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BACKGROUND AND AIMS: The estimated glucose disposal rate (eGDR) is an easily accessible clinical parameter for assessing insulin resistance in patients with diabetes mellitus. In this study, we aimed to investigate the link between eGDR and subclinical coronary atherosclerosis in an asymptomatic middle-aged Korean population. METHODS AND RESULTS: This study involved 4004 subjects who underwent routine health checkups with coronary multidetector computed tomography (MDCT) at Asan Medical Center from 2007 to 2011, among whom 913 had a follow-up analysis through 2014. The eGDR was calculated using: 21.16 - (0.09 ∗ waist circumference [cm]) - (3.41 ∗ hypertension) - (0.55 ∗ glycated hemoglobin [%]). Patients were categorized into three groups according to the tertiles of eGDR. Subclinical coronary atherosclerosis was defined by significant coronary stenosis (≥50%), presence of plaques, coronary artery calcification (CAC) score, and its progression. As a result, a lower eGDR level was associated with higher prevalence of significant coronary stenosis, plaques, moderate to severe CAC, and CAC progression. Compared to other markers or risk scores, eGDR was superior to other biomarkers of insulin resistance but did not provide additional information beyond classic cardiovascular risk models like the Framingham Risk Score and Pooled Cohort Equations. CONCLUSION: Decreased eGDR values were significantly associated with higher subclinical coronary atherosclerosis burdens in an asymptomatic middle-aged Korean population. However, its clinical implications remain uncertain due to its weaker performance compared to established cardiovascular risk models.
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OBJECTIVE: This study assessed whether cholecystectomy is a risk factor for newly developed type 2 diabetes mellitus (T2DM) in the Korean population. BACKGROUND: There is a lack of evidence that cholecystectomy is independently associated with insulin resistance and T2DM. METHODS: This study included all patients aged more than 20 years who had undergone cholecystectomy from 2010 to 2015 (n=55,166) and age-matched and sex-matched control subjects without cholecystectomy (n=110,332) using the National Health Insurance Service database. They were followed up until the date of newly developed T2DM or study end and the incidence of T2DM was traced over a maximum observation period of 7 years. RESULTS: Overall, 55,166 patients who underwent cholecystectomy and 110,332 age-matched and sex-matched controls were followed up for â¼4.7 years, during which, incident T2DM occurred in 5982 (3.61%) patients. Cholecystectomy was associated with 20% higher risk of T2DM after adjustment for all covariates. The cumulative incidence of T2DM also significantly increased in the cholecystectomy group for â¼7 years ( P <0.001). The adjusted hazard ratio (HR) for T2DM was the highest in the group with both cholecystectomy and obesity using the control without both cholecystectomy and obesity as a reference [HR=1.41, 95% confidence interval (CI): 1.29-1.56]. The group with cholecystectomy without obesity showed the comparable risk of incident T2DM compared with the group without cholecystectomy with obesity (HR=1.29, 95% CI: 1.20-1.40 for cholecystectomy without obesity and HR=1.24, 95% CI: 1.14-1.36 for control with obesity). CONCLUSIONS: These results provide evidence that cholecystectomy is associated with an increased risk of newly developed T2DM in the Korean population. Further research is required to elucidate the mechanism of the association between cholecystectomy and incident diabetes.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Fatores de Risco , Obesidade/complicações , Colecistectomia/efeitos adversos , República da Coreia/epidemiologia , IncidênciaRESUMO
BACKGROUND: Elevated remnant cholesterol (remnant-C) is considered a risk factor for cardiovascular disease (CVD); however, whether this notion applies to the East Asian population with type 2 diabetes (T2D) has not been established. This study investigated the association between remnant-C concentrations and the risk of CVD in Korean patients with T2D. METHODS: By using the Korean National Health Insurance Service database, 1,956,452 patients with T2D and without atherosclerotic CVD who underwent regular health checks between 2009 and 2012 were included. Cox regression analyses were conducted to assess the association between remnant-C concentrations and incident CVD comprising myocardial infarction (MI) and ischemic stroke. RESULTS: In total, 50,120 (2.56%) cases of MI and 73,231 (3.74%) cases of ischemic strokes occurred during a median follow-up of 8.1 years. The adjusted hazard ratios for MI and stroke in the highest remnant-C quartile were 1.281 (95% confidence interval [CIs], 1.249-1.314) for MI and 1.22 (1.195-1.247) for ischemic stroke, compared to those in the lowest quartiles. The results were similar, based on stratified analysis by age, sex, use of statin or fibrate, and levels of other cholesterol. The increased risk of CVD in the highest remnant-C quartile was profound in patients who had a longer T2D duration. A remnant-C concentration ≥ 30 mg/dL differentiated patients who were at a higher risk of CVD, compared to patients with a lower concentrations, regardless of whether LDL-C levels were or were not on target at ≤ 100 mg/dL. CONCLUSION: In Korean patients with T2D, remnant-C was associated with CVD, independent of the LDL-C level or other conventional CVD risk factors. Our finding confirmed evidence of the causal role of remnant-C on CVD, as a residual risk of CVD, in East Asian patients with T2D.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Hiperlipidemias , AVC Isquêmico , Infarto do Miocárdio , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol , Estudos Longitudinais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Colesterol , Estudos de Coortes , Fatores de Risco , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologiaRESUMO
BACKGROUND: The atherogenic index of plasma (AIP) is composed of triglycerides and high-density lipoprotein cholesterol and is a novel marker for assessing the risk of atherogenicity and cardiometabolic health. An association between AIP and greater frequency of major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus and high cardiovascular (CV) disease risk has been reported. However, only few studies have examined the correlation between AIP and CV risk in general populations. We thus aimed to evaluate the relationship between AIP and CV diseases using a large-scale population dataset from the Korean National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). METHODS: A total of 514,866 participants were enrolled from the NHIS-HEALS and classified according to the AIP quartiles. We performed univariate and multivariate Cox proportional hazards regression analyses to determine the association between AIP and MACEs, CV events, and CV mortality. RESULTS: During follow-up, we documented 12,133, 11,055, and 1942 cases of MACEs, CV events, and CV mortality, respectively. The multivariate-adjusted hazard ratios [HRs; 95% confidence interval (CI)] for MACEs gradually and significantly increased with the AIP quartiles [1.113 (1.054-1.175) in Q2, 1.175 (1.113-1.240) in Q3, and 1.278 (1.209-1.350) in Q4], following an adjustment for the conventional CV risk factors, including age, sex, body mass index, smoking, alcohol drinking, physical activities, household income, fasting glucose, systolic blood pressure, low-density lipoprotein cholesterol, and estimated glomerular filtration rate. In subgroup analyses, the association of AIP with MACEs and CV events was particularly outstanding in patients with diabetes. CONCLUSIONS: AIP was significantly associated with CV risks after adjusting for the traditional risk factors. Therefore, it may be used as an effective mass screening method to identify patients at a high risk of CV events.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , HDL-Colesterol , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Fatores de Risco de Doenças Cardíacas , Humanos , Fatores de RiscoRESUMO
Although obesity is commonly associated with numerous cardiometabolic pathologies, some people with obesity are resistant to detrimental effects of excess body fat, which constitutes a condition called "metabolically healthy obesity" (MHO). Metabolic features of MHO that distinguish it from metabolically unhealthy obesity (MUO) include differences in the fat distribution, adipokine types, and levels of chronic inflammation. Murine models are available that mimic the phenotype of human MHO, with increased adiposity but preserved insulin sensitivity. Clinically, there is no established definition of MHO yet. Despite the lack of a uniform definition, most studies describe MHO as a particular case of obesity with no or only one metabolic syndrome components and lower levels of insulin resistance or inflammatory markers. Another clinical viewpoint is the dynamic and changing nature of MHO, which substantially impacts the clinical outcome. In this review, we explore the pathophysiology and some murine models of MHO. The definition, variability, and clinical implications of the MHO phenotype are also discussed. Understanding the characteristics that differentiate people with MHO from those with MUO can lead to new insights into the mechanisms behind obesity-related metabolic derangements and diseases.
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Resistência à Insulina , Síndrome Metabólica , Obesidade Metabolicamente Benigna , Animais , Índice de Massa Corporal , Modelos Animais de Doenças , Humanos , Síndrome Metabólica/metabolismo , Camundongos , Obesidade , Fatores de RiscoRESUMO
OBJECTIVE: Lipotoxic hepatocyte injury is a primary event in non-alcoholic steatohepatitis (NASH), but the mechanisms of lipotoxicity are not fully defined. Sphingolipids and free cholesterol (FC) mediate hepatocyte injury, but their link in NASH has not been explored. We examined the role of free cholesterol and sphingomyelin synthases (SMSs) that generate sphingomyelin (SM) and diacylglycerol (DAG) in hepatocyte pyroptosis, a specific form of programmed cell death associated with inflammasome activation, and NASH. DESIGN: Wild-type C57BL/6J mice were fed a high fat and high cholesterol diet (HFHCD) to induce NASH. Hepatic SMS1 and SMS2 expressions were examined in various mouse models including HFHCD-fed mice and patients with NASH. Pyroptosis was estimated by the generation of the gasdermin-D N-terminal fragment. NASH susceptibility and pyroptosis were examined following knockdown of SMS1, protein kinase Cδ (PKCδ), or the NLR family CARD domain-containing protein 4 (NLRC4). RESULTS: HFHCD increased the hepatic levels of SM and DAG while decreasing the level of phosphatidylcholine. Hepatic expression of Sms1 but not Sms2 was higher in mouse models and patients with NASH. FC in hepatocytes induced Sms1 expression, and Sms1 knockdown prevented HFHCD-induced NASH. DAG produced by SMS1 activated PKCδ and NLRC4 inflammasome to induce hepatocyte pyroptosis. Depletion of Nlrc4 prevented hepatocyte pyroptosis and the development of NASH. Conditioned media from pyroptotic hepatocytes activated the NOD-like receptor family pyrin domain containing 3 inflammasome (NLRP3) in Kupffer cells, but Nlrp3 knockout mice were not protected against HFHCD-induced hepatocyte pyroptosis. CONCLUSION: SMS1 mediates hepatocyte pyroptosis through a novel DAG-PKCδ-NLRC4 axis and holds promise as a therapeutic target for NASH.
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Hepatócitos/enzimologia , Hepatopatia Gordurosa não Alcoólica/enzimologia , Piroptose , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVES: The hemoglobin glycation index (HGI) quantifies interindividual variations in glycated hemoglobin (HbA1c) and is associated with diabetic complications and metabolic diseases. However, information on the association between HGI and non-alcoholic fatty liver disease (NAFLD) in healthy subjects is limited, particularly in Asian populations. This study aimed to investigate the association between HGI and NAFLD in a healthy Korean cohort. DESIGN: Subjects were stratified in quartiles according to their HGI level. NAFLD was diagnosed by hepatic ultrasonography, hepatic steatosis index and fatty liver index. Multiple logistic regression analysis was performed to evaluate the association between HGI quartiles and the risk of NAFLD. PATIENTS: Data from subjects without diabetes who underwent liver ultrasonography during routine health examinations were retrospectively reviewed. RESULTS: Data from 14 465 subjects were included in the analysis. The prevalence of NAFLD increased significantly with each HGI quartile (24.8%, 29.7%, 32.6% and 40.6% in quartiles 1-4, respectively; P < 0.001). In comparison with the lowest HGI quartile group, the highest quartile exhibited worse metabolic parameters, including body weight, waist circumference, body mass index and lipid profiles. Multiple logistic regression analysis adjusted for multiple factors showed that the odds ratio of having NAFLD was 1.564 (95% CI: 1.350-1.813, P < 0.001) in the highest HGI quartile. CONCLUSIONS: Elevated HGI levels are independently associated with NAFLD in a healthy Asian population.
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Hemoglobinas Glicadas/análise , Voluntários Saudáveis/estatística & dados numéricos , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto , Ásia/epidemiologia , Povo Asiático/estatística & dados numéricos , Índice de Massa Corporal , Feminino , Inquéritos Epidemiológicos/métodos , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos , Lipídeos/sangue , Fígado/diagnóstico por imagem , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , Estudos Retrospectivos , Ultrassonografia/métodos , Circunferência da CinturaRESUMO
OBJECTIVE: SFRP5 (secreted frizzled-related protein 5) is an endogenous inhibitor of WNT5A (wingless-type family member 5a), which has been implicated in atherosclerosis. However, contradictory results have been reported about the role of SFRP5 in atherosclerosis. We aimed to investigate whether SFRP5 could restore WNT5A-induced endothelial dysfunction in vitro and ex vivo. In addition, we sought to determine whether the serum concentration of SFRP5 is associated with atherosclerosis in humans. APPROACH AND RESULTS: We measured endothelium-dependent vasorelaxation in the isolated thoracic aorta of Sprague-Dawley rats. In addition, we measured intracellular nitric oxide (NO) in human endothelial cells. The protein abundance of total and phosphorylated JNK (c-Jun N-terminal kinase), AKT (protein kinase B), and endothelial NO synthase was analyzed in human endothelial cells. Circulating SFRP5 and WNT5A levels and brachial-ankle pulse wave velocity were measured in 282 human subjects with type 2 diabetes mellitus. SFRP5 dose dependently restored Wnt5-induced impaired vasorelaxation in rat thoracic aorta by an endothelial NO synthase-dependent mechanism. SFRP5 treatment restored the WNT5A-induced reduction of NO production via endothelial NO synthase in human endothelial cells. WNT5A-induced changes in the phosphorylation of JNK, AKT, and endothelial NO synthase were ameliorated with SFRP5 administration. In humans with type 2 diabetes mellitus, the serum SFRP5 concentration positively correlated with brachial-ankle pulse wave velocity (r=0.146; P=0.024). Multivariate linear regression analysis demonstrated that the serum SFRP5 concentration was independently associated with brachial-ankle pulse wave velocity after adjustment for potential confounders [B (SE)=7.40 (3.35); P=0.028]. CONCLUSIONS: Our data suggest the possible compensatory action of SFRP5 against atherosclerosis under conditions of metabolic dysfunction.
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Aorta Torácica/metabolismo , Diabetes Mellitus Tipo 2/sangue , Proteínas do Olho/sangue , Proteínas de Membrana/sangue , Rigidez Vascular , Vasodilatação , Proteína Wnt-5a/sangue , Proteínas Adaptadoras de Transdução de Sinal , Adiponectina/sangue , Idoso , Animais , Índice Tornozelo-Braço , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiopatologia , Biomarcadores/sangue , Células Cultivadas , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Proteínas do Olho/farmacologia , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Proteínas de Membrana/farmacologia , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Vasodilatação/efeitos dos fármacos , Proteína Wnt-5a/farmacologiaRESUMO
The Manual Function Test (MFT) is a tool to assess upper extremity motor impairment associated with stroke. This study investigated psychometric properties of the Korean version of the MFT and to establish normative data. Eighty-one patients were enrolled to evaluate MFT, Fugl-Meyer Assessment (FMA) and manual muscle test (MMT). MFT was completed by eight raters on two occasions separated by 6 weeks. Absolute and relative reliability and validity were examined. Additionally, MFT was assessed on 75 healthy controls of different ages. Intraclass correlation coefficient (ICC) (2,1) values for total and each dimension of Korean MFT ranged from 0.984 to 0.998 in the affected side of hemiplegic patients, indicating inter-rater reliability. Percentage values of standard error of measurement (SEM) and smallest real difference (SRD) ranged 3.10-10.57% and 8.58-29.29% respectively. Test-retest reliability ICCs for all raters were above 0.98. Effect size (ES) and standardized response mean (SRM) were larger in the acute-subacute group (onset to initial evaluation ≤ 4 months) (ES = 0.12; SRM = 0.41) than those in the chronic group (onset to evaluation > 4 months) (ES = 0.01; SRM = 0.11). MFT score was significantly correlated with FMA score (p < 0.001) and MMT score (p < 0.001). In healthy controls, regression analysis indicated that age significantly predicts manual function scores on both dominant and non-dominant. The Korean MFT showed good reliability and validity. Modest responsiveness was observed in patients evaluated early after stroke onset. The Korean MFT is useful in evaluating upper extremity motor deficits for clinical and research purposes.
