25～44岁糖耐量正常的腹型肥胖男性患者睾酮和25羟基维生素D3水平变化及其与胰岛素抵抗关系的研究

目的 探讨25～44岁糖耐量正常的腹型肥胖男性患者的睾酮、25羟基维生素D3[25(OH)D3]水平变化及其与IR的关系. 方法 选取25～44岁糖耐量正常的男性129名,根据WC分为腹型肥胖组和腰围正常组,检测两组血清总睾酮(TT)、25(OH)D3和其他生化指标,分析睾酮水平下降的危险因素. 结果 腹型肥胖组胰岛素抵抗指数(HOMA-IR)较腰围正常组高[2.18(1.33,3.21) vs1.13(0.34,1.62),P＜0.01],TT[(6.12±0.24) vs (7.50±0.63)ng/ml,P＜0.01]、25(OH)D3[(39.89±5.34)vs(51.91±8.72) mmol/L,P＜0.01]低.腹型肥胖组TT与HDL-C、25 (OH)D3呈正相关,与WC、FIns和HOMA-IR呈负相关.多元线性回归分析显示,TT与25(OH)D3、HOMA-IR相关性最显著. 结论 25～44岁糖耐量正常的腹型肥胖男性患者已出现IR以及睾酮、维生素D(VitD)水平下降,VitD水平下降、IR与睾酮水平下降的相关性最显著.     

二甲双胍、吡格列酮对初诊糖代谢异常伴腹型肥胖患者血脂及尿酸的影响

目的 探讨二甲双胍、吡格列酮对初诊糖代谢异常伴腹型肥胖患者血脂及尿酸的影响.方法 选择初诊糖代谢异常伴腹型肥胖患者36例,随机分为二甲双胍组20例(1 500 mg/d)、吡格列酮组16例(30 mg/d).治疗3个月后,观察两组治疗前后血糖、胰岛素、糖化血红蛋白、血脂和血尿酸等指标变化.结果 二甲双胍组治疗后LDL-C较治疗前明显下降(P＜0.05);吡格列酮组治疗后TG、血尿酸水平较治疗前明显下降(P均＜0.05).结论 在治疗剂量下,二甲双胍主要降低LDL-C水平,吡格列酮主要降低TG、血尿酸水平.     

成都地区中老年高血压人群糖代谢异常流行状况及其影响因素

目的 探讨成都地区中老年高血压人群糖代谢异常流行状况及影响因素.方法 于2008年采用分层整群抽样的方法,调查成都城乡地区40～79岁中老年人口4685例,进行血压、口服葡萄糖耐量试验(OGTT)等检测,已确诊糖尿病患者只测空腹血糖,开展问卷调查.比较高血压及非高血压人群糖代谢异常患病率,获取中老年高血压人群单纯性糖耐量异常及单纯性负荷后高血糖情况,分析中老年高血压人群糖代谢异常的影响因素.结果 成都地区中老年高血压人群糖代谢异常患病率(53.4%)显著高于非高血压人群(25.1%);若不行OGTT,仅依靠检测空腹血糖,将漏诊中老年高血压人群中72.9%的糖尿病前期患者和54.4%的新诊断糖尿病患者;年龄、一级亲属糖尿病史、超重或肥胖为成都地区中老年男性高血压人群发生糖代谢异常的独立危险因素,体育锻炼、文化程度高为保护因素;年龄、一级亲属糖尿病史、腹型肥胖、高TG血症为成都地区中老年女性高血压人群发生糖代谢异常的独立危险因素.结论 成都地区中老年高血压人群超过半数合并糖代谢异常,需要通过OGTT及时发现这些合并糖代谢异常的患者.适当运动,了解糖尿病相关的保健知识以采取合理的生活方式,干预超重或肥胖、腹型肥胖及高TG血症等代谢性因素,对于减少中老年高血压人群糖代谢异常的发生有着较为重要的作用.     

