Pub Date : 2024-09-28DOI: 10.1186/s12933-024-02436-3
Paul Valensi
Prevalence of heart failure (HF) and diabetes are markedly increasing globally. In a population of HF patients, approximately 40% have diabetes which is associated with a more severe HF, poorer cardiovascular outcomes and higher hospitalization rates for HF than HF patients without diabetes. Similar trends were shown in HF patients with prediabetes. In addition, the association between HF and renal function decline was demonstrated in patients with or without diabetes. However, the exact prevalence of dysglycemia in HF patients requires further investigation aiming to clarify the most accurate test to detect dysglycemia in this population. The relationship between HF and diabetes is complex and probably bidirectional. In one way, patients with diabetes have a more than two-fold risk of developing incident HF with reduced or preserved ejection fraction than those without diabetes. In the other way, patients with HF, when compared with those without HF, show an increased risk for the onset of diabetes due to several mechanisms including insulin resistance (IR), which makes HF emerging as a precursor for diabetes development. This article provides epidemiological evidence of undetected dysglycemia (prediabetes or diabetes) in HF patients and reviews the pathophysiological mechanisms which favor the development of IR and the risks associated with these disorders in HF patients. This review also offers a discussion of various strategies for the prevention of diabetes in HF patients, based first on fasting plasma glucose and HbA1c measurement and if normal on an oral glucose tolerance test as diagnostic tools for prediabetes and unknown diabetes that should be performed more extensively in those patients. It discusses the implementation of diabetes prevention measures and well-structured management programs for HF patients who are generally overweight or obese, as well as current pharmacotherapeutic options for prediabetes, including sodium-glucose cotransporter 2 inhibitors which are among the pillars of HF treatment and which recently showed a benefit in the reduction of incident diabetes in HF patients. Thus, there is an urgent need of routine screening for dysglycemia in all HF patients, which should contribute to reduce the incidence of diabetes and to treat earlier diabetes when already present.
{"title":"Evidence of a bi-directional relationship between heart failure and diabetes: a strategy for the detection of glucose abnormalities and diabetes prevention in patients with heart failure.","authors":"Paul Valensi","doi":"10.1186/s12933-024-02436-3","DOIUrl":"https://doi.org/10.1186/s12933-024-02436-3","url":null,"abstract":"<p><p>Prevalence of heart failure (HF) and diabetes are markedly increasing globally. In a population of HF patients, approximately 40% have diabetes which is associated with a more severe HF, poorer cardiovascular outcomes and higher hospitalization rates for HF than HF patients without diabetes. Similar trends were shown in HF patients with prediabetes. In addition, the association between HF and renal function decline was demonstrated in patients with or without diabetes. However, the exact prevalence of dysglycemia in HF patients requires further investigation aiming to clarify the most accurate test to detect dysglycemia in this population. The relationship between HF and diabetes is complex and probably bidirectional. In one way, patients with diabetes have a more than two-fold risk of developing incident HF with reduced or preserved ejection fraction than those without diabetes. In the other way, patients with HF, when compared with those without HF, show an increased risk for the onset of diabetes due to several mechanisms including insulin resistance (IR), which makes HF emerging as a precursor for diabetes development. This article provides epidemiological evidence of undetected dysglycemia (prediabetes or diabetes) in HF patients and reviews the pathophysiological mechanisms which favor the development of IR and the risks associated with these disorders in HF patients. This review also offers a discussion of various strategies for the prevention of diabetes in HF patients, based first on fasting plasma glucose and HbA<sub>1c</sub> measurement and if normal on an oral glucose tolerance test as diagnostic tools for prediabetes and unknown diabetes that should be performed more extensively in those patients. It discusses the implementation of diabetes prevention measures and well-structured management programs for HF patients who are generally overweight or obese, as well as current pharmacotherapeutic options for prediabetes, including sodium-glucose cotransporter 2 inhibitors which are among the pillars of HF treatment and which recently showed a benefit in the reduction of incident diabetes in HF patients. Thus, there is an urgent need of routine screening for dysglycemia in all HF patients, which should contribute to reduce the incidence of diabetes and to treat earlier diabetes when already present.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"354"},"PeriodicalIF":8.5,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1186/s12933-024-02435-4
Li Jiang, Hua‑Yan Xu, Yuan Li, Ke Shi, Han Fang, Wei‑Feng Yan, Ying‑Kun Guo, Zhi-Gang Yang
It remains unclear whether the association between dyslipidemia status and triglyceride-glucose (TyG) index with myocardial damage varies in the context of type 2 diabetes mellitus (T2DM). This study aimed to determine the differential effects of dyslipidemia status and TyG index on left ventricular (LV) global function and myocardial microcirculation in patients with T2DM using cardiac magnetic resonance (CMR) imaging. A total of 226 T2DM patients and 72 controls who underwent CMR examination were included. The T2DM group was further categorized into subgroups based on the presence or absence of dyslipidemia (referred to as T2DM (DysL+) and T2DM (DysL-)) or whether the TyG index exceeded 9.06. CMR-derived LV perfusion parameters, remodeling index, and global function index (GFI) were assessed and compared among groups. A multivariable linear regression model was employed to evaluate the effects of various variables on LV myocardial microcirculation, remodeling index, and GFI. The LV GFI sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (p < 0.001), and was lower (p = 0.003) in T2DM with higher TyG index group than in lower TyG index group. The LV remodeling index was higher in higher TyG index group than in lower TyG index group (p = 0.002), but there was no significant difference in whether the subgroup was accompanied by dyslipidemia. Multivariable analysis revealed that the TyG index, but not dyslipidemia status, was independently associated with LV remodeling index (β coefficient[95% confidence interval], 0.152[0.025, 0.268], p = 0.007) and LV GFI (− 0.159[− 0.281, − 0.032], p = 0.014). For LV myocardial microcirculation, perfusion index, upslope, and max signal intensity sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (all p < 0.001). Dyslipidemia status independently correlated with perfusion index (− 0.147[− 0.272, − 0.024], p = 0.02) and upslope (− 0.200[− 0.320, 0.083], p = 0.001), while TyG index was independently correlated with time to maximum signal intensity (0.141[0.019, 0.257], p = 0.023). Both dyslipidemia status and higher TyG index were associated with further deterioration of LV global function and myocardial microvascular function in the context of T2DM. The effects of dyslipidemia and a higher TyG index appear to be differential, which indicates that not only the amount of blood lipids and glucose but also the quality of blood lipids are therapeutic targets for preventing further myocardial damage.