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Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/psicologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos TestesRESUMO
BACKGROUND: There is growing evidence that the combination of non-invasive brain stimulation and motor skill training is an effective new treatment option in neurorehabilitation. We investigated the beneficial effects of the application of transcranial direct current stimulation (tDCS) combined with virtual reality (VR) motor training. METHODS: In total, 15 healthy, right-handed volunteers and 15 patients with stroke in the subacute stage participated. Four different conditions (A: active wrist exercise, B: VR wrist exercise, C: VR wrist exercise following anodal tDCS (1 mV, 20 min) on the left (healthy volunteer) or affected (stroke patient) primary motor cortex, and D: anodal tDCS without exercise) were provided in random order on separate days. We compared during and post-exercise corticospinal excitability under different conditions in healthy volunteers (A, B, C, D) and stroke patients (B, C, D) by measuring the changes in amplitudes of motor evoked potentials in the extensor carpi radialis muscle, elicited with single-pulse transcranial magnetic stimulation. For statistical analyses, a linear mixed model for a repeated-measures covariance pattern model with unstructured covariance within groups (healthy or stroke groups) was used. RESULTS: The VR wrist exercise (B) facilitated post-exercise corticospinal excitability more than the active wrist exercise (A) or anodal tDCS without exercise (D) in healthy volunteers. Moreover, the post-exercise corticospinal facilitation after tDCS and VR exercise (C) was greater and was sustained for 20 min after exercise versus the other conditions in healthy volunteers (A, B, D) and in subacute stroke patients (B, D). CONCLUSIONS: The combined effect of VR motor training following tDCS was synergistic and short-term corticospinal facilitation was superior to the application of VR training, active motor training, or tDCS without exercise condition. These results support the concept of combining brain stimulation with VR motor training to promote recovery after a stroke.
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Terapia por Exercício/métodos , Tratos Piramidais/fisiologia , Reabilitação do Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua/métodos , Interface Usuário-Computador , Adulto , Idoso , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Magnética Transcraniana/métodos , Punho/fisiologia , Adulto JovemRESUMO
AIMS: In this study, we aimed to evaluate the impact of overall cardiovascular disease (CVD) risk on the development of incident T2DM in patients with prediabetes. METHODS: We retrospectively enrolled 5,908 subjects with prediabetes who underwent health check-ups at the Asan Medical Center. CVD risk was estimated using the Framingham Risk Score (FRS). We compared moderate- to high-risk groups with low-risk controls based on the FRS. Cox proportional hazards regressions were conducted to estimate the time-to-develop incident T2DM. RESULTS: Among the 5908 subjects with prediabetes, 3031 (51.8 %) were identified to have either moderate or high CVD risk scores. During a median follow-up of 5.2 years, 278 (9.2 %) patients from the moderate- to high-risk group and 171 (5.9 %) from the low-risk group were diagnosed with T2DM. The covariate-adjusted hazard ratio for the incident T2DM was 1.30 (95 % CI, 1.06-1.60, p = 0.011) in the moderate- to high-risk group compared to the low-risk controls. CONCLUSION: Among patients with prediabetes, those with high CVD risk were more likely to develop incident T2DM, as determined by the FRS. CVD risk factors should be properly evaluated and managed in individuals with prediabetes to reduce the risk of both incident T2DM and associated cardiovascular complications.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Humanos , Diabetes Mellitus Tipo 2/complicações , Estado Pré-Diabético/diagnóstico , Estudos Retrospectivos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/complicações , Fatores de RiscoRESUMO
PURPOSE: Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist that is not cleared by the kidneys and has proven efficacy and safety in patients with diabetic kidney disease. We aimed to evaluate the 1-year efficacy of dulaglutide in patients with diabetic kidney disease who have used the drug for more than 1 year. METHODS: This retrospective, observational study comprised 131 patients with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73 m2 who had received dulaglutide for more than one year between June 2016 and May 2023. The primary outcome measures were changes in glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and body weight from baseline to the 12-month follow-up, with assessments performed at six-month intervals. Subgroup analyses were conducted based on age, sex, baseline body mass index, FPG, and HbA1c, and insulin administration at baseline and last follow-up. FINDINGS: The mean age was 60.0 ± 10.2 years, and 61.1% of the participants were males. Baseline HbA1c, FPG, and body weight were 9.1% (76.0 mmol/mol), 186.8 mg/dL, and 79.3 kg, respectively. Dulaglutide significantly reduced HbA1c, FPG, and body weight from baseline to the 12-month follow-up (mean ± standard error: -1.2 ± 0.1%, -34.8 ± 6.9 mg/dL, and -2.3 ± 0.5 kg, respectively; P < 0.001). Subgroup analysis revealed significant differences in HbA1c reduction based on baseline HbA1c. IMPLICATIONS: Dulaglutide exhibited sustained glucose-lowering and weight-reduction effects during the initial 1 year of treatment in patients with diabetic kidney disease. Altogether, dulaglutide could serve as a favorable long-term therapeutic option for patients with diabetic kidney disease in real-world clinical settings.
