Epicardial fat thickness in type 2 diabetes outpatient care.

BACKGROUND AND AIM: Visceral fat is an independent predictor of the cardiovascular risk in subjects with type 2 diabetes (T2DM), but it is rarely assessed during an outpatient visit. Epicardial fat (EAT), the visceral fat of the heart, plays a role in coronary artery disease (CAD). EAT thickness can be clinically assessed with standard ultrasound. In this study we sought to evaluate the association of ambulatory ultrasound measured EAT thickness with CAD in asymptomatic well controlled T2DM subjects on metformin monotherapy during outpatient visits. METHODS AND RESULTS: This was single center, pragmatic study in 142 T2DM patients. Each subject underwent baseline ultrasound EAT thickness measurement, anthropometric and biomarkers. The incidence of CAD was detected after 1 year. At baseline, HbA1c was 6.7 % and BMI 34.9 kg/m2, EAT thickness was 8.3 ± 2.3 in women and 9.4 ± 2.4 mm in men, higher than threshold values for high cardiovascular risk. In multivariate models, EAT was the only statistically significant correlate of CAD at 1-year f/u (p = 0.04). CONCLUSIONS: Point of care ultrasound measured EAT thickness is a good correlate of CAD in well controlled and asymptomatic T2DM subjects on metformin monotherapy. EAT thickness predicted CAD better than traditional risk factors, such as BMI, HbA1c, age, blood pressure or duration of diabetes.

Amino acids contribute to adaptive thermogenesis. New insights into the mechanisms of action of recent drugs for metabolic disorders are emerging.

Adaptive thermogenesis is the heat production by muscle contractions (shivering thermogenesis) or brown adipose tissue (BAT) and beige fat (non-shivering thermogenesis) in response to external stimuli, including cold exposure. BAT and beige fat communicate with peripheral organs and the brain through a variegate secretory and absorption processes - controlling adipokines, microRNAs, extracellular vesicles, and metabolites - and have received much attention as potential therapeutic targets for managing obesity-related disorders. The sympathetic nervous system and norepinephrine-releasing adipose tissue macrophages (ATM) activate uncoupling protein 1 (UCP1), expressed explicitly in brown and beige adipocytes, dissolving the electrochemical gradient and uncoupling tricarboxylic acid cycle and the electron transport chain from ATP production. Mounting evidence has attracted attention to the multiple effects of dietary and endogenously synthesised amino acids in BAT thermogenesis and metabolic phenotype in animals and humans. However, the mechanisms implicated in these processes have yet to be conclusively characterized. In the present review article, we aim to define the principal investigation areas in this context, including intestinal microbiota constitution, adipose autophagy modulation, and secretome and metabolic fluxes control, which lead to increased brown/beige thermogenesis. Finally, also based on our recent epicardial adipose tissue results, we summarise the evidence supporting the notion that the new dual and triple agonists of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon (GCG) receptor - with never before seen weight loss and insulin-sensitizing efficacy - promote thermogenic-like amino acid profiles in BAT with robust heat production and likely trigger sympathetic activation and adaptive thermogenesis by controlling amino acid metabolism and ATM expansion in BAT and beige fat.

Targeting Epicardial Fat in Obesity and Diabetes Pharmacotherapy.

Epicardial adipose tissue surrounds and infiltrates the heart. Epicardial fat displays unique anatomic, genetic, and biomolecular properties. People with obesity and in particular, those with abdominal obesity and associated type 2 diabetes mellitus, have an increased amount of epicardial adipose tissue (EAT). Epicardial fat works well as therapeutic target due to its fast-responding metabolism, organ fat specificity, and easy measurability. Epicardial fat responds to thiazolidinediones (TZD), glucagon-like peptide 1-receptor agonists (GLP1A), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i), and statins. Modulating epicardial fat morphology and genetic profile with targeted pharmacological agents suggests novel strategies in the pharmacotherapy of diabetes and obesity.

The density of crown-like structures in epicardial adipose tissue could play a role in cardiovascular diseases.

