Serum leptin is elevated in Saudi Arabian patients with metabolic syndrome and coronary artery disease.

AIMS: To compare plasma leptin in Saudi subjects with Type 2 diabetes and coronary heart disease (CHD) with non-diabetic control subjects and to examine the relationship of plasma leptin to other CHD risk factors. RESEARCH DESIGN AND METHOD: Serum leptin concentrations were measured in 144 Saudi men. Subjects studied included 59 with Type 2 diabetes mellitus [BMI 27.5 (3.7) kg/m2 mean (sd)], 34 with coronary heart disease [BMI 29.6 (1.8) kg/m2], and 51 non-diabetic controls [BMI 28.0 (3.5) kg/m2]. There was no significant difference in BMI between the groups. Fasting serum leptin, lipids, insulin, apolipoproteins and glucose were measured. BMI, blood pressure; smoking habit and age were also recorded. Insulin resistance was assessed using the HOMA model. RESULTS: Leptin concentrations were significantly higher in diabetic and CHD patients than in controls (P = 0.024 and 0.016, respectively). Multiple regression analysis showed that body weight (P < 0.0006), serum triglyceride concentration (P = 0.046) and systolic blood pressure (P = 0.013) were all significantly related to the logarithm of the serum leptin concentration (R2 = 0.549) in CHD patients. A subgroup analysis, comparing those patients who had the metabolic syndrome, as defined by WHO, with controls, showed higher serum leptin in those with metabolic syndrome (P = 0.05). CONCLUSIONS: Serum leptin is increased in Saudi subjects with diabetes mellitus, metabolic syndrome and CHD. Leptin may be a marker of risk of CHD, at least in men, and contribute to the CHD risk profile in subjects with insulin resistance. Further studies are needed to evaluate this relationship prospectively.     

代谢综合征患者血清瘦素水平及其与某些指标的相关性

目的:分析代谢综合征患者血清瘦素（leptin）水平的变化,探讨其关系。方法:选择拟行冠状动脉造影患者共76例,根据最新ATPⅢ代谢综合征诊断标准分为代谢综合征组和对照组,ELISA法测定其血清瘦素浓度。结果:代谢综合征组血清瘦素浓度明显高于对照组,并且血清瘦素与体质量指数、甘油三脂、高密度脂蛋白水平呈正相关。结论:代谢综合征患者血清瘦素水平显著升高。     

Role of microRNAs in obesity and the metabolic syndrome

Obesity and the metabolic syndrome are major public health concerns, and present a formidable therapeutic challenge. Many patients remain recalcitrant to conventional lifestyle changes and medical therapies. Bariatric surgery has made laudable progress in the treatment of obesity and its related metabolic disorders, yet carries inherent risks. Unravelling the molecular mechanisms of metabolic disorders is essential in order to develop novel, valid therapeutic strategies. Mi(cro)RNAs play important regulatory roles in a variety of biological processes including adipocyte differentiation, metabolic integration, insulin resistance and appetite regulation. Investigation of these molecules and their genetic targets may potentially identify new pathways involved in complex metabolic disease processes, improving our understanding of metabolic disorders and influence future approaches to the treatment of obesity. This review discusses the role of miRNAs in obesity and related components of the metabolic syndrome, and highlights the potential of using miRNAs as novel biomarkers and therapeutic targets for these diseases.     

The metabolic syndrome and incidence of cardiovascular disease in non-diabetic subjects--a population-based study comparing three different definitions.