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Background: Myosteatosis, ectopic fat accumulation in skeletal muscle, is a crucial component of sarcopenia, linked to various cardiometabolic diseases. This study aimed to analyze the association between dyslipidemia and myosteatosis using abdominal computed tomography (CT) in a large population. Methods: This study included 11,823 patients not taking lipid-lowering medications with abdominal CT taken between 2012 and 2013. Total abdominal muscle area (TAMA), measured at the L3 level, was segmented into skeletal muscle area (SMA) and intramuscular adipose tissue. SMA was further classified into normal attenuation muscle area (NAMA: good quality muscle) and low attenuation muscle area (poor quality muscle). NAMA divided by TAMA (NAMA/TAMA) represents good quality muscle. Atherosclerotic dyslipidemia was defined as high-density lipoprotein cholesterol (HDL-C) less than 40 mg/dL in men and 50 mg/dL in women, low-density lipoprotein cholesterol (LDL-C) greater than 160 mg/dL, triglycerides (TG) greater than 150 mg/dL, small dense LDL-C (sdLDL-C) greater than 50.0 mg/dL, or apolipoprotein B/A1 (apoB/A1) greater than 0.08. Results: The adjusted odds ratios (ORs) of dyslipidemia according to the HDL-C and sdLDL definitions were greater in both sexes in the lower quartiles (Q1~3) of NAMA/TAMA compared with Q4. As per other definitions, the ORs were significantly increased in only women for LDL-C and only men for TG and ApoB/A1. In men, all lipid parameters were significantly associated with NAMA/TAMA, while TG and ApoB/A1 did not show significant association in women. Conclusion: Myosteatosis measured in abdominal CT was significantly associated with a higher risk of dyslipidemia. Myosteatosis may be an important risk factor for dyslipidemia and ensuing cardiometabolic diseases.
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Aterosclerose , Dislipidemias , Músculo Esquelético , Humanos , Masculino , Feminino , Dislipidemias/metabolismo , Pessoa de Meia-Idade , Idoso , Músculo Esquelético/metabolismo , Músculo Esquelético/diagnóstico por imagem , Aterosclerose/metabolismo , Tomografia Computadorizada por Raios X , Sarcopenia/metabolismo , Sarcopenia/patologia , Sarcopenia/diagnóstico por imagem , Adulto , LDL-Colesterol/sangue , LDL-Colesterol/metabolismo , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Fatores de RiscoRESUMO
BACKGROUND: In 2023, the concept of metabolic dysfunction-associated steatotic liver disease (MASLD) was introduced as an alternative to non-alcoholic fatty liver disease (NAFLD). We aimed to assess the quantity and quality of skeletal muscle using each of these diagnostic classifications. METHODS: This cross-sectional study included 18 154 participants (11 551 [63.6%] men and 6603 [36.4%] women, mean age 53.0 ± 8.8). The participants were classified into four categories: neither steatotic liver disease (SLD), NAFLD only, MASLD only or both SLDs. An appendicular skeletal muscle mass adjusted for body mass index of <0.789 for men and <0.512 for women was defined as sarcopenia. The total abdominal muscle area (TAMA) at the L3 vertebral level was segmented into normal-attenuation muscle area (NAMA), low-attenuation muscle area and intermuscular/intramuscular adipose tissue. Myosteatosis was defined by a T-score < -1.0 of the NAMA/TAMA index, which was calculated by dividing the NAMA by the TAMA and multiplying by 100. RESULTS: Using subjects with neither SLD as a reference, the multivariable-adjusted odds ratios (ORs) for sarcopenia were significantly increased in those with MASLD, with adjusted ORs (95% confidence interval [CI]) of 2.62 (1.94-3.54) in the MASLD-only group and 2.33 (1.92-2.82) in the both SLDs group, while the association was insignificant in those with NAFLD only (adjusted OR [95% CI]: 2.16 [0.67-6.94]). The OR for myosteatosis was also elevated in the MASLD groups, with an OR (95% CI) of 1.75 (1.52-2.02) in subjects with MASLD only and 1.70 (1.57-1.84) in those with both SLDs, while it was slightly decreased in subjects with NAFLD only (0.52 [0.29-0.95]). CONCLUSIONS: Employing the MASLD concept rather than that of the NAFLD proved to be more effective in distinguishing individuals with reduced muscle mass and compromised muscle quality.
