Young, metal-enriched cores in early-type dwarf galaxies in the Virgo cluster based on colour gradients

Early-type dwarf galaxies are not simply featureless, old objects, but were found to be much more diverse, hosting substructures and a variety of stellar population properties. To explore the stellar content of faint early-type galaxies, and to investigate in particular those with recent central star formation, we study colours and colour gradients within one effective radius in optical (g-r) and near-infrared (i-H) bands for 120 Virgo cluster early types with -19 mag < $M_{r}$ < -16 mag. Twelve galaxies turn out to have blue cores, when defined as g-r colour gradients larger than 0.10 mag/$R_{\rm eff}$, which represents the positive tail of the gradient distribution. For these galaxies, we find that they have the strongest age gradients, and that even outside the blue core, their mean stellar population is younger than the mean of ordinary faint early types. The metallicity gradients of these blue-cored early-type dwarf galaxies are, however, in the range of most normal faint early types, which we find to have non-zero gradients with higher central metallicity. The blue central regions are consistent with star formation activity within the last few 100 Myr. We discuss that these galaxies could be explained by environmental quenching of star formation in the outer galaxy regions, while the inner star formation activity has continued

A Novel Insulin/Glucose Model after a Mixed-Meal Test in Patients with Type 1 Diabetes on Insulin Pump Therapy

Current closed-loop insulin delivery methods stem from sophisticated models of the glucose-insulin (G/I) system, mostly based on complex studies employing glucose tracer technology. We tested the performance of a new minimal model (GLUKINSLOOP 2.0) of the G/I system to characterize the glucose and insulin dynamics during multiple mixed meal tests (MMT) of different sizes in patients with type 1 diabetes (T1D) on insulin pump therapy (continuous subcutaneous insulin infusion, CSII). The GLUKINSLOOP 2.0 identified the G/I system, provided a close fit of the G/I time-courses and showed acceptable reproducibility of the G/I system parameters in repeated studies of identical and double-sized MMTs. This model can provide a fairly good and reproducible description of the G/I system in T1D patients on CSII, and it may be applied to create a bank of "virtual" patients. Our results might be relevant at improving the architecture of upcoming closed-loop CSII systems

Association of free-living physical activity measures with metabolic phenotypes in type 2 diabetes at the time of diagnosis. The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS)

Objective: Lifestyle is considered a major determinant of risk of type 2 diabetes (T2D). We investigated whether daily physical activity (DPA) is associated with beta-cell function (BF) and/or insulin sensitivity (IS) in patients with T2D at the time of diagnosis. Methods: In 41 subjects enrolled in the Verona Newly-Diagnosed Type 2 Diabetes Study we assessed: (1) IS, by euglycaemic insulin clamp; (2) BF, estimated by prolonged-OGTT minimal modeling and expressed as derivative and proportional control; (3) DPA and energy expenditure (EE), assessed over 48-hours monitoring by a validated wearable armband system. Results: Study participants (median[IQR]; age: 62 [53-67] years, BMI: 30.8 [26.5-34.3] Kg c5m-2, HbA1c: 6.7 [6.3-7.3]%; 49.7 [45.4-56.3] mmol/mol) were moderately active (footsteps/day: 7,773 [5,748-10,927]; DPA 653MET: 70 [38-125] min/day), but none of them exercised above 6 metabolic equivalents (MET). EE, expressed as EETOT (total daily-EE) and EE 653MET (EE due to DPA 653MET) were 2,398 [2,226-2,801] and 364 [238-617] Kcal/day, respectively. IS (M-clamp 630 [371-878] \u3bcmol/min/m2) was positively associated with DPA and EE, independent of age, sex and BMI (p&lt;0.05). Among the DPA and EE parameters assessed, DPA 653MET and EETOT were independent predictors of IS in multivariable regression analyses, adjusted for age, sex, BMI (R2=16%, R2=19%, respectively; p&lt;0.01). None of model-derived components of BF was significantly associated with DPA or accompanying EE. Conclusions Our study highlighted moderate levels of DPA and total EE as potential determinants of IS, but not BF, in T2D at the time of diagnosis. Intervention studies are needed to conclusively elucidate the effect of DPA on these features

Glucose tolerance stages in Cystic Fibrosis are idenfied by a unique pattern of defects of Beta-cell function