{"title":"The differential effects of dyslipidemia status and triglyceride-glucose index on left ventricular global function and myocardial microcirculation in diabetic individuals: a cardiac magnetic resonance study","authors":"Li Jiang, Hua‑Yan Xu, Yuan Li, Ke Shi, Han Fang, Wei‑Feng Yan, Ying‑Kun Guo, Zhi-Gang Yang","doi":"10.1186/s12933-024-02435-4","DOIUrl":"https://doi.org/10.1186/s12933-024-02435-4","url":null,"abstract":"It remains unclear whether the association between dyslipidemia status and triglyceride-glucose (TyG) index with myocardial damage varies in the context of type 2 diabetes mellitus (T2DM). This study aimed to determine the differential effects of dyslipidemia status and TyG index on left ventricular (LV) global function and myocardial microcirculation in patients with T2DM using cardiac magnetic resonance (CMR) imaging. A total of 226 T2DM patients and 72 controls who underwent CMR examination were included. The T2DM group was further categorized into subgroups based on the presence or absence of dyslipidemia (referred to as T2DM (DysL+) and T2DM (DysL-)) or whether the TyG index exceeded 9.06. CMR-derived LV perfusion parameters, remodeling index, and global function index (GFI) were assessed and compared among groups. A multivariable linear regression model was employed to evaluate the effects of various variables on LV myocardial microcirculation, remodeling index, and GFI. The LV GFI sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (p < 0.001), and was lower (p = 0.003) in T2DM with higher TyG index group than in lower TyG index group. The LV remodeling index was higher in higher TyG index group than in lower TyG index group (p = 0.002), but there was no significant difference in whether the subgroup was accompanied by dyslipidemia. Multivariable analysis revealed that the TyG index, but not dyslipidemia status, was independently associated with LV remodeling index (β coefficient[95% confidence interval], 0.152[0.025, 0.268], p = 0.007) and LV GFI (− 0.159[− 0.281, − 0.032], p = 0.014). For LV myocardial microcirculation, perfusion index, upslope, and max signal intensity sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (all p < 0.001). Dyslipidemia status independently correlated with perfusion index (− 0.147[− 0.272, − 0.024], p = 0.02) and upslope (− 0.200[− 0.320, 0.083], p = 0.001), while TyG index was independently correlated with time to maximum signal intensity (0.141[0.019, 0.257], p = 0.023). Both dyslipidemia status and higher TyG index were associated with further deterioration of LV global function and myocardial microvascular function in the context of T2DM. The effects of dyslipidemia and a higher TyG index appear to be differential, which indicates that not only the amount of blood lipids and glucose but also the quality of blood lipids are therapeutic targets for preventing further myocardial damage.","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"53 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1186/s12933-024-02419-4
Emmanuel Cosson, Marie Auzanneau, Gloria A. Aguayo, Wolfram Karges, Jean-Pierre Riveline, Petra Augstein, Laura Sablone, Peter Jehle, Guy Fagherazzi, Reinhard W. Holl
To evaluate whether cardiovascular risk factors and their management differ in primary prevention between adult males and females with type 1 diabetes (T1D) in two European countries in 2020–2022 and sex inequalities in achievement of standards of care in diabetes. We used 2020–2022 data of patients without a cardiovascular history in the Prospective Diabetes Follow-up registry (DPV) centres, in Germany, and the Société Francophone du Diabète– Cohorte Diabète de Type 1 cohort (SFDT1), in France. We included 2,657 participants from the DPV registry and 1,172 from the SFDT1 study. Body mass indexes were similar in females and males with similar proportions of HbA1c < 7% (DPV: 36.6 vs 33.0%, p = 0.06, respectively; SFDT1: 23.4 vs 25.7%, p = 0.41). Females were less overweight compared to men in DPV (55.4 vs 61.0%, p < 0.01) but not in SFDT1 (48.0 vs 44.9%, p = 0.33) and were less prone to smoke (DPV: 19.7 vs 25.8%, p < 0.01; SFDT1: 21.0 vs 26.0%, p = 0.07). Systolic blood pressure was lower in females than males with a higher rate of antihypertensive therapy in case of hypertension in females in DPV (70.5 vs 63.7%, p = 0.02) but not in SFDT1 (73.3 vs 68.6%, p = 0.64). In the case of microalbuminuria, ACEi-ARB were less often prescribed in women than men in DPV (21.4 vs 37.6%, p < 0.01) but not SFDT1 (73.3 vs 67.5.0%, p = 0.43). In females compared to males, HDL-cholesterol levels were higher; triglycerides were lower in both countries. In those with LDL-cholesterol > 3.4 mmol/L (DPV: 19.9 (females) vs 23.9% (males), p = 0.01; SFDT1 17.0 vs 19.2%, p = 0.43), statin therapy was less often prescribed in females than males in DPV (7.9 vs 17.0%, p < 0.01), SFDT1 (18.2 vs 21.0%, p = 0.42). In both studies, females in primary prevention have a better cardiovascular risk profile than males. We observed a high rate of therapeutic inertia, which might be higher in females for statin treatment and nephroprotection with ACEi-ARB, especially in Germany. Diabetologists should be aware of sex-specific differences in the management of cardiorenal risk factors to develop more personalized prevention strategies.