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PURPOSE: The purpose of this study was to determine the efficacy and safety profile of pioglitazone compared with placebo (PBO) in patients with type 2 diabetes (T2D) inadequately controlled with metformin and dapagliflozin. METHODS: In this prospective, multicenter, randomized, double-blind, PBO-controlled trial, 366 patients with T2D who did not meet glycemic targets (7.0% ≤ glycosylated hemoglobin [HbA1c] ≤ 10.5%), despite treatment with metformin ≥1000 mg and dapagliflozin 10 mg, received either a PBO, 15 mg of pioglitazone daily (PIO15), or 30 mg of pioglitazone daily (PIO30). The primary end point was the mean change in HbA1c from baseline at 24 weeks across the groups. FINDINGS: For the 366 participants (PBO, n = 124; PIO15, n = 118; PIO30, n = 124), the mean age was 55.6 years and mean duration of diabetes was 8.7 years, with a baseline HbA1c of 7.9%. After 24 weeks, HbA1c reduced significantly in the PIO15 and PIO30 groups from baseline, with intergroup differences of -0.38% and -0.83%, respectively, compared with the PBO group. The proportion of patients with HbA1c levels <7% was significantly higher in the PIO15 and PIO30 groups than in the PBO group. The adverse event rates did not significantly differ across the groups, indicating favorable safety profiles for triple combination therapy using metformin, dapagliflozin, and pioglitazone. IMPLICATIONS: The addition of pioglitazone as a third oral antidiabetic medication is an appropriate option for patients with T2D inadequately controlled with metformin and dapagliflozin based on the resulting significant efficacy in glycemic control and favorable safety profile. CLINICALTRIALS: gov identifier: NCT04885712.
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Vascular endothelial growth factor (VEGF) and its receptor kinase insert domain-containing receptor (KDR) play crucial roles in angiogenesis, which contributes to the development and progression of solid tumors. The aim of this study was to investigate the associations of VEGF (-2578C > A, -1154G > A, -634G > C, and 936C > T) and KDR (-604T > C and 1192G > A) polymorphisms with the development of colorectal cancer (CRC). A total of 882 participants (390 CRC patients and 492 controls) were enrolled in the study. The genotyping of VEGF and KDR polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism assay. We found that the CT and TT genotype of the 936C > T was associated with an increased risk of CRC compared with the CC genotype as the dominant model for the T allele. In addition, we also found a increased CRC risk with TC + CC genotype of KDR -604T > C compared with TT genotype in CRC patients and control subjects. Similarly, KDR 1192G > A also showed significant association between 1192G > A variants and risk of CRC. In the haplotype analyses, haplotype -2578A/-1154A/-634G/936T of VEGF polymorphisms and haplotype -604C/1192G and -604C/1192A of KDR polymorphisms were associated with an increased susceptibility of CRC. Our results suggest that the VEGF 936C > T, KDR -604T > C, and KDR 1192G > A polymorphisms may be contribute to CRC risk in the Korean population.
