人血浆瘦素水平与肥胖及血糖、胰岛素的关系

目的　探讨人血浆瘦素水平与肥胖程度、血糖、胰岛素浓度的关系。方法　免疫放射法测定171例检查者(2型DM84例，IGT36例，NGT51例；男90例，女81例)的空腹血浆瘦素水平，并行口服葡萄糖耐量试验，测定血浆胰岛素和葡萄糖浓度，同时测量身高、体重，计算体重指数(BMI)。结果　空腹血浆瘦素水平与体重指数呈正相关(男r=0.6772,P＜0.01；女r=0.7191,P＜0.01)，但性别差异显著(P＜0.001)，女性是男性的2～3倍。采用多元逐步回归法分析，去除体重指数等因素的影响后，瘦素与胰岛素曲线下面积呈正相关，与血糖浓度无相关性。结论　肥胖者空腹血浆瘦素升高，血浆高瘦素水平与高胰岛素血症的相关性提示瘦素可能在2型糖尿病的发病中起一定作用。     

T2DM患者血浆内脏脂肪素、瘦素与胰岛素抵抗的相关性研究

目的 探讨2型糖尿病(T2DM)患者血浆内脏脂肪素、瘦素水平与胰岛素抵抗(IR)的相关性.方法 102例T2DM患者和64例正常糖耐量(NGT)对照者,根据BMl分为肥胖组(Ob)和非肥胖(Non-Ob)组,均测定空腹血浆内脏脂肪素、瘦素和相关临床指标,计算胰岛素抵抗指数(HOMA-IR)和腰臀比(WHR).结果 T2DM组与NGT组比较空腹血浆内脏脂肪素和瘦素水平明显升高(t=3.922,P=0.00;t=2.128,P=0.038).相关分析显示T2DM患者空腹血浆内脏脂肪紊与HOMA-IR、WHR、瘦素、HbA<,1> c和TG正相关(r=0.543,P=0.001;r=0.442,P=0.008;r=0.385,P=0.013,r=0.345,P=0.025;r=0.427,P=0.005),瘦素与HOMA-IR、性别、BMI正相关(r=0.578,P<0.01;r=0.547,P<0.01;r=0.607,P<0.01).结论 T2DM患者空腹血浆内脏脂肪素和瘦素水平显著升高,且与IR关系密切.     

局部体脂及内分泌脂肪调节激素对瘦素水平的影响

目的　研究中国人非超重、超重及肥胖者瘦素水平与局部体脂、内分泌脂肪调节激素之间的关系。方法　用核磁共振 (MRI)测量 15 0例正常糖耐量的非超重、超重及肥胖者的局部体脂。同时测定瘦素、空腹胰岛素、皮质醇、生长激素、总睾酮、游离睾酮、硫酸去氢表雄酮等内分泌脂肪调节激素。结果　 (1)超重或肥胖者瘦素水平升高 ,女性瘦素水平显著高于男性 ;(2 )体脂对瘦素的影响有性别差异 ,在男性 ,瘦素与腹部皮下脂肪显著相关 (r =0 .75 ,P <0 .0 0 1) ;在女性 ,瘦素与体重指数相关 (r =0 .6 5 ,P <0 .0 0 1) ;(3)胰岛素是独立于体脂之外的调节瘦素的因素 ;(4 )游离睾酮参与瘦素的调节 ,但对瘦素的影响因性别而不同。结论　皮下脂肪是影响瘦素的局部体脂因素 ,胰岛素及雄性激素参与瘦素水平的调节     

肿瘤坏死因子α和瘦素在肥胖及胰岛素抵抗中的作用

目的探讨血清TNFα及瘦素在肥胖和胰岛素抵抗中的作用。方法2型糖尿病病人84例,健康对照84例,分别测定血清TNFα、瘦素、血脂、空腹及餐后血糖、血清免疫反应性胰岛素(IRI)水平。并准确测量血压、身高、体重、腰臀围比(WHR)。结果肥胖者的TNFα及瘦素显著高于体重正常者,女性的瘦素血清水平高于男性2倍以上。相关分析结果显示,TNFα与HOMA胰岛素抵抗指数(HOMAIR)、WHR、空腹IRI呈正相关(r值分别为0.43、0.53、0.59,P<0.01),与高密度脂蛋白胆固醇呈负相关(r=-0.35,P<0.01)。瘦素与HOMAIR、空腹IRI呈正相关(r=0.31、0.29,P<0.05),男性的瘦素与WHR显著相关。TNFα与瘦素之间存在显著的正相关(r=0.29,P<0.05)。多元逐步回归分析表明,HOMAIR与TNFα的相关性最强,瘦素次之。血清TNFα水平与空腹血糖呈正相关。结论肥胖者的血清TNFα及瘦素水平与胰岛素抵抗密切相关,高水平的TNFα可能直接作用于脂肪组织调节瘦素的释放,而TNFα和瘦素协同作用诱导胰岛素的分泌,从而导致胰岛素抵抗。     

