A prospective cohort study in patients with type 2 diabetes mellitus for validation of biomarkers (PROVALID) –study design and baseline characteristics

Background/Aims: The prevalence of diabetes mellitus type 2 and kidney disease in these patients varies widely between European countries. Methods: In addition to store biosamples the “Prospective cohort study in patients with type 2 diabetes mellitus for validation of biomarkers” collects information on history, physical status, laboratory measurements and medication in 4000 patients with diabetes mellitus type 2, being taken care of at the primary level of healthcare in 5 European countries (Austria, Hungary, Netherlands, Poland and Scotland). Next to comparing the rate of loss of eGFR between the countries, a further objective of the PROVALID study is to determine the 5-year cumulative incidence of renal and cardiovascular outcomes. Results: The mean age of the population recruited is 62.9±10 years, 54.6% are male and the mean BMI is 30.9±5.4 kg/m2 . Metabolic control (median HBA1c 6.8 % (6.2;7.5)) is achieved via administration of metformin in 67.4% of the patients and insulin in 30.3%. Median systolic and diastolic blood pressure at recruitment is 135 (125;146) and 80 (72;85) mmHg, 65.4% of subjects received RAAS blocking agents. Mean eGFR is 80.7±29.2 ml/min/1.73m2 and median baseline albumin/creatinine ratio 8.3 mg (IQR: 3.8 and 25.1). Conclusion: PROVALID will provide information on incidence and progression of renal and cardiovascular disease and therapy in patients with type 2 diabetes mellitus in different European countries. Thus, in contrast to many other cohort studies we will be able to associate national clinical practise pattern with outcome in this highly vulnerable patient population

A behavioural trait displayed in an artificial novel environment correlates with dispersal in a wild bird

Behaviour shown in a novel environment has important consequences for fitness in many animals. It is widely studied with standard tests by placing the individuals into an unfamiliar experimental area, that is the so-called open-field or novel environment test. The biological relevance of traits measured under such artificial conditions is questionable and could be validated by establishing a link with variables that truly reflect exploration in the wild. Our aim in this field study was to characterize behaviours measured in an artificial novel environment (an aviary) and assess the biological relevance of them in the collared flycatcher (Ficedula albicollis). Therefore, we measured the repeatability and the association of multiple behavioural traits, as well as their relationship with breeding dispersal (that reflects exploration in the wild). We found evidence for non-zero repeatability for number of crosses between the quarters, number of hops and perching latency in the aviary, and these repeatabilities were high when assessed at shorter time windows. Additionally, birds with short perching latency in the novel environment were more likely residents and bred closer to their breeding nest box in the previous year, which may suggest that latency to perch is connected to dispersal in the wild. In sum, our results indicate that behaviours assessed in an artificial environment are individual-specific at least on smaller timescales, and at least, one component of these behaviours is correlated with an ecologically relevant trait

Validation of plasma biomarker candidates for the prediction of eGFR decline in patients with type 2 diabetes

Objective: The decline of estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes is variable and early interventions would likely be cost effective. We elucidated the contribution of 17 plasma biomarkers to the prediction of eGFR loss on top of clinical risk factors. Research Design and Methods: We studied participants in PROVALID, a prospective multinational cohort study of patients with type 2 diabetes and a follow up of more than 24 months (n = 2560; baseline median eGFR 84 mL/min/1.73m2, UACR 8.1 mg/g). The 17 biomarkers were measured at baseline in 481 samples using Luminex technology and ELISA. The prediction of eGFR decline was evaluated by linear mixed modeling. Results: In univariable analyses nine of the 17 markers showed significant differences in median concentration between the two groups. A linear mixed model for eGFR obtained by variable selection exhibited an adjusted R2 of 62%. A panel of twelve biomarkers was selected by the procedure and accounted for 34% of the total explained variability, of which 32% were due to five markers. Each biomarker’s individual contribution to the prediction of eGFR decline on top of clinical predictors was generally low. When included into the model, baseline eGFR exhibited the largest explained variability of eGFR decline (R2 of 79%) and the contribution of each biomarker dropped below 1%. Conclusions: In this longitudinal study of patients with type 2 diabetes and maintained eGFR at baseline, 12 of the 17 candidate biomarkers were associated with eGFR decline, but their predictive power was low

Data from: Digit ratio predicts the number of lifetime recruits in female collared flycatchers

The early environment in which an organism grows can have long-lasting impact on both its phenotype and fitness. However, assessing this environment comprehensively is a formidable task. The relative length of the second to the fourth digit (2D:4D) is a broadly studied skeletal trait that is fixed for life during ontogeny. 2D:4D has been shown to indicate various early effects including the perinatal steroid milieu in both humans and non-human animals. However, the fitness relevance of the early effects indicated by 2D:4D remains unknown. Here, we investigated hindlimb 2D:4D and measures of lifetime performance in wild collared flycatcher (Ficedula albicollis) females. We found that females with higher 2D:4D had a greater number of recruiting offspring to the breeding population. This was the case despite the fact that such females did not lay more eggs or breed more times during their reproductive life. Our results support that 2D:4D, known to be a retrospective marker of perinatal development, positively associates with female quality in the collared flycatcher

Long-term breeding data and 2D:4D measures from collared flycatchers.

Long-term breeding data and 2D:4D measures from a Hungarian population of collared flycatchers. Variables are detailed in the sheet named "variables"