目的：评估 2020-2022 年两个欧洲国家的 1 型糖尿病（T1D）成年男性和女性患者在一级预防中的心血管风险因素及其管理是否存在差异，以及在达到糖尿病护理标准方面的性别不平等。我们使用了德国前瞻性糖尿病随访登记中心（DPV）和法国 1 型糖尿病法语协会队列（SFDT1）2020-2022 年无心血管病史患者的数据。我们纳入了 DPV 登记的 2,657 名参与者和 SFDT1 研究的 1,172 名参与者。女性和男性的体重指数相似，HbA1c 3.4 mmol/L的比例也相似（DPV：19.9（女性） vs 23.9%（男性），p = 0.01；SFDT1：17.0 vs 19.2%，p = 0.43），DPV（7.9 vs 17.0%，p < 0.01）和SFDT1（18.2 vs 21.0%，p = 0.42）中，他汀类药物的处方女性少于男性。在这两项研究中，女性一级预防者的心血管风险状况优于男性。我们观察到女性的治疗惰性较高，尤其是在德国，在他汀类药物治疗和 ACEi-ARB 肾保护方面，女性的治疗惰性可能更高。糖尿病医生应了解心肾风险因素管理中的性别差异，以制定更个性化的预防策略。
{"title":"Sex inequalities in cardiovascular risk factors and their management in primary prevention in adults living with type 1 diabetes in Germany and France: findings from DPV and SFDT1","authors":"Emmanuel Cosson, Marie Auzanneau, Gloria A. Aguayo, Wolfram Karges, Jean-Pierre Riveline, Petra Augstein, Laura Sablone, Peter Jehle, Guy Fagherazzi, Reinhard W. Holl","doi":"10.1186/s12933-024-02419-4","DOIUrl":"https://doi.org/10.1186/s12933-024-02419-4","url":null,"abstract":"To evaluate whether cardiovascular risk factors and their management differ in primary prevention between adult males and females with type 1 diabetes (T1D) in two European countries in 2020–2022 and sex inequalities in achievement of standards of care in diabetes. We used 2020–2022 data of patients without a cardiovascular history in the Prospective Diabetes Follow-up registry (DPV) centres, in Germany, and the Société Francophone du Diabète– Cohorte Diabète de Type 1 cohort (SFDT1), in France. We included 2,657 participants from the DPV registry and 1,172 from the SFDT1 study. Body mass indexes were similar in females and males with similar proportions of HbA1c < 7% (DPV: 36.6 vs 33.0%, p = 0.06, respectively; SFDT1: 23.4 vs 25.7%, p = 0.41). Females were less overweight compared to men in DPV (55.4 vs 61.0%, p < 0.01) but not in SFDT1 (48.0 vs 44.9%, p = 0.33) and were less prone to smoke (DPV: 19.7 vs 25.8%, p < 0.01; SFDT1: 21.0 vs 26.0%, p = 0.07). Systolic blood pressure was lower in females than males with a higher rate of antihypertensive therapy in case of hypertension in females in DPV (70.5 vs 63.7%, p = 0.02) but not in SFDT1 (73.3 vs 68.6%, p = 0.64). In the case of microalbuminuria, ACEi-ARB were less often prescribed in women than men in DPV (21.4 vs 37.6%, p < 0.01) but not SFDT1 (73.3 vs 67.5.0%, p = 0.43). In females compared to males, HDL-cholesterol levels were higher; triglycerides were lower in both countries. In those with LDL-cholesterol > 3.4 mmol/L (DPV: 19.9 (females) vs 23.9% (males), p = 0.01; SFDT1 17.0 vs 19.2%, p = 0.43), statin therapy was less often prescribed in females than males in DPV (7.9 vs 17.0%, p < 0.01), SFDT1 (18.2 vs 21.0%, p = 0.42). In both studies, females in primary prevention have a better cardiovascular risk profile than males. We observed a high rate of therapeutic inertia, which might be higher in females for statin treatment and nephroprotection with ACEi-ARB, especially in Germany. Diabetologists should be aware of sex-specific differences in the management of cardiorenal risk factors to develop more personalized prevention strategies. ","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"2 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1186/s12933-024-02417-6
Jiwon Park, Hangyul Song, Shinje Moon, Yumin Kim, Sungsoo Cho, Kyungdo Han, Cheol-Young Park, Sung Woo Cho, Chang-Myung Oh
Heart failure (HF) is a serious and common condition affecting millions of people worldwide, with obesity being a major cause of metabolic disorders such as diabetes and cardiovascular disease. This study aimed to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, on the obese- and diabetes-related cardiomyopathy. We used db/db mice and high fat diet-streptozotocin induced diabetic mice to investigate the underlying mechanisms of fenofibrate’s beneficial effects on heart function. Fenofibrate reduced fibrosis, and lipid accumulation, and suppressed inflammatory and immunological responses in the heart via TNF signaling. In addition, we investigated the beneficial effects of fenofibrate on HF hospitalization. The Korean National Health Insurance database was used to identify 427,154 fenofibrate users and 427,154 non-users for comparison. During the 4.22-year follow-up, fenofibrate use significantly reduced the risk of HF hospitalization (hazard ratio, 0.907; 95% CI 0.824–0.998). The findings suggest that fenofibrate may be a useful therapeutic agent for obesity- and diabetes-related cardiomyopathy.
{"title":"Cardiometabolic benefits of fenofibrate in heart failure related to obesity and diabetes","authors":"Jiwon Park, Hangyul Song, Shinje Moon, Yumin Kim, Sungsoo Cho, Kyungdo Han, Cheol-Young Park, Sung Woo Cho, Chang-Myung Oh","doi":"10.1186/s12933-024-02417-6","DOIUrl":"https://doi.org/10.1186/s12933-024-02417-6","url":null,"abstract":"Heart failure (HF) is a serious and common condition affecting millions of people worldwide, with obesity being a major cause of metabolic disorders such as diabetes and cardiovascular disease. This study aimed to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, on the obese- and diabetes-related cardiomyopathy. We used db/db mice and high fat diet-streptozotocin induced diabetic mice to investigate the underlying mechanisms of fenofibrate’s beneficial effects on heart function. Fenofibrate reduced fibrosis, and lipid accumulation, and suppressed inflammatory and immunological responses in the heart via TNF signaling. In addition, we investigated the beneficial effects of fenofibrate on HF hospitalization. The Korean National Health Insurance database was used to identify 427,154 fenofibrate users and 427,154 non-users for comparison. During the 4.22-year follow-up, fenofibrate use significantly reduced the risk of HF hospitalization (hazard ratio, 0.907; 95% CI 0.824–0.998). The findings suggest that fenofibrate may be a useful therapeutic agent for obesity- and diabetes-related cardiomyopathy.","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"11 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diabetic macroangiopathy is a leading cause of diabetes-related mortality worldwide. Both genetic and environmental factors, through a multitude of underlying molecular mechanisms, contribute to the pathogenesis of diabetic macroangiopathy. MicroRNAs (miRNAs), a class of non-coding RNAs known for their functional diversity and expression specificity, are increasingly recognized for their roles in the initiation and progression of diabetes and diabetic macroangiopathy. In this review, we will describe the biogenesis of miRNAs, and summarize their functions in diabetic macroangiopathy, including atherosclerosis, peripheral artery disease, coronary artery disease, and cerebrovascular disease, which are anticipated to provide new insights into future perspectives of miRNAs in basic, translational and clinical research, ultimately advancing the diagnosis, prevention, and treatment of diabetic macroangiopathy.
