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PURPOSE: Patients with tumors involving the hypothalamic region are at high risk of developing morbid obesity due to disturbances in the appetite regulative nuclei in hypothalamus. We evaluated the effect of the Glucagon-like peptide 1 (GLP-1) analogue semaglutide in patients with hypothalamic obesity. METHODS: We recorded weight changes from real-time data before and after treatment with semaglutide in patients with hypothalamic obesity from our outpatient clinic at the Department of Endocrinology at Rigshospitalet, from September 2020 to November 2023. RESULTS: A total of 26 patients were included in this study (15 females, median age at initiation of semaglutide was 52 (range 18-65) years). Body mass index (BMI) at initial diagnosis was median 25 (range 20-38) kg/m2 while BMI at initiation of semaglutide was median 38 (range 28-58) kg/m2. All but one patient lost weight during semaglutide treatment with a mean weight loss of 13.4 kg (95% CI 10.3-16.5 kg, p = < 0.001) after 12 months corresponding to a loss in BMI of 4.4 kg/m2 (95% CI 3.4-5.4 kg/m2, p = < 0.001) with a median dosage of semaglutide of 1.6 (range 0.5-2.5) mg. Fifteen patients (58%) lost more than 10% and two patients (8%) lost more than 20% of initial body weight, respectively. CONCLUSION: Treatment with semaglutide shows promising results in reducing body weight in patients with acquired hypothalamic obesity. Whether the weight reduction remains stable after long time follow-up needs further investigation.
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BACKGROUND: Accelerometer-measured physical activity is an increasingly used endpoint in heart failure (HF) trials. We investigated the determinants of accelerometer-measured physical activity and the relationship with patient-reported health status. METHODS: Post-hoc analysis of the Empire HF trial, including outpatients with HF with reduced ejection fraction (HFrEF). Physical activity was quantified as average accelerometer counts per minute (CPM) with higher values representing higher activity. We investigated associations between activity level and clinical variables, including age, sex, and body mass index, as well as patient-reported health status assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ). RESULTS: Complete data were available in 180 (95%) patients (86% male, mean age 65 year). Baseline median physical activity level was 1318 CPM (Q1-Q3 1111-1585). Age and anemia were independently associated with activity level (ß-coefficients: -10 CPM per year age increase [95% CI -16 to -5.1], p=0.00015, and -126 CPM for anemia [95% CI -9.1 to -244], p=0.035). Significant independent associations were observed between activity level and all KCCQ summary scores (ß-coefficient point estimates of 3.7, 4.6, and 4.9 CPM, all p<0.02). For 12-week changes in KCCQ-summary scores, only the KCCQ-CSS was associated with activity level; mean increase of 17.5 CPM [95% CI 1.5 to 34.0], p=0.032, per 5-point increase in KCCQ-CSS. Associations were not modified by treatment allocation (interaction p-values>0.05). CONCLUSIONS: In patients with HFrEF, older age and anemia were independently associated with lower activity. Moreover, physical activity only weakly increased with better health status, suggesting that changes in physical activity reflect improvements in patients' health status to a limited degree. This highlights the need to better understand the endpoint with regards to all other health parameters to ease interpretation in future HF trials.