PURPOSE: The visceral fat of patients affected by abdominal obesity is inflamed, and the main histopathologic feature is the high density of crown-like structures (CLS). Epicardial adipose tissue (EAT) is a visceral fat of paramount importance for its relationships with coronary vessels and myocardium. Its inflammation in patients with abdominal obesity could be of clinical relevance, but histopathological studies on CLS density in EAT are lacking. This study aimed to assess the histopathology of EAT biopsies obtained from patients undergoing open-heart surgery. METHODS: We collected EAT biopsies from 10 patients undergoing open-heart surgery for elective coronary artery bypass grafting (CABG) (n = 5) or valvular replacement (VR) (n = 5). Biopsies were treated for light microscopy and immunohistochemistry. We quantify the CLS density in each EAT sample. RESULTS: Despite all patients having abdominal obesity, in EAT samples, no CLS were detected in the VR group; in contrast, CLS were detected in the CABG group (about 17 CLS/104 adipocytes vs. 0.0 CLS/104 adipocytes, CABG vs. VR group, respectively). An impressive density of CLS (100 times that of other patients) was found in one patient (LS) in the CABG group that had a relevant anamnestic aspect: relatively rapid increase of weight gain, especially in abdominal adipose tissue, coincident with myocardial infarction. CONCLUSIONS: CLS density could be an important predictive tool for cardiovascular diseases. Furthermore, the LS case implies a role for timing in weight gain. LEVEL OF EVIDENCE: No level of evidence; this is a basic science study.

Abdominal obesity phenotype is associated with COVID-19 chest X-ray severity score better than BMI-based obesity.

PURPOSE: Chest X-ray (CXR) severity score and BMI-based obesity are predictive risk factors for COVID-19 hospital admission. However, the relationship between abdominal obesity and CXR severity score has not yet been fully explored. METHODS: This retrospective cohort study analyzed the association of different adiposity indexes, including waist circumference and body mass index (BMI), with CXR severity score in 215 hospitalized patients with COVID-19. RESULTS: Patients with abdominal obesity showed significantly higher CXR severity scores and had higher rates of CXR severity scores ≥ 8 compared to those without abdominal obesity (P < 0.001; P = 0.001, respectively). By contrast, patients with normal weight, with overweight and those with BMI-based obesity showed no significant differences in either CXR severity scores or in the rates of CXR severity scores ≥ 8 (P = 0.104; P = 0.271, respectively). Waist circumference and waist-to-height ratio (WHtR) correlated more closely with CXR severity scores than BMI (r = 0.43, P < 0.001; r = 0.41, P < 0.001; r = 0.17, P = 0.012, respectively). The area under the curves (AUCs) for waist circumference and WHtR were significantly higher than that for BMI in identifying a high CXR severity score (≥ 8) (0.68 [0.60-0.75] and 0.67 [0.60-0.74] vs 0.58 [0.51-0.66], P = 0.001). A multivariate analysis indicated abdominal obesity (risk ratio: 1.75, 95% CI: 1.25-2.45, P < 0.001), bronchial asthma (risk ratio: 1.73, 95% CI: 1.07-2.81, P = 0.026) and oxygen saturation at admission (risk ratio: 0.96, 95% CI: 0.94-0.97, P < 0.001) as the only independent factors associated with high CXR severity scores. CONCLUSION: Abdominal obesity phenotype is associated with a high CXR severity score better than BMI-based obesity in hospitalized patients with COVID-19. Therefore, when visiting the patient in a hospital setting, waist circumference should be measured, and patients with abdominal obesity should be monitored closely. Level of evidence Cross-sectional descriptive study, Level V.

Liraglutide hospital discharge trial: A randomized controlled trial comparing the safety and efficacy of liraglutide versus insulin glargine for the management of patients with type 2 diabetes after hospital discharge.