Aims Between 1998 and 2005, a number of definitions of the metabolic syndrome (MetS) have been proposed. The aim of this population‐based cohort study was to compare prevalence rates and the prediction of cardiovascular disease (CVD) using different definitions of MetS. Methods A total of 5047 non‐diabetic subjects (66% women), from the city of Malmö, Sweden, were followed. The incidence of fatal and non‐fatal CVD (cardiac events, n = 176, and stroke, n = 171) was monitored over 11 years of follow‐up. MetS was defined in three different ways [by International Diabetes Federation (IDF), National Cholesterol Education Program—Adult Treatment Panel III (NCEP‐ATPIII), or European Group for the study of Insulin Resistance (EGIR) criteria] based on data on waist circumference, blood pressure, serum triglycerides, High‐density lipoprotein cholesterol and fasting blood glucose. The IDF definition identified 21.9% of the subjects having the MetS. Corresponding figures for the NCEP‐ATPIII and EGIR definitions were 20.7 and 18.8%, respectively. Results After taking age, gender, low‐density lipoprotein cholesterol and lifestyle factors into account, the hazard ratio (HR) for CVD event according to the IDF, NCEP‐ATPIII and EGIR definitions were HR 1.11 (95% CI: 0.86–1.44), 1.59 (1.25–2.03) and 1.35 (1.05–1.74), respectively. The results were largely similar for cardiac and stroke events. Conclusions The prevalence of Mets according to the IDF definition was higher in comparison with NCEP‐ATPIII and EGIR definitions, but the IDF definition was not superior to these definitions for prediction of CVD events. This was true for both genders and questions the usefulness of the current IDF criteria of MetS in a North‐European, Caucasian population. In addition, single risk factors such as smoking had an equal prediction as the metabolic syndrome.     

National Cholesterol Education Program and International Diabetes Federation definitions of metabolic syndrome in the prediction of diabetes. Results from the FIrenze-Bagno A Ripoli study

Background:  The International Diabetes Federation (IDF) proposed to modify the diagnostic criteria for metabolic syndrome (MS) previously issued by the National Cholesterol Education Program (NCEP). Aim of the present investigation is to compare the predictive value for diabetes of NCEP and IDF definitions of MS in a large sample of predominantly Caucasian subjects.
Methods:  A prospective observational study was performed on a cohort study (n = 3096) enrolled in a diabetes-screening programme, the FIrenze-Bagno A Ripoli study. All subjects with fasting glucose >126 mg/dl and/or post-load glucose ≥200 mg/dl (5.7%) were excluded from the present analysis. Follow-up of each subject was continued until diagnosis of diabetes, death or until 31 December 2005. Mean follow-up was 27.7 ± 11.3 months.
Results:  Among subjects enrolled, 13.7 and 25.2% were affected by MS using NCEP and IDF criteria respectively. During follow-up, 38 new cases of diabetes were diagnosed, with a yearly incidence rate of 0.5%. The relative risk for diabetes in subjects with MS was 10.10 [5.13; 20.00] and 7.87 [3.70; 16.7] using NCEP and IDF definitions respectively. After adjustment for age, sex, fasting glucose and waist circumference, NCEP-defined MS, but not IDF-, was significantly associated with incident diabetes (hazard ratio, 95% CI: 2.41 [1.01; 5.95] and 2.05 [0.80; 5.29] respectively).
Conclusions:  Although the reasons for the proposed changes in diagnostic criteria for MS are easily understandable, the newer IDF definition, while increasing estimates of prevalence of the syndrome, reduces the effectiveness of MS in identifying subjects at risk for diabetes. Further research is needed before the previous NCEP criteria are abandoned.     

Effects of testosterone on Type 2 diabetes and components of the metabolic syndrome

Observations from clinical studies suggest that low serum levels of testosterone in men are often associated with obesity, insulin resistance, and metabolic compromise. Indeed, the clinical symptoms of late-onset hypogonadism are markedly similar to those of Type 2 diabetes mellitus (T2DM) and metabolic syndrome, and may share a similar pathophysiology. Observational and experimental data suggest that testosterone treatment improves a number of hallmark features of T2DM and metabolic syndrome, namely insulin resistance, obesity, dyslipidemia, and sexual dysfunction. Consequently, clinical studies have been undertaken to assess the impact of testosterone-replacement therapy in this patient group. The present article reviews the observational clinical data suggesting an association between low serum testosterone and metabolic impairment, the clinical data relating to the effects of testosterone treatment on components of the metabolic syndrome, and the randomized clinical trails that have formally investigated whether testosterone-replacement therapy provides clinical benefit to hypogonadal men with T2DM and/or metabolic syndrome.     