老年男性非酒精性脂肪肝患者腹部脂肪面积及血清脂联素和瘦素水平的变化

目的 研究老年男性非酒精性脂肪肝(NAFLD)患者腹部脂肪面积及血清脂联素和瘦素水平的变化.方法 选择238名年龄≥60岁的老年男性,应用B超诊断脂肪肝,依据病史排除酒精性及病毒性脂肪肝.分为3组:脂肪肝组76例,年龄、体重指数与脂肪肝组匹配的非脂肪肝组77名(肥胖组),非肥胖非脂肪肝组85名(对照组).采用放射免疫法测定血清脂联素、瘦素水平;采用CT扫描测定腹部内脏脂肪面积.组间比较采用方差分析.结果 (1)脂肪肝组与肥胖组的体重指数、腹部皮下、内脏、总脂肪面积分别为(26.87±2.62)kg/m2与(26.63±1.97)kg/m2、(166.59±54.27)cm2与(147.89±50.14)cm2、(148.94±53.72)cm2与(150.06±45.47)cm2、(315.25±89.42)cm2与(297.93±75.12)cm2,均高于对照组(P＜0.01).脂肪肝组的腹部皮下脂肪面积高于肥胖组(P＜0.05),而两者的腹部内脏及总脂肪面积差异无统计学意义.(2)脂肪肝组与肥胖组间的瘦素水平差异无统计学意义,但均高于对照组.NAFLD组的脂联素水平明显低于肥胖组[(6.31±3.31)μg/ml对比(9.87±7.07)μg/ml,P＜0.01],也明显低于对照组[(6.31±3.31)μg/ml对比(11.05±7.19)μg/ml,P＜0.01];肥胖组与对照组间脂联素水平差异无统计学意义.(3)非酒精性脂肪肝的高危因素包括天冬氨酸转氨酶、甘油三酯、腹部内脏及皮下脂肪面积.血脂联素水平是非酒精性脂肪肝的保护性因素.结论 老年男性非酒精性脂肪肝患者的特征是腹型肥胖,瘦素水平高,脂联素水平低.其中脂联素水平的下降在其中起关键作用.     

2型糖尿病患者血浆瘦素的测定及其相关因素分析

目的研究2型糖尿病患者血浆瘦素与年龄、性别、体重指数、胰岛素、血糖的关系.方法用放射免疫分析法测定59例2型糖尿病患者血浆瘦素和胰岛素,用葡萄糖氧化酶法测血糖,并测量身高、体重,计算体重指数.结果平均瘦素水平男性(7.96±6.29) ng/ml,女性(16.07±13.14) ng/ml,女性较男性明显为高.血浆瘦素与 BMI呈显著相关(男性r=0.650,P＜0.001,女性r=0.654,P＜0.001).血浆瘦素与胰岛素显著相关(r=0.310,P＜0.05).瘦素与年龄无关(P＞0.5),与血糖无关(r=0.026,P＞0.5).结论血浆瘦素浓度与BMI 显著相关,显示存在瘦素抵抗,瘦素与胰岛素有显著相关性,提示瘦素可能与2型糖尿病之间有一定的内在联系.     