AIM: To compare a glucagon-like peptide-1 receptor agonist with basal insulin at hospital discharge in patients with uncontrolled type 2 diabetes in a randomized clinical trial. METHODS: A total of 273 patients with glycated haemoglobin (HbA1c) 7%-10% (53-86 mol/mol) were randomized to liraglutide (n = 136) or insulin glargine (n = 137) at hospital discharge. The primary endpoint was difference in HbA1c at 12 and 26 weeks. Secondary endpoints included hypoglycaemia, changes in body weight, and achievement of HbA1c <7% (53 mmol/mol) without hypoglycaemia or weight gain. RESULTS: The between-group difference in HbA1c at 12 weeks and 26 weeks was -0.28% (95% CI -0.64, 0.09), and at 26 weeks it was -0.55%, (95% CI -1.01, -0.09) in favour of liraglutide. Liraglutide treatment resulted in a lower frequency of hypoglycaemia <3.9 mmol/L (13% vs 23%; P = 0.04), but there was no difference in the rate of clinically significant hypoglycaemia <3.0 mmol/L. Compared to insulin glargine, liraglutide treatment was associated with greater weight loss at 26 weeks (-4.7 ± 7.7 kg vs -0.6 ± 11.5 kg; P < 0.001), and the proportion of patients with HbA1c <7% (53 mmol/mol) without hypoglycaemia was 48% versus 33% (P = 0.05) at 12 weeks and 45% versus 33% (P = 0.14) at 26 weeks in liraglutide versus insulin glargine. The proportion of patients with HbA1c <7% (53 mmol/mol) without hypoglycaemia and no weight gain was higher with liraglutide at 12 (41% vs 24%, P = 0.005) and 26 weeks (39% vs 22%; P = 0.014). The incidence of gastrointestinal adverse events was higher with liraglutide than with insulin glargine (P < 0.001). CONCLUSION: Compared to insulin glargine, treatment with liraglutide at hospital discharge resulted in better glycaemic control and greater weight loss, but increased gastrointestinal adverse events.

Effect of caloric restriction with or without physical activity on body composition and epicardial fat in type 2 diabetic patients: A pilot randomized controlled trial.

BACKGROUND AND AIMS: There is debate over the independent and combined effects of caloric restriction (CR) and physical activity (PA) on reduction in fat mass and in epicardial fat thickness. We compared the impact of a similar energy deficit prescription by CR or by CR combined with PA on total fat mass, epicardial fat thickness, and cardiometabolic profile in individuals with type 2 diabetes. METHODS AND RESULTS: In this 16-week randomized controlled study, 73 individuals were randomly enrolled to receive: 1) a monthly motivational phone call (Control), 2) a caloric deficit of -700 kilocalories/day (CR), or 3) a caloric deficit of -500 kilocalories/day combined with a PA program of -200 kilocalories/day (CR&PA). Total fat mass, epicardial fat, and cardiometabolic profile were measured at baseline and after 16 weeks. While comparable weight loss occurred in both intervention groups (-3.9 ± 3.5 kg [CR], -5.1 ± 4.7 kg [CR&PA], -0.2 ± 2.9 kg [Control]), changes in total fat mass were significantly different between all groups (-2.4 ± 2.9 kg [CR], -4.5 ± 3.4 kg [CR&PA], +0.1 ± 2.1 kg [Control]; p < 0.05) as well as epicardial fat thickness (-0.4 ± 1.6 mm [CR], -1.4 ± 1.4 mm [CR&PA], +1.1 ± 1.3 mm [Control]; p < 0.05). There were no significant differences in trends for cardiometabolic parameters improvement between groups. CONCLUSIONS: For a similar energy deficit prescription and comparable weight loss, the combination of CR&PA provides a greater reduction in fat mass and epicardial fat thickness than CR alone in individuals with comparable weight loss and with a similar energy deficit prescription. These results, however, do not translate into significant improvements in cardiometabolic profiles. CLINICALTRIALS. GOV IDENTIFIER: NCT01186952.

Tri-Ponderal Mass Index vs body Mass Index in discriminating central obesity and hypertension in adolescents with overweight.

