Control of risk factors for nephropathy among Nigerian outpatients with Type 2 diabetes mellitus

Background and Objectives: To determine the proportion of type 2 diabetic  outpatients with adequate control of risk factors for nephropathy in a Nigerian teaching hospital.Methods: Between April and July 2005, 160 type 2 diabetic outpatients were  assessed for control of average fasting blood glucose and blood pressure over 3 visits, and current use of ACE inhibitors. All patients were over 30 years of age and had been followed up for at least one year with at least 6 prior clinic visits.Results: We studied 58 male and 102 female subjects with a mean (±SD) age of 54±10 years. The majority (54.7%) had diabetes between 1 and 5 years, and 95% were on antidiabetic drugs, most commonly both a sulphonylurea and metformin (64.5%). 114 (71.2%) were being treated for hypertension. The mean fasting blood glucose (FBS) was 7.6±2.9mmol/L, and 73 (45.6%) had good glycaemic control  (mean FBS≤ 5.6mmol/L). A total of 51 (31.9%) had good blood pressure control (<140/90mmHg in non-hypertensives and <130/80mmHg in hypertensives), and 73 (45.6%) were currently receiving ACE inhibitors. Only five (3.1%) had the combination of good glycaemic control, good blood pressure control and received ACE inhibitors. Conversely, 23 (14.4%) had a combination of poor glycaemic control, poor blood pressure control, and were not receiving ACE inhibitors. Duration of diabetes (p<0.01), elevated creatinine (p<0.01), and elevated systolic blood  pressure (p<0.01) were independently associated with proteinuria.Conclusion: Despite the availability of measures to prevent the progression of diabetic nephropathy, control of risk factors was poor. Physicians and diabetic patients in Nigeria must work together to improve their management of risk factors for nephropathy.Key words: Diabetes mellitus, chronic kidney disease, renoprotectio

Fin development in a cartilaginous fish and the origin of vertebrate limbs

Recent fossil finds and experimental analysis of chick and mouse embryos highlighted the lateral fin fold theory, which suggests that two pairs of limbs in tetrapods evolved by subdivision of an elongated single fin1. Here we examine fin development in embryos of the primitive cartilaginous fish, Scyliorhinus canicula (dogfish) using scanning electron microscopy and investigate expression of genes known to be involved in limb positioning, identity and patterning in higher vertebrates. Although we did not detect lateral fin folds in dogfish embryos, Engrailed-1 expression suggests that the body is compartmentalized dorso-ventrally. Furthermore, specification of limb identity occurs through the Tbx4 and Tbx5 genes, as in higher vertebrates. In contrast, unlike higher vertebrates, we did not detect Shh transcripts in dogfish fin-buds, although dHand (a gene involved in establishing Shh) is expressed. In S. canicula, the main fin axis seems to lie parallel to the body axis. 'Freeing' fins from the body axis and establishing a separate 'limb' axis has been proposed to be a crucial step in evolution of tetrapod limbs2, 3. We suggest that Shh plays a critical role in this process

Determinants of the urinary and serum metabolome in children from six European populations

Background Environment and diet in early life can affect development and health throughout the life course. Metabolic phenotyping of urine and serum represents a complementary systems-wide approach to elucidate environment–health interactions. However, large-scale metabolome studies in children combining analyses of these biological fluids are lacking. Here, we sought to characterise the major determinants of the child metabolome and to define metabolite associations with age, sex, BMI and dietary habits in European children, by exploiting a unique biobank established as part of the Human Early-Life Exposome project (http://www.projecthelix.eu). Methods Metabolic phenotypes of matched urine and serum samples from 1192 children (aged 6–11) recruited from birth cohorts in six European countries were measured using high-throughput 1H nuclear magnetic resonance (NMR) spectroscopy and a targeted LC-MS/MS metabolomic assay (Biocrates AbsoluteIDQ p180 kit). Results We identified both urinary and serum creatinine to be positively associated with age. Metabolic associations to BMI z-score included a novel association with urinary 4-deoxyerythronic acid in addition to valine, serum carnitine, short-chain acylcarnitines (C3, C5), glutamate, BCAAs, lysophosphatidylcholines (lysoPC a C14:0, lysoPC a C16:1, lysoPC a C18:1, lysoPC a C18:2) and sphingolipids (SM C16:0, SM C16:1, SM C18:1). Dietary-metabolite associations included urinary creatine and serum phosphatidylcholines (4) with meat intake, serum phosphatidylcholines (12) with fish, urinary hippurate with vegetables, and urinary proline betaine and hippurate with fruit intake. Population-specific variance (age, sex, BMI, ethnicity, dietary and country of origin) was better captured in the serum than in the urine profile; these factors explained a median of 9.0% variance amongst serum metabolites versus a median of 5.1% amongst urinary metabolites. Metabolic pathway correlations were identified, and concentrations of corresponding metabolites were significantly correlated (r > 0.18) between urine and serum. Conclusions We have established a pan-European reference metabolome for urine and serum of healthy children and gathered critical resources not previously available for future investigations into the influence of the metabolome on child health. The six European cohort populations studied share common metabolic associations with age, sex, BMI z-score and main dietary habits. Furthermore, we have identified a novel metabolic association between threonine catabolism and BMI of children

Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi