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1.
CONTEXT: Retinol binding protein (RBP4), secreted primarily from the liver and adipose tissues, was recently proposed as a link between obesity and insulin resistance. The role of RBP4 in pediatric obesity, its relationship with subclinical inflammation, and its response to lifestyle changes are not elucidated. OBJECTIVE: The objective of the study was to determine in children: 1) the status of RBP4 levels in lean vs. obese; 2) the relationship between RBP4 levels and subclinical inflammation; and 3) the effect of lifestyle-only intervention on RBP4 levels. DESIGN, SETTING, AND PATIENTS: Lean and obese children (n = 21) matched for age (>14 yr to < 18 yr) and maturity stage (Tanner IV) were studied at baseline and with lifestyle intervention in obese subjects only (n = 15). INTERVENTION: Patients received 3 months of randomized and controlled physical activity-based lifestyle intervention. MAIN OUTCOME MEASURE: RBP4 levels in children before and after intervention and the relationship between RBP4 and subclinical inflammation were measured. RESULTS: Higher RBP4 levels were found in the obese group vs. lean group (P = 0.005). RBP4 correlated with not only indices of obesity and insulin resistance but also inflammatory factors (r = 0.63 and 0.64 for C-reactive protein and IL-6, respectively, P < 0.01). Intervention reduced RBP4 levels by approximately 30% (P = 0.001), and RBP4 reduction was correlated with the magnitude of decrease in inflammatory factors (P = 0.01). CONCLUSION: Alterations in serum RBP4 occur at an early age in the clinical course of obesity and appear to correlate with subclinical inflammation. Lifestyle intervention almost entirely reversed the raised RBP4 levels in obese children. Future studies should determine whether elevation of RBP4 is a direct trigger for the insulin resistance and subclinical inflammation implicated in the premature development of cardiovascular disease and diabetes.  相似文献   

2.
Retinol-binding protein 4 (RBP4) is an adipokine bound in plasma to transthyretin (TTR), which prevents its glomerular filtration and subsequent catabolism in the kidney. Alterations of this interaction have been suggested to be implicated in the elevation of RBP4 that are thought to contribute to the development of insulin resistance associated with obesity and type 2 diabetes mellitus (T2DM). However, the factors linking RBP4 to TTR in humans are not clear. Therefore, this study evaluated parameters influencing the RBP4-TTR interaction and their relation to obesity and T2DM. The RBP4 and TTR levels were quantified in plasma of 16 lean controls, 28 overweight controls, and 14 overweight T2DM patients by enzyme-linked immunosorbent assay. Transthyretin isoforms involved in RBP4 binding were determined by linear matrix-assisted laser desorption/ionization-time of flight-mass spectrometry after RBP4 coimmunoprecipitation. Holo-RBP4 (retinol-bound) and apo-RBP4 (retinol-free) were assessed by immunoblotting using nondenaturating polyacrylamide gel electrophoresis. Plasma levels of both RBP4 and TTR did not differ among the groups of lean controls, overweight controls, and overweight T2DM subjects. Using RBP4 immunoprecipitation, 4 mass signals were observed for TTR representing native, S-cysteinylated, S-cysteinglycinylated, and S-glutathionylated TTR. No differences in peak intensity of TTR isoforms were observed among the groups. Moreover, no differences in the ratio of holo- and apo-RBP4 were evident. The results suggest that circulating RBP4 and TTR were not affected by human obesity or T2DM, which might be attributed to the absence of alterations of TTR isoforms and the ratio of holo- and apo-RBP4 that might modify the TTR-RBP4 interaction.  相似文献   