上海市成人饮酒与代谢综合征关系的流行病学调查

目的　通过流行病学调查 ,探讨饮酒与代谢综合征的关系。方法　随机多级分层整群抽查上海市成年居民 ,内容涉及问卷咨询、体检、葡萄糖耐量试验和血脂全套。结果　 42 0 5例成人完成调查 ,年龄 (5 3 .3± 14 .9)岁 ,男女之比为 1∶1.5 5 ,其中有饮酒习惯者 44 8名 (10 .65 % ) ,男性 40 5例 ,女性 43例 ,男性饮酒率显著高于女性 (2 4.5 3 %对 1.72 % ,P <0 .0 0 0 1)。饮酒组、过量饮酒组腹型肥胖、糖代谢异常、低HDL C血症患病率显著低于相应对照组 ,而高三酰甘油(TG)血症、高血压病患病率则显著高于相应对照组 ,代谢综合征患病率在各组之间差异均无显著性。然而 ,空腹血糖水平和体重指数改变与上述结果并不平行。结论　饮酒对多元代谢紊乱影响复杂 ,一方面饮酒可升高血压和TG ,另一方面又可降低腹型肥胖、糖代谢异常以及低HDL C血症患病率。     

基于倾向性评分匹配法的老年男性腹型肥胖与血清性激素水平的相关性分析

目的评估老年男性腹型肥胖与血清性激素水平的相关性。方法选取2015年1月～2016年12月北京市海淀区万寿路社区老年男性776例,年龄60～94(71.00±5.24)岁。以腰高比≥0.5为标准分为腹型肥胖组251例和非腹型肥胖组525例。对2组进行1?1倾向性评分匹配,匹配后腹型肥胖组204例,非腹型肥胖组204例。收集一般临床资料及血清性激素指标等。匹配后数据采用logistic回归与限制性立方样条(RCS)法进行分析。结果匹配前腹型肥胖组年龄、高血压、当前吸烟、当前饮酒、收缩压、舒张压、空腹血糖、TG、腰高比较非腹型肥胖组明显升高,HDL-C、总睾酮和性激素结合球蛋白(SHBG)水平较非腹型肥胖组明显降低(P0.05,P0.01)。匹配后腹型肥胖组腰高比较非腹型肥胖组明显升高,总睾酮和SHBG水平较非腹型肥胖组明显降低(P0.05,P0.01)。多因素logistic回归分析显示,血清性激素指标中,仅SHBG是老年男性腹型肥胖的独立危险因素(OR=0.993,95%CI:0.989～0.998,P=0.003)。RCS分析表明,老年男性血清SHBG的连续变化与腹型肥胖风险的关联呈非线性负相关(r=-0.372,P0.01)。结论老年男性血清SHBG水平与腹型肥胖风险相关。     

代谢综合征对冠心病介入治疗影响的研究进展

代谢综合征（metabolic syndrome，MS）是一组由环境因素与遗传因素共同作用导致的临床综合征，主要包括肥胖特别是腹型肥胖、糖代谢异常和胰岛素抵抗，致动脉硬化、血脂异常与血压增高等代谢异常。这些异常是心血管疾病的重要危险因素。2007年6月12日最新公布的欧洲高血压指南（ESH／ESC）将MS作为一个独立的心血管危险因素写入指南。MS是冠心病预测因素，并对冠心病经皮冠脉介入术产生影响。     

Relationship between serum testosterone and metabolic syndrome in overweight and obese young

目的 探讨肥胖青少年血清睾酮与代谢综合征(MS)的关系.方法 选取14～30岁的肥胖青少年574例为研究对象,分为MS组(n=305例,其中男87例,女218例)和非MS组(n=269例,其中男60例,女209例).应用化学发光法测定血清睾酮水平.结果 男性中,MS组的睾酮水平低于非MS组[(3.0±1.1) ng/ml和(3.5±1.4) ng/ml,P＜0.01];睾酮与体质量指数(BMI)、腰围、空腹血糖(FPG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、三酰甘油(TG)呈负相关.女性中,MS组与非MS组睾酮水平比较差异无统计学意义[(0.8±0.3)ng/ml和(0.8±0.4)ng/ml,P＞0.05].睾酮与收缩压(SBP)、FINS、HOMA-IR呈正相关.无论男性还是女性,睾酮与MS各组分的多重回归分析显示只有HOMA-IR与睾酮水平独立相关.结论 肥胖青少年男性血清睾酮水平与代谢综合征密切相关.肥胖青少年女性睾酮与代谢综合征之间的关系仍需进一步研究.胰岛素抵抗可能是代谢综合征与睾酮之间相互作用的关键因素.     

