Biomarkers for Type 2 Diabetes and Impaired Fasting Glucose Using a Nontargeted Metabolomics Approach

Using a nontargeted metabolomics approach of 447 fasting plasma metabolites, we searched for novel molecular markers that arise before and after hyperglycemia in a large population-based cohort of 2,204 females (115 type 2 diabetic [T2D] case subjects, 192 individuals with impaired fasting glucose [IFG], and 1,897 control subjects) from TwinsUK. Forty-two metabolites from three major fuel sources (carbohydrates, lipids, and proteins) were found to significantly correlate with T2D after adjusting for multiple testing; of these, 22 were previously reported as associated with T2D or insulin resistance. Fourteen metabolites were found to be associated with IFG. Among the metabolites identified, the branched-chain keto-acid metabolite 3-methyl-2-oxovalerate was the strongest predictive biomarker for IFG after glucose (odds ratio [OR] 1.65 [95% CI 1.39–1.95], P = 8.46 × 10⁻⁹) and was moderately heritable (h² = 0.20). The association was replicated in an independent population (n = 720, OR 1.68 [ 1.34–2.11], P = 6.52 × 10⁻⁶) and validated in 189 twins with urine metabolomics taken at the same time as plasma (OR 1.87 [1.27–2.75], P = 1 × 10⁻³). Results confirm an important role for catabolism of branched-chain amino acids in T2D and IFG. In conclusion, this T2D-IFG biomarker study has surveyed the broadest panel of nontargeted metabolites to date, revealing both novel and known associated metabolites and providing potential novel targets for clinical prediction and a deeper understanding of causal mechanisms.Currently, stratification of individuals at risk for type 2 diabetes (T2D) within the general population is based on well-established factors such as age, BMI, and fasting glucose (1). Although these factors contribute considerably to disease risk, they may not identify at-risk individuals before the disease process is well under way.Recently, a number of studies have found several metabolites to be correlated with insulin resistance and T2D (2–6), and T2D-associated metabolic profiles have been identified 10–15 years before the diagnosis/onset of the disease (7–9). To help preventive strategies, and maximize the potential for existing effective interventions, it is important to characterize the molecular changes that take place in the development of T2D.We aim to understand other biochemical changes, in addition to hyperglycemia, that take place at the onset of T2D using the largest metabolomic screening approach to date. We assessed >400 metabolites to determine which metabolomic profiles are correlated with T2D and impaired fasting glucose (IFG) in a large cohort of females from TwinsUK with independent replication.     

Acute-on-Chronic Liver Failure: What are the Implications?

Acute-on-chronic liver failure (ACLF) is a clinical entity that is well recognized by those who care for patients with cirrhosis, however in spite of this widespread recognition, there remains little consensus with regard to definition and clinical features. While many similarities exist between ACLF and decompensated cirrhosis, there are also key differences, the implications of which are far reaching for both clinicians and patients alike. Among these differences are the possibility of a reversible component, the presence of a defined insult, prognosis, and outcomes associated with ACLF (see Fig. 1). However, for ACLF to have meaningful clinical implications, it first must be defined. If ACLF can be clearly defined and more easily recognized, then clinicians may be better able to prevent, treat, prognosticate, and counsel such patients.     

Colletotrichum species associated with cultivated citrus in China

There have been considerable advances in the understanding of species concepts in the genus Colletotrichum. This has lead to the need to carry out fresh surveys of Colletotrichum species associated with important hosts. Colletotrichum species are associated with Citrus plants as saprobes, important pre-harvest and post-harvest pathogens, as well as endophytes. In this study, a total of 312 Colletotrichum strains were isolated from leaves, shoots and fruits of cultivated Citrus and Fortunella species with or without disease symptoms across the main citrus production areas in China. The morphology of all strains were studied and multilocus (ACT, TUB2, CAL, GAPDH, GS, ITS) phylogeny established. Strains were from four important species complexes of Colletotrichum, namely C. gloeosporioides species complex, C. boninense species complex, C. acutatum species complex and a final group including C. truncatum, which was rare on Citrus species. The species belonging to the C. gloeosporioides species complex comprised C. gloeosporioides and C. fructicola, the C. boninense complex comprised C. karstii and a new species C. citricola and the C. acutatum complex included a new species, C. citri. The ability of strains to cause anthracnose on citrus fruits was tested by inoculation and strains of Colletotrichum gloeosporioides, C. fructicola and C. truncatum were pathogenic.     