代谢综合征患者颈动脉粥样硬化的观察

目的探讨代谢综合征（MS）患者颈动脉粥样硬化的特征。方法108例患者分别为MS 40例、高血压病（EH）33例、糖尿病（DM）35例,并以此相应分成3组,比较3组患者血脂改变及颈动脉超声检测结果,以125例健康体检者作对照组。结果MS组和DM组患者血浆TG水平均明显升高。DM组和MS组颈动脉阻力指数均显著升高,3组颈总动脉内-中膜厚度明显增厚。MS组患者斑块指数较单纯EH组明显增高。结论MS患者发生颈动脉粥样硬化的危险性较单纯高血压组明显增加。     

老年干部体检人群代谢综合征与心脑血管病的关系

目的探讨老年干部体检人群代谢综合征(MS)的患病率,各年龄段MS的分布及合并心脑血管病的状况。方法1680例老年人进行健康体检,按年龄分为60~69岁,70~79岁,≥80岁3组;同时有500例非老年人(<60岁)进行体验。分析各年龄组冠心病、高血压、肥胖、血脂异常等患病情况。结果老年组MS患病率为29.7%,非老年组为17.0%;老年组高血压患病率为53.4%,肥胖42.8%,血脂异常35.0%,高血糖34.8%。499例老年组MS患者中,高血压患病率91.9%,肥胖83.5%,血脂异常74.0%,高血糖70.8%。MS患者各年龄组冠心病患病率最高。MS患者中冠心病、高尿酸血症、脂肪肝和脑卒中等疾病的患病率显著高于非MS受检者。结论MS的高患病率预示心脑血管病患病率的增加。     

Characterization of a new animal model of metabolic syndrome: the DahlS.Z-Leprfa/Leprfa rat

Objective:

The DahlS.Z-Lepr^fa/Lepr^fa (DS/obese) rat strain was established from a cross between Dahl salt-sensitive rats and Zucker fatty (fa/fa) rats, the latter of which harbor a missense mutation in the leptin receptor gene (Lepr). We examined whether DS/obese rats might be a suitable animal model of metabolic syndrome in humans.

Methods:

The systemic pathophysiological and metabolic characteristics of DS/obese rats were determined and compared with those of homozygous lean littermates, namely, DahlS.Z-Lepr⁺/Lepr⁺ (DS/lean) rats.

Results:

Systolic blood pressure was higher in DS/obese rats fed a normal diet than in DS/lean rats at 11 weeks of age and thereafter. The survival rate of DS/obese rats was significantly lower than that of DS/lean rats at 18 weeks. Body weight, visceral and subcutaneous fat mass, as well as heart, kidney and liver weights, were increased in DS/obese rats at 18 weeks compared with DS/lean rats. Serum low-density lipoprotein (LDL)-cholesterol, triglyceride and insulin concentrations, as well as the ratio of LDL-cholesterol to high-density lipoprotein-cholesterol levels, were increased in DS/obese rats, whereas serum glucose concentration did not differ significantly between DS/obese and DS/lean rats. Creatinine clearance was decreased and urinary protein content was increased in DS/obese rats, which also manifested lipid accumulation in the liver and elevation of serum alanine aminotransferase levels.

Conclusion:

These results show that the phenotype of DS/obese rats is similar to that of humans with metabolic syndrome, and that these animals may thus be an appropriate model for this condition.     