BACKGROUND AND AIMS: Recently, it has been hypothesized that Tri-Ponderal Mass Index (TMI) may be a valid alternative to Body Mass Index (BMI) when measuring body fat in adolescents. We aimed to verify whether TMI has better accuracy than BMI in discriminating central obesity and hypertension in adolescents with overweight. METHODS AND RESULTS: This monocentric and retrospective cross-sectional study included 3749 pupils, 1889 males and 1860 females, aged 12-13. BMI (kg/m2) was calculated and expressed as percentiles and as z-scores. TMI (kg/m3) was calculated, and we used pre-defined cut-off previously proposed by Peterson et al.. For central obesity we adopted the Waist-to-Height Ratio (WHtR) discriminatory value of 0.5. Hypertension was defined as blood pressure ≥95th percentile of age- sex-, and height-specific references recommended by NHBPEP Working Group. The discriminant ability of TMI, BMI and BMI z-score, with respect to central obesity and hypertension, was investigated using non-parametric receiver operating characteristic analysis. The overall misclassification rate for central obesity was 8.88% for TMI vs 14.10% for BMI percentiles and vs 14.92% for BMI z-scores (P < 0.001). The overall misclassification rate for hypertension was 7.50% for TMI vs 22.03% for BMI percentiles and vs 25.19% for BMI z-scores (P < 0.001). CONCLUSION: TMI is a superior body fat index and it could discriminate body fat distribution more accurately than BMI. This supports the use of TMI, in association with WHtR, to characterize adolescents with overweight and high cardio-metabolic risk. Our analysis needs to be extended to other ethnic groups and replicated in a wider age range and in longitudinal studies.

Epicardial Adipose Tissue: Clinical Biomarker of Cardio-Metabolic Risk.

Epicardial adipose tissue (EAT) is part of the visceral adipose tissue (VAT) that surrounds the heart and it is a quantifiable, modifiable, and multifaceted tissue that has both local and systemic effects. When EAT is enlarged, EAT contributes to atherosclerotic cardiovascular disease (ASCVD) risk and plays a role in the development of metabolic syndrome (MetS). In this review, we will discuss the role of EAT in various facets of MetS, including type 2 diabetes mellitus (T2DM) and insulin resistance. We examine the association between EAT and liver steatosis. We also address the correlations of EAT with HIV therapy and with psoriasis. We discuss racial differences in baseline EAT thickness. We conclude that EAT measurement serves as a powerful potential diagnostic tool in assessing cardiovascular and metabolic risk. Measurement of EAT is made less costly, more convenient, and yet accurate and reliable by transthoracic echocardiography. Furthermore, modification of EAT thickness has therapeutic implications for ASCVD, T2DM, and MetS.

Epicardial Fat Thickness in Non-Obese Neurologically Impaired Children: Association with Unfavorable Cardiometabolic Risk Profile.

BACKGROUND: Cardiovascular risk is reported in disabled children and epicardial fat (EF) is considered an independent predictor of cardiovascular disease (CVD). No data on the EF thickness (EFT) evaluation in disabled children have been published. OBJECTIVE: We investigated EFT in neurologically impaired (NI) children; its relationship with their metabolic profile was also considered. METHODS: Clinical data, body composition estimation, biochemical profile, and ultrasound-measured EFT were performed in 32 disabled patients (12.4 ± 6.3 years). Pathological parameters were defined using the following criteria: waist circumference >95th percentile, waist to height ratio (WHtR) >0.5, total cholesterol and triglycerides (TG) values >95th percentile, high density lipoprotein cholesterol <5th percentile, fasting blood glucose >100 mg/dL, homeostasis model assessment for insulin resistance (HOMA) >97.5th percentile, and EFT >3.6 mm. RESULTS: EFT values in NI children were higher compared with control group values (p = 0.02). EFT correlated with gender (p < 0.001), age (p = 0.02), pubertal stage (p = 0.04), as well as WHtR (p = 0.03). A correlation between EFT and leptin was also noted (p = 0.04). EFT levels significantly correlated with pathological TG (p = 0.01) and HOMA-IR (p = 0.04). CONCLUSIONS: Higher EFT was observed in NI children compared with controls. EFT values correlated with clinical, metabolic, and endocrinological parameters. Ultrasound-measured EFT could be used to promptly detect subclinical CVD and to prevent adverse outcomes in disabled children.