颈围判断代谢综合征的意义

代谢综合征是以多种心血管疾病危险因素,如腹型肥胖、糖脂代谢异常、高血压、胰岛素抵抗等聚集在同一个体为特征。肥胖尤其是腹型肥胖在代谢综合征中处于中心地位,在临床医疗及大规模流行病学调查中常用腰围作为衡量腹型肥胖的简易参数,但腰围的体表测量标志不明显,冬季测量尤其不便,易受进食、运动等因素干扰。近年,有学者提出经喉结下缘的颈部水平围长即颈围（neckcircumference,NC）,可能是反映上半身肥胖的指标,不仅测量简便、稳定,且与多种心血管疾病风险因素有关{1-3},因此现将国内外关于颈围作为一项新的人体测量学指标用于辅助判断代谢综合征及其组分的研究作进一步综述。     

男性睾酮与血脂代谢相关性及其机制

近年来,与血脂代谢异常相关的疾病,如动脉粥样硬化、冠心病等发病率逐渐升高.目前研究表明,男性睾酮水平与血脂代谢的发生、发展密切相关.男性在中年以后,随着年龄的增长,血清睾酮水平逐渐下降,而其血脂代谢异常的发生率相应增加.因此,低睾酮水平与血脂代谢异常发生率的升高可能存在相关性.但睾酮对血脂代谢的影响及机制尚不十分清楚,仍存在较大争议.     

代谢综合征与动脉粥样硬化性心血管病

代谢综合征(metabolic syndrome,MS)是一种代谢紊乱疾病的总称,表现为多重心血管危险因素在同一个体聚集倾向.主要包括中心性肥胖、糖代谢异常、高血压及脂代谢异常等.     

Testosterone and obesity

Testosterone is a key hormone in the pathology of metabolic diseases such as obesity. Low testosterone levels are associated with increased fat mass (particularly central adiposity) and reduced lean mass in males. These morphological features are linked to metabolic dysfunction, and testosterone deficiency is associated with energy imbalance, impaired glucose control, reduced insulin sensitivity and dyslipidaemia. A bidirectional relationship between testosterone and obesity underpins this association indicated by the hypogonadal–obesity cycle and evidence weight loss can lead to increased testosterone levels. Androgenic effects on enzymatic pathways of fatty acid metabolism, glucose control and energy utilization are apparent and often tissue specific with differential effects noted in different regional fat depots, muscle and liver to potentially explain the mechanisms of testosterone action. Testosterone replacement therapy demonstrates beneficial effects on measures of obesity that are partially explained by both direct metabolic actions on adipose and muscle and also potentially by increasing motivation, vigour and energy allowing obese individuals to engage in more active lifestyles. The degree of these beneficial effects may be dependent on the treatment modality with longer term administration often achieving greater improvements. Testosterone replacement may therefore potentially be an effective adjunctive treatment for weight management in obese men with concomitant hypogonadism.     

Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes

OBJECTIVE: Low levels of testosterone in men have been shown to be associated with type 2 diabetes, visceral adiposity, dyslipidaemia and metabolic syndrome. We investigated the effect of testosterone treatment on insulin resistance and glycaemic control in hypogonadal men with type 2 diabetes. DESIGN: This was a double-blind placebo-controlled crossover study in 24 hypogonadal men (10 treated with insulin) over the age of 30 years with type 2 diabetes. METHODS: Patients were treated with i.m. testosterone 200 mg every 2 weeks or placebo for 3 months in random order, followed by a washout period of 1 month before the alternate treatment phase. The primary outcomes were changes in fasting insulin sensitivity (as measured by homeostatic model index (HOMA) in those not on insulin), fasting blood glucose and glycated haemoglobin. The secondary outcomes were changes in body composition, fasting lipids and blood pressure. Statistical analysis was performed on the delta values, with the treatment effect of placebo compared against the treatment effect of testosterone. RESULTS: Testosterone therapy reduced the HOMA index (-1.73 +/- 0.67, P = 0.02, n = 14), indicating an improved fasting insulin sensitivity. Glycated haemoglobin was also reduced (-0.37 +/- 0.17%, P = 0.03), as was the fasting blood glucose (-1.58 +/- 0.68 mmol/l, P = 0.03). Testosterone treatment resulted in a reduction in visceral adiposity as assessed by waist circumference (-1.63 +/- 0.71 cm, P = 0.03) and waist/hip ratio (-0.03 +/- 0.01, P = 0.01). Total cholesterol decreased with testosterone therapy (-0.4 +/- 0.17 mmol/l, P = 0.03) but no effect on blood pressure was observed. CONCLUSIONS: Testosterone replacement therapy reduces insulin resistance and improves glycaemic control in hypogonadal men with type 2 diabetes. Improvements in glycaemic control, insulin resistance, cholesterol and visceral adiposity together represent an overall reduction in cardiovascular risk.     

Evalution of the castrated male Sprague-Dawley rat as a model of the metabolic syndrome and type 2 diabetes

OBJECTIVE: Low testosterone levels have been shown to be predictive for the development of the metabolic syndrome in men. The aim of this study was to describe effects of testosterone deficiency on metabolic syndrome-related parameters in male rats in order to evaluate the rat as a model for the human metabolic syndrome related to low testosterone levels. METHODS: Male Sprague-Dawley rats were castrated or sham operated at 16 weeks of age and fed either a standard or a high energy diet. Measured parameters were: food intake, body weight, fat distribution, energy expenditure, physical activity and blood/plasma parameters related to glucose and lipid metabolism. RESULTS: Castration led to an increase in the amount of subcutaneous fat, but did not result in any changes in the visceral fat. Fasting blood glucose levels were increased and free fatty acids concentration decreased in the castrated rats from 2 weeks after castration and throughout the study, whereas no significant differences between the groups were found in any of the other parameters measured. A high-energy diet did not change the response to castration in male Sprague-Dawley rats. CONCLUSION: Compared to humans rats respond differently to testosterone deficiency. Only few of the features typical for the human metabolic syndrome were observed in castrated male Sprague-Dawley rats. Therefore, we conclude that with the present experimental setup the castrated rat is not an optimal model for studies on the influence of testosterone deficiency on body fat distribution and the development of other central components of the metabolic syndrome.     

Using insulin as a drug rather than as a replacement hormone during acute illness: a new paradigm

The direct correlation between glucose levels and cardiovascular disease in individuals with type 2 diabetes can now be applied to individuals that share an abnormal metabolic milieu similar to that found in central obesity, the metabolic syndrome, and type 2 diabetes. Premature macrovascular complications with a very high morbidity and mortality rate can be found in these nondiabetic populations. The typical phenotype has visceral or central obesity, excess of free fatty acids, insulin resistance, increased insulin secretion, and hypertension. A more complex metabolic-cardiovascular syndrome develops that includes dyslipidemia, abnormal production of cytokines, chronic inflammatory state, and abnormal coagulation. The interplay of all these cardiovascular risk factors is responsible for the accelerated atherosclerotic process. The different terminologies used for populations sharing this common ground for premature cardiovascular disease now generally accepted as the metabolic syndrome, are also discussed. Aggressive insulin treatment during acute illness in individuals with the abnormal metabolic milieu is beneficial. Insulin treatment is changing from using insulin as a hormone to treat only severe hyperglycemia, to a new paradigm using insulin in high doses as a drug. Aggressive insulin regimens should be used to treat only minimal elevations of blood glucose or to prevent hyperglycemia. The newly observed properties of insulin are reviewed which include suppression of inflammatory cytokines and adhesion molecules, improved hemostasis, and other cardiac beneficial effects. The concomitant administration of intravenous glucose and insulin permits the administration of higher insulin doses that can result in improved outcome due to its nonglycemic-related benefits. The use of aggressive insulin therapy requires both better and more cost-effective algorithms to successfully treat this high-risk population during acute illness.     