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AIMS: Patients with type 2 diabetes (T2D) have a high prevalence of diastolic dysfunction and heart failure with preserved ejection fraction (HFpEF), which in turn leads to an increased risk of hospitalization and death. However, the factors of risk and their relative importance in leading to higher left ventricular filling pressures are still disputed. We sought to clarify the associations of a wide range of invasive and non-invasive risk factors with cardiac filling pressures in high-risk T2D patients. METHODS AND RESULTS: Patients with T2D at high risk of cardiovascular events were prospectively enrolled in this study. Participants were thoroughly phenotyped including right heart catheterization at rest and during exercise, echocardiography, urinary excretion of albumin (UACR), and quantification of their myocardial blood flow rate (MFR) using cardiac 82Rb-PET/CT. Of the 37 patients included in the study, 22 (59%) patients met invasive criteria for HFpEF. Only 2 out of 39 variables emerged as independent factors associated with left ventricular filling pressure as assessed by pulmonary capillary wedge pressure (PCWP) at rest; history of hypertension (coefficient: 2.6 mmHg [0.3; 5.0], P = 0.030) and MFR (P = 0.026). We found a significant inverse association between MFR and PCWP with a coefficient of -2.3 mmHg (-4.3; -0.3) in PCWP per integer change of MFR. The MFR ranged from 1.18 to 3.68 in our study, which corresponds to a difference in PCWP of approximately 6 mmHg between patients with the lowest compared to the highest MFR. During exercise, only 2 variables emerged as borderline independent factors associated with PCWP: myocardial flow reserve (coefficient: -4.4 [-9.6; 0.8], P = 0.091) and beta-blockers use (coefficient: 6.1 [-0.1; 12.4], P = 0.053). CONCLUSIONS: In patients with type 2 diabetes without known HFpEF but risk factors for cardiovascular disease, myocardial blood flow rate was independently associated with PCWP at rest across the range from normal to abnormal left heart filling pressures. A clinically significant difference of 6 mmHg in PWCP was attributable to differences in MFR in patients with the lowest compared with the highest MFR values. This suggests that strategies than attenuate microvascular dysfunction could slow progression of increased left ventricular left heart filling pressures in patients at increased risk.
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INTRODUCTION: The use of androgenic anabolic steroids (AASs) among recreational athletes is steadily increasing. However, knowledge regarding the potentially harmful effects of AAS primarily originates from case reports and small observational studies. This large-scale study aims to investigate the impact of AAS use on vascular plaque formation, preclinical coronary disease, cardiac function, circulating cardiovascular risk markers, quality of life (QoL) and mental health in a broad population of illicit AAS users. METHODS AND ANALYSES: A nationwide cross-sectional cohort study including a diverse population of men and women aged ≥18 years, with current or previous illicit AAS use for at least 3 months. Conducted at Odense University Hospital, Denmark, the study comprises two parts. In part A (the pilot study), 120 recreational athletes with an AAS history will be compared with a sex-matched and age-matched control population of 60 recreational athletes with no previous AAS use. Cardiovascular outcomes include examination of non-calcified coronary plaque volume and calcium score using coronary CT angiography, myocardial structure and function via echocardiography, and assessing carotid and femoral artery plaques using ultrasonography. Retinal microvascular status is evaluated through fundus photography. Cardiovascular risk markers are measured in blood. Mental health outcomes include health-related QoL, interpersonal difficulties, body image concerns, aggression dimensions, anxiety symptoms, depressive severity and cognitive function assessed through validated questionnaires. The findings of our comprehensive study will be used to compose a less intensive investigatory cohort study of cardiovascular and mental health (part B) involving a larger group of recreational athletes with a history of illicit AAS use. ETHICS AND DISSEMINATION: The study received approval from the Regional Committee on Health Research Ethics for Southern Denmark (S-20210078) and the Danish Data Protection Agency (21/28259). All participants will provide signed informed consent. Research outcomes will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT05178537.
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Atletas , Dopagem Esportivo , Saúde Mental , Qualidade de Vida , Adulto , Feminino , Humanos , Masculino , Anabolizantes/efeitos adversos , Esteróides Androgênicos Anabolizantes , Androgênios/efeitos adversos , Atletas/psicologia , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Estudos Transversais , Dinamarca/epidemiologia , Fatores de Risco de Doenças Cardíacas , Projetos Piloto , Projetos de Pesquisa , Congêneres da Testosterona/efeitos adversosRESUMO
INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have previously demonstrated cardioprotective properties in patients with type 2 diabetes, suggesting a preventive effect on heart failure (HF). The Empire Prevent trial program investigates the therapeutic potential for HF prevention by evaluating the cardiac, metabolic, and renal effects of the SGLT2 inhibitor empagliflozin in patients with increased risk of developing HF, but without diabetes or established HF. METHODS: The Empire Prevent trial program is an investigator-initiated, double-blind, randomized clinical trial program including elderly and obese patients (60-84 years, body mass index >28 kg/m2) with at least one manifestation of hypertension, cardiovascular or chronic kidney disease, but no history of diabetes or HF. The aims are to investigate the effects of empagliflozin on 1) physical capacity and left ventricular and atrial structural changes with peak oxygen consumption and left ventricular mass as primary endpoints (Empire Prevent Cardiac), and 2) cardiac-adipose tissue interaction and volume homeostasis with primary endpoints of changes in epicardial adipose tissue and estimated extracellular volume (Empire Prevent Metabolic). At present, 138 of 204 patients have been randomized in the Empire Prevent trial program. Patients are randomized 1:1 to 180 days treatment with empagliflozin 10 mg daily or placebo, while undergoing a comprehensive examination program at baseline and follow-up. DISCUSSION: The Empire Prevent trial program will mark the first step towards elucidating the potential of SGLT2 inhibition for HF prevention in an outpatient setting in elderly and obese patients with increased risk of developing HF, but with no history of diabetes or established HF. Furthermore, the Empire Prevent trial program will supplement the larger event-driven trials by providing mechanistic insights to the beneficial effects of SGLT2 inhibition. TRIAL REGISTRATION: Both parts of the trial program have been registered on September 13th 2021 (Clinical Trial Registration numbers: NCT05084235 and NCT05042973) before enrollment of the first patient. All patients will provide oral and written informed consent. The trial is approved by The Regional Committee on Health Research Ethics and the Danish Medicines Agency. Data will be disseminated through scientific meetings and peer-reviewed journals irrespective of outcome.
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Compostos Benzidrílicos , Glucosídeos , Insuficiência Cardíaca , Obesidade , Inibidores do Transportador 2 de Sódio-Glicose , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/prevenção & controle , Insuficiência Cardíaca/etiologia , Obesidade/complicações , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Acromegaly is a rare disease and thus challenging to accurately quantify epidemiologically. In this comprehensive literature review, we compare different approaches to studying acromegaly from an epidemiological perspective and describe the temporal evolution of the disease pertaining to epidemiological variables, clinical presentation and mortality. We present updated epidemiological data from the population-based Danish cohort of patients with acromegaly (AcroDEN), along with meta-analyses of existing estimates from around the world.Based on this, we conclude that the incidence, prevalence and age at acromegaly diagnosis are all steadily increasing, but with considerable variation between studies. An increased number of incidental cases may contribute to the increase in incidence and age at diagnosis, respectively. The clinical features at presentation are trending toward a milder disease phenotype at diagnosis, and advances in therapeutic options have reduced the mortality of patients with acromegaly to a level similar to that of the general population. Moreover, the underlying cause of death has shifted from cardiovascular to malignant neoplastic diseases.
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Acromegalia , Humanos , Acromegalia/epidemiologia , Acromegalia/diagnóstico , Acromegalia/terapia , Prevalência , Incidência , Dinamarca/epidemiologiaRESUMO
BACKGROUND: The inherited X-linked disorder, Fabry disease, is caused by deficient lysosomal enzyme α-galactosidase A, with progressive accumulation of globotriaosylceramide in multiple organs including the upper and lower airways. OBJECTIVES: To assess pulmonary function at the time of the first pulmonary function test (PFT) performed among the National Danish Fabry cohort and define the prevalence of affected lung function variables. MATERIALS AND METHOD: A cross-sectional retrospective cohort study of 86 adult patients enrolled in one or both international patient registry databases for Fabry disease, Fabry Registry or FollowME with at least one PFT. The Mainz Severity Score Index (MSSI) was calculated to determine the disease severity. Lung function variables were examined by multivariate regression adjusted for important variables for developing airway illness. RESULTS: Seventeen patients (20%) showed obstructive airflow limitation and 7 (8%) a restrictive lung deficiency. Smoking status (p = .016) and MSSI (p < .001) were associated with increasing obstructive airway limitation. CONCLUSION: The prevalence of affected lung function among the National Danish Fabry cohort was 28%. Patients with classic gene variants frequently developed a decrease in lung function regardless of their smoking status, with significant relationship with disease severity.
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Doença de Fabry , Adulto , Humanos , Doença de Fabry/complicações , Doença de Fabry/epidemiologia , Doença de Fabry/genética , Estudos Transversais , Estudos Retrospectivos , alfa-Galactosidase/genética , PulmãoRESUMO
AIMS: In patients with chronic heart failure with reduced ejection fraction (HFrEF), myocardial ketone metabolism is increased and short-term treatment with the ketone body 3-hydroxy butyrate (3-OHB) has beneficial haemodynamic effects. In patients with HFrEF, we investigated whether the level of circulating 3-OHB predicted all-cause mortality and sought to identify correlations between patient characteristics and circulating 3-OHB levels. METHODS AND RESULTS: We conducted a cohort study in 218 patients with HFrEF. Plasma 3-OHB levels were measured using high-performance liquid chromatography tandem mass spectrometry. Data on all-cause mortality were obtained by reviewing the patients' medical records, which are linked to the national 'Central Person Registry' that registers the timing of all deaths in the country. Mean left ventricular ejection fraction was 35 ± 8.6%, mean age was 67 ± 10 years, 54% were New York Heart Association II, and 27% had type 2 diabetes mellitus. Median follow-up time was 7.3 (interquartile range 6.3-8.4) years. We observed large variations in 3-OHB levels between patients (median 59 µM, range: 14-694 µM). Patients with 3-OHB levels above the median displayed a markedly increased risk of death compared with those with low levels {hazard ratio [HR]: 2.1 [95% confidence interval (CI): 1.3-3.5], P = 0.003}. In a multivariate analysis, 3-OHB predicted mortality independently of known chronic heart failure risk factors [HR: 1.004 (95% CI: 1.001-1.007), P = 0.02] and with a similar statistical strength as N-terminal pro-brain natriuretic peptide (NT-proBNP) [HR: 1.0005 (95% CI: 1.000-1.001), P = 0.02]. For every 100 µmol increase in plasma 3-OHB, the hazard of death increased by 49%. The following factors significantly predicted 3-OHB levels in the univariate analysis: free fatty acids (FFAs) [ß: 238 (95% CI: 185-292), P < 0.0001], age [ß: 2.43 (95% CI: 1.14-3.72), P < 0.0001], plasma insulin {ß: -0.28 [95% CI: -0.54-(-0.02)], P = 0.036}, body mass index {ß: -3.15 [95% CI: -5.26-(-0.05)], P = 0.046}, diabetes [ß: 44.49 (95% CI: 14.84-74.14), P = 0.003], glycosylated haemoglobin [ß: 1.92 (95% CI: 0.24-3.59), P = 0.025], New York Heart Association class [ß: 26.86 (95% CI: 5.99-47.72), P = 0.012], and NT-proBNP [ß: 0.03 (95% CI: 0.01-0.04), P = 0.001]. In a multivariate analysis, only FFAs predicted 3-OHB levels [ß: 216 (95% CI: 165-268), P > 0.001]. CONCLUSIONS: In patients with HFrEF, circulating 3-OHB was a strong predictor of all-cause mortality independently of NT-proBNP. Circulating FFAs were the best predictor of 3-OHB levels.
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Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Humanos , Pessoa de Meia-Idade , Idoso , Volume Sistólico , Função Ventricular Esquerda , Prognóstico , Ácido 3-Hidroxibutírico , Estudos de CoortesRESUMO
BACKGROUND AND OBJECTIVES: Quality of life (QoL) has never been assessed in previous illicit users of androgens years following androgen cessation. Therefore, the objective of this study was to assess QoL in previous illicit androgen users compared with current illicit androgen users and controls who had never used androgens. METHODS: Cross-sectional study including men involved in recreational strength training grouped according to their history of androgen use. We used the RAND Short-Form-36 questionnaire to assess physical and mental health-related QoL. RESULTS: We included 77 previous and 118 current androgen users and 39 healthy nonusers. The mean (SD) age of all participants was 33 (8) years. The elapsed duration since androgen cessation, geometric mean (95% CI), was 2.0 (1.5-2.6) years in former users. Median (25th-75th percentiles) serum total testosterone was lower in former users than controls, 14 (11-17) vs 19 (16-21) nmol/L, P < .001. Previous users displayed lower mean (SD) across both mental and physical (PCS) component summary scores, 48 (10) vs 54 (4) (P = .004) and 48 (9) vs 53 (3) (P = .002) compared with controls.Using multivariate linear regressions, evaluating physical and mental component scores as dependent variables, lower serum total testosterone, longer duration since androgen cessation, study recruitment from an endocrine outpatient clinic, and established chronic diseases were all independently associated with reduced QoL in previous users, P < .05. CONCLUSIONS: Previous illicit androgen users exhibited reduced QoL 2 years after androgen discontinuation, which may be a persistent condition.
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Androgênios , Qualidade de Vida , Masculino , Humanos , Adulto , Estudos Transversais , Nível de Saúde , TestosteronaRESUMO
Aims: Hyperglucagonaemia contributes to the pathophysiology in type 2 diabetes (T2D), but the mechanisms behind the inappropriate glucagon secretion are not fully understood. Glucagon and amino acids are regulated in a feedback loop referred to as the liver-α cell axis. Individuals with non-alcoholic fatty liver disease (NAFLD) appear to be glucagon resistant, disrupting the liver-α cell axis resulting in hyperglucagonaemia and hyperaminoacidaemia. We investigated the associations between circulating glucagon, amino acids, and liver fat content in a cohort of individuals with T2D. Methods: We included 110 individuals with T2D in this cross-sectional study. Liver fat content was quantified using 1H magnetic resonance spectroscopy (MRS). Associations between liver fat content and plasma glucagon and amino acids, respectively, were estimated in multivariate linear regression analyses. Results: Individuals with NAFLD (n = 52) had higher plasma glucagon concentrations than individuals without NAFLD (n = 58). The positive association between plasma glucagon concentrations and liver fat content was confirmed in the multivariable regression analyses. Plasma concentrations of isoleucine and glutamate were increased, and glycine and serine concentrations were decreased in individuals with NAFLD. Concentrations of other amino acids were similar between individuals with and without NAFLD, and no clear association was seen between liver fat content and amino acids in the regression analyses. Conclusion: MRS-diagnosed NAFLD in T2D is associated with hyperglucagonaemia and elevated plasma concentrations of isoleucine and glutamate and low plasma concentrations of glycine and serine. Whether NAFLD and glucagon resistance per se induce these changes remains to be elucidated.
