新诊断糖尿病成年男性患者性激素结合球蛋白的变化及其意义

目的 观察新诊断糖尿病成年男性患者性激素结合球蛋白（SHBG）的变化,探讨其与IR及胰岛早相分泌功能的关系. 方法 纳入新诊断糖尿病男性患者56例为糖尿病组,另选健康成年男性38名为正常对照组,测定SHBG,进行精氨酸刺激试验. 结果 两组SHBG、胰岛素抵抗指数（HOMA-IR）差异有统计学意义（P＜0.01）.相关分析显示,SHBG与HOMA-IR呈负相关（r=-0.219,P＜0.05）.Logistic回归分析显示,SHBG是IR的唯一有效自变量（β=-0.75,P＜0.05,OR=0.47）.二元Logistic回归分析得出HOMA-IR是糖尿病的危险因素,SHBG是糖尿病的保护因素.胰岛2 min分泌高峰值与HOMA-IR呈正相关（β=0.567,P＜0.05）. 结论 新诊断糖尿病成年男性患者存在血清SHBG降低,SHBG与HOMA-IR呈负相关.SHBG是新诊断糖尿病成年男性患者的独立保护因素.胰岛β细胞第一时相分泌功能减退与IR相关,与SHBG无相关性.     

The association of age-related differences in serum total testosterone and sex hormone-binding globulin levels with the prevalence of diabetes

BackgroundAge-related differences of sex hormones are traditionally considered detrimental to certain diseases particularly in middle-aged and elderly males, however, it is imprudent to conclude without elucidating the influences of other age-related pathophysiology apart from reproductive aging. We sought to examine serum testosterone and sex hormone-binding globulin (SHBG) levels from different decades of life and their associations with the prevalence of diabetes in each respective decade.Materials and methodsA total of 6296 males participated in this multicenter cross-sectional study, aged between 40–79 years. Information on diabetes and associated risk factors were obtained by questionnaires. Serum total testosterone (TT), SHBG and calculated free testosterone (fT) were determined.ResultsAge-related stable level of TT even with significantly lower level of fT did not result in a higher age-related odds of diabetes. Whereas, age-related higher SHBG level was associated with a lower age-related odds of diabetes [−5.88 % (p = 0.038), −14.28 % (p = 0.003) and −23.53 % (p = 0.001) for males aged 50–59, 60–69, 70–79 years, respectively]. Also, the combined age-related differences of TT and SHBG levels were found associated with a lower age-related odds of diabetes [−2.21 % (p = 0.040), −8.16 % (p = 0.025) and −14.37 % (p = 0.002) for males aged 50–59, 60–69, 70–79 years, respectively].ConclusionsThe differences in hormonal levels of each age group category showed a negative association with the prevalence of diabetes in middle-aged and elderly males, however, this association could be deterred in the presence of obesity.     

Hypogonadism in male outpatients with sarcoidosis

Hypogonadism is assumed to be present in sarcoidosis. Nevertheless, a comparison of circulating sex hormone concentrations of male sarcoidosis patients with those of healthy men has never been done. Moreover, it remains unknown if hypogonadism may contribute to a reduced muscle function, exercise intolerance, diminished vitality and depressed mood in male sarcoidosis patients. Pulmonary function, muscle function, exercise tolerance, vitality, mood, circulating sex hormone concentrations and C-reactive protein were assessed in 30 male sarcoidosis patients and 26 age-matched men with a normal pulmonary function. On average, patients had a restrictive pulmonary function, worse inspiratory and quadriceps muscle function, functional exercise intolerance, diminished vitality, depressed mood and increased systemic inflammation. Moreover, patients had significantly lower circulating (free) testosterone concentrations, while circulating sex hormone-binding globulin tended to be lower (p=0.0515). Circulating gonadotrophin concentrations were comparable. Non-significant relationships were found between sex hormones, clinical outcomes and C-reactive protein in patients with sarcoidosis. A significant number of male outpatients with sarcoidosis (46.7%) had low circulating testosterone concentrations, which was most probably caused by hypogonadotrophism. The clinical relevance of hypogonadism in male outpatients with sarcoidosis, however, remains currently unknown. Indeed, poor inspiratory and quadriceps muscle function, exercise intolerance, diminished vitality and depressed mood were not related to hypogonadism in these patients.     