To assess the order of severity of the defects of three direct determinants of glucose regulation, i.e., beta-cell function, insulin clearance and insulin sensitivity, in patients with CF categorized according their glucose tolerance status, including early elevation of mid-OGTT glucose values (&gt;140 and &lt; 200&nbsp;mg/dL), named AGT140

COLD GASS, an IRAM legacy survey of molecular gas in massive galaxies: I. Relations between H2, HI, stellar content and structural properties

We are conducting COLD GASS, a legacy survey for molecular gas in nearby galaxies. Using the IRAM 30m telescope, we measure the CO(1-0) line in a sample of ~350 nearby (D=100-200 Mpc), massive galaxies (log(M*/Msun)>10.0). The sample is selected purely according to stellar mass, and therefore provides an unbiased view of molecular gas in these systems. By combining the IRAM data with SDSS photometry and spectroscopy, GALEX imaging and high-quality Arecibo HI data, we investigate the partition of condensed baryons between stars, atomic gas and molecular gas in 0.1-10L* galaxies. In this paper, we present CO luminosities and molecular hydrogen masses for the first 222 galaxies. The overall CO detection rate is 54%, but our survey also uncovers the existence of sharp thresholds in galaxy structural parameters such as stellar mass surface density and concentration index, below which all galaxies have a measurable cold gas component but above which the detection rate of the CO line drops suddenly. The mean molecular gas fraction MH2/M* of the CO detections is 0.066+/-0.039, and this fraction does not depend on stellar mass, but is a strong function of NUV-r colour. Through stacking, we set a firm upper limit of MH2/M*=0.0016+/-0.0005 for red galaxies with NUV-r>5.0. The average molecular-to-atomic hydrogen ratio in present-day galaxies is 0.3, with significant scatter from one galaxy to the next. The existence of strong detection thresholds in both the HI and CO lines suggests that "quenching" processes have occurred in these systems. Intriguingly, atomic gas strongly dominates in the minority of galaxies with significant cold gas that lie above these thresholds. This suggests that some re-accretion of gas may still be possible following the quenching event.Comment: Accepted for publications in MNRAS. 32 pages, 25 figure

Abstracts of 51st EASD Annual Meeting

Background and aims: Presence and frequency of beta cell (BC) dysfunction(BCD) and insulin resistance (IR) in patients with newly diagnosedtype 2 diabetes mellitus (NDT2D) are imperfectly known, becauseprevious studies used small cohorts and/or only surrogate indexes of BCfunction and IR.We sought to assess BC function and IR with state-of-artmethods in the VNDS.Materials and methods: In 712 GADA-negative, drug naïve, consecutiveItalian NDT2D patients we assessed: 1. standard parameters; 2. insulinsensitivity (IS) by the euglycaemic insulin clamp); 3. BC functionby state-of-art modeling of prolonged (5 hours) OGTT-derived glucose/C-peptide curves. Thresholds for BCD and IR were the 25th percentilesof BC function and IS assessed with the same methods of the VNDS inItalian subjects with normal glucose regulation of the GENFIEV (n=340)and GISIR (n=386) studies, respectively.Results: In the VNDS, 89.8% [95% C.I.: 87.6 - 92.0%] and87.8% [85.4 - 90.2] patients had BCD and IR, respectively. Patientswith only one defect were 19.7% [16.8 - 22.6]. IsolatedBCD and isolated IR were present in 10.9% [8.6 - 13.2] and8.9% [6.8 - 11.0] patients, respectively. Coexistence of BCDand IR was observed in 78.9% [75.9 - 81.9] of the patients.1.4% [0.5 - 2.3] of the patients had no detectable alterations inBC function and IS. Patients (19.7%) with only one metabolicdefect had lower BMI, fasting glucose, HbA1c, triglycerides andBC function, and higher HDL-cholesterol and IS than patientswith both BCD and IR (p<0.01 or less after Bonferroni’scorrection).Conclusion: In conclusion, in NDT2DM patients: 1. at least 75.9% haveboth BCD and IR; 2. At least 87.6% and 85.4% have BCD and IR,respectively; 3. At least 16.8% have only one defect and a significantlydifferent (milder) metabolic phenotype compared to patients with bothdefects. These findings may be relevant to therapeutic strategies centeredon the metabolic phenotype of the patient.Clinical Trial Registration Number: NCT00879801; NCT01526720Supported by: University of Veron