3.
Retinol-binding protein 4 (RBP4) has been suggested as new adipokine, possibly linking obesity to type 2 diabetes mellitus (T2DM). Since the kidneys are the main site of RBP4 degradation and since renal failure is a frequent co-morbid condition with diabetes mellitus, we evaluated the association among RBP4, renal function and T2DM in an Asian population. RBP4 serum levels were analyzed in 110 subjects (50 with T2DM) using an enzyme-linked immunosorbent assay (ELISA). Based on a cut-off estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m2 (calculated according the abbreviated MDRD formula which uses serum creatinine level, age and gender) and on the T2DM status, subjects were assigned to four subgroups: Group A- controls with an eGFR > 60 ml/min per 1.73 m2, Group B - controls with an eGFR < 60 ml/min per 1.73 m2, Group C- T2DM subjects with an eGFR > 60 ml/min per 1.73 m2, and Group D - T2DM subjects with an eGFR < 60 ml/ min per 1.73 m2. In both the T2DM and control groups, RBP4 levels were higher in subjects with an eGFR < 60 ml/min per 1.73 m2 than in subjects with an eGFR > 60 ml/min per 1.73 m2. However, the difference was only significant between the control groups (p < 0.05). After adjusting for age, gender, BMI, eGFR and the presence of T2DM, eGFR, not T2DM, was associated with plasma RBP4 levels (p < 0.05). These results suggest among Asians the eGFR, but not the presence of T2DM, is a major determinant of RBP4 serum levels. The eGFR should be taken into account when evaluating the role of RBP4 in the pathogenesis of insulin resistance and T2DM.  相似文献   

4.
CONTEXT: There are limited and controversial data concerning the relationships between retinol-binding protein 4 (RBP4), weight status, and insulin resistance in obese humans and especially in children. OBJECTIVE: Our objective was to study the longitudinal relationships among RBP4, insulin resistance and weight status in obese children. DESIGN, SETTING, AND PATIENTS: We conducted a 1-yr longitudinal follow-up study in a primary-care setting with 43 obese children (median age 10.8 yr) and 19 lean children of same the age and gender. INTERVENTION: Our outpatient 1-yr intervention program was based on exercise, behavior, and nutrition therapy. MAIN OUTCOMES MEASURES: Changes of weight status (body mass index sd score), RBP4, molar RBP4/serum retinol (SR) ratio, insulin resistance index homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI). RESULTS: Obese children had significantly (P < 0.01) higher RBP4 concentrations and a higher RBP4/SR ratio compared with lean children. In multiple linear regression analyses adjusted to age, gender, and pubertal stage, RBP4 was significantly correlated to insulin and body mass index. Pubertal children demonstrated significantly decreased QUICKI and significantly increased HOMA index, insulin, and RBP4 concentrations compared with prepubertal children. Changes of RBP4 correlated significantly to changes of insulin (r = 0.29), HOMA index (r = 0.29), QUICKI (r = 0.22), and weight status (r = 0.31). Substantial weight loss in 25 children led to a significant (P < 0.001) decrease of RBP4, RBP4/SR, blood pressure, triglycerides, insulin, and HOMA index and an increase in QUICKI in contrast to the 18 children without substantial weight loss. CONCLUSION: RBP4 levels were related to weight status and insulin resistance in both cross-sectional and longitudinal analyses, suggesting a relationship between RBP4, obesity, and insulin resistance in children.  相似文献   

5.
OBJECTIVE: Insulin resistance and obesity are common features of the polycystic ovary syndrome (PCOS). Retinol-binding protein 4 (RBP4), a new fat-derived adipokine, has been described to be elevated in obesity and type 2 diabetes. The aim of the present study was to investigate whether serum RBP4 levels are correlated with metabolic parameters, indices of insulin resistance, and endocrine variables in German PCOS women. DESIGN: We assessed the correlation between metabolic and endocrine parameters with RBP4 levels in 200 PCOS patients and 64 healthy controls. METHODS: Serum RBP4 was measured by enzyme-linked immunosorbent assay (Immundiagnostik AG, Bensheim, Germany). In addition, anthropometric variables, clinical signs of hyperandrogenism, and body fat were evaluated, and a glucose tolerance test was performed to assess parameters of insulin resistance and glucose metabolism. RESULTS: Taking the entire PCOS cohort, RBP4 levels were positively correlated with body mass index (BMI), body fat, waist circumference, fasting glucose, and area under the curve for glucose (all P<0.05), but not with indices of insulin resistance. On the other hand, PCOS women with impaired glucose metabolism had higher RBP4 levels than PCOS women with normal glucose metabolism (median 30.6, range 23.3-73.9 versus median 26.3, range 6.4-61.4, P<0.05). Furthermore, no differences were found in RBP4 levels between lean PCOS women and BMI-matched healthy controls. CONCLUSION: In German PCOS women, serum RBP4 levels are associated with obesity and parameters of glucose metabolism but not with PCOS per se.  相似文献   