Structural analyses of sex hormone-binding globulin reveal novel ligands and function

Plasma sex hormone-binding globulin (SHBG) regulates the access of androgens and estrogens to their target tissues and cell types. An SHBG homologue, known as the androgen-binding protein, is expressed in Sertoli cells of many mammalians, but testicular expression of human SHBG is restricted to germ cells. The primary structure of SHBG comprises tandem laminin G-like (LG) domains. The amino-terminal LG-domain includes the steroid-binding site and dimerization interface, and its tertiary structure, resolved in complex with natural and synthetic sex steroids, has revealed unanticipated mechanisms of steroid binding at the atomic level. This LG-domain interacts with fibulin-1D and fibulin-2 in a ligand-specific manner, and this is attributed to the unique way estrogens reside within the steroid-binding site, and the ordering of an otherwise flexible loop structure covering the entrance of the steroid-binding pocket. This mechanism enables estradiol to enhance the sequestration of plasma SHBG by the stroma of some tissues through binding to these extra-cellular matrix-associated proteins. The human SHBG amino-terminal LG-domain also contains several cation-binding sites, and occupancy of a zinc-binding site influences its affinity for estradiol. The complete quaternary structure of SHBG remains unresolved but structural predictions suggest that the carboxy-terminal LG-domains extend laterally from the dimerized amino-terminal LG-domains. The carboxy-terminal LG-domain contains two N-glycosylation sites, but their biological significance remains obscure. Knowledge of the SHBG tertiary structure has helped develop computational techniques based on the use of a “bench-mark data set” of steroid ligands, and created novel drug discovery and toxicology risk assessment platforms.     

Genome-wide association studies on serum sex steroid levels

Even though the levels of circulating sex steroid hormones are to a large extent heritable, their genetic determinants are largely unknown. With the advent of genome-wide association studies (GWAS), much progress has been made and several genetic loci have been identified to be associated with serum levels of dehydroepiandrosterone sulfate, testosterone and sex hormone-binding globulin. The variants identified so far only explain a small amount of the overall heritability, but may help to elucidate the role of sex steroid hormones in common disorders such as hypogonadism, type 2 diabetes and hormone-sensitive cancers. This review provides an overview of the current state of knowledge of the genetic determinants of sex steroid hormones, with a focus on recent GWAS and brief directions for elucidating the remaining heritability.     

The relationship between visceral adiposity and left ventricular diastolic function: Results from the Baltimore Longitudinal Study of Aging

Background and aimsIt is unclear whether subcutaneous and visceral fat are differentially correlated to the decline in left ventricular (LV) diastolic function with aging. This study sought to examine the hypothesis that age-related changes in the regional fat distribution account for changes in LV diastolic function and to explore potential mediators of this association.Methods and resultsIn this cross-sectional study, we evaluated 843 participants of the Baltimore Longitudinal Study of Aging with echocardiogram, dual-energy X-ray absorptiometry (DEXA), abdominal computed tomography (CT) and blood tests performed at the same visit. LV diastolic function was assessed by parameters of LV relaxation (E/A ratio, Em and Em/Am ratio) and LV filling pressures (E/Em ratio). Total body fat was computed by DEXA, while visceral and subcutaneous fat were determined from abdominal CT. In multivariate models adjusted for demographics, cardiovascular risk factors, antihypertensive medications, physical activity and LV mass, both visceral and subcutaneous fat were associated with LV diastolic dysfunction. When both measures of adiposity were simultaneously included in the same model, only visceral fat was significantly associated with LV diastolic dysfunction. Triglycerides and sex-hormone binding globulin, but not adiponectin and leptin, were found to be significant mediators of the relationship between visceral fat and LV diastolic function, explaining 28–47% of the association. Bootstrapping analyses confirmed the significance of these findings.ConclusionsIncreased visceral adiposity is associated with LV diastolic dysfunction, possibly through a metabolic pathway involving blood lipids and ectopic fat accumulation rather than adipokines.     

