road safety and avoidance/defensive behavior, and between perceived incivilities, perceived personal safety, victimization and defensive behavior.
Conclusions
Associations between perceived safety/victimization and constrained behavior are complex. Findings may guide the design of interventions that aim to improve actual and perceived levels of safety and reduce perceptions of risk. This is of particular importance for adolescent girls among whom low and declining levels of physical activity have been observed worldwide.

Increased nicotinamide nucleotide transhydrogenase levels predispose to insulin hypersecretion in a mouse strain susceptible to diabetes

Aims/hypothesis Insulin hypersecretion may be an independent predictor of progression to type 2 diabetes. Identifying genes affecting insulin hypersecretion are important in understanding disease progression. We have previously shown that diabetes-susceptible DBA/2 mice congenitally display high insulin secretion. We studied this model to map and identify the gene(s) responsible for this trait.

Methods Intravenous glucose tolerance tests followed by a genome-wide scan were performed on 171 (C57BL/6 × DBA/2) × C57BL/6 backcross mice.

Results A quantitative trait locus, designated hyperinsulin production-1 (Hip1), was mapped with a logarithm of odds score of 7.7 to a region on chromosome 13. Production of congenic mice confirmed that Hip1 influenced the insulin hypersecretion trait. By studying appropriate recombinant inbred mouse strains, the Hip1 locus was further localised to a 2 Mb interval, which contained only nine genes. Expression analysis showed that the only gene differentially expressed in islets isolated from the parental strains was Nnt, which encodes the mitochondrial proton pump, nicotinamide nucleotide transhydrogenase (NNT). We also found in five mouse strains a positive correlation (r 2  = 0.90, p < 0.01) between NNT activity and first-phase insulin secretion, emphasising the importance of this enzyme in beta cell function. Furthermore, of these five strains, only those with high NNT activity are known to exhibit severe diabetes after becoming obese.

Conclusions/interpretation Insulin hypersecretion is associated with increased Nnt expression. We suggest that NNT must play an important role in beta cell function and that its effect on the high insulin secretory capacity of the DBA/2 mouse may predispose beta cells of these mice to failure.

Parental factors associated with obesity in children with disability: a systematic review

The current literature on obesity in typically developing children shows that the family context, and specifically the way parents parent their children are major determinants of childhood obesity. The influence of these factors on obesity in children with disability, however, remains unclear. A systematic review of the literature was undertaken to identify the parental and parenting risk factors associated with obesity in children and adolescents with disability. Articles were identified through Medline, Academic Search Complete, PsycINFO, ProQuest, ISI, CINAHL, Cochrane and Scopus databases. There was no restriction on publication dates. The inclusion criteria were empirical papers that tested associations between parental and parenting risk factors and obesity in children and adolescents with intellectual and other developmental disabilities. Only 11 studies met the selection criteria and subsequently included in this review. Results suggest that obesity in children and adolescents with disability may be associated with socioeconomic status; parents' body mass index, perception and attitude towards their children's weight and physical activity; and levels of activity in both parents and children. Firm conclusions about these associations cannot be reached, however, due to mixed findings and methodological limitations of the studies. Recommendations for future research are provided.

How significant is partnership formation in area-based projects to increase parental attendance at maternal and child health services

Objectives: 

Recombinant human growth hormone for the treatment of growth disorders in children: a systematic review and economic evaluation