Vaspin:一种新的具有胰岛素增敏作用的脂肪因子

腹内脂肪来源的丝氨酸蛋白酶抑制剂(vaspin)是从OLETF(Otsuka Long-Evans Tokushima fatty)大鼠的腹内脂肪分离鉴定出来的一种脂肪因子.人类血清vaspin水平具有性别差异,并与肥胖、胰岛素抵抗指数相关.动物实验表明,vaspin可以改善糖耐量和胰岛素敏感性.因此,vaspin或其类似物有望成为治疗代谢综合征的一种新药.     

Vaspin与代谢综合征发病机制的关系

脂肪组织是特殊的内分泌器官,可参与能量代谢并分泌多种细胞及组织因子.Vaspin是一种新发现的内脏脂肪特异性蛋白酶抑制剂,属丝氨酸蛋白酶抑制剂超家族.研究发现,vaspin与代谢综合征的发病机制密切相关.其具有胰岛素增敏作用,可以改善糖耐量,调节糖、脂代谢,在肥胖或肥胖相关的功能失调中可能发挥作用.肥胖时脂肪组织的堆积...     

Testosterone or 17{beta}-estradiol exposure reveals sex-specific effects on glucose and lipid metabolism in human myotubes

Changes in sex hormone levels with aging or illness may lead to metabolic disorders. Moreover, the ratio changes in men versus women may have distinct pathological responses. Since little is known about sex hormone action on muscle metabolism, we examined the role of testosterone or 17β-estradiol (E(2)) in metabolism and investigated whether either hormone may mediate a sex-specific effect. Myotubes from postmenopausal women and age-matched male donors were treated with 10?nM testosterone or E(2) for 4 days, and assays were performed to measure metabolic readouts, signal transduction, and mRNA expression. Testosterone and E(2) treatment enhanced insulin-stimulated glucose incorporation into glycogen and AKT phosphorylation in myotubes from female donors, highlighting a sex-specific role of sex hormone in glucose metabolism. Testosterone treatment increased palmitate oxidation in myotubes from both female and male donors, while E(2) enhanced palmitate oxidation in myotubes from male donors only. Testosterone-mediated increase in palmitate oxidation was attenuated at the presence of androgen receptor antagonist, which may indicate a role of nuclear steroid receptor in muscle lipid oxidation. Testosterone treatment increased mRNA expression of the insulin receptor substrate 2 in myotubes from male and female donors, whereas it increased mRNA expression of glycogen synthase 1 only in myotubes from male donors. E(2) treatment increased pyruvate dehydrogenase kinase 4 mRNA expression in myotubes from female donors. Thus, our data suggest that testosterone or E(2) modulates muscle glucose and lipid metabolism and may play a role in metabolism in a sex-dependent manner.     

Low sex hormone-binding globulin is associated with the metabolic syndrome in postmenopausal women

Although an association between the metabolic syndrome and hyperandrogenism has been suggested in women with polycystic ovarian syndrome, few studies have investigated this relationship in postmenopausal women. We measured estradiol, testosterone, and sex hormone-binding globulin (SHBG) and calculated the free androgen index (FAI) in 212 postmenopausal women not using hormone therapy in the Women's Health Study. A modified definition of the metabolic syndrome (3 or more of the following: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein, elevated blood pressure, and abnormal glucose metabolism) from the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults was used. Women with the metabolic syndrome had higher mean levels of estradiol, testosterone, and FAI values and lower SHBG levels. Higher FAI and lower SHBG were associated with all components of the metabolic syndrome. After adjustment for BMI and other factors, women in the highest tertile of FAI had an odds ratio of 12.6 (95% confidence interval, 3.8-41.6) for the metabolic syndrome, whereas those in the lowest SHBG tertile had an odds ratio of 7.3 (95% confidence interval, 2.7-19.8). When stratified by body mass index, the associations with high FAI and low SHBG remained significant even in women with body mass index less than 26.7 kg/m2. An androgenic hormone profile is associated with both the individual components of the metabolic syndrome and clustering of metabolic abnormalities in postmenopausal women.     