{"title":"MicroRNAs in diabetic macroangiopathy","authors":"Guocheng Rao, Boqiang Peng, Guixiang Zhang, Xianghui Fu, Jingyan Tian, Yan Tian","doi":"10.1186/s12933-024-02405-w","DOIUrl":"https://doi.org/10.1186/s12933-024-02405-w","url":null,"abstract":"Diabetic macroangiopathy is a leading cause of diabetes-related mortality worldwide. Both genetic and environmental factors, through a multitude of underlying molecular mechanisms, contribute to the pathogenesis of diabetic macroangiopathy. MicroRNAs (miRNAs), a class of non-coding RNAs known for their functional diversity and expression specificity, are increasingly recognized for their roles in the initiation and progression of diabetes and diabetic macroangiopathy. In this review, we will describe the biogenesis of miRNAs, and summarize their functions in diabetic macroangiopathy, including atherosclerosis, peripheral artery disease, coronary artery disease, and cerebrovascular disease, which are anticipated to provide new insights into future perspectives of miRNAs in basic, translational and clinical research, ultimately advancing the diagnosis, prevention, and treatment of diabetic macroangiopathy.","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"49 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nonischemic cardiomyopathy (NISCM) is a clinical challenge with limited therapeutic targets. This study aims to identify promising drug targets for NISCM. We utilized cis-pQTLs from the deCODE study, which includes data from 35,559 Icelanders, and SNPs from the FinnGen study, which includes data from 1,754 NISCM cases and 340,815 controls of Finnish ancestry. Mendelian randomization (MR) analysis was performed to estimate the causal relationship between circulating plasma protein levels and NISCM risk. Proteins with significant associations underwent false discovery rate (FDR) correction, followed by Bayesian colocalization analysis. The expression of top two proteins, LILRA5 and NELL1, was further analyzed using various NISCM datasets. Descriptions from the Human Protein Atlas (HPA) validated protein expression. The impact of environmental exposures on LILRA5 was assessed using the Comparative Toxicogenomics Database (CTD), and molecular docking identified the potential small molecule interactions. MR analysis identified 255 circulating plasma proteins associated with NISCM, with 16 remaining significant after FDR correction. Bayesian colocalization analysis identified LILRA5 and NELL1 as significant, with PP.H4 > 0.8. LILRA5 has a protective effect (OR = 0.758, 95% CI, 0.670–0.857) while NELL1 displays the risk effect (OR = 1.290, 95% CI, 1.199–1.387) in NISCM. Decreased LILRA5 expression was found in NISCM such as diabetic, hypertrophic, dilated, and inflammatory cardiomyopathy, while NELL1 expression increased in hypertrophic cardiomyopathy. HPA data indicated high LILRA5 expression in neutrophils, macrophages and endothelial cells within normal heart and limited NELL1 expression. Immune infiltration analysis revealed decreased neutrophil in diabetic cardiomyopathy. CTD analysis identified several small molecules that affect LILRA5 mRNA expression. Among these, Estradiol, Estradiol-3-benzoate, Gadodiamide, Topotecan, and Testosterone were found to stably bind to the LILRA5 protein at the conserved VAL-15 or THR-133 residues in the Ig-like C2 domain. Based on European Ancestry Cohort, this study reveals that LILRA5 and NELL1 are potential therapeutic targets for NISCM, with LILRA5 showing particularly promising prospects in diabetic cardiomyopathy. Several small molecules interact with LILRA5, implying potential clinical implication.
{"title":"Identification of potential therapeutic targets for nonischemic cardiomyopathy in European ancestry: an integrated multiomics analysis","authors":"Kaijia Shi, Xu Chen, Yangyang Zhao, Peihu Li, Jinxuan Chai, Jianmin Qiu, Zhihua Shen, Junli Guo, Wei Jie","doi":"10.1186/s12933-024-02431-8","DOIUrl":"https://doi.org/10.1186/s12933-024-02431-8","url":null,"abstract":"Nonischemic cardiomyopathy (NISCM) is a clinical challenge with limited therapeutic targets. This study aims to identify promising drug targets for NISCM. We utilized cis-pQTLs from the deCODE study, which includes data from 35,559 Icelanders, and SNPs from the FinnGen study, which includes data from 1,754 NISCM cases and 340,815 controls of Finnish ancestry. Mendelian randomization (MR) analysis was performed to estimate the causal relationship between circulating plasma protein levels and NISCM risk. Proteins with significant associations underwent false discovery rate (FDR) correction, followed by Bayesian colocalization analysis. The expression of top two proteins, LILRA5 and NELL1, was further analyzed using various NISCM datasets. Descriptions from the Human Protein Atlas (HPA) validated protein expression. The impact of environmental exposures on LILRA5 was assessed using the Comparative Toxicogenomics Database (CTD), and molecular docking identified the potential small molecule interactions. MR analysis identified 255 circulating