Obesity Associated Insulin Resistance Occurs in Hypopituitary Subjects

The study aimed to assess the role of pituitary hormones in the relationship between insulin resistance and obesity. Twelve male subjects with hypopituitarism secondary to surgery for a non-functioning pituitary adenoma were recruited. Subjects were receiving replacement hormones. Fasting plasma samples were taken for insulin, C-peptide, glucose, and lipids. Body mass index and blood pressure were measured. In hypopituitary subjects on replacement therapy, a positive association between body mass index and fasting plasma insulin levels (r = 0.76, p < 0.004) was similar to that found in normal subjects. In conclusion pituitary function does not have a direct role in determining the relationship between fasting plasma insulin, an index of insulin resistance, and obesity.     

睾酮与男性代谢综合征

男性血清睾酮水平与代谢综合征的发生、发展密切相关.低睾酮水平可能导致腹型肥胖、糖代谢异常、血脂紊乱及高血压,给予睾酮水平低下者睾酮替代治疗(TRT)能明显改善其相关代谢指标.同时,腹型肥胖、糖代谢异常也可通过抑制Leydig细胞功能、增加芳香化酶活性等引起睾酮水平下降.     

对抵抗素在肥胖性胰岛素抵抗中作用及作用机制的争议

抵抗素是近年来发现的一种脂肪细胞分泌的多肽类信号分子,最初发现在肥胖小鼠中血清抵抗素水平上升,免疫中和血清抵抗素能改善胰岛素的敏感性,因此认为它可能是联系肥胖和胰岛素抵抗的关键因子。但是,后来有学者发现肥胖鼠白色脂肪组织中抵抗素mRNA水平下降,这与抵抗素主要来源于脂肪细胞相矛盾,而且大多数的人类实验都发现血清抵抗素水平上升与胰岛素抵抗并不相关。因此,目前对于抵抗素和胰岛素抵抗之间的关系尚存在很大争议。     

Gonadal function in young adult males with metabolic syndrome

AimsAim of the study was to assess the gonadal function of young adult males with metabolic syndrome and to compare them with healthy age matched controls.MethodsForty young male subjects of age group 20–40 years who fulfilled the IDF criteria (2005) for diagnosis of metabolic syndrome were included in the study. Thorough evaluation of the subjects was done and history of sexual dysfunction if any was noted. Pooled blood samples were collected from each subject in fasting state for total testosterone, SHBG, FSH, LH, prolactin and insulin levels. All hormonal analyses were done by radio immune assay (RIA). Hypogonadism was defined as total testosterone less than 3 ng/ml. Eighteen healthy age matched controls were also taken for the study.ResultsTwenty percent of subjects with metabolic syndrome had eugonadotropic hypogonadism compared to 5.5% controls. Subjects with metabolic syndrome also had significantly lower SHBG level compared to the controls.ConclusionFrom this study it has been observed that eugonadotropic hypogonadism with low total testosterone and normal or low normal gonadotropin levels may be a feature of the metabolic syndrome in young adult males. Significant low SHBG levels as compared to controls could be one of the factors responsible for various biochemical alteration seen in these cases. This study highlights the importance of evaluating gonadal function in young adult males with the metabolic syndrome and has therapeutic implications in the management of such subjects with gonadal dysfunction.     