6.
Insulin resistance is a hallmark of obesity, the cardiorenal metabolic syndrome and type 2 diabetes mellitus (T2DM). The progression of insulin resistance increases the risk for cardiovascular disease (CVD). The significance of insulin resistance is underscored by the alarming rise in the prevalence of obesity and its associated comorbidities in the Unites States and worldwide over the last 40–50 years. The incidence of obesity is also on the rise in adolescents. Furthermore, premenopausal women have lower CVD risk compared to men, but this protection is lost in the setting of obesity and insulin resistance. Although systemic and cardiovascular insulin resistance is associated with impaired insulin metabolic signaling and cardiovascular dysfunction, the mechanisms underlying insulin resistance and cardiovascular dysfunction remain poorly understood. Recent studies show that insulin resistance in obesity and diabetes is linked to a metabolic inflammatory response, a state of systemic and tissue specific chronic low grade inflammation. Evidence is also emerging that there is polarization of macrophages and lymphocytes towards a pro-inflammatory phenotype that contributes to progression of insulin resistance in obesity, cardiorenal metabolic syndrome and diabetes. In this review, we provide new insights into factors, such as, the renin–angiotensin–aldosterone system, sympathetic activation and incretin modulators (e.g., DPP-4) and immune responses that mediate this inflammatory state in obesity and other conditions characterized by insulin resistance.  相似文献   

7.
视黄醇结合蛋白4主要由肝脏合成,是血液中一种运送视黄醇的结合蚩白,亦是脂肪组织分泌的一种脂肪细胞因子.小鼠实验发现,其在组织中的过度表达可使磷脂酰肌醇3激酶活性下降,胰岛素受体底物1酪氨酸磷酸化降低.可能与胰岛素抵抗的发生有关.肥胖、糖耐量减低、胰岛素抵抗、多囊卵巢综合征、妊娠糖尿病患者血清中视黄醇结合蛋白4含量与正常者相比升高,其可能与此类疾病的发病机制有关.  相似文献   

8.
Overweight/obesity continues to increase in children and adolescents, and annual obesity-related hospital costs in 6-17 yr olds have reached 127 million dollars per year. Overweight children and adolescents are now being diagnosed with impaired glucose tolerance and type 2 diabetes, and they show early signs of the insulin resistance syndrome and cardiovascular risk. Several risk factors have been identified as contributors to the development of type 2 diabetes and cardiovascular risk in youth. These factors include increased body fat and abdominal fat, insulin resistance, ethnicity (with greater risk in African-American, Hispanic, and Native American children), and onset of puberty. There is no clear explanation of how these factors increase risk, but they appear to act in an additive fashion. We hypothesize that the constellation of these risk factors may be especially problematic during the critical period of adolescent development, especially in individuals who may have compromised beta-cell function and an inability to compensate for severe insulin resistance. Therefore, the purpose of this paper is to review the pathophysiology of type 2 diabetes and cardiovascular risk in obese children and adolescents.  相似文献   

9.
The emerging epidemic of type 2 diabetes (T2DM) in young people reflects increasing rates of obesity and parallels the increasing frequency of T2DM in adults. As in adults, T2DM in children is part of the insulin resistance syndrome that includes hyperandrogenism seen as premature adrenarche and polycystic ovary syndrome, hypertension, dyslipidemia, and other atherosclerosis risk factors. Recent studies in children document risk factors for T2DM, and associated cardiovascular risk factors, including obesity, family history, diabetic gestation, and underweight or overweight for gestational age. Genetically determined insulin resistance or limited β-cell reserve has been demonstrated in high-risk individuals, including first-degree relatives of girls with premature adrenarche. This genetic background, considered advantageous in a feast-and-famine existence (the thrifty genotype), is rendered detrimental with abundant food and physical inactivity, a lifestyle demonstrated to be typical of families of children with T2DM. The increasing incidence of T2DM in children and adolescents threatens to become a major public health problem. Risk factors for cardiovascular disease, hypertension, hyperlipidemia, and microalbuminuria are present at diagnosis of T2DM in Native American adolescents, indicating that insulin resistance has been present for some time before the diagnosis of diabetes was made. Case finding is likely to be beneficial in high-risk youths. Treatment is the same as that of adults. The only data on use of oral hypoglycemic agents in children have been with metformin. Community and governmental efforts to educate all children and their parents about the need for physical activity and dietary modification are essential to control this epidemic.  相似文献   

