Osteoprotegerin levels are associated with liver fat and liver markers in dysmetabolic adults

AIM: This study aimed to determine the association between visceral adipose tissue (VAT), liver fat (LF) content, and other markers of the metabolic syndrome (MetS) and osteoprotegerin (OPG) in dysmetabolic adults. METHODS: Subjects from the NUMEVOX cohort were included if they fulfilled at least one MetS criterion. They then underwent a thorough metabolic and cardiovascular evaluation, including arterial stiffness, atherosclerotic plaques, homoeostasis model assessment for insulin resistance (HOMA-IR) indices and OPG. VAT and LF content were measured by magnetic resonance imaging (MRI). Ultrasound examination of arteries and arterial stiffness were recorded, and age- and gender-adjusted paired correlations calculated. RESULTS: Body mass index, waist circumference and MRI-derived VAT correlated with OPG, whereas abdominal subcutaneous fat did not. OPG levels were strongly correlated with LF content (r=0.25, P=0.003), liver markers such as alanine aminotransferase (r=0.39, P<0.001) and HOMA-IR index (r=0.39, P<0.0001). Plasma OPG also correlated with arterial stiffness and the number of atherosclerotic sites. CONCLUSION: Plasma OPG levels are positively associated with both liver markers and increased LF content, but not with subcutaneous fat in dysmetabolic men. These findings suggest that elevated OPG levels may play a role in the link between fatty liver disease and enhanced cardiovascular risk

From Analogical Proportion to Logical Proportions

International audienceGiven a 4-tuple of Boolean variables (a, b, c, d), logical proportions are modeled by a pair of equivalences relating similarity indicators ( a∧b and a¯∧b¯), or dissimilarity indicators ( a∧b¯ and a¯∧b) pertaining to the pair (a, b), to the ones associated with the pair (c, d). There are 120 semantically distinct logical proportions. One of them models the analogical proportion which corresponds to a statement of the form “a is to b as c is to d”. The paper inventories the whole set of logical proportions by dividing it into five subfamilies according to what they express, and then identifies the proportions that satisfy noticeable properties such as full identity (the pair of equivalences defining the proportion hold as true for the 4-tuple (a, a, a, a)), symmetry (if the proportion holds for (a, b, c, d), it also holds for (c, d, a, b)), or code independency (if the proportion holds for (a, b, c, d), it also holds for their negations (a¯,b¯,c¯,d¯)). It appears that only four proportions (including analogical proportion) are homogeneous in the sense that they use only one type of indicator (either similarity or dissimilarity) in their definition. Due to their specific patterns, they have a particular cognitive appeal, and as such are studied in greater details. Finally, the paper provides a discussion of the other existing works on analogical proportions

Associations between visceral adipose tissue, inflammation and sex steroid concentrations in men

CONTEXT: In men, obesity and the metabolic syndrome are accompanied by decreased testosterone levels, but little is known about the associations between visceral adipose tissue (VAT), VAT-related inflammation and sex steroids.OBJECTIVE: To examine the relative impact of VAT, abdominal subcutaneous adipose tissue (SAT) and interleukin 6 (IL-6), a marker of VAT-induced inflammation, on testosterone (T) and 17β-oestradiol (E2) levels in dysmetabolic men. METHODS: We study the NUMEVOX cohort of 229 men, aged 27-77 years, who all had at least one metabolic syndrome criterion (on average three). IL-6, C-reactive protein, Homeostasis Model Assessment of (HOMA) insulin resistance index (HOMA-IR), liver enzymes, E2, LH, sex hormone-binding globulin (SHBG), T, waist circumference and body mass index (BMI) were measured; bioavailable testosterone (BT) was calculated from T and SHBG; MRI-assessed VAT and SAT were analysed in 109 of these men. RESULTS: Visceral adipose tissue was strongly correlated with E2 (Spearman r = 0.38, P < 0.001) and with BT/E2 ratio (r = -0.42, P < 0.001), while SAT was not correlated with either. IL-6 was correlated with E2 (r = 0.19, P = 0.007), BT (r = -0.19, P = 0.006) and BT/E2 ratio (r = -0.30 P < 0.001). In multivariate linear analysis, the relation between VAT and E2 was independent of age, BMI (P = 0.008), leptin (P < 0.001), T and SHBG. Log(IL-6) was significantly inversely related with log(BT) (P = 0.032) independently of age, VAT, leptin and HOMA-IR. CONCLUSIONS: 17β-oestradiol levels were positively associated with VAT, but not with SAT, while T and BT were negatively and independently associated with IL-6. The significant inverse association between IL-6 and T suggests an important role of low-grade visceral fat inflammation in the central hypogonadism associated with the metabolic syndrome

Increased liver stiffness in patients with severe sleep apnoea and metabolic comorbidities

The goal of this study was to assess the relationship between the severity of obstructive sleep apnoea (OSA) and liver stiffness measurement (LSM), one of the most accurate noninvasive screening tools for liver fibrosis in nonalcoholic fatty liver disease.The study included 147 patients with at least one criterion for the metabolic syndrome, assessed by polysomnography for suspected OSA. LSM was performed using transient elastography (FibroScan). Significant liver disease and advanced liver fibrosis were defined as LSM ≥7.3 and ≥9.6 kPa, respectively.23 patients were excluded because of unreliable LSM. Among 124 patients, 34 (27.4%) had mild OSA, 38 (30.6%) had moderate OSA and 52 (42.0%) had severe OSA. LSM values were 7.3- <9.6 kPa in 18 (14.5%) patients and ≥9.6 kPa in 15 (12.1%) patients. A dose-response relationship was observed between OSA severity and LSM values (p=0.004). After adjustment for age, sex, metabolic syndrome and insulin resistance, severe OSA was associated with an increased risk of LSM ≥7.3 kPa (OR 7.17, 95% CI 2.51-20.50) and LSM ≥9.6 kPa (OR 4.73, 95% CI 1.25-17.88).In patients with metabolic comorbidities, severe OSA is independently associated with increased liver stiffness, which may predispose to a higher risk of significant liver disease and poorer prognosis

