Ekspresja adiponektyny w otyłości trzewnej jest istotnym wyznacznikiem insulinooporności w otyłości olbrzymiej

Introduction: Visceral adiposity is associated with decreased serum adiponectin levels, peripheral resistance to insulin and an increased risk of cardio-metabolic complications. However, the link between adiponectin expression in visceral adipose tissue (VAT), its serum levels and metabolic protection is controversial. The aim of this study was to investigate the relationship between the adiponectin gene expression in VAT and clinical and metabolic parameters in patients with severe obesity. Material and Methods: This is a cross-sectional study that included 51 severely obese patients (age 43.24±11.29 years, BMI 45.13±8.67 kg/m2), extensively evaluated clinically and biologically (metabolic tests, serum adiponectin measurements, HOMA-IR) before bariatric surgery. Omental adipose tissue was sampled during the intervention and the relative quantification of adiponectin gene expression was performed by real-time PCR, using beta-actin as reference gene. Results. Adiponectin mRNA in VAT was significantly higher in obese insulin-sensitive patients than in the rest of obese patients (p < 0.05) and negatively correlated with HOMA-IR (r =-0.354, p=0.016) and uric acid (r =-0.304, p=0.045). After adjustment for gender, TG/HDL ratio and uric acid, adiponectin expresion (β= -0.439, p=0.001), waist circumference (β=0.467, p=0.001) and serum adiponectin (β =-0.339, p=0.011) remained significantly associated with HOMA-IR, together explaining more than 50% of its variation. Conclusions. In severely obese patients, adiponectin gene expression in VAT is negatively correlated with serum levels of uric acid and is an independent determinant, together with anthropometric parameters of visceral obesity and serum adiponectin levels, of insulin resistance.Wstęp: Otyłość trzewna związana jest ze zmniejszonym stężeniem adiponektyny w surowicy krwi, obwodową opornością na działanie insuliny oraz ze zwiększonym ryzykiem powikłań sercowo-metabolicznych. Jednak związek między ekspresją adiponektyny w trzewnej tkance tłuszczowej, jej stężeniem w surowicy krwi a ochroną metaboliczną jest kwestią sporną. Celem niniejszej pracy było zbadanie związku między ekspresją genu adiponektyny w trzewnej tkance tłuszczowej a klinicznymi i metabolicznymi parametrami pacjentów ze znaczną otyłością. Materiał i metody: To przekrojowe badanie obejmowało 51 znacznie otyłych pacjentów (wiek 43,24 ± 11,29 roku, BMI 45,13 ± 8,67 kg/m2), szczegółowo ocenionych pod względem klinicznym i biologicznym (testy metaboliczne, pomiary stężenia adiponektyny w surowicy krwi, wskaźnik HOMA-IR) przed operacją bariatryczną. Podczas operacji pobrano tkankę tłuszczową sieci. Względna ocena ilościowa ekspresji genu adiponektyny była przeprowadzona metodą PCR w czasie rzeczywistym. Wyniki: Poziom mRNA adiponektyny w trzewnej tkance tłuszczowej był znacząco wyższy u otyłych pacjentów wrażliwych na insulinę niż u pozostałych otyłych pacjentów (p &lt; 0,05) oraz ujemnie skorelowany ze wskaźnikiem HOMA-IR (r = –0,354, p = 0,016) i kwasem moczowym (r = –0,304, p = 0.045). Po uwzględnieniu płci, wskaźnika TG/HDL i kwasu moczowego, ekspresja adiponektyny (β = –0,439, p = 0,001), obwód talii (β = 0,467, p = 0,001) i poziom adiponektyny w surowicy krwi (β = –0,339, p = 0,011) pozostały istotnie związane ze wskaźnikiem HOMA-IR, łącznie wyjaśniając ponad 50% jego wariancji. Wnioski: W przypadku znacznie otyłych pacjentów ekspresja genu adiponektyny w trzewnej tkance tłuszczowej jest ujemnie skorelowana ze stężeniem kwasu moczowego w surowicy krwi i razem z antropometrycznymi parametrami otyłości trzewnej oraz stężeniem adiponektyny w surowicy krwi jest niezależnym wyznacznikiem insulinooporności