plasma proteins associated with NISCM, with 16 remaining significant after FDR correction. Bayesian colocalization analysis identified LILRA5 and NELL1 as significant, with PP.H4 > 0.8. LILRA5 has a protective effect (OR = 0.758, 95% CI, 0.670–0.857) while NELL1 displays the risk effect (OR = 1.290, 95% CI, 1.199–1.387) in NISCM. Decreased LILRA5 expression was found in NISCM such as diabetic, hypertrophic, dilated, and inflammatory cardiomyopathy, while NELL1 expression increased in hypertrophic cardiomyopathy. HPA data indicated high LILRA5 expression in neutrophils, macrophages and endothelial cells within normal heart and limited NELL1 expression. Immune infiltration analysis revealed decreased neutrophil in diabetic cardiomyopathy. CTD analysis identified several small molecules that affect LILRA5 mRNA expression. Among these, Estradiol, Estradiol-3-benzoate, Gadodiamide, Topotecan, and Testosterone were found to stably bind to the LILRA5 protein at the conserved VAL-15 or THR-133 residues in the Ig-like C2 domain. Based on European Ancestry Cohort, this study reveals that LILRA5 and NELL1 are potential therapeutic targets for NISCM, with LILRA5 showing particularly promising prospects in diabetic cardiomyopathy. Several small molecules interact with LILRA5, implying potential clinical implication.","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"117 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1186/s12933-024-02407-8
Stephan Sachs, Anna Götz, Brian Finan, Annette Feuchtinger, Richard D. DiMarchi, Yvonne Döring, Christian Weber, Matthias H. Tschöp, Timo D. Müller, Susanna M. Hofmann
<p><b>Correction to: Cardiovasc Diabetol (2023) 22:217</b></p><p>https://doi.org/10.1186/s12933-023-01940-2</p><p>Following publication of the original article [1], the author noticed the errors in Fig. 2 and in Results section.</p><p>The bar graph is mistakenly duplicated in “percentage of plaque area of the aortic valves” of Fig. 2E. The corrected figure is given below:</p><figure><figcaption><b data-test="figure-caption-text">Fig. 2</b></figcaption><picture><source srcset="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12933-024-02407-8/MediaObjects/12933_2024_2407_Fig2_HTML.png?as=webp" type="image/webp"/><img alt="figure 2" aria-describedby="Fig2" height="344" loading="lazy" src="//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12933-024-02407-8/MediaObjects/12933_2024_2407_Fig2_HTML.png" width="685"/></picture><p>Acyl-GIP ameliorates dyslipidemia and atherosclerotic plaque formation in LDLR-/- male mice. Plasma (<b>A</b>) triglycerides, (<b>B</b>) cholesterol and (<b>C</b>) lipoprotein fractions as well as (<b>D</b> and <b>E</b>) the percentage of plaque area in aortic arches and valves and along the descending aorta of male LDLR-/- mice treated daily with either vehicle or acyl-GIP via subcutaneous injections for 28 days. <i>n</i> = 7. Blood lipids were determined from sac plasma at the end of the study. Data represent means ± SEM. *<i>P</i> < 0.05, **<i>P</i> < 0.01, *** <i>P</i> < 0.001, determined by unpaired two-sided t-test</p><span>Full size image</span><svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-chevron-right-small" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></figure><p>In Result section under the heading “GIPR-agonist acyl-GIP ameliorates dyslipidemia and atherosclerotic plaque formation in male LDLR-/- mice independently of weight loss”, the last sentence should read “Most importantly, acyl-GIP treatment was accompanied by reduced atherosclerotic plaque formation within the aortic valve and a trend to decrease fat streaks along the descending aorta (Fig. 2E)“ instead of “Most importantly, acyl-GIP treatment was accompanied by reduced atherosclerotic plaque formation within the aortic valve (Fig. 2G–H) and decreased fat streaks along the descending aorta (Fig. 2I)”.</p><ol data-track-component="outbound reference" data-track-context="references section"><li data-counter="1."><p>Sachs S, Götz A, Finan B, et al. GIP receptor agonism improves dyslipidemia and atherosclerosis independently of body weight loss in preclinical mouse model for cardio-metabolic disease. Cardiovasc Diabetol. 2023;22:217.https://doi.org/10.1186/s12933-023-01940-2</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-download-medium" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></p><
创作共用 "许可协议允许以任何媒介或格式使用、共享、改编、分发和复制文章，但必须注明原作者和出处，提供指向 "创作共用 "许可协议的链接，并说明是否进行了修改。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中，除非在材料的署名栏中另有说明。如果材料未包含在文章的知识共享许可协议中，且您打算使用的材料不符合法律规定或超出许可使用范围，您需要直接从版权所有者处获得许可。要查看该许可的副本，请访问 http://creativecommons.org/licenses/by/4.0/。除非在数据的信用行中另有说明，否则创作共用公共领域专用免责声明 (http://creativecommons.org/publicdomain/zero/1.0/) 适用于本文提供的数据。转载与许可引用本文Sachs, S., Götz, A., Finan, B. et al. Correction：GIP受体激动在心血管代谢疾病临床前小鼠模型中改善血脂异常和动脉粥样硬化，与体重减轻无关。Cardiovasc Diabetol 23, 341 (2024). https://doi.org/10.1186/s12933-024-02407-8Download citationPublished: 12 September 2024DOI: https://doi.org/10.1186/s12933-024-02407-8Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative.