超声测量的内脏脂肪厚度和代谢综合征的关系

目的 探讨由超声测量的内脏脂肪厚度(VFT)评价内脏性肥胖的价值及其和代谢综合征(MS)的关系.方法 收集了2005-03-12在我院体检中心符合入选标准的可用资料210份,测定MS相关的人体指标测量、空腹血生化检查和经超声测量内脏脂肪厚度.根据国际糖尿病联盟(IDF)MS标准,分成MS组及非MS组.结果 VFT和腰围(WC)呈正相关(男r=0.61,P=0.01;女r=0.60,P=0.01),MS组VFT明显大于非MS组,男性MS组为(49.4±14.6)mm与非MS组(37.1±14.9)mm比较,女性MS组(34.5±9.4)mm与非MS组(24.6±8.7)mm比较,两者差异均有非常显著性(P=0.01).VFT与收缩压(SBP)、舒张压(DBP)、空腹血糖(FPG)、甘油三酯(TG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)呈正相关(P＜0.05或P＜0.01),与胰岛素敏感性指数(INSI)呈负相关(男性r=-0.309,女性r=-0.433,P＜0.01),男性VFT与高密度脂蛋白胆固醇(HDL-C)呈负相关(r=-0.249,P＜0.01),女性VFT与胆固醇(TC)呈正相关(r=0.255,P=0.065).逐步法多元线性回归分析显示,男性VFT和WC、SBP、载脂蛋白B(apoB)呈正相关,和HDL-C呈负相关,相关系数分别为(r=6.746,2.75,2.86,-2.03,P＜0.05或P＜0.01);女性VFT和体重指数(BMI)和HOMA-IR呈正相关,相关系数分别为(r=3.60,2.98,P＜0.01);而无论男女,WC和皮下脂肪仅仅和BMI呈正相关.MS发病率随着VFT的增加而增加(P＜0.05或P＜0.01).经超声测量的VFT诊断MS的ROC曲线下面积男性0.74,女性0.79,最佳切点值男性43.5 mm,女性23.8 mm.结论 经超声测量的VFT是一项简便、可靠和实用的评价内脏性肥胖的指标.并认为VFT大于此切点,即可推断存在有MS.     

2型糖尿病患者腹部脂肪分布与胰岛素敏感性及血清瘦素水平的关系

目的 探讨2型糖尿病患者腹部脂肪分布与瘦素和胰岛素抵抗的关系。方法 48例2型糖尿病患者均进行高胰岛素正血糖钳夹试验，根据体重指数(BMI)和葡萄糖利用率(GIR)将患者分为非肥胖型胰岛素敏感组(NIS，16例)，非肥胖型胰岛素抵抗组(NIR，15例)和肥胖型胰岛素抵抗组(OIR，17例)，同时洲定血清瘦素，胰岛素水平和腹部脂肪面积。结果 两非肥胖组(NIS和NIR)之间的BMI相似，但NIR组的GIR要明显低于NIS组，NIR组的内脏脂肪面积比NIS组明显增高，NIR组的瘦素水平在皮下脂肪校正之后与NIS组差异无显著性。OIR组的皮下脂肪，内脏脂肪和瘦素水平比非肥胖组(NIS和NIR)明显增高，OIR的GIR明显低于NIS和NIR组。多元回归分析显示，无论肥胖组还是非肥胖组，内脏脂肪是预测胰岛素抵抗的最重要变量；皮下脂肪是血清瘦素水平的最重要变量。结论 两种代谢不同的脂肪分布是胰岛素抵抗和瘦素水平的决定因素。     

腹部内脏脂肪沉积的老年非代谢综合征患者脂联素瘦素比值的变化

目的 观察体质指数正常、腹部内脏脂肪沉积的非代谢综合征老年男性患者血清脂联素、瘦素水平及脂联素瘦素比值的变化.方法 将入选的老年非代谢综合征男性患者109例分为2组,内脏无脂肪沉积组67例,内脏脂肪沉积组42例.采用CT方法测定内脏脂肪面积,当腹部内脏脂肪面积≥100cm2,为内脏脂肪沉积;采用LINCO公司提供的放射免疫试剂盒测定空腹血脂联素、瘦素水平;代谢综合征的诊断采用2004年中国糖尿病学会制定的标准.结果 (1)脂肪沉积组与无脂肪沉积组比较,体质指数、内脏脂肪面积均显著升高,体质指数分别为(22.94±1.35)kg/m2对(21.38±2.55)kg/m2(P＜O.001),内脏脂肪面积(135.6±31.7)cm2对(68.6±22.6)cm2(P＜O.001);脂联素瘦素比值降低.分别为2.17±1.77对4.54±7.00(P=0.031);而脂联素、瘦素水平在两者间差异无统计学意义;(2)脂联素瘦素比值与体质指数(r=-0.552,P＜0.001)、腰围(r=-0.390,P＜0.001)、腹部内脏脂肪面积(r=-0.311,P＜0.001)呈负相关.结论 体质指数正常有内脏脂肪沉积与无内脏脂肪沉积的老年男性比较.脂联素瘦素比值明显下降.并与腹部脂肪面积显著负相关.提示血清脂联素瘦素比值可能可用于筛选体质指数正常有腹部内脏脂肪肪沉积的患者.     