肥胖病人血清胰岛素样生长因子结合蛋白1、3水平与代谢因素的关系

目的　观察肥胖病人血清胰岛素样生长因子结合蛋白 1、3 (IGFBP 1、IGFBP 3 )水平 ,分析其与年龄、性别、体重指数、糖代谢、脂代谢等指标的关系。方法　应用ELISA法测定 92例肥胖病人和 84例正常人血清IGFBP 3、IGFBP 1及真胰岛素水平。结果　肥胖组与对照组比较 ,IGFBP 3明显增高 (P <0 .0 1) ;IGFBP 1下降 (P <0 .0 5 )。IGFBP 1与BMI(r =-0 .418,P <0 .0 1)、FINS(r =-0 .3 5 7,P <0 .0 5 )和Homa IR指数 (r =-0 .3 1,P <0 .0 5 )呈负相关。IGFBP 3与FINS呈正相关 (r =0 .2 6,P <0 .0 5 )。结论　肥胖病人血清IGFBP 1浓度降低 ;IGFBP 1水平可能反映胰岛素抵抗状态     

男性Ⅱ型糖尿病患者胰岛素敏感性与性激素结合球蛋白浓度相关性研究

以初次诊断未经治疗１９例男性ＩＩ型糖尿病患者为研究对象，以空腹血糖（ＦＰＧ）与空腹胰岛素（ＦＩＮＳ）浓度乘积的倒数作为胰岛素依赖型指数（ＩＳＩ）。分析ＩＳＩ与年龄，腰臂围比（ＷＨＲ），体重指数（ＢＭＩ），性激素结合球蛋白（ＳＨＢＧ）以及睾酮（Ｔ）的相关性，结果发现ＩＳＩ与ＳＨＢＧ呈极显著性正相关（ｒ＝０．５６，Ｐ＝０．０１）。在以ＩＳＩ为变量，以年龄，ＷＨＲ，ＢＭＩ，ＳＨＢＧ和Ｔ为自变量的逐步回归     

性激素结合蛋白基因多态性与肝细胞癌患者术后复发关系研究

目的探讨性激素结合蛋白(SHBG)基因Asp327Ash位点单核苷酸多态性与肝细胞癌(Hepa-tocellular Carcinoma,HCC)根治术后早期复发的关系。方法收集131例实施根治性切除术的原发性HCC患者临床病理、血液DNA及预后生存资料,以单因素分析、多因素Cox风险回归分析临床病理及Asp327Asn位点多态性与HCC术后复发关系,用Kaplan-Meier生存曲线描述各基因型的无复发生存时间,并对不同基因型无复发生存曲线进行Log-Rank检验比较。结果全组病例1、2年生存率分别为87%、76%,累积复发率分别为17%、19%。单因素及多因素分析均显示结节数可能与术后复发有关,而Asp327Asn位点多态性可能与术后复发无关。生存分析显示,在单一结节数的HCC患者中,虽然Asp/Asn+Asn/Asn、Asp/Asp基因型无复发生存时间比较差异无统计学意义(P=0.21),但生存曲线后半段明显分离。结论 SHBG基因Asp327Asn位点多态性可能与HCC术后复发无关,但是对于肝脏基本状况较好的HCC患者,该位点多态性可能对其术后远期预后有一定的影响。     

肥胖与骨质疏松

肥胖和骨质疏松是两种密切相关的疾病,成骨细胞和脂肪细胞由骨髓间充质干细胞分化而来,脂肪组织可通过分泌细胞因子影响间充质细胞的分化.肥胖者体内胰源性激素及雌激素水平升高,与瘦素、脂联素、白细胞介索等脂肪细胞因子一起共同组成复杂的网络,影响骨重构.此外,肥胖和骨质疏松还有着共同的基因学基础.对肥胖与骨质疏松关系的研究对骨质疏松的预防有重要意义.     

肥胖与骨质疏松

肥胖和骨质疏松是两种密切相关的疾病,成骨细胞和脂肪细胞由骨髓间充质干细胞分化而来,脂肪组织可通过分泌细胞因子影响间充质细胞的分化.肥胖者体内胰源性激素及雌激素水平升高,与瘦素、脂联素、白细胞介索等脂肪细胞因子一起共同组成复杂的网络,影响骨重构.此外,肥胖和骨质疏松还有着共同的基因学基础.对肥胖与骨质疏松关系的研究对骨质疏松的预防有重要意义.     