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AIMS: To investigate the effects of empagliflozin on measured glomerular filtration rate (mGFR), estimated plasma volume (PV) and estimated extracellular volume (ECV) in a cohort of patients with type 2 diabetes (T2D) and high risk of cardiovascular events. MATERIALS AND METHODS: In this prespecified substudy of the randomized, placebo-controlled SIMPLE trial, patients with T2D at high risk of cardiovascular events were allocated to either empagliflozin 25 mg or placebo once daily for 13 weeks. The prespecified outcome was between-group change in mGFR, measured by the 51 Cr-EDTA method after 13 weeks; changes in estimated PV and estimated ECV were included. RESULTS: From April 4, 2017 to May 11, 2020, 91 participants were randomized. Of these, 45 patients from the empagliflozin group and 45 patients from the placebo group were included in the intention-to-treat analysis. Treatment with empagliflozin reduced mGFR by -7.9 mL/min (95% confidence interval [CI] -11.1 to -4.7; P < 0.001), estimated ECV by -192.5 mL (95% CI -318.0 to -66.9; P = 0.003) and estimated PV by -128.9 mL (95% CI -218.0 to 39.8; P = 0.005) at Week 13. CONCLUSIONS: Treatment with empagliflozin for 13 weeks reduced mGFR, estimated ECV and estimated PV in patients with T2D and high risk of cardiovascular events.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Taxa de Filtração Glomerular , Volume Plasmático , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Compostos Benzidrílicos/efeitos adversosRESUMO
CONTEXT: No information exists on the long-lasting effects of supraphysiological anabolic androgenic steroids (AASs) usage on the myocellular properties of human skeletal muscle in previous AAS users. OBJECTIVE: We hypothesized that former AAS users would demonstrate smaller myonuclei domains (ie, higher myonuclei density) than matched controls. METHODS: A community-based cross-sectional study in men aged 18-50 years engaged in recreational strength training. Muscle biopsies were obtained from the m. vastus lateralis. Immunofluorescence analyses were performed to quantify myonuclei density and myofiber size. RESULTS: Twenty-five males were included: 8 current and 7 previous AAS users and 10 controls. Median (25th-75th percentiles) accumulated duration of AAS use was 174 (101-206) and 140 (24-260) weeks in current and former AAS users, respectively (P = .482). Geometric mean (95% CI) elapsed duration since AAS cessation was 4.0 (1.2; 12.7) years among former AAS users. Type II muscle fibers in former AAS users displayed higher myonuclei density and DNA to cytoplasm ratio than controls, corresponding to smaller myonuclei domains (P = .013). Longer accumulated AAS use (weeks, log2) was associated with smaller myonuclei domains in previous AAS users: beta-coefficient (95% CI) -94 (-169; -18), P = .024. Type I fibers in current AAS users exhibited a higher amount of satellite cells per myofiber (P = .031) than controls. CONCLUSION: Muscle fibers in former AAS users demonstrated persistently higher myonuclei density and DNA to cytoplasm ratio 4 years after AAS cessation suggestive of enhanced retraining capacity.
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Anabolizantes , Esteróides Androgênicos Anabolizantes , Masculino , Humanos , Estudos Transversais , Congêneres da Testosterona/efeitos adversos , Fibras Musculares Esqueléticas , DNA , Anabolizantes/efeitos adversosRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0277767.].
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BACKGROUND: Serum insulin-like factor 3 (INSL3) is a Leydig cell biomarker, but little is known about the circulating concentration of INSL3 during hypothalamus-pituitary-testicular suppression. AIM: To study the concomitant changes in serum concentrations of INSL3, testosterone, and LH during experimental and therapeutic testicular suppression. METHODS: We included serum samples from 3 different cohorts comprising subjects before and after testicular suppression: (1) 6 healthy young men who were treated with androgens (Sustanon, Aspen Pharma, Dublin, Ireland); 2) 10 transgender girls (male sex assigned at birth) who were treated with 3-monthly GnRH agonist injections (Leuprorelinacetat, Abacus Medicine, Copenhagen, Denmark); and (3) 55 patients with prostate cancer who were randomized to surgical castration (bilateral subcapsular orchiectomy) or treatment with GnRH agonist (Triptorelin, Ipsen Pharma, Kista, Sweden). Serum INSL3 and testosterone concentrations were quantified in stored serum samples using validated liquid chromatography-tandem mass spectrometry methodologies, and LH was measured by an ultrasensitive immunoassay. RESULTS: The circulating concentrations of INSL3, testosterone, and LH decreased during experimental testicular suppression in healthy young men by Sustanon injections and subsequently returned to baseline levels after release of suppression. All 3 hormones decreased during therapeutic hormonal hypothalamus-pituitary-testicular suppression in transgender girls and in patients with prostate cancer. CONCLUSION: INSL3 resembles testosterone as a sensitive marker of testicular suppression and reflects Leydig cell function, also during exposure to exogenous testosterone. Serum INSL3 measurements may complement testosterone as a Leydig cell marker in male reproductive disorders, during therapeutic testicular suppression as well as in surveillance of illicit use of androgens.