多囊卵巢综合征患者血浆酰化刺激蛋白和瘦素与胰岛素抵抗的关系

目的 探讨多囊卵巢综合征(PCOS)患者血浆酰化刺激蛋白(ASP)和瘦素水平的变化及其与胰岛素抵抗(IR)的关系.方法 将39例PCOS患者分为肥胖PCOS组和非肥胖PCOS组,42名健康孕龄妇女分为单纯肥胖组和正常体重对照组.测定血浆ASP、瘦素、空腹血糖(FPG)、空腹胰岛素(Fins)水平,并计算胰岛素抵抗指数(HOMA-IR).结果 ①与正常体重对照组相比,其余三组ASP水平显著升高(P＜0.01);单纯肥胖组和肥胖PCOS组的血浆瘦素水平显著高于正常体重对照组(P＜0.05;P＜0.01),而非肥胖PCOS组与正常体重对照组无显著性差异(P＞0.05);与正常体重对照组相比,非肥胖PCOS组和肥胖PCOS组的HOMA-IR显著升高(P＜0.05;P＜0.01 ).②在PCOS患者中,ASP与Fins、HOMA-IR成正相关(r=0.284,P=0.04;r=0.297,P=0.03);瘦素与BMI、Fins、HOMA-IR成正相关(r=0.677,P＜0.01;r=0.609,P＜0.01;r=0.588,P＜0.01);ASP与瘦素不相关(r=-0.043).结论 PCOS患者存在胰岛素抵抗,其血浆ASP水平显著升高;ASP、瘦素可能与PCOS的胰岛素抵抗有关.     

A strong association between biologically active testosterone and leptin in non-obese men and women is lost with increasing (central) adiposity

OBJECTIVE: In both humans and rodents, males have lower levels of leptin than females at any level of adiposity. Experimental data support the idea that testosterone exerts a negative influence on leptin levels. There are, however, major inconsistencies in available data concerning the possible association between androgenicity and leptin in humans. Reasons could be the influence of androgenicity on leptin production being dependent on body composition, and incomplete measures of biologically active testosterone levels. In the present study we have characterized the relationship between biologically active testosterone and leptin after careful stratification for gender and adiposity. DESIGN AND SUBJECTS: Healthy subjects (n=158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cross-sectional design. MEASUREMENTS: Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Circulating levels of leptin, insulin, testosterone, androstenedione, sex hormone-binding globulin (SHBG) and insulin-like growth factor-1 (IGF-1) were measured by radioimmunoassays or microparticle enzyme immunoassays. Apparent concentrations of free testosterone and non-SHBG-bound testosterone were calculated. RESULTS: After adjustments for age, BMI and insulin, leptin levels were inversely correlated to testosterone levels in non-obese men (r=-0.56, P<0.01) and obese women (r=-0.48, P<0.05). In contrast, leptin and testosterone correlated in a positive manner in non-obese women (r=0.59, P<0.01). Levels of SHBG were negatively associated with leptin in men with low waist circumference (r=-0.59, P<0.01). The following factors were associated with leptin in a multivariate model: low levels of biologically active testosterone and SHBG in men with low and medium waist circumference, insulin in men with high waist circumference, high levels of testosterone and insulin in non-obese women, and BMI in obese women. CONCLUSION: We conclude that low leptin levels are associated with androgenicity in non-obese men and women and that the direction of this association is dependent on gender and body fat distribution. Based on these results we suggest that the relation between testosterone and leptin contributes to the gender difference in circulating leptin levels. International Journal of Obesity (2001) 25, 98-105     

Elevated plasma levels of alpha-melanocyte stimulating hormone (alpha-MSH) are correlated with insulin resistance in obese men