Human Epicardial Fat Expresses Glucagon-Like Peptide 1 and 2 Receptors Genes.

Epicardial adipose tissue (EAT) is an easily measurable visceral fat of the heart with unique anatomy, functionality, and transcriptome. EAT can serve as a therapeutic target for pharmaceutical agents targeting the fat. Glucagon-like peptide-1 (GLP-1) and GLP-2 analogues are newer drugs showing beneficial cardiovascular and metabolic effects. Whether EAT expresses GLP- 1 and 2 receptors (GLP-1R and GLP-2R) is unknown. RNA-seq analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to evaluate the presence of GLP-1R and GLP-2R in EAT and subcutaneous fat (SAT) obtained from 8 subjects with coronary artery disease and type 2 diabetes mellitus undergoing elective cardiac surgery. Immunofluorescence was also performed on EAT and SAT samples using Mab3f52 against GLP-1R. Our RNA-sequencing (RNA-seq) analysis showed that EAT expresses both GLP-1R and GLP-2R genes. qRT-PCR analysis confirmed that GLP-1R expression was low but detected by 2 different sets of intron-spanning primers. GLP-2R expression was detected in all patients and was found to be 5-fold higher than GLP-1R. The combination of accurately spliced reads from RNA-seq and successful amplification using intron-spanning primers indicates that both GLP-1R and GLP-2R are expressed in EAT. Immunofluorescence clearly showed that GLP-1R is present and more abundant in EAT than SAT. This is the first time that human EAT is found to express both GLP-1R and GLP-2R genes. Pharmacologically targeting EAT may induce beneficial cardiovascular and metabolic effects.

Epicardial fat thickness correlates with carotid intima-media thickness, arterial stiffness, and cardiac geometry in children and adolescents.

To determine the association between epicardial fat thickness and carotid arterial stiffness, carotid intima-media thickness (CMIT), left atrial (LA) volume, and left-ventricular (LV) geometry parameters in obese children and adolescents compared with controls. A case-control study was performed in 96 children and adolescents (obese n = 66, controls n = 30) age 9-16 years old (38 female and 58 male, mean age 11.7 ± 2.8 years) undergoing transthoracic echocardiography and carotid artery ultrasound. Clinical, anthropometric, and biochemical determinations were also recorded. Epicardial fat thickness (2.76 ± 1.2 vs. 1.36 ± 0.7 mm, p < 0.001), LA volume (35.7 ± 13.2 vs. 28.9 ± 9.8 mL, p = 0.008), LV mass (118.3 ± 38.6 vs. 96.4 ± 35.4 mL, p = 0.008), CIMT (0.48 ± 0.07 vs. 0.44 ± 0.05 mm, p = 0.019), and local pulse wave velocity (LPWV; 3.7 ± 0.5 vs. 3.2 ± 0.4 m/seg, p = 0.007) were significantly increased in obese children and adolescents compared with controls. Epicardial fat showed a significant and positive correlation with LA volume, LV mass, and LPWV as well as a significant and independent association with increased CIMT (odds ratio (OR) = 3.19 [1.88-7.99], p = 0.005) in the study population. Epicardial fat thickness is linked to obesity, carotid subclinical atherosclerosis, and cardiac geometry parameters and might be a useful tool for the cardiovascular risk stratification in children and adolescents.

Targeting the Substrate for Atrial Fibrillation: JACC Review Topic of the Week.

The identification of the pulmonary veins as a trigger source for atrial fibrillation (AF) has established pulmonary vein isolation (PVI) as a key target for AF ablation. However, PVI alone does not prevent recurrent AF in many patients, and numerous additional ablation strategies have failed to improve on PVI outcomes. This therapeutic limitation may be due, in part, to a failure to identify and intervene specifically on the pro-fibrillatory substrate within the atria and pulmonary veins. In this review paper, we highlight several emerging approaches with clinical potential that target atrial cardiomyopathy-the underlying anatomic, electrical, and/or autonomic disease affecting the atrium-in various stages of practice and investigation. In particular, we consider the evolving roles of risk factor modification, targeting of epicardial adipose tissue, tissue fibrosis, oxidative stress, and the inflammasome, along with aggressive early anti-AF therapy in AF management. Attention to combatting substrate development promises to improve outcomes in AF.