10.
11.
CONTEXT: Retinol binding protein 4 (RBP4) was recently found to be expressed and secreted by adipose tissue, and was strongly associated with insulin resistance. OBJECTIVE: The aim was to determine the relationship between RBP4 and obesity, insulin resistance, and other markers of insulin resistance in humans. DESIGN AND PATIENTS: RBP4 mRNA levels in adipose tissue and muscle of nondiabetic human subjects with either normal or impaired glucose tolerance (IGT) were studied, along with plasma RBP4. RBP4 gene expression was also measured in adipose tissue fractions, and from visceral and sc adipose tissue (SAT) from surgical patients. SETTING: The study was conducted at University Hospital and General Clinical Research Center. INTERVENTION: Insulin sensitivity (S(I)) was measured, and fat and muscle biopsies were performed. In IGT subjects, these procedures were performed before and after treatment with metformin or pioglitazone. MAIN OUTCOME MEASURES: The relationship between RBP4 expression and obesity, S(I), adipose tissue inflammation, and intramyocellular lipid level, and response to insulin sensitizers was measured. RESULTS: RBP4 was expressed predominantly from the adipocyte fraction of SAT. Although SAT RBP4 expression and the plasma RBP4 level demonstrated no significant relationship with body mass index or S(I), there was a strong positive correlation between RBP4 mRNA and adipose inflammation (monocyte chemoattractant protein-1 and CD68), and glucose transporter 4 mRNA. Treatment of IGT subjects with pioglitazone resulted in an increase in S(I) and an increase in RBP4 gene expression in both adipose tissue and muscle, but not in plasma RBP4 level, and the in vitro treatment of cultured adipocytes with pioglitazone yielded a similar increase in RBP4 mRNA. CONCLUSIONS: RBP4 gene expression in humans is associated with inflammatory markers, but not with insulin resistance. The increase in RBP4 mRNA after pioglitazone treatment is unusual, suggesting a complex regulation of this novel adipokine.  相似文献   

12.
Recent reports indicate an increasing prevalence of type 2 diabetes mellitus (TD2M) in children and adolescents in Germany, possibly due to the increasing prevalence of obesity. Manifestation of T2DM is usually at mid- to late puberty, with few symptoms. Most children and adolescents with T2DM are extremely obese, have relatives with T2DM, and show other clinical features of the insulin resistance syndrome such as hypertension, dyslipidemia, or acanthosis nigricans. Hispanics, African-Americans, Asians, and Indians suffer more frequently from T2DM compared with Caucasians. Primary therapy is weight reduction, which is difficult to achieve in everyday life. Metformin is regarded as the drug of choice, and insulin therapy is necessary in severe cases. Treatment of T2DM comorbidities is important but seldom practiced.  相似文献   

13.
Concurrent with the epidemic of childhood obesity, an unprecedented increase in the prevalence of several adiposity-related complications in this age group has emerged. In particular, type 2 diabetes (T2D), once considered an illness restricted to adulthood, is progressively affecting more and more adolescents, and represents now roughly 20-45% of new-onset cases in this age group. To unravel the pathogenesis of diabetes development during adolescence, many studies have focused on defining early defects in both insulin sensitivity and secretion that might be implicated in the natural history of the disease. Although a lot still need to be clarified, studies have shown that the progression from normal glucose tolerance to T2D involves intermediate stages of impaired fasting glucose and/or impaired glucose tolerance, also known as prediabetes. Insulin resistance and β-cell dysfunction represent the two major key pathogenetic defects underlying the progression to diabetes in obese youth. In this review, we have sought to mainly describe the role of β-cell function in relation to the ambient insulin resistance in the development of T2D in obese adolescents.  相似文献   

14.
视黄醇结合蛋白(RBP)4是近年来新发现的一种脂肪细胞因子,在动物与人类的研究中均发现其与肥胖、胰岛素抵抗及糖、脂代谢密切相关。本文介绍了有关RBP4的结构和功能、RBP4血清水平及基因多态性与肥胖、胰岛素抵抗和糖、脂代谢关系等方面的研究进展。  相似文献   