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations.This work was supported by the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health (FIS; PI16/00425 and PI19/00321), Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER, 06/07/0036), IIS-FJD BioBank (PT13/0010/0012), Comunidad de Madrid (CAM, RAREGenomics Project, B2017/BMD-3721), European Regional Development Fund (FEDER), the Organización Nacional de Ciegos Españoles (ONCE), Fundación Ramón Areces, Fundación Conchita Rábago and the University Chair UAM-IIS-FJD of Genomic Medicine. Irene Perea-Romero is supported by a PhD fellowship from the predoctoral Program from ISCIII (FI17/00192). Ionut F. Iancu is supported by a grant from the Comunidad de Madrid (CAM, PEJ-2017-AI/BMD7256). Marta del Pozo-Valero is supported by a PhD grant from the Fundación Conchita Rábago. Berta Almoguera is supported by a Juan Rodes program from ISCIII (JR17/00020). Pablo Minguez is supported by a Miguel Servet program from ISCIII (CP16/00116). Marta Corton is supported by a Miguel Servet program from ISCIII (CPII17/00006). The funders played no role in study design, data collection, data analysis, manuscript preparation and/or publication decisions

DXA Android-to-Gynoid Ratio and Cardiovascular Risk Assessment in Age and BMI Propensity-Matched Early Postmenopausal Women

Background and Objectives: The literature suggests that physiological menopause (MP) seems linked with increased adiposity with a preference for intra-abdominal fat accumulation, greater than what can be attributed only by aging, which could magnify this period’s increased cardiovascular risk. Materials and Methods: We retrospectively analyzed two age and body mass index (BMI) propensity-matched subgroups each formed of 90 clinically healthy, 40–60-year-old postmenopausal women, within the first 5 and 5–10 years of MP. The 10-year ASCVD risk was assessed using medical history, anthropometric data, and lipid profile blood tests. The android-to-gynoid (A/G) ratio was computed using Lunar osteodensitometry lumbar spine and hip scans. Results: The A/G ratio was significantly higher for the subgroup evaluated in years 5–10 of MP than in the first 5 years of MP, even after controlling for BMI (1.05 vs. 0.99, p = 0.005). While displaying a significant negative correlation with HDL cholesterol (r = 0.406), the A/G ratio also had positive correlations with systolic blood pressure (BP) values (r = 0.273), triglycerides (r = 0.367), and 10-year ASCVD risk (r = 0.277). After adjusting for smoking, hypertension treatment, and type 2 diabetes, the 10-year ASCVD risk became significantly different for women in the first 5 years (3.28%) compared to those in years 5–10 of MP (3.74%), p = 0.047. Conclusions: In women with similar age and BMI, the A/G ratio appears to vary based on the number of years since menopause onset and correlates with either independent cardiovascular risk parameters like BP, triglycerides, and HDL cholesterol or with composite scores, such as 10-year ASCVD risk

Degraded Bone Microarchitecture in Women with PHPT–Significant Predictor of Fracture Probability

Introduction: Patients with primary hyperparathyroidism (PHPT) experience bone mineral density (BMD) loss and trabecular bone score (TBS) alteration, which current guidelines recommend assessing. Considering TBS alongside BMD for a 10-year fracture risk assessment (FRAX) may improve PHPT management. Design: Retrospective, cross-sectional study composed of 49 Caucasian females (62 ± 10.6 years, 27.7 ± 0.87 kg/m 2 ) with PHPT and 132 matched control subjects (61.3 ± 10.5 years, 27.5 ± 0.49 kg/m 2 ) evaluated in 3 years. We assessed lumbar spine (LS) and femoral neck (FN) BMD, T and Z scores (GE Healthcare Lunar Osteodensitometer) and TBS (iNsight 1.8), major osteoporotic fracture (MOF), and hip FRAX. Results: Patients with PHPT had statistically lower mean values for lumbar spine bone mineral density (LS BMD) (0.95 ± 0.25 vs 1.01 ± 0.14 g/cm 2 , P  = .01), LS T-scores (−2 ± 0.2 vs −1.4 ± 0.1 SD, P  = .009), LS Z scores (−0.9 ± 0.19 vs −0.1 ± 0.11 SD, P  = .009), femoral neck bone mineral density (FN BMD) (0.79 ± 0.02 vs 0.83 ± 0.01 g/cm 2 , P  = .02), FN T-scores (−1.8 ± 0.13 vs −1.5 ± 0.07 SD, P  = .017), FN Z scores (−0.51 ± 0.87 vs −0.1 ± 0.82 SD, P  = .006), and TBS (0.95 ± 0.25 vs 1.01 ± 0.14 g/cm 2 , P  = .01) compared with control subjects. 22.4% of patients with PHPT had degraded microarchitecture (TBS < 1.2) vs. 7.6% in control group (χ 2  = 0.008). PHPT proved to be a covariate with unique contribution ( P  = .031) alongside LS BMD ( P  = .040) in a linear regression model [ R 2  = 0.532, F(4,16)  = 4.543] for TBS < 1.2. TBS adjustment elevated MOF FRAX both for PHPT (4.35  ± 0.6% vs 5.25% ± 0.73%, P  < .001) and control groups (4.5  ± 0.24% vs 4.7% ± 0.26%, P  < .001) compared with BMD-bases FRAX, but also increased differently between the 2 study groups (1.1-folds for PHPT patients and 1.04 for control subjects, P  = .034). Conclusion: Compared with control, TBS-adjusted FRAX provides significantly higher MOF risk than BMD-based FRAX in PHPT women