Ethnic differences in beta cell function occur independently of insulin sensitivity and pancreatic fat in black and white men

Introduction It is increasingly recognized that type 2 diabetes (T2D) is a heterogenous disease with ethnic variations. Differences in insulin secretion, insulin resistance and ectopic fat are thought to contribute to these variations. Therefore, we aimed to compare postprandial insulin secretion and the relationships between insulin secretion, insulin sensitivity and pancreatic fat in men of black West African (BA) and white European (WE) ancestry.Research design and methods A cross-sectional, observational study in which 23 WE and 23 BA men with normal glucose tolerance, matched for body mass index, underwent a mixed meal tolerance test with C peptide modeling to measure beta cell insulin secretion, an MRI to quantify intrapancreatic lipid (IPL), and a hyperinsulinemic-euglycemic clamp to measure whole-body insulin sensitivity.Results Postprandial insulin secretion was lower in BA versus WE men following adjustment for insulin sensitivity (estimated marginal means, BA vs WE: 40.5 (95% CI 31.8 to 49.2) × 103 vs 56.4 (95% CI 48.9 to 63.8) × 103 pmol/m2 body surface area × 180 min, p=0.008). There was a significantly different relationship by ethnicity between IPL and insulin secretion, with a stronger relationship in WE than in BA (r=0.59 vs r=0.39, interaction p=0.036); however, IPL was not a predictor of insulin secretion in either ethnic group following adjustment for insulin sensitivity.Conclusions Ethnicity is an independent determinant of beta cell function in black and white men. In response to a meal, healthy BA men exhibit lower insulin secretion compared with their WE counterparts for their given insulin sensitivity. Ethnic differences in beta cell function may contribute to the greater risk of T2D in populations of African ancestry

Interleukin-6 as a potential positive modulator of human beta-cell function: an exploratory analysis-the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 6

Recent studies in mouse models of T2D showed that interleukin-6 (IL-6), released from skeletal muscle, is associated with increased glucose-dependent insulin secretion. Few data currently exist exploring the relationship between IL-6 and beta-cell function in humans. We investigated whether IL-6 is positively associated with beta-cell function in newly diagnosed T2D. We extended the same analyses to IL-10, because it regulated similarly to IL-6 in skeletal muscle, and TNF-\u3b1 and C-reactive protein (CRP), as general biomarkers of inflammation

Is common genetic variation at IRS1, ENPP1 and TRIB3 loci associated with cardiometabolic phenotypes in type 2 diabetes? An exploratory analysis of the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 5

Background and Aims - Insulin resistance is a hallmark of type 2 diabetes (T2DM), it is often accompanied by defective beta-cell function (BF) and is involved in the pathophysiology of cardiovascular disease (CVD). Commonalities among these traits may recognize a genetic background, possibly involving the genetic variation of insulin signaling pathway genes. We conducted an exploratory analysis by testing whether common genetic variability at IRS1, ENPP1 and TRIB3 loci is associated with cardiovascular risk traits and metabolic phenotypes in T2DM.Methods and Results - In 597 drug-na\uefve, GADA-negative, newly-diagnosed T2DM patients we performed: 1) genotyping of 10 independent single-nucleotide polymorphisms covering ~90% of common variability at IRS1, ENPP1 and TRIB3 loci; 2) carotid artery ultrasound; 3) standard ECG (n=450); 4) euglycaemic insulin clamp to assess insulin sensitivity; 5) 75g-OGTT to estimate BF (derivative and proportional control) by mathematical modeling. False discovery rate of multiple comparisons was set at 0.20. After adjustment for age, sex and smoking status, rs4675095-T (IRS1) and rs4897549-A (ENPP1) were significantly associated with carotid atherosclerosis severity, whilst rs7265169-A (TRIB3) was associated with ECG abnormalities. Rs858340-G (ENPP1) was significantly associated with decreased insulin sensitivity, independently of age, sex and body-mass-index. No consistent relationships were found with BF.Conclusion - Some associations were found between intermediate phenotypes of CVD and common genetic variation of gatekeepers along the insulin signaling pathway. These results need be replicated to support the concept that in T2DM the CVD genetic risk clock may start ticking long before hyperglycemia appears. ClinicalTrials.gov Identifier: NCT01526720