Adiponectin--a key adipokine in the metabolic syndrome

Adiponectin is a recently described adipokine that has been recognized as a key regulator of insulin sensitivity and tissue inflammation. It is produced by adipose tissue (white and brown) and circulates in the blood at very high concentrations. It has direct actions in liver, skeletal muscle and the vasculature, with prominent roles to improve hepatic insulin sensitivity, increase fuel oxidation [via up-regulation of adenosine monophosphate-activated protein kinase (AMPK) activity] and decrease vascular inflammation. Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Recent data indicate that the high-molecular weight (HMW) complexes have the predominant action in the liver. In contrast to other adipokines, adiponectin secretion and circulating levels are inversely proportional to body fat content. Levels are further reduced in subjects with diabetes and coronary artery disease. Adiponectin antagonizes many effects of tumour necrosis factor-alpha(TNF-alpha) and this, in turn, suppresses adiponectin production. Furthermore, adiponectin secretion from adipocytes is enhanced by thiazolidinediones (which also act to antagonize TNF-alpha effects). Thus, adiponectin may be the common mechanism by which TNF-alpha promotes, and the thiazolidinediones suppress, insulin resistance and inflammation. Two adiponectin receptors, termed AdipoR1 and AdipoR2, have been identified and these are ubiquitously expressed. AdipoR1 is most highly expressed in skeletal muscle and has a prominent action to activate AMPK, and hence promote lipid oxidation. AdipoR2 is most highly expressed in liver, where it enhances insulin sensitivity and reduces steatosis via activation of AMPK and increased peroxisome-proliferator-activated receptor alpha ligand activity. T-cadherin, which is expressed in endothelium and smooth muscle, has been identified as an adiponectin-binding protein with preference for HMW adiponectin multimers. Given the low levels of adiponectin in subjects with the metabolic syndrome, and the beneficial effect of the adipokine in animal studies, there is exciting potential for adiponectin replacement therapy in insulin resistance and related disorders.     

非酒精性脂肪性肝病与代谢综合征关系研究进展

非酒精性脂肪性肝病的发病与胰岛素抵抗及其表型有关。胰岛素抵抗和代偿性高胰岛素血症是代谢综合征的中心环节。非酒精性脂肪性肝病是代谢综合征的临床疾病谱之一。非酒精性脂肪性肝病与动脉粥样硬化性心血管疾病、2型糖尿病及代谢综合征临床症候群的关系密切,本文就非酒精性脂肪肝与代谢综合征的关系作一综述。     

Diagnosis and management of the metabolic syndrome in obesity

The metabolic syndrome is a constellation of interrelated abnormalities that increase the risk for cardiovascular disease and progression to type 2 diabetes. The prevalence of this syndrome is increasing because of the 'obesity epidemic'. The National Cholesterol Education Program Adult Treatment Panel III defined practical criteria for the diagnosis of the metabolic syndrome and established the basic principles for its management. Also, the International Diabetes Federation recently proposed another definition. The metabolic syndrome is a secondary target for cardiovascular risk reduction. Clinicians should identify individuals with this condition, assess their cardiovascular risk and treat them by an aggressive and multifaceted approach. The most effective therapeutic intervention in patients with the metabolic syndrome should focus on modest weight reduction and regular physical activity. Adoption of a healthier diet and smoking cessation are necessary. Drug therapy may be needed to achieve recommended goals if therapeutic lifestyle changes are not sufficient. Low-density lipoprotein cholesterol is the primary target of therapy (new aggressive goals should be achieved). Statins are probably the drugs of choice. Fibrates and nicotinic acid are also useful options. Hypertension should be managed aggressively probably starting with an inhibitor of the renin-angiotensin system or a calcium channel blocker and adding a low dose of a thiazide diuretic if necessary. Aspirin should be administered if the cardiovascular risk is high. In the future acarbose, metformin, meglitinides and thiazolidinediones may be used in patients with the metabolic syndrome to delay the onset of type 2 diabetes and reduce cardiovascular risk. Such an intense and multifactorial approach is likely to reverse the bad prognosis associated with the metabolic syndrome.     