{"title":"Correction: GIP receptor agonism improves dyslipidemia and atherosclerosis independently of body weight loss in preclinical mouse model for cardio-metabolic disease","authors":"Stephan Sachs, Anna Götz, Brian Finan, Annette Feuchtinger, Richard D. DiMarchi, Yvonne Döring, Christian Weber, Matthias H. Tschöp, Timo D. Müller, Susanna M. Hofmann","doi":"10.1186/s12933-024-02407-8","DOIUrl":"https://doi.org/10.1186/s12933-024-02407-8","url":null,"abstract":"<p><b>Correction to: Cardiovasc Diabetol (2023) 22:217</b></p><p>https://doi.org/10.1186/s12933-023-01940-2</p><p>Following publication of the original article [1], the author noticed the errors in Fig. 2 and in Results section.</p><p>The bar graph is mistakenly duplicated in “percentage of plaque area of the aortic valves” of Fig. 2E. The corrected figure is given below:</p><figure><figcaption><b data-test=\"figure-caption-text\">Fig. 2</b></figcaption><picture><source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12933-024-02407-8/MediaObjects/12933_2024_2407_Fig2_HTML.png?as=webp\" type=\"image/webp\"/><img alt=\"figure 2\" aria-describedby=\"Fig2\" height=\"344\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs12933-024-02407-8/MediaObjects/12933_2024_2407_Fig2_HTML.png\" width=\"685\"/></picture><p>Acyl-GIP ameliorates dyslipidemia and atherosclerotic plaque formation in LDLR-/- male mice. Plasma (<b>A</b>) triglycerides, (<b>B</b>) cholesterol and (<b>C</b>) lipoprotein fractions as well as (<b>D</b> and <b>E</b>) the percentage of plaque area in aortic arches and valves and along the descending aorta of male LDLR-/- mice treated daily with either vehicle or acyl-GIP via subcutaneous injections for 28 days. <i>n</i> = 7. Blood lipids were determined from sac plasma at the end of the study. Data represent means ± SEM. *<i>P</i> < 0.05, **<i>P</i> < 0.01, *** <i>P</i> < 0.001, determined by unpaired two-sided t-test</p><span>Full size image</span><svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></figure><p>In Result section under the heading “GIPR-agonist acyl-GIP ameliorates dyslipidemia and atherosclerotic plaque formation in male LDLR-/- mice independently of weight loss”, the last sentence should read “Most importantly, acyl-GIP treatment was accompanied by reduced atherosclerotic plaque formation within the aortic valve and a trend to decrease fat streaks along the descending aorta (Fig. 2E)“ instead of “Most importantly, acyl-GIP treatment was accompanied by reduced atherosclerotic plaque formation within the aortic valve (Fig. 2G–H) and decreased fat streaks along the descending aorta (Fig. 2I)”.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Sachs S, Götz A, Finan B, et al. GIP receptor agonism improves dyslipidemia and atherosclerosis independently of body weight loss in preclinical mouse model for cardio-metabolic disease. Cardiovasc Diabetol. 2023;22:217.https://doi.org/10.1186/s12933-023-01940-2</p><p>Article CAS PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"18 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1186/s12933-024-02426-5
Anja Pammer, Anna Obermayer, Julia T. Stadler, Peter N. Pferschy, Norbert J. Tripolt, Hansjörg Habisch, Tobias Madl, Harald Sourij, Gunther Marsche
Cardiovascular disease represents a significant risk factor for mortality in individuals with type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) is believed to play a crucial role in maintaining cardiovascular health through its multifaceted atheroprotective effects and its capacity to enhance glycemic control. The impact of dietary interventions and intermittent fasting (IF) on HDL functionality remains uncertain. The objective of this study was to assess the effects of dietary interventions and IF as a strategy to safely improve glycemic control and reduce body weight on functional parameters of HDL in individuals with T2DM. Before the 12-week intervention, all participants (n = 41) of the INTERFAST-2 study were standardized to a uniform basal insulin regimen and randomized to an IF or non-IF group. Additionally, all participants were advised to adhere to dietary recommendations that promoted healthy eating patterns. The IF group (n = 19) followed an alternate-day fasting routine, reducing their calorie intake by 75% on fasting days. The participants’ glucose levels were continuously monitored. Other parameters were measured following the intervention: Lipoprotein composition and subclass distribution were measured by nuclear magnetic resonance spectroscopy. HDL cholesterol efflux capacity, paraoxonase 1 (PON1) activity, lecithin cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity were assessed using cell-based assays and commercially available kits. Apolipoprotein M (apoM) levels were determined by ELISA. Following the 12-week intervention, the IF regimen significantly elevated serum apoM levels (p = 0.0144), whereas no increase was observed in the non-IF group (p = 0.9801). ApoM levels correlated with weight loss and fasting glucose levels in the IF group. Both groups exhibited a robust enhancement in HDL cholesterol efflux capacity (p < 0.0001, p = 0.0006) after 12 weeks. Notably, only the non-IF group exhibited significantly elevated activity of PON1 (p = 0.0455) and LCAT (p = 0.0117) following the 12-week intervention. In contrast, the changes observed in the IF group did not reach statistical significance. A balanced diet combined with meticulous insulin management improves multiple metrics of HDL function. While additional IF increases apoM levels, it does not further enhance other aspects of HDL functionality. The study was registered at the German Clinical Trial Register (DRKS) on 3 September 2019 under the number DRKS00018070.