OBJECTIVE: The role of alpha-melanocyte stimulating hormone (MSH) in obesity has been well-documented. However, circulating alpha-MSH concentrations in obese men and their relationship with clinical indicators of obesity and glucose metabolism have not as yet been evaluated. METHODS: We measured the plasma concentrations of alpha-MSH in 15 obese and 15 non-obese male subjects. The relationship of the plasma concentrations of alpha-MSH with body mass index (BMI), body fat mass (measured by bioelectric impedance), body fat distribution (measured by computed tomography), insulin levels, insulin resistance (assessed by the glucose infusion rate (GIR) during an euglycemic hyperinsulinemic clamp study) and with the serum concentrations of leptin and TNF-alpha were also evaluated. RESULTS: In obese men, the plasma alpha-MSH concentrations were significantly increased compared with those in non-obese men (P< 0.02). The plasma levels of alpha-MSH were positively correlated with BMI (r= 0.560, P< 0.05), fasting insulin levels (r=0.528, P< 0.05) and with visceral fat area (r=0.716, P<0.01), but negatively correlated with GIR (r= -0.625, P< 0.02) in obese male subjects. There were significant correlations between plasma concentrations of alpha-MSH and visceral fat area (r=0.631, P< 0.02), and GIR (r = -0.549, P< 0.05) in non-obese male subjects. Circulating concentrations of alpha-MSH were not significantly correlated with the serum concentrations of leptin and TNF-alpha in both obese and non-obese men. CONCLUSION: Circulating concentrations of alpha-MSH are significantly increased and correlated with insulin resistance in obese men.     

Mechanisms behind gender differences in circulating leptin levels

OBJECTIVES: To investigate gender differences in circulating leptin levels and adipose tissue production of leptin. DESIGN SETTING AND SUBJECTS: Thirty-two men and 63 women with a large interindividual variation in body mass index (BMI), but otherwise healthy, were investigated after an overnight fast. Body fat (bioimpedance), abdominal subcutaneous adipose tissue secretion of leptin in vitro and serum leptin were determined. RESULTS: Although there was no gender difference in mean BMI or fat cell size, mean percentage body fat was 49 in women and 36 in men (P < 0.001). At each level of BMI, serum leptin levels were about two times higher in women than in men (P < 0.001). Adipose tissue secretion rate of leptin in men was two-thirds of that in women (P < 0.05). The gender differences in body fat content, serum leptin and leptin secretion were observed in obese (BMI > 27 kg m-2) as well as non-obese subjects. Serum leptin levels (P < 0.001) and leptin secretion rate (P < 0.01) correlated positively with body fat content in either sex. However, the gender differences in serum leptin (P < 0.001) and leptin secretion rate (P < 0.01) remained statistically significantly different even when the values were adjusted for body fat. CONCLUSION: The gender difference in circulating leptin concentrations can be due to at least two different mechanisms. A higher proportion of adipose tissue and increased production rate of leptin per unit mass of adipose tissue might explain why women have higher circulating leptin levels than men.     

Obesity is associated with decreasing levels of the circulating soluble leptin receptor in humans

OBJECTIVE: Leptin plays a major role in the regulation of body weight. It circulates in both free and bound form. One of the leptin receptor isoforms exists in a circulating soluble form that can bind leptin. In the present study, we measured the soluble leptin receptor (SLR) levels in lean and obese humans. We investigated the relationship between plasma SLR levels, plasma leptin levels and the degree of obesity. We also examined whether SLR concentrations could be modulated by fat mass loss induced by a 3 month weight-reducing diet. SUBJECTS: A total of 112 obese (age 18-50 y; body mass index (BMI) 30-44 kg/m2; 23 men and 89 women), 38 overweight (age 19-48 y; BMI 25-29 kg/m2; 10 men and 28 women) and 63 lean (age 18-50 y; BMI 17-24 kg/m2; 16 men and 47 women) humans. MEASUREMENTS: A direct double monoclonal sandwich enzyme-linked immunosorbent assay (ELISA) was used for the quantitative measurement of the soluble human leptin receptor. Leptin was measured by radioimmunoassay (RIA). Body composition was assessed by biphotonic absorptiometry DEXA (dual energy X-ray absorptiometry). RESULTS: We observed that the SLR is present in human plasma (range 10-100 ng/ml). SLR levels were lower in obese and overweight than lean subjects (28.7+/-8.8, 40.2+/-14.9, 51.2+/-12.5 ng/ml, respectively) and were inversely correlated to leptin and percentage of body fat (r=-0