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Insulina , Neoplasias da Próstata , Testosterona , Humanos , Recém-Nascido , Masculino , Androgênios , Hormônio Liberador de Gonadotropina , Insulina/sangue , Células Intersticiais do Testículo , Neoplasias da Próstata/sangue , Neoplasias da Próstata/tratamento farmacológico , Proteínas , Testículo , Testosterona/sangue , Hormônio Luteinizante/sangueRESUMO
OBJECTIVE: Although preterm-born and low-birth-weight individuals have an increased risk of cardiovascular diseases in adulthood, little is known regarding early cardiovascular and renal damage (CVRD) or hypertension in adulthood. Our study investigated the association of birth weight with early CVRD markers as well as the heritability of birth weight in an initially healthy family-based cohort. METHODS: This study was based on 1028 individuals from the familial longitudinal STANISLAS cohort (399âparents/629 children) initiated in 1993-1995, with a fourth examination conducted in 2011-2016. Analyses performed at the fourth visit included pulse-wave velocity, central pressure, ambulatory blood pressure, hypertension status, diastolic dysfunction/distensibility, left ventricular mass indexed (LVMI), carotid intima-media thickness and kidney damage. The family structure of the cohort allowed birth weight heritability estimation. RESULTS: Mean (±SD) birth weight was 3.3â±â0.6âkg. Heritability was moderate (42-44%). At the fourth visit, individuals were 37âyears old (32.0-57.0), 56% were women and 13% had antihypertensive treatment. Birth weight was strongly and negatively associated with hypertension [odds ratio (OR) 95% confidence interval (CI) 0.61 (0.45-0.84)]. A nonlinear association was found with LVMI, participants with a birth weight greater than 3âkg having a higher LVMI. A positive association ( ß 95% CI 5.09 (1.8-8.38)] was also observed between birth weight and distensibility for adults with normal BMI. No associations were found with other CVRD. CONCLUSION: In this middle-aged population, birth weight was strongly and negatively associated with hypertension, and positively associated with distensibility in adults with normal BMI and with LVMI for higher birth weights. No associations were found with other CVRD markers.
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Espessura Intima-Media Carotídea , Hipertensão , Adulto , Pessoa de Meia-Idade , Criança , Recém-Nascido , Humanos , Feminino , Masculino , Estudos de Coortes , Pressão Sanguínea/fisiologia , Peso ao Nascer , Monitorização Ambulatorial da Pressão Arterial , Fatores de Risco , RimRESUMO
BACKGROUND: Early heart failure prevention is central in patients with type 2 diabetes, and mineralocorticoid receptor antagonists (MRAs) have shown to improve prognosis. We investigated the effect of high-dose MRA, eplerenone, on cardiac function and structure in patients with type 2 diabetes and established or increased risk of cardiovascular disease but without heart failure. METHODS: In the current randomized, placebo-controlled clinical trial, 140 patients with high-risk type 2 diabetes were randomized to high-dose eplerenone (100-200 mg daily) or placebo as add-on to standard care for 26 weeks. Left ventricular systolic and diastolic function, indexed left ventricular mass (LVMi), and global longitudinal strain (GLS) were assessed using echocardiography at baseline and after 26 weeks of treatment. RESULTS: Of the included patients, 138 (99%) had an echocardiography performed at least once. Baseline early diastolic in-flow velocity (E-wave) indexed by mitral annulus velocity (e') was mean (SD) 11.1 (0.5), with 31% of patients reaching above 12. No effect of treatment on diastolic function was observed measured by E/e' (0.0, 95%CI [-1.2 to 1.2], P = 0.992) or E/A (-0.1, 95%CI [-0.2 to 0.0], P = 0.191). Mean left ventricular ejection fraction (LVEF) at baseline was 59.0% (8.0). No improvement in systolic function was observed when comparing groups after 26 weeks (LVEF: 0.9, 95%CI [-1.1 to 2.8], P = 0.382; GLS: -0.4%, 95%CI [-1.5 to 0.6], P = 0.422), nor in LVMi (-3.8 g/m2 95%CI [-10.2 to 2.7], P = 0.246). CONCLUSION: In the present echo sub-study, no change in left ventricular function was observed following high-dose MRA therapy in patients with type 2 diabetes when evaluated by conventional echocardiography. TRIAL REGISTRATION: Date of registration 25/08/2015 (EudraCT number: 2015-002,519-14).