15.
CONTEXT: Although retinol-binding protein (RBP)-4 concentrations are elevated in animal models of obesity and insulin resistance (IR), the link between RBP4 and IR in humans is less clear. There are few published data on RBP4 levels in overweight children, and most previous studies did not control for vitamin A (VA) status and/or subclinical inflammation. OBJECTIVE: The objective of the study was to measure serum RBP4, serum retinol (SR), the RBP4-to-SR molar ratio, and dietary VA intakes in normal-weight and overweight children and investigate the relationship of these variables to IR, subclinical inflammation, and the metabolic syndrome in this age group. DESIGN: This was a cross-sectional study. SETTING: The study was conducted in Northern Switzerland. PATIENTS: Patients included 6- to 14-yr-old normal-weight, overweight, and obese children (n = 79). MAIN OUTCOME MEASURES: Body mass index, body fat percentage, waist-to-hip ratio, dietary VA intakes, serum RBP4, and SR were determined. IR was assessed using fasting insulin and the quantitative insulin sensitivity check index, and components of the metabolic syndrome and indices of subclinical inflammation were measured. RESULTS: Only 3% of children had low VA status. Independent of age, VA intakes, and C-reactive protein, body mass index, body fat percentage, and waist-to-hip ratio were significant predictors of RBP4, SR, and RBP4/SR. Independent of adiposity, RBP4 and RBP4/SR were significantly correlated with serum triglycerides, and RBP4/SR was correlated with fasting insulin. The RBP4-to-SR ratio more strongly correlated with components of the metabolic syndrome than serum RBP4. CONCLUSION: Independent of subclinical inflammation and vitamin A intakes, serum RBP4 and the RBP4-to-SR ratio are correlated with obesity, central obesity, and components of the metabolic syndrome in prepubertal and early pubertal children.  相似文献   

16.
OBJECTIVE: Previous studies have shown that adipose-derived serum retinol-binding protein 4 (RBP4) levels are increased in insulin-resistant mouse models and in subjects with insulin resistance or type 2 diabetes. However, the association of visceral fat and serum RBP4 has not been studied. The purpose of this study was to investigate the relationship between serum RBP4 and regional fat distribution in Chinese subjects with and without type 2 diabetes. DESIGN: We measured serum RBP4 concentrations from 1033 Chinese subjects with various degrees of obesity and tested the association between visceral adiposity and serum RBP4. In a subgroup of this study, euglycemic-hyperinsulinemic clamp was performed to measure insulin sensitivity. The association between visceral adiposity and serum RBP4 was also determined in response to rosiglitazone treatment in a subgroup of patients with diabetes. RESULTS: Serum RBP4 level was positively correlated with visceral adipose area in male (r = 0.171; P < 0.001) and female (r = 0.215; P < 0.001) subjects. However, there was no correlation between serum RBP4 and body mass index. Subjects with visceral obesity had higher serum RBP4 concentrations than those without visceral obesity in both men and women. Rosiglitazone treatment in patients with diabetes resulted in a lower serum RBP4 level (35.2 +/- 10.2 vs. 24.9 +/- 5.6 microg/ml, before vs. after treatment). These changes were accompanied by improved insulin sensitivity and reductions in visceral fat area. The latter was found to be highly correlated with the decline of serum RBP4 levels (r = 0.471; P = 0.027). CONCLUSIONS: Serum RBP4 level is positively associated with visceral adiposity in both men and women. Our data suggest that RBP4 may contribute to the development of insulin resistance along with other adipokines.  相似文献   

17.
Insulin resistance constitutes a pathophysiologic link between obesity, atherosclerosis, and/or cardiovascular complications. Retinol binding protein 4 (RBP4) is a newly discovered adipocyte product that modulates glucose metabolism and consequently induces insulin resistance. We investigated the association between serum RBP4 levels and insulin resistance in obese and nonobese adolescents. A total of 87 nonobese (60 males and 27 females) and 85 obese (62 males and 23 females) apparently healthy adolescents, 12 to 18 years old, were included in this study. A questionnaire was used to obtain participant medical history and lifestyle information, such as smoking and alcohol ingestion habits. Subjects' anthropometric measurements were taken to calculate for body mass index and waist-to-hip ratio. Serum RBP4 levels were measured by an enzyme immunoassay kit. High-sensitivity C-reactive protein, fasting glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and fasting insulin were measured. Low-density lipoprotein cholesterol level and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Males had significantly higher RBP4 levels than females. Serum RBP4 levels were significantly higher in the obese group compared with the nonobese group. In all subjects, RBP4 was positively correlated with adiposity index (body mass index, waist circumference, waist-to-hip ratio), systolic and diastolic blood pressures, glucose tolerance index (fasting glucose, insulin, HOMA-IR), lipid profile (total cholesterol, triglycerides), and inflammatory indices (high-sensitivity C-reactive protein, white blood cell count). In multiple linear regression analysis, RBP4 was independently associated with age, HOMA-IR, and triglyceride levels in the nonobese group and with sex and triglyceride levels in the obese group. These results suggest that serum RBP4 might have clinical implications for lipid metabolism and insulin action in adolescents.  相似文献   

18.
Type 2 diabetes mellitus in children and adolescents   总被引:2,自引:0,他引:2  
Over the last decade, there has been an alarming increase of Type 2 diabetes mellitus (T2DM) in youths, concomitant with the rise of obesity in this age group. T2DM is a progressive disease with a gradual increase in insulin resistance associated later with a decline in insulin secretion with fasting hyperglycemia. Prevalence of T2DM in children is mostly linked to some risk factors: obesity and sedentary lifestyle, puberty, membership of ethnic minorities, features of insulin resistance, family history of T2DM, female gender and perinatal factors. Prevention is essential and can be considered a public health approach directed to the general population. Treatment of T2DM in youth is complex and based on different strategies: diet, exercise and pharmacotherapy. An appropriated intervention program must be started early, in order to prevent or retard the progression of the disease and associated comorbidities.  相似文献   

19.
Lee JW  Lee HR  Shim JY  Im JA  Lee DC 《Endocrine journal》2008,55(5):811-818
The adipocytokine retinol binding protein-4 (RBP4) has recently been shown to link obesity and insulin resistance, although their relationship remains controversial in human studies. The influence of weight reduction with changes of fat distribution on serum RBP4 concentration in nondiabetics is also unknown. We assessed the effect of weight reduction (especially abdominal visceral fat loss) on serum RBP4 levels after a structuralized weight-reduction program. We conducted a prospective intervention study consisting of a 16-week weight reduction program, including lifestyle modification and adjuvant appetite suppressants. A total of 52 nondiabetic subjects aged 37.4 +/- 11 years with a body mass index of 27.4 +/- 4 kg/m (2) were included. Serum RBP4 concentrations with other metabolic parameters and abdominal adipose tissue areas as determined by computed tomography scan were measured both before and 16 weeks after the weight reduction program. Subjects had a 10.9% loss of body weight accompanied by a 25.5% decrease in serum RBP4 levels, with improved ( ) insulin sensitivity after the program. The changes in RBP4 levels were significantly correlated with the amounts of abdominal visceral fat loss (r = 0.38, p<0.01) but were not associated with the amount of total body fat loss or abdominal subcutaneous fat loss. Weight reduction, especially the loss of abdominal visceral fat, lowers serum RBP4 concentrations in nondiabetic subjects. The relationship between individual changes in RBP4 and abdominal visceral fat indicated that RBP4 may be involved in the beneficial effect of visceral fat reduction on the improvement of insulin resistance and metabolic syndrome.  相似文献   

20.
Hypertension and obesity are both common health problems in children and adolescents. More than 17% of children are obese and even more children are overweight. Hypertension, although defined differently in children than in adults, can be detected in 3% to 4% of children, and approximately 30% of obese adolescents have high blood pressure (BP) associated with obesity. Children with high BP and obesity frequently have other risk factors that are components of the metabolic syndrome. Evidence of target organ damage, including left ventricular hypertrophy, is detectable in many children with hypertension and is more commonly found in children with high BP and obesity. Both obesity and hypertension are considered inflammatory conditions. There are some emerging data in the young that show an association of insulin resistance, obesity, and high BP with inflammatory markers. Children and adolescents with hypertension and especially obesity-associated hypertension can be identified and should be evaluated for additional metabolic risk factors. Considering the heightened risk for premature cardiovascular (CV) disease, therapeutic interventions, including lifestyle changes and medications, when indicated, are important for all children and adolescents with obesity-associated hypertension.  相似文献   

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