Showing papers by "Ian J. Griffin published in 2015"

Catch-Up Growth: Basic Mechanisms.

Abstract: The neuroendocrine model of catch-up growth has been well studied in a number of animal models. During nutritional inadequacy, which invariably precedes catch-up growth, growth hormone (GH) levels increase under the influence of the oxygenic 'hunger signal' ghrelin. This increase in GH would usually be accompanied by an increase in IGF-1. However, malnutrition also induces the nutritionally responsive proteins sirtuin 1 (SIRT1) and fibroblast growth factor 21 (FGF21) that block GH signal transduction in the liver by blocking the JAK/STAT pathway, limiting IGF-1 production. The result is that GH's action is shifted from hepatic effects to effects in other tissues (for example muscle and adipose) and shifted away from IGF-1-mediated effects and towards GH-mediated effects. Once nutrients become more available, SIRT1 and FGF21 levels, and hepatic GH sensitivity return to normal, and production of IGF-1 resumes. This shifts GH signaling away from GH-mediated effects, and towards IGF-1-mediated effects both in the liver and in other tissues. It presumably leads to greatly increased IGF-1 signaling that would have been expected without the prior episode of nutritional inadequacy. Although much work remains to be done, it does appear that ghrelin is increased in in utero and postnatal malnutrition, that elevations in ghrelin may be prolonged after malnutrition resolves, and that higher ghrelin levels are associated with increased rates of catch-up growth. Prolonged increases in circulating ghrelin and GH, combined with a rapid return in hepatic GH sensitivity would provide an elegant mechanism to drive catch-up growth after periods of nutritional insufficiency.

The smallest of the small: short-term outcomes of profoundly growth restricted and profoundly low birth weight preterm infants.

Abstract: The smallest of the small: short-term outcomes of profoundly growth restricted and profoundly low birth weight preterm infants

Effects of postnatal growth restriction and subsequent catch-up growth on neurodevelopment and glucose homeostasis in rats.

Abstract: There is increasing evidence that poor growth of preterm infants is a risk factor for poor long-term development, while the effects of early postnatal growth restriction are not well known. We utilized a rat model to examine the consequences of different patterns of postnatal growth and hypothesized that early growth failure leads to impaired development and insulin resistance. Rat pups were separated at birth into normal (N, n = 10) or restricted intake (R, n = 16) litters. At d11, R pups were re-randomized into litters of 6 (R-6), 10 (R-10) or 16 (R-16) pups/dam. N pups remained in litters of 10 pups/dam (N-10). Memory and learning were examined through T-maze test. Insulin sensitivity was measured by i.p. insulin tolerance test and glucose tolerance test. By d10, N pups weighed 20 % more than R pups (p < 0.001). By d15, the R-6 group caught up to the N-10 group in weight, the R-10 group showed partial catch-up growth and the R-16 group showed no catch-up growth. All R groups showed poorer scores in developmental testing when compared with the N-10 group during T-Maze test (p < 0.05). Although R-16 were more insulin sensitive than R-6 and R-10, all R groups were more glucose tolerant than N-10. In rats, differences in postnatal growth restriction leads to changes in development and in insulin sensitivity. These results may contribute to better elucidating the causes of poor developmental outcomes in human preterm infants.

Childhood growth patterns following congenital heart disease.

Abstract: Author(s): Aguilar, David C; Raff, Gary W; Tancredi, Daniel J; Griffin, Ian J | Abstract: IntroductionPrenatal and early postnatal growth are known to be abnormal in patients with CHD. Although adult metabolic risk is associated with growth later in childhood, little is known of childhood growth in CHD.Patients and methodsRetrospective data were collected on 551 patients with coarctation of the aorta, hypoplastic left heart syndrome, single ventricle physiology, tetralogy of Fallot, transposition of the great arteries, or ventricular septal defects. Weight, height, and body mass index data were converted to Z-scores. Body size at 2 years and growth between 2 and 20 years, 2 and 7 years, and 8 and 15 years were compared with Normative data using a sequential series of mixed-effects linear models.ResultsA total of 4660 weight, 2989 height, and 2988 body mass index measurements were analysed. Body size at 2 years of age was affected by cardiac diagnosis and gender. Abnormal growth was frequent and varied depending on cardiac diagnosis, gender, and the time period considered. The most abnormal patterns were seen in patients with tetralogy of Fallot, hypoplastic left heart syndrome, or single ventricle physiology. Potentially high-risk growth, a combination of small body size at 2 years and rapid subsequent growth, was seen in several groups.ConclusionsChildhood and adolescent growth patterns were gender- and lesion-specific. Several lesions were associated with abnormal patterns of childhood growth known to be associated with an increased risk of adult adiposity or metabolic risk in other populations. Further information is needed on the long-term metabolic risks of survivors of CHD.

Assessing Nutritional Requirements for Preterm Infants

Abstract: Although the macrominerals calcium, phosphorus, and magnesium are of primary concern in bone health, other minerals, including trace minerals can also play an important role. In this chapter, the role of some of these will be considered. In general, the data supporting and defining the role of the trace minerals in bone health is much less well developed than for the macrominerals. In many cases, studies have used animal models, which are difficult to extrapolate to humans. In others, the relationship between serum levels of minerals and markers of bone health or assessment of bone mineral density are described. These are difficult to interpret, and even if a correlation between low serum copper and low bone mineral density (for example) is demonstrated this does not mean that additional dietary copper would improve bone mineral density. Such relationships are confounded by the other lifestyle and socioeconomic factors that may cause such differences in dietary intakes. In addition, low-quality diets may be deficient in more than one nutrient, making it extremely difficult to ascribe the change to any single nutrient. There are very few well-designed intervention studies in humans that address the importance of trace and ultratrace minerals in human bone metabolism. The one exception appears to be strontium, where there is increasing good-quality data (i.e. randomized controlled studies) suggesting that high-risk adults may benefit from strontium supplementation.