血清性激素结合球蛋白与2型糖尿病患者大血管病变的关系

目的研究血清性激素结合球蛋白与2型糖尿病患者大血管病变的关系及其可能机制。方法入选2010年1月至2011年12月在我院老年内分泌科门诊及住院部就诊的80例2型糖尿病患者[男48例,女32例,平均年龄（61±8）岁],根据是否合并大血管病变分为未合并大血管病变组[B组,n=40,男23例,女17例,平均年龄（60±11）岁]和合并大血管病变组[C组,n=40,男25例,女15例,平均年龄（63±11）岁]。另以同期在我院进行健康体检者40名为健康对照组[A组,男25名,女15名,平均年龄（58±10）岁]。测定和计算3组受试者血清性激素结合球蛋白水平、体质指数、腰臀比、血压、血脂、糖化血红蛋白、空腹及餐后血糖、血清胰岛素、尿蛋白／肌酐比值、胰岛素抵抗指数。2组问均数比较采用t检验,3组问均数比较采用方差分析,性激素结合球蛋白相关因素分析采用Spearman相关分析和逐步线性回归分析。结果C组血清性激素结合球蛋白水平[（31±6）u/L]明显低于B组[（46±17）u/L]及A组[（56±14）阻∥L]（F=9．763,P〈0．01）。Spearman相关分析显示,血清性激素结合球蛋白水平与腰臀比、甘油三酯、空腹及餐后胰岛素水平、胰岛素抵抗指数、尿蛋白／肌酐比值呈负相关（r值分别为-0．216、-0．156、-0．144、-0．108、-0．263、-0．126,均P〈0．05）。多元逐步回归分析表明,血清性激素结合球蛋白水平与甘油三酯、腰臀比、胰岛素抵抗指数具有直线回归关系（r2值分别为-1．132、-0．862、-2．650,均P〈0．05）。非条件logistic回归分析显示,血清性激素结合球蛋白水平对大血管病变具有-定影响。结论血清性激素结合球蛋白可能作为危险因素参与2型糖尿病及其大血管病变的发生和发展。     

绝经后2型糖尿病患者性激素结合球蛋白与动脉粥样硬化危险因子的相关性

目的研究绝经后2型糖尿病（T2DM）患者的性激素结合球蛋白（SHBG）与动脉粥样硬化（AS）危险因子的相关性。方法绝经后T2DM患者45例（20例合并大血管并发症,25例无大血管并发症）,测定SHBG、FPG、Fins、FC—P、TC、TG、HDL—C、LDL-C、纤维蛋白原（FIB）。以ISI=-Ln（FPG·Fins）作为胰岛素敏感性指标。对SHBG与BMI、WHR、FPG、Fins、FC—P、ISI、脂代谢指标、FIB的相关性进行分析。结果有大血管并发症组SHBG、ISI显著低于无大血管并发症组,而WHR、FPG、Fins、FC-P、TC、LDLC、FIB显著高于无大血管并发症组。在简单相关分析中,SHBG与ISI呈显著正相关（R=0．731,P〈0．01）。在逐步叫归分析中,FC-P为预测SHBG最强的指标。结论低水平的SHBG是绝经后2型糖尿病患者动脉粥样硬化的危险因素之一。     

肥胖与阻塞性睡眠呼吸暂停低通气综合征

肥胖患者下颌及咽周脂肪沉积阻塞气道,可导致阻塞性睡眠呼吸暂停低通气综合征(OSAHS),可能作为OSAHS的预测指标.OSAHS是一种由于睡眠期间反复发生上气道塌陷导致睡眠呼吸暂停以及反复低氧的一种疾病,可引起一系列内分泌和代谢异常.OSAHS患者夜间缺氧可导致脂代谢异常、胰岛素敏感性下降、瘦素抵抗,从而在肥胖的发生、发展中起一定作用.