Coping and metabolic syndrome indicators in urban black South African men: the SABPA study

Urbanisation is associated with obesity, hypertension and development of the metabolic syndrome (MS). We aimed to assess the use of different coping styles and their influence on increases in MS indicators and target end-organ damage (TOD) in urban black African men. A sample of 53 men was classified as clear high active (AC, n = 30) or passive coping (PC, n = 23) responders, using the Amirkhan African validated coping style indicator. Blood pressure (BP) was recorded with an aneroid sphygmomanometer and waist circumference (WC) was determined. Carotid intima-media thickness (CIMT) and microalbuminuria were analysed to determine TOD. Fasting serum and eight-hour urine samples revealed elevated MS indicators in AC men. Strong associations existed between MS indicators and TOD in AC but not PC men. To conclude, only BP and seeking social support were positively associated with TOD in urban PC African men, while in urban AC African men, most MS indicators were positively associated with TOD, i.e. sub-clinical atherosclerosis and renal impairment.     

不同代谢综合征诊断标准对靶器官损害的检出

目的探讨不同的代谢综合征(MS)诊断标准对靶器官损害的检出情况。方法分别采用世界卫生组织(WHO)、美国国家胆固醇教育计划成人治疗组(NCEP-ATPⅢ)和WHO亚太(体重指数采用亚太地区肥胖标准)、ATPⅢ亚太(腰围采用亚太地区肥胖标准)、仿WHO(体重指数采用中国肥胖标准)、仿ATPⅢ(腰围采用中国肥胖标准)代谢综合征(MS)诊断标准对1 363例临床住院高血压、糖尿病及高血压合并糖尿病患者进行诊断,并应用超声心动图、颈动脉超声和免疫比浊法检测MS患者的心肾血管的损害情况。结果采用6种诊断标准,女性的MS诊断率明显高于男性(P<0.01)。女性MS患者的左室肥厚发生率均明显高于男性(P<0.05)。采用不同的WHO标准,男性MS患者的颈动脉内膜中层厚度明显高于女性(P<0.05)。采用不同的ATPⅢ标准,女性MS患者的肌酐轻度升高发生率均明显高于男性(P<0.05)。结论不同MS诊断标准对MS不同的靶器官损害检出率有所差异,且受性别影响较大。     

Relationship between metabolic syndrome and follicle-stimulating hormone in postmenopausal women

Depletion of ovarian reserve during menopausal transition raises follicle-stimulating hormone (FSH) markedly and menopause is related to an increased risk for metabolic syndrome (MetS). This study examined the relationship between FSH and MetS in postmenopausal women.We evaluated the anthropometric values, lipid profiles, high-sensitivity C-reactive protein (hs-CRP) level, Homeostasis model assessment for insulin resistance (HOMA-IR), and serum adipokines levels in 219 postmenopausal women. Serum FSH and estradiol levels were significantly lower in the MetS group than in the non-MetS group. An inverse correlation was observed between FSH with body fat mass (BFM), and HOMA-IR, and a positive correlation was found between FSH and adiponectin level after adjustment for age, years since menopause, BMI, and serum estradiol.The odds ratio for MetS was higher significantly in the lowest quartile of FSH level than the highest quartile of FSH level (odd ratio = 1.32, 95% CI = 1.09–1.75). Our study showed an increased FSH level favored insulin sensitivity with a higher adiponectin and lower HOMA-IR as well as a lower incidence of MetS in postmenopausal women.These findings suggest a new approach to the role of FSH for regulating energy metabolism and for use as a biomarker of MetS risk in postmenopausal women.This systematic review is based on published researches, so there is no ethical approval required.     