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Neoplasias Colorretais/etiologia , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Feminino , Interação Gene-Ambiente , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , República da Coreia , Fatores de RiscoRESUMO
OBJECTIVES: Recent studies have shown that there may be an interaction between duty cycle and other factors related to the quality of chest compression. Duty cycle represents the fraction of compression phase. We aimed to investigate the effect of shorter compression phase on average chest compression depth during metronome-guided cardiopulmonary resuscitation. METHODS: Senior medical students performed 12 sets of chest compressions following the guiding sounds, with three down-stroke patterns (normal, fast and very fast) and four rates (80, 100, 120 and 140 compressions/min) in random sequence. Repeated-measures analysis of variance was used to compare the average chest compression depth and duty cycle among the trials. RESULTS: The average chest compression depth increased and the duty cycle decreased in a linear fashion as the down-stroke pattern shifted from normal to very fast (p<0.001 for both). Linear increase of average chest compression depth following the increase of the rate of chest compression was observed only with normal down-stroke pattern (p=0.004). CONCLUSIONS: Induction of a shorter compression phase is correlated with a deeper chest compression during metronome-guided cardiopulmonary resuscitation.
Assuntos
Reanimação Cardiopulmonar/métodos , Serviços Médicos de Emergência/métodos , Parada Cardíaca/terapia , Massagem Cardíaca/métodos , Adulto , Análise de Variância , Reanimação Cardiopulmonar/educação , Reanimação Cardiopulmonar/normas , Estudos Cross-Over , Serviços Médicos de Emergência/normas , Feminino , Humanos , Masculino , Manequins , Simulação de Paciente , Estudos Prospectivos , Estudantes de Medicina/psicologia , Fatores de TempoRESUMO
With the increasing use of immune-checkpoint inhibitors (ICIs), such as anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and anti-programmed cell death-1 (PD-1), for the treatment of malignancies, cases of ICI-induced type 1 diabetes mellitus (ICI-T1DM) have been reported globally. This review focuses on the features and pathogenesis of this disease. T1DM is an immune-related adverse event that occurs following the administration of anti-PD-1 or anti-programmed death ligand-1 (PDL1) alone or in combination with anti-CTLA-4. More than half of the reported cases presented as abrupt-onset diabetic ketoacidosis. The primary mechanism of ICI-T1DM is T-cell stimulation, which results from the loss of interaction between PD-1 and PD-L1 in pancreatic islet. The similarities and differences between ICI-T1DM and classical T1DM may provide insights into this disease entity. ICI-T1DM is a rare but often life-threatening medical emergency that healthcare professionals and patients need to be aware of. Early detection of and screening for this disease is imperative. At present, the only known treatment for ICI-T1DM is insulin injection. Further research into the mechanisms and risk factors associated with ICI-T1DM development may contribute to a better understanding of this disease entity and the identification of possible preventive strategies.
Assuntos
Diabetes Mellitus Tipo 1 , Neoplasias , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Receptor de Morte Celular Programada 1/uso terapêutico , Fatores de RiscoRESUMO
Glucagon-like peptide-1 (GLP-1) receptor agonists have been used extensively in the clinic and have an established safety profile in cardiovascular disease settings. For the treatment of peptide-secreting enteroendocrine cells, most research has focused on developing peptide multi-agonists as most of these cells are multihormonal. Among the various peptides secreted by enteroendocrine cells, the combination of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) is an attractive strategy for treating type 2 diabetes mellitus (T2DM) because both of these hormones have glucose-lowering actions. Tirzepatide, a synthetic peptide composed of 39 amino acids, functions as a dual receptor agonist of both the GIP and GLP-1 receptors. This unique mechanism of action has earned tirzepatide the nickname "twincretin." Tirzepatide's dual agonist activity may be the mechanism by which tirzepatide significantly reduces glycated hemoglobin levels and body weight in patients with T2DM as observed in phase 3 clinical trials. Besides its glucose-lowering and anti-obesity effects, tirzepatide has been reported to have potential cardiovascular benefits. In this review, we discuss the cardiovascular effects of tirzepatide based on the available preclinical and clinical data.