Epicardial fat links obesity to cardiovascular diseases.

Patients with obesity have been historically associated with higher risk to develop cardiovascular diseases (CVD). However, regional, visceral, organ specific adiposity seems to play a stronger role in the development of those cardiovascular diseases than obesity by itself. Epicardial adipose tissue is the visceral fat depot of the heart with peculiar anatomy, regional differences, genetic profile and functions. Due to its unobstructed contiguity with heart and intense pro inflammatory and pro arrhythmogenic activities, epicardial fat is directly involved in major obesity-related CVD complications, such as coronary artery disease (CAD), atrial fibrillation (AF) and heart failure (HF). Current and developing imaging techniques can measure epicardial fat thickness, volume, density and inflammatory status for the prediction and stratification of the cardiovascular risk in both symptomatic and asymptomatic obese individuals. Pharmacological modulation of the epicardial fat with glucagon like peptide-1 receptor (GLP1R) analogs, sodium glucose transporter-2 inhibitors, and potentially dual (glucose-dependent insulinotropic polypeptide -GLP1R) agonists, can reduce epicardial fat mass, resume its original cardio-protective functions and therefore reduce the cardiovascular risk. Epicardial fat assessment is poised to change the traditional paradigm that links obesity to the heart.

Weight Loss Effects of Glucagon-Like Peptide-One Receptor Analog Treatment in a Severely Obese Patient During Hospital Admission.

Obesity is considered an independent risk factor for increased hospital length of stay and can be an obstacle to a safe discharge. Although typically prescribed in the outpatient setting, initiating glucagon-like peptide-one receptor agonists (GLP-1RAs) in the inpatient setting can be efficacious in reducing weight and increasing functional status. We report the use of GLP-1RA therapy with liraglutide and subsequent transition to subcutaneous semaglutide weekly in a 37-year-old female with severe obesity, weighing 694 lbs (314 kg) with a body mass index (BMI) of 108 kg/m2. Multiple medical and socioeconomic factors impaired the patient from being safely discharged and ultimately led to prolonged hospitalization. The patient received 31 consecutive weeks of GLP-1RA therapy in the inpatient setting along with a very low-calorie diet (800 kcal/day). Initiation and up-titration doses were completed using liraglutide for a total of five weeks. Subsequently, the patient was transitioned to receive weekly semaglutide and completed 26 weeks of therapy. At the end of week 31, the patient's weight decreased by 174 lbs (79 kg), or 25% of baseline weight, and BMI decreased from 108 to 81 kg/m2. GLP-1RAs offer a promising avenue for weight loss interventions in patients with severe obesity in addition to lifestyle modifications. The weight loss observed in our patient at the halfway point of the total treatment duration is a milestone in the pathway to gaining functional independence and meeting the criteria for future bariatric surgery. Semaglutide, a GLP-1RA, can be an effective intervention for severely obese patients with BMI greater than 100 kg/m2.

Comparison of Glycemic Control Between In-Person and Virtual Diabetes Consults in Hospitalized Patients With Diabetes.