Preconceptional Counseling in Women with Hyperthyroidism

Preconception evaluation of couples wishing to conceive is an important step toward a healthy pregnancy and it is especially important in people with a chronic condition or at genetic risk. The most common endocrine disorders in women at reproductive age are those involving the thyroid gland and it is well recognized that hyperthyroidism (HT), over-function of the thyroid gland, is associated with risks of maternal, fetal, and neonatal complications. The aim of this paper is to review the latest evidence regarding the components of preconception counseling in women with HT that contemplate a pregnancy. We also want to raise awareness among healthcare professionals about the importance of periconceptional counseling in improving pregnancy outcomes and avoid maternal and fetal complications related to thyroid dysfunction. In women with Graves’ disease seeking pregnancy, it is essential to discuss all the treatment options along with the associated risks and benefits. Extensive prospective studies are still needed to understand the implications of current recommended strategies for the management of HT in preconception and during pregnancy

Body Composition as a Modulator of Bone Health Changes in Patients with Inflammatory Bowel Disease

Background: Bone impairment of multifactorial etiology is a common feature in inflammatory bowel disease (IBD). Body composition parameters, which might be selectively modified in these patients, are important determinants of bone strength. Our aim was to investigate the relationship between components of body composition and bone parameters in IBD patients. Methods: This is a cross-sectional, retrospective study including 80 IBD patients (43 women, 37 men). Lumbar spine (LS), femoral neck (FN) and whole body DXA scans were performed to analyze regional bone mineral density (BMD), as well as body composition, including appendicular skeletal muscle mass index (ASMI), total and visceral fat mass (VAT). Trabecular bone score (TBS) was assessed using iNsight Software. Results: Twenty (25%) IBD patients had inadequate LS-BMD z scores (&lt;=&minus;2DS). Lean mass (LM) was a significant determinant of LS-BMD, after adjusting for age, gender, BMI and fat mass (p &lt; 0.01), while fat mass% remained associated with FN-BMD (p &lt; 0.01). TBS correlated positively with BMI (r = 0.24, p &lt; 0.05), LS-BMD (r = 0.56, p &lt; 0.001), ASMI (r = 0.34, p &lt; 0.001) and negatively with VAT/total fat% (r = &minus;0.27, p &lt; 0.05). Multivariate analysis showed that ASMI, LS-BMD (positively) and VAT/total fat% (negatively) were independently associated with TBS. Conclusions: In IBD patients, skeletal muscle mass and fat percentage and distribution are important factors associated with bone health

How Many Times Can One Go Back to the Drawing Board before the Accurate Diagnosis and Surgical Treatment of Glucagonoma?

Glucagonomas are neuroendocrine tumors (NETs) that arise from the alpha cells of the pancreatic islets. They are typically slow-growing tumors associated with abnormal glucagon secretion, resulting in one or more non-specific clinical features, such as necrolytic migratory erythema (NME), diabetes, diarrhea, deep vein thrombosis, weight loss, and depression. Here, we report the case of a 44-year-old male with a history of diabetes mellitus, presenting with a pruritic and painful disseminated cutaneous eruption of erythematous plaques, with scales and peripheral pustules, misdiagnosed as disseminated pustular psoriasis and treated for 2 years with oral retinoid and glucocorticoids. During this period, the patient complained of weight loss of 32 kg and diarrhea and developed deep vein thrombosis. These symptoms, together with an inadequate response to therapy of the skin lesions, led to the reassessment of the initial diagnosis. Laboratory tests confirmed elevated plasma glucagon levels (>1000 pg/mL) and computed tomography (CT) scans revealed a 35/44 mm tumor in the pancreatic tail. Due to considerable disease complications and the COVID-19 pandemic, the surgical removal of the tumor was delayed for nearly 2 years. During this time, somatostatin analogue therapy efficiently controlled the glucagonoma syndrome and likely prevented tumor progression. As in other functional pancreatic NETs, the early clinical recognition of hormonal hypersecretion syndrome and the multidisciplinary approach are the keys for best patient management