Caregiver acceptability and preferences for preventive dental treatments for young African-American children

Our prior research focused on parental treatment acceptability (TA) and treatment preferences (TPs) for preventive dental treatments for young Hispanic children. We adapted the interview for administration to parents of young African‐American children. Objective: In a sample of African‐American parents, determine parental TA and TP for five dental treatments to prevent early childhood caries. Methods: Interviewed 48 parents/caregivers of African‐American children attending Head Start, assessing TA and TP for three treatments for children: toothbrushing (TB) with fluoride toothpaste, fluoride varnish (FV), and xylitol in food (XF); and two treatments for mothers: xylitol gum (XG) and chlorhexidine (CHX) rinse. The interview included verbal information, illustrated treatment cards, photos/video clips, and samples. Parents provided TA of each treatment (one to five scale), TP between each of 10 pairs of the five treatments, and open‐ended reasons for their preferences. TPs were summed (zero to four) to create overall preference. Results: All treatments were acceptable (means 4.4‐4.9). TB was more acceptable than FV and XF (P < 0.05). Summed TP revealed a strong preference for TB (mean 3.1) above other treatments (all P < 0.01). Primary reasons for preferring TB were the following: promotes healthy habits; child focused; and effectiveness. Conclusions: All treatments were acceptable, however, parents/guardians strongly preferred TB. Parents' emphasis on healthy habits and child‐focused treatment supports efforts for oral health education programs in early childhood settings. Some parents expressed concerns about FV, XF, and CHX. Results may be useful in planning prevention programs for young children in African‐American communities.     

Analyse du parcours de santé au cours des maladies neurologiques handicapantes et évolutives

Neurological diseases are characterized by the complexity of care and by a constant and changing disability. More and more frequently, their impact on the clinical pathway remains unknown. Seven postgraduate rehabilitation students (Master coordination du handicap, université Pierre-et-Marie-Curie, Paris) reconstructed the clinical pathway of 123 patients with various neurological diseases: multiple sclerosis, Alzheimer disease, amyotrophic lateral sclerosis, spinal trauma, Parkinson disease and brain tumors. There was a significant correlation between disease duration and the number of specialists involved in care, the number of prescribed drugs and the number of short-term hospitalizations; there was no correlation with age. This result suggests that with time an increasing number of complications related to the initial neurological disease developed. Hospitalization in rehabilitation units was highly correlated with the degree of disability and also with the help received by the patients during the course of their disease. This result suggests that these hospitalizations were a direct consequence of burn out among relatives. General practitioners (GP) were highly involved only during the initial part of the pathway, and their involvement rapidly declined thereafter, suggesting a probable relation with the specificities and the complexity of care for neurological diseases which induces a progressive transfer of responsibilities from the GP to the hospital. Social care was always incomplete and occurred too late during the course of the disease. The feeling by the patients that their care pathway was chaotic was highly correlated with the quality of the information given to the patient at the time of the announcement of their disease. This study confirms that cares for neurological diseases is highly specific and that expert centers and coordination networks are in a key position to ensure an efficient care pathway.     

Morphometry of the respiratory tract: avoiding the sampling, size, orientation, and reference traps

The extrapolation to humans of studies of infectious or toxic agents injurious to the respiratory system using animal models assumes comparability in the structure and function of animal models and humans. Measurement of conducting airways and parenchyma yields quantitative data for parameters like volume, surface area, length, cell number and cell size. Over the past few decades, there has been an evolution of rigorous uniform sampling designs of stereology that ensure unbiased estimates of number, length, surface area, and volume. This approach has been termed 'design-based' stereology because of the reliance on sampling design rather than geometric model-based stereology that makes assumptions. The aim of this paper is to define new design-based stereological approaches for the direct estimation of anatomical structures and epithelial, interstitial and endothelial cells of specific regions of the lung independent of the sampling, size, orientation and reference traps. An example is provided using wildtype and transgenic mice expressing transforming growth factor-alpha to show the importance of the reference trap in stereologic estimates of postnatal lung growth.