心血管疾病是导致 2 型糖尿病（T2DM）患者死亡的一个重要风险因素。高密度脂蛋白（HDL）具有多方面的动脉粥样硬化保护作用，并能加强血糖控制，因此被认为在维护心血管健康方面发挥着至关重要的作用。饮食干预和间歇性禁食（IF）对高密度脂蛋白功能的影响仍不确定。本研究旨在评估饮食干预和间歇性禁食作为一种安全改善血糖控制和减轻体重的策略对 T2DM 患者高密度脂蛋白功能参数的影响。在进行为期 12 周的干预之前，INTERFAST-2 研究的所有参与者（n = 41）都被标准化为统一的基础胰岛素方案，并被随机分配到 IF 组或非 IF 组。此外，所有参与者都被建议遵守促进健康饮食模式的饮食建议。IF 组（n = 19）采用隔日禁食法，在禁食日减少 75% 的卡路里摄入量。参与者的血糖水平受到持续监测。干预后还测量了其他参数：通过核磁共振波谱测量脂蛋白组成和亚类分布。高密度脂蛋白胆固醇外排能力、副氧自由基酶 1 (PON1) 活性、卵磷脂胆固醇酰基转移酶 (LCAT) 活性和胆固醇酯转移蛋白 (CETP) 活性通过细胞检测法和市售试剂盒进行评估。载脂蛋白 M（apoM）水平通过酶联免疫吸附法测定。经过 12 周的干预后，IF 方案显著提高了血清载脂蛋白 M 的水平（p = 0.0144），而非 IF 组则没有提高（p = 0.9801）。在 IF 组中，载脂蛋白 M 水平与体重下降和空腹血糖水平相关。12 周后，两组的高密度脂蛋白胆固醇外排能力均有显著增强（p < 0.0001，p = 0.0006）。值得注意的是，在 12 周的干预后，只有非 IF 组的 PON1（p = 0.0455）和 LCAT（p = 0.0117）活性明显升高。相比之下，胰岛素转换组观察到的变化未达到统计学意义。均衡饮食结合细致的胰岛素管理可改善高密度脂蛋白的多种功能指标。虽然额外的 IF 能提高载脂蛋白水平，但并不能进一步增强高密度脂蛋白功能的其他方面。该研究于2019年9月3日在德国临床试验注册中心（DRKS）注册，注册号为DRKS00018070。
{"title":"Effects of dietary interventions and intermittent fasting on HDL function in obese individuals with T2DM: a randomized controlled trial","authors":"Anja Pammer, Anna Obermayer, Julia T. Stadler, Peter N. Pferschy, Norbert J. Tripolt, Hansjörg Habisch, Tobias Madl, Harald Sourij, Gunther Marsche","doi":"10.1186/s12933-024-02426-5","DOIUrl":"https://doi.org/10.1186/s12933-024-02426-5","url":null,"abstract":"Cardiovascular disease represents a significant risk factor for mortality in individuals with type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) is believed to play a crucial role in maintaining cardiovascular health through its multifaceted atheroprotective effects and its capacity to enhance glycemic control. The impact of dietary interventions and intermittent fasting (IF) on HDL functionality remains uncertain. The objective of this study was to assess the effects of dietary interventions and IF as a strategy to safely improve glycemic control and reduce body weight on functional parameters of HDL in individuals with T2DM. Before the 12-week intervention, all participants (n = 41) of the INTERFAST-2 study were standardized to a uniform basal insulin regimen and randomized to an IF or non-IF group. Additionally, all participants were advised to adhere to dietary recommendations that promoted healthy eating patterns. The IF group (n = 19) followed an alternate-day fasting routine, reducing their calorie intake by 75% on fasting days. The participants’ glucose levels were continuously monitored. Other parameters were measured following the intervention: Lipoprotein composition and subclass distribution were measured by nuclear magnetic resonance spectroscopy. HDL cholesterol efflux capacity, paraoxonase 1 (PON1) activity, lecithin cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity were assessed using cell-based assays and commercially available kits. Apolipoprotein M (apoM) levels were determined by ELISA. Following the 12-week intervention, the IF regimen significantly elevated serum apoM levels (p = 0.0144), whereas no increase was observed in the non-IF group (p = 0.9801). ApoM levels correlated with weight loss and fasting glucose levels in the IF group. Both groups exhibited a robust enhancement in HDL cholesterol efflux capacity (p < 0.0001, p = 0.0006) after 12 weeks. Notably, only the non-IF group exhibited significantly elevated activity of PON1 (p = 0.0455) and LCAT (p = 0.0117) following the 12-week intervention. In contrast, the changes observed in the IF group did not reach statistical significance. A balanced diet combined with meticulous insulin management improves multiple metrics of HDL function. While additional IF increases apoM levels, it does not further enhance other aspects of HDL functionality. The study was registered at the German Clinical Trial Register (DRKS) on 3 September 2019 under the number DRKS00018070. ","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"33 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-12DOI: 10.1186/s12933-024-02408-7
Eun Ju Cho, Goh Eun Chung, Jeong-Ju Yoo, Yuri Cho, Kyu Na Lee, Dong Wook Shin, Yoon Jun Kim, Jung-Hwan Yoon, Kyungdo Han, Su Jong Yu
The association between nonalcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) has been inconsistent, and the impact of hepatic fibrosis on this relationship remains uncertain. We investigated the association between NAFLD and the risk of new-onset AF across different age groups. A total of 3,179,582 participants from the 2009 Korean National Health Screening Program were divided into five groups based on NAFLD status: no NAFLD (fatty liver index [FLI] < 30); grade 1 NAFLD without advanced fibrosis (FLI 30–59 & BARD < 2); grade 1 NAFLD with advanced fibrosis (FLI 30–59 & BARD ≥ 2); grade 2 NAFLD without advanced fibrosis (FLI ≥ 60 & BARD < 2); and grade 2 NAFLD with advanced fibrosis (FLI ≥ 60 & BARD ≥ 2). The primary outcome was incident AF. During the median follow-up of 9.3 years, 62,542 patients were diagnosed with new-onset AF. In the age- and sex-adjusted model, the risk of new-onset AF increased across NAFLD grades and fibrosis categories: grade 1 NAFLD without advanced fibrosis (hazard ratio [HR] 1.120, 95% confidence interval [CI]: 1.081–1.161); grade 1 NAFLD with advanced fibrosis (HR 1.275, 95% CI 1.251–1.300); grade 2 NAFLD without advanced fibrosis (HR 1.305, 95% CI: 1.252–1.360); and grade 2 NAFLD with advanced fibrosis (HR 1.627, 95% CI: 1.586–1.670). In the multivariate model, the excess risk of AF in patients with NAFLD and advanced fibrosis remained significant, even in participants aged 20–39 years. Patients with NAFLD had a higher risk of new-onset AF, which increased progressively with NAFLD severity, particularly in those aged 20–29 years.