Recombinant human growth hormone (rhGH) is licensed for short stature associated with growth hormone deficiency (GHD), Turner syndrome (TS), Prader-Willi syndrome (PWS), chronic renal insufficiency (CRI), short stature homeobox-containing gene deficiency (SHOX-D) and being born small for gestational age (SGA). To assess the clinical effectiveness and cost-effectiveness of rhGH compared with treatment strategies without rhGH for children with GHD, TS, PWS, CRI, SHOX-D and those born SGA. The systematic review used a priori methods. Key databases were searched (e.g. MEDLINE, EMBASE, NHS Economic Evaluation Database and eight others) for relevant studies from their inception to June 2009. A decision-analytical model was developed to determine cost-effectiveness in the UK. Two reviewers assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers, and screened them against inclusion criteria. Data from included studies were extracted by one reviewer and checked by a second. Quality of included studies was assessed using standard criteria, applied by one reviewer and checked by a second. Clinical effectiveness studies were synthesised through a narrative review. Twenty-eight randomised controlled trials (RCTs) in 34 publications were included in the systematic review. GHD: Children in the rhGH group grew 2.7 cm/year faster than untreated children and had a statistically significantly higher height standard deviation score (HtSDS) after 1 year: -2.3 ± 0.45 versus -2.8 ± 0.45. TS: In one study, treated girls grew 9.3 cm more than untreated girls. In a study of younger children, the difference was 7.6 cm after 2 years. HtSDS values were statistically significantly higher in treated girls. PWS: Infants receiving rhGH for 1 year grew significantly taller (6.2 cm more) than those untreated. Two studies reported a statistically significant difference in HtSDS in favour of rhGH. CRI: rhGH-treated children in a 1-year study grew an average of 3.6 cm more than untreated children. HtSDS was statistically significantly higher in treated children in two studies. SGA: Criteria were amended to include children of 3+ years with no catch-up growth, with no reference to mid-parental height. Only one of the RCTs used the licensed dose; the others used higher doses. Adult height (AH) was approximately 4 cm higher in rhGH-treated patients in the one study to report this outcome, and AH-gain SDS was also statistically significantly higher in this group. Mean HtSDS was higher in treated than untreated patients in four other studies (significant in two). SHOX-D: After 2 years' treatment, children were approximately 6 cm taller than the control group and HtSDS was statistically significantly higher in treated children. The incremental cost per quality adjusted life-year (QALY) estimates of rhGH compared with no treatment were: 23,196 pounds for GHD, 39,460 pounds for TS, 135,311 pounds for PWS, 39,273 pounds for CRI, 33,079 pounds for SGA and 40,531 pounds for SHOX-D. The probability of treatment of each of the conditions being cost-effective at 30,000 pounds was: 95% for GHD, 19% for TS, 1% for PWS, 16% for CRI, 38% for SGA and 15% for SHOX-D.

Australian children's independent mobility levels: secondary analyses of cross-sectional data between 1991 and 2012

This study investigated changes in Australian children's independent mobility levels between1991 and 2012. Data from five cross-sectional studies conducted in 1991, 1993, 2010, 2011 and 2012 were analysed. Parent and child surveys were used to assess parental licences for independent mobility and actual independent mobility behaviour in children aged 8–13 years. Findings show declines in the proportion of young children (≤10 years of age) being allowed to travel home from school alone (1991: 68%, 1993: 50%, 2010: 43%, 2011: 45%, 2012: 31%) and travel on buses alone (1991: 31%, 1993: 15%, 2010: 8%, 2011: 6%, 2012: 9%). Furthermore, the proportion of children travelling independently to school decreased (1991: 61%, 1993: 42%, 2010: 31%, 2011: 32%, 2012: 32%). Significantly fewer girls than boys travelled independently to school at each time point (p ≤ .001). Overall, the findings suggest that Australian children's independent mobility levels declined between 1991 and 2012.

α-Melanocyte stimulating hormone promotes muscle glucose uptake via melanocortin 5 receptors

OBJECTIVE: Central melanocortin pathways are well-established regulators of energy balance. However, scant data exist about the role of systemic melanocortin peptides. We set out to determine if peripheral α-melanocyte stimulating hormone (α-MSH) plays a role in glucose homeostasis and tested the hypothesis that the pituitary is able to sense a physiological increase in circulating glucose and responds by secreting α-MSH.

METHODS: We established glucose-stimulated α-MSH secretion using humans, non-human primates, and mouse models. Continuous α-MSH infusions were performed during glucose tolerance tests and hyperinsulinemic-euglycemic clamps to evaluate the systemic effect of α-MSH in glucose regulation. Complementary ex vivo and in vitro techniques were employed to delineate the direct action of α-MSH via the melanocortin 5 receptor (MC5R)-PKA axis in skeletal muscles. Combined treatment of non-selective/selective phosphodiesterase inhibitor and α-MSH was adopted to restore glucose tolerance in obese mice.

RESULTS: Here we demonstrate that pituitary secretion of α-MSH is increased by glucose. Peripheral α-MSH increases temperature in skeletal muscles, acts directly on soleus and gastrocnemius muscles to significantly increase glucose uptake, and enhances whole-body glucose clearance via the activation of muscle MC5R and protein kinase A. These actions are absent in obese mice, accompanied by a blunting of α-MSH-induced cAMP levels in skeletal muscles of obese mice. Both selective and non-selective phosphodiesterase inhibition restores α-MSH induced skeletal muscle glucose uptake and improves glucose disposal in obese mice.

CONCLUSION: These data describe a novel endocrine circuit that modulates glucose homeostasis by pituitary α-MSH, which increases muscle glucose uptake and thermogenesis through the activation of a MC5R-PKA-pathway, which is disrupted in obesity.