MRI measurement of liver fat content predicts the metabolic syndrome

BACKGROUND AND AIMS: The prevalence of non-alcoholic fatty liver disease among cardiometabolic patients is not completely known because liver biopsy cannot be routinely performed. However, as magnetic resonance imaging (MRI) allows accurate and safe measurement of the hepatic fat fraction (HFF), the aim of this study was to quantify liver fat content in a dysmetabolic adult population. METHODS: A total of 156 adults were included in this cross-sectional study. Liver and visceral fat were assessed by MRI in these subjects, who presented with zero to five metabolic components of the metabolic syndrome (MetS). Arterial stiffness was recorded by ultrasonography, and the maximum Youden index was used to set the optimal HFF cutoff value predictive of the presence of the MetS. RESULTS: Overall, 72% of participants displayed three or more MetS components. HFF ranged from 0.3% to 52% (mean 13.4%). Age- and gender-adjusted HFF was positively correlated with BMI (r=0.44), blood pressure (r=0.19), triglyceridaemia (r=0.22) and glycaemia (r=0.31). MRI-measured visceral adipose tissue did not influence the relationship of steatosis with glycaemia, HOMA-IR and carotid stiffness, but there was a dose-response relationship between the number of MetS components and mean HFF. The optimal HFF for predicting the MetS was found to be 5.2% according to the maximum Youden index point. CONCLUSION: This study highlighted the impact of liver steatosis on cardiometabolic abnormalities with an optimal cutoff value of 5.2% for defining increased metabolic risk

The Type and the Position of HNF1A Mutation Modulate Age at Diagnosis of Diabetes in Patients with Maturity-Onset Diabetes of the Young (MODY)-3

OBJECTIVE—The clinical expression of maturity-onset diabetes of the young (MODY)-3 is highly variable. This may be due to environmental and/or genetic factors, including molecular characteristics of the hepatocyte nuclear factor 1-α (HNF1A) gene mutation. RESEARCH DESIGN AND METHODS—We analyzed the mutations identified in 356 unrelated MODY3 patients, including 118 novel mutations, and searched for correlations between the genotype and age at diagnosis of diabetes. RESULTS—Missense mutations prevailed in the dimerization and DNA-binding domains (74%), while truncating mutations were predominant in the transactivation domain (62%). The majority (83%) of the mutations were located in exons 1- 6, thus affecting the three HNF1A isoforms. Age at diagnosis of diabetes was lower in patients with truncating mutations than in those with missense mutations (18 vs. 22 years, P = 0.005). Missense mutations affecting the dimerization/DNA-binding domains were associated with a lower age at diagnosis than those affecting the transactivation domain (20 vs. 30 years, P = 10−4). Patients with missense mutations affecting the three isoforms were younger at diagnosis than those with missense mutations involving one or two isoforms (P = 0.03). CONCLUSIONS—These data show that part of the variability of the clinical expression in MODY3 patients may be explained by the type and the location of HNF1A mutations. These findings should be considered in studies for the search of additional modifier genetic factors

The Clinical Variability of Maternally Inherited Diabetes and Deafness Is Associated with the Degree of Heteroplasmy in Blood Leukocytes

Context: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue. Objective: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes. Participants: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded. Results: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA1c was also found and remained significant after adjustment for age at molecular sampling and gender. Conclusions: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD. Heteroplasmy levels are at least one of the determinants of the severity of the phenotype of maternally inherited diabetes and deafness

Search for a light Higgs resonance in radiative decays of the (1S) with a charm tag

A search is presented for the decay (1S)→γA0, A0→cc¯, where A0 is a candidate for the CP-odd Higgs boson of the next-to-minimal supersymmetric standard model. The search is based on data collected with the BABAR detector at the (2S) resonance. A sample of (1S) mesons is selected via the decay (2S)→π+π-(1S). The A0→cc¯ decay is identified through the reconstruction of hadronic D0, D+, and D∗(2010)+ meson decays. No significant signal is observed. The measured 90% confidence-level upper limits on the product branching fraction B((1S)→γA0)×B(A0→cc¯) range from 7.4×10-5 to 2.4×10-3 for A0 masses from 4.00 to 8.95GeV/c2 and 9.10 to 9.25GeV/c2, where the region between 8.95 and 9.10GeV/c2 is excluded because of background from (2S)→γχbJ(1P), χbJ(1P)→γ(1S) decays

Angular distributions in the decay B -> K*l(+)l(-)

We use a sample of 384 million BBbar events collected with the Babar detector at the PEP-II e+e- collider to study angular distributions in the rare decays B -> K* l+l-, where l+l- is either e+e- or mu+mu-. For low dilepton invariant masses, m(l+l-)3.2$ GeV/c^2, we measure AFB=0.76 (+0.52,-0.32) +/- 0.07 FL=0.71 (+0.20,-0.22) +/- 0.04.We are grateful for the excellent luminosity and machine conditions provided by our PEP-II colleagues, and for the substantial dedicated effort from the computing organizations that support BABAR. The collaborating institutions wish to thank SLAC for its support and kind hospitality. This work is supported by DOE and NSF (USA), NSERC (Canada), CEA and CNRS-IN2P3 (France), BMBF and DFG (Germany), INFN (Italy), FOM (The Netherlands), NFR (Norway), MES (Russia), MEC (Spain), and STFC (United Kingdom). Individuals have received support from the Marie Curie EIF (European Union) and the A. P. Sloan Foundation.Peer reviewe