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Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Eplerenona/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Função Ventricular Esquerda , Volume Sistólico/fisiologia , Insuficiência Cardíaca/tratamento farmacológico , Ecocardiografia , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/induzido quimicamenteRESUMO
BACKGROUND: The presence of diabetes in patients with heart failure (HF) is associated with a worse prognosis. It is unclear if hemodynamics in HF patients with DM differ from those of non-diabetic patients and how this might influence outcome. This study aims to discover the impact of DM on hemodynamics in HF patients. METHODS: Consecutive patients (n = 598) with HF and reduced ejection fraction (LVEF ≤40%) undergoing invasive hemodynamic evaluation were included (non-DM: n = 473, DM: n = 125). Hemodynamic parameters included pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), cardiac index (CI) and mean arterial pressure (MAP). Mean follow-up was 9.5 ± 5.1 years. RESULTS: Patients with DM (82.7% male, mean age 57.1 ± 10.1 years, mean HbA1c 60 ± 21 mmol/mol) had higher PCWP, mPAP, CVP and higher MAP. Adjusted analysis demonstrated that DM patients had higher PCWP and CVP. Increasing HbA1c-values were correlated with higher PCWP (p = 0.017) and CVP (p = 0.043). CONCLUSION: Patients with DM, especially those with poor glycemic control, have higher filling pressures. This may be a feature of diabetic cardiomyopathy, however, other unknown mechanisms beyond hemodynamic factors are likely to explain the increased mortality associated with diabetes in HF.
Assuntos
Diabetes Mellitus , Insuficiência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Hemoglobinas Glicadas , Hemodinâmica , Insuficiência Cardíaca/diagnóstico , Pressão Propulsora Pulmonar , Volume SistólicoRESUMO
OBJECTIVE: Ectopic accumulation of cardiac adipose tissue volume (CAT) has been associated with cardiac remodelling and cardiac dysfunction in type 2 diabetes and may be a future therapeutic target. In this substudy from the SIMPLE-trial, we investigated short-term empagliflozin therapy's effects on CAT in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Between 4 April 2017 and 11 May 2020, we randomized 90 patients with type 2 diabetes and established or high risk of cardiovascular disease to 25 mg empagliflozin or placebo for 13 weeks. The substudy focused on change in CAT evaluated by images acquired during 82 Rubidium-positron emissions tomography/computed tomography. The analysis included 78 patients who had at least one scan. Furthermore, we report on the relation to the concurrent effects on left ventricular mass, end-diastolic volume and end-systolic volume, body composition and glucometabolic status. RESULTS: Mean ± SD baseline CAT was 258.5 ± 117.9 ml. Empagliflozin reduced CAT after 13 weeks by 12.41 ml [95% CI (-23.83 to -0.99), p = .034] as compared with placebo. Similarly, left ventricular mass [-5.16 g, 95% CI (-8.80 to -1.52), p = .006], end-diastolic volume and end-systolic volume decreased with empagliflozin. In addition, significant improvements were observed in body composition, with reduced total fat mass, and in measures of glucose and lipid metabolism. However, no correlation was observed between changes in CAT and changes in cardiac parameters and change in CAT appeared mediated primarily by concurrent change in weight. CONCLUSIONS: Empagliflozin provides an early reduction of CAT; however, no association was observed with concurrent changes in cardiac volumetrics.