Effects of testosterone supplementation on whole body and regional fat mass and distribution in human immunodeficiency virus-infected men with abdominal obesity

BACKGROUND: Whole body and abdominal obesity are associated with increased risk of diabetes mellitus and heart disease. The effects of testosterone therapy on whole body and visceral fat mass in HIV-infected men with abdominal obesity are unknown. OBJECTIVE: The objective of this study was to determine the effects of testosterone therapy on intraabdominal fat mass and whole body fat distribution in HIV-infected men with abdominal obesity. METHODS: IN this multicenter, randomized, placebo-controlled, double-blind trial, 88 HIV-positive men with abdominal obesity (waist-to-hip ratio > 0.95 or mid-waist circumference > 100 cm) and total testosterone 125-400 ng/dl, or bioavailable testosterone less than 115 ng/dl, or free testosterone less than 50 pg/ml on stable antiretroviral regimen, and HIV RNA less than 10,000 copies per milliliter were randomized to receive 10 g testosterone gel or placebo daily for 24 wk. Fat mass and distribution were determined by abdominal computerized tomography and dual energy x-ray absorptiometry during wk 0, 12, and 24. We used an intention-to-treat approach and nonparametric statistical methods. RESULTS: Baseline characteristics were balanced between groups. In 75 subjects evaluated, median percent change from baseline to wk 24 in visceral fat did not differ significantly between groups (testosterone 0.3%, placebo 3.1%, P = 0.75). Total (testosterone -1.5%, placebo 4.3%, P = 0.04) and sc (testosterone-7.2%, placebo 8.1%, P < 0.001) abdominal fat mass decreased in testosterone-treated men, but increased in placebo group. Testosterone therapy was associated with significant decrease in whole body, trunk, and appendicular fat mass by dual energy x-ray absorptiometry (all P < 0.001), whereas whole body and trunk fat increased significantly in the placebo group. The percent of individuals reporting a decrease in abdomen (P = 0.01), neck (P = 0.08), and breast size (P = 0.01) at wk 24 was significantly greater in testosterone-treated than placebo-treated men. Testosterone-treated men had greater increase in lean body mass than placebo (testosterone 1.3%, placebo -0.3, P = 0.02). Plasma insulin, fasting glucose, and total high-density lipoprotein and low-density lipoprotein cholesterol levels did not change significantly. Testosterone therapy was well tolerated. CONCLUSIONS: Testosterone therapy in HIV-positive men with abdominal obesity and low testosterone was associated with greater decrease in whole body, total, and sc abdominal fat mass and a greater increase in lean mass compared to placebo. However, changes in visceral fat mass were not significantly different between groups. Further studies are needed to determine testosterone effects on insulin sensitivity and cardiovascular risk.     

睾酮对钙离子通道和心脏功能的影响

睾酮对人体的全身代谢、心脏的生理和病理均有着重要的影响。较高浓度的睾酮或其慢性作用可以提高T型、L型钙离子通道的密度,较低浓度或急性作用可以阻滞T型、L型钙离子通道,缩短男性Q-Tc 间期,提高对胰岛素的敏感性及改善血脂代谢。睾酮可上调钙调节蛋白、β2受体的表达,在提高细胞内钙离子浓度的情况下,可增加钙瞬变的幅度,减少钙超载。一定浓度的睾酮可以维持血管的一定张力,改善心脏传导或扩张冠脉;减少胰岛素抵抗、代谢综合征的发生,改善心肌缺血、减少心肌细胞凋亡及纤维化,保护心脏,改善心脏收缩舒张效率。