BACKGROUND: There is limited evidence that the diabetes in-person consult in hospitalized patients can be replaced by a virtual consult. During COVID-19 pandemic, the diabetes in-person consult service at the University of Miami and Miami Veterans Affairs Healthcare System transitioned to a virtual model. The aim of this study was to assess the impact of telemedicine on glycemic control after this transition. METHODS: We retrospectively analyzed glucose metrics from in-person consults (In-person) during January 16 to March 14, 2020 and virtual consults during March 15 to May 14, 2020. Data from virtual consults were analyzed by separating patients infected with COVID-19, who were seen only virtually (Virtual-COVID-19-Pos), and patients who were not infected (Virtual-COVID-19-Neg), or by combining the two groups (Virtual-All). RESULTS: Patient-day-weighted blood glucose was not significantly different between In-person, Virtual-All, and Virtual-COVID-19-Neg, but Virtual-COVID-19-Pos had significantly higher mean ± SD blood glucose (mg/dL) compared with others (206.7 ± 49.6 In-person, 214.6 ± 56.2 Virtual-All, 206.5 ± 57.2 Virtual-COVID-19-Neg, 229.7 ± 51.6 Virtual-COVID-19-Pos; P = .015). A significantly less percentage of patients in this group also achieved a mean ± SD glucose target of 140 to 180 mg/dL (23.8 ± 22.5 In-person, 21.5 ± 20.5 Virtual-All, 25.3 ± 20.8 Virtual-COVID-19-Neg, and 14.4±18.1 Virtual-COVID-19-Pos, P = .024), but there was no significant difference between In-person, Virtual-All, and Virtual-COVID-19-Neg. The occurrence of hypoglycemia was not significantly different among groups. CONCLUSIONS: In-person and virtual consults delivered by a diabetes team at an academic institution were not associated with significant differences in glycemic control. These real-world data suggest that telemedicine could be used for in-patient diabetes management, although additional studies are needed to better assess clinical outcomes and safety.

Semaglutide therapy decreases epicardial fat inflammation and improves psoriasis severity in patients affected by abdominal obesity and type-2 diabetes.

Summary: Psoriasis is often associated with abdominal obesity and type-2 diabetes (T2D). The inflammatory process in psoriasis can target adipose tissue depots, especially those surrounding the heart and coronary arteries, exposing to an increased risk of cardiovascular diseases. A 50-year-old female patient referred to us for abdominal obesity and T2D, which were not controlled with lifestyle modifications. She had suffered from psoriasis for some years and was treated with guselkumab, without success. Epicardial adipose tissue (EAT) attenuation and pericoronary adipose tissue (PCAT) attenuation for each coronary, defined as mean attenuation expressed in Hounsfield unit (HU), were assessed by routine coronary computed tomography angiography. At baseline, EAT attenuation was -80 HU and PCAT attenuation of the right coronary artery (RCA) was -68 HU, values associated with an increased cardiac mortality risk. Psoriasis area and severity index (PASI) was 12.0, indicating severe psoriasis, while dermatology life quality index (DLQI) was 20, indicating a negative effect on the patient's life. Semaglutide (starting with 0.25 mg/week for 4 weeks, increased to 0.50 mg/week for 16 weeks, and then to 1 mg/week) was started. After 10 months, semaglutide treatment normalized glycated hemoglobin and induced weight loss, particularly at abdominal level, also followed by a reduction in computed tomography-measured EAT volume. EAT attenuation and PCAT attenuation of RCA decreased, showing an important reduction of 17.5 and 5.9% respectively, compared with baseline. PASI and DLQI decreased by 98.3 and 95% respectively, indicating an improvement in psoriasis skin lesions and an important amelioration of the patient's quality of life, compared with baseline. Learning points: Psoriasis patients affected by obesity and type-2 diabetes (T2D) are often resistant to biologic therapies. Psoriasis is often associated with abdominal obesity, T2D, and cardiovascular diseases (CVD), given their shared inflammatory properties and pathogenic similarities. Epicardial adipose tissue (EAT) inflammation can cause the distinctive pattern of CVD seen in psoriasis. EAT and pericoronary adipose tissue (PCAT) attenuation, assessed by routine coronary computed tomography angiography (CCTA), can be used as biomarkers of inflammation and allow monitoring of medical anti-inflammatory therapies. The actions of semaglutide to reduce energy intake, improve glycemic control, and produce effective weight loss, particularly at the visceral fat depot level, can diminish adipose tissue dysfunction, reduce EAT attenuation and PCAT attenuation of the right coronary artery (RCA) and concomitantly ameliorate the clinical severity of psoriasis. Semaglutide therapy may be considered in psoriasis patients affected by T2D and abdominal obesity, despite low cardiovascular risk by traditional risk scores, who are resistant to biologic therapies.