Platelet activation in obesity and metabolic syndrome

Obesity is associated with increased cardiovascular disease. Metabolic syndrome (MS) identifies substantial additional cardiovascular risk beyond the individual risk factors, and is a powerful predictor of cardiovascular events even regardless of body mass index, thus suggesting a common downstream pathway conferring increased cardiovascular risk. Platelet hyper-reactivity/activation plays a central role to accelerate atherothrombosis and is the result of the interaction among the features clustering in obesity and MS: insulin resistance, inflammation, oxidative stress, endothelial dysfunction. Interestingly, the same pathogenic events largely account for the less-than-expected response to antiplatelet agents, namely low-dose aspirin. The proposed explanations for this phenomenon, besides underdosing of drug and/or reduced bioavailability, subsequent to excess of adipose tissue, include enhanced platelet turnover, leading to unacetylated COX-1 and COX-2 in newly formed platelets as a source of aspirin-escaping thromboxane formation; extraplatelet sources of thromboxane, driven by inflammatory triggers; and enhanced lipid peroxidation, activating platelets with a mechanism bypassing COX-1 acetylation or limiting COX-isozyme acetylation by aspirin. This review will address the complex interactions between platelets and the pathogenic events occurring in obesity and MS, trying to translate this body of mechanistic information into a clinically relevant read-out, in order to establish novel strategies in the prevention/treatment of atherothrombosis.     

A simple linear model for the effect of changes in metabolic risk factors on coronary heart disease

OBJECTIVES: The risk of having one or more metabolic risk factors in the development of coronary heart disease (CHD) is well estimated, but it still remains to be shown which influence any given change in the number of risk factors has on the overall risk of CHD. DESIGN: In this prospective cardiovascular population study, 10 194 participants were examined twice with a 5-year interval for metabolic risk factors such as obesity, hypertension, hypercholesterolaemia and diabetes mellitus. RESULTS: During 14 years of follow-up, 1724 incident cases of CHD were identified, 973 in men and 751 in women. The effect of an increase in the number of metabolic risk factors during a 5-year interval on the relative risk of CHD could be determined to be statistically significant for both genders. But only for men, the effect of a decrease in the number of metabolic risk factors was statistically significant during the same time interval. Hence, by statistical analysis, a simple linear model could be constructed for men with two linear trend parameters, one corresponding to the number of metabolic risk factors at the first examination and one corresponding to the change in the number of metabolic risk factors from the first to the second examination. The parameters were 1.50 (1.39-1.63); P < 0.001 and 1.29 (1.18-1.41); P < 0.001, respectively. CONCLUSIONS: This study suggests that it is possible to fit a simple linear model for the effect of changed number of metabolic risk factors on the risk of CHD.     

Markers of inflammation and fibrosis are related to cardiovascular damage in hypertensive patients with metabolic syndrome

BACKGROUND: Previous studies have shown that metabolic syndrome (MS) is associated with an increased susceptibility to develop cardiovascular damage (CD). Experimental evidence indicates that inflammation and fibrosis could play a critical role in the development of CD in hypertension. This issue has not been clarified yet in patients with MS. The aim of our study was to investigate the relationship between markers of inflammation and fibrosis with CD in hypertensive patients with and without MS. METHODS: One hundred twenty-eight essential hypertensive patients were included in the study: 51 with MS and 77 without MS. Clinical, biochemical parameters, 24-h urinary albumin excretion rate (UAER), levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and procollagen type 1 carboxy-terminal propeptide (PICP) were measured. All patients underwent an echocardiographic examination with transmitral Doppler and tissue Doppler imaging (TDI). RESULTS: Left ventricular mass indexed by height(2.7) (LVM/h(2.7)) (P < .001), early diastolic peak flow velocity/early myocardial diastolic velocity ratio (E/Em ratio), a TDI index of diastolic function (P < .001), and 24-h UAER (P < .05) were significantly higher in the group with MS, whereas peak myocardial systolic velocity (Sm), a TDI index of systolic function (P < .001), was lower. Serum levels of CRP (P < .001), TNF-alpha (P < .05), TGF-beta (P < .01), and PICP (P < .001) were significantly increased in MS. These markers were significantly related to higher LVMI(2.7), higher E/Em ratio, and increased 24-h UAER and a lower Sm in the whole population, with a further significant enhancement in MS. CONCLUSIONS: Cardiovascular damage is more frequent in hypertensives with MS than in hypertensives without MS, and this is significantly related to the increased levels of inflammation and fibrosis found in hypertensives with MS.