{"title":"Association of nonalcoholic fatty liver disease with new-onset atrial fibrillation stratified by age groups","authors":"Eun Ju Cho, Goh Eun Chung, Jeong-Ju Yoo, Yuri Cho, Kyu Na Lee, Dong Wook Shin, Yoon Jun Kim, Jung-Hwan Yoon, Kyungdo Han, Su Jong Yu","doi":"10.1186/s12933-024-02408-7","DOIUrl":"https://doi.org/10.1186/s12933-024-02408-7","url":null,"abstract":"The association between nonalcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) has been inconsistent, and the impact of hepatic fibrosis on this relationship remains uncertain. We investigated the association between NAFLD and the risk of new-onset AF across different age groups. A total of 3,179,582 participants from the 2009 Korean National Health Screening Program were divided into five groups based on NAFLD status: no NAFLD (fatty liver index [FLI] < 30); grade 1 NAFLD without advanced fibrosis (FLI 30–59 & BARD < 2); grade 1 NAFLD with advanced fibrosis (FLI 30–59 & BARD ≥ 2); grade 2 NAFLD without advanced fibrosis (FLI ≥ 60 & BARD < 2); and grade 2 NAFLD with advanced fibrosis (FLI ≥ 60 & BARD ≥ 2). The primary outcome was incident AF. During the median follow-up of 9.3 years, 62,542 patients were diagnosed with new-onset AF. In the age- and sex-adjusted model, the risk of new-onset AF increased across NAFLD grades and fibrosis categories: grade 1 NAFLD without advanced fibrosis (hazard ratio [HR] 1.120, 95% confidence interval [CI]: 1.081–1.161); grade 1 NAFLD with advanced fibrosis (HR 1.275, 95% CI 1.251–1.300); grade 2 NAFLD without advanced fibrosis (HR 1.305, 95% CI: 1.252–1.360); and grade 2 NAFLD with advanced fibrosis (HR 1.627, 95% CI: 1.586–1.670). In the multivariate model, the excess risk of AF in patients with NAFLD and advanced fibrosis remained significant, even in participants aged 20–39 years. Patients with NAFLD had a higher risk of new-onset AF, which increased progressively with NAFLD severity, particularly in those aged 20–29 years.","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"8 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-11DOI: 10.1186/s12933-024-02395-9
Álvaro González-Domínguez, Otto Savolainen, Jesús Domínguez-Riscart, Rikard Landberg, Alfonso Lechuga-Sancho, Raúl González-Domínguez
Although insulin resistance (IR) is among the most frequent and pathogenically relevant complications accompanying childhood obesity, its role in modulating and exacerbating obesity pathophysiology has not yet been completely clarified. To get deeper insights into the interplay between childhood obesity and IR, we leveraged a comprehensive experimental design based on a combination of observational data, in vivo challenge tests (i.e., oral glucose tolerance test), and ex vivo assays (i.e., incubation of erythrocytes with insulin) using a population comprising children with obesity and IR, children with obesity without IR, and healthy controls, from whom plasma and erythrocyte samples were collected for subsequent metabolomics analysis. Children with concomitant IR showed exacerbated metabolic disturbances in the crosstalk between endogenous, microbial, and environmental determinants, including failures in energy homeostasis, amino acid metabolism, oxidative stress, synthesis of steroid hormones and bile acids, membrane lipid composition, as well as differences in exposome-related metabolites associated with diet, exposure to endocrine disruptors, and gut microbiota. Furthermore, challenge tests and ex vivo assays revealed a deleterious impact of IR on individuals’ metabolic flexibility, as reflected in blunted capacity to regulate homeostasis in response to hyperinsulinemia, at both systemic and erythroid levels. Thus, we have demonstrated for the first time that metabolite alterations in erythrocytes represent reliable and sensitive biomarkers to disentangle the metabolic complexity of IR and childhood obesity. This study emphasizes the crucial need of addressing inter-individual variability factors, such as the presence of comorbidities, to obtain a more accurate understanding of obesity-related molecular mechanisms.
虽然胰岛素抵抗（IR）是儿童肥胖症最常见、最具病理相关性的并发症之一，但它在调节和加重肥胖症病理生理学方面的作用尚未完全阐明。为了更深入地了解儿童肥胖与 IR 之间的相互作用，我们采用了综合实验设计，将观察数据、体内挑战测试（即口服葡萄糖耐量测试）和体外检测（即用胰岛素培养红细胞）结合起来，研究对象包括肥胖合并 IR 的儿童、肥胖合并 IR 的儿童以及健康对照组，并收集他们的血浆和红细胞样本进行代谢组学分析。在内源性、微生物和环境决定因素的相互影响下，合并有红外症的儿童表现出更严重的代谢紊乱，包括能量平衡失调、氨基酸代谢、氧化应激、类固醇激素和胆汁酸的合成、膜脂组成，以及与饮食、内分泌干扰物暴露和肠道微生物群相关的暴露相关代谢物的差异。此外，挑战测试和体内外试验显示，红外热反应对个体的代谢灵活性有有害影响，这反映在对高胰岛素血症做出反应时，在全身和红细胞水平上调节平衡的能力减弱。因此，我们首次证明，红细胞中代谢物的改变是可靠而灵敏的生物标志物，可用于揭示红外热与儿童肥胖症代谢的复杂性。这项研究强调，要更准确地了解与肥胖相关的分子机制，就必须解决个体间的变异因素，如是否存在合并症等。
{"title":"Probing erythrocytes as sensitive and reliable sensors of metabolic disturbances in the crosstalk between childhood obesity and insulin resistance: findings from an observational study, in vivo challenge tests, and ex vivo incubation assays","authors":"Álvaro González-Domínguez, Otto Savolainen, Jesús Domínguez-Riscart, Rikard Landberg, Alfonso Lechuga-Sancho, Raúl González-Domínguez","doi":"10.1186/s12933-024-02395-9","DOIUrl":"https://doi.org/10.1186/s12933-024-02395-9","url":null,"abstract":"Although insulin resistance (IR) is among the most frequent and pathogenically relevant complications accompanying childhood obesity, its role in modulating and exacerbating obesity pathophysiology has not yet been completely clarified. To get deeper insights into the interplay between childhood obesity and IR, we leveraged a comprehensive experimental design based on a combination of observational data, in vivo challenge tests (i.e., oral glucose tolerance test), and ex vivo assays (i.e., incubation of erythrocytes with insulin) using a population comprising children with obesity and IR, children with obesity without IR, and healthy controls, from whom plasma and erythrocyte samples were collected for subsequent metabolomics analysis. Children with concomitant IR showed exacerbated metabolic disturbances in the crosstalk between endogenous, microbial, and environmental determinants, including failures in energy homeostasis, amino acid metabolism, oxidative stress, synthesis of steroid hormones and bile acids, membrane lipid composition, as well as differences in exposome-related metabolites associated with diet, exposure to endocrine disruptors, and gut microbiota. Furthermore, challenge tests and ex vivo assays revealed a deleterious impact of IR on individuals’ metabolic flexibility, as reflected in blunted capacity to regulate homeostasis in response to hyperinsulinemia, at both systemic and erythroid levels. Thus, we have demonstrated for the first time that metabolite alterations in erythrocytes represent reliable and sensitive biomarkers to disentangle the metabolic complexity of IR and childhood obesity. This study emphasizes the crucial need of addressing inter-individual variability factors, such as the presence of comorbidities, to obtain a more accurate understanding of obesity-related molecular mechanisms.","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"99 1","pages":""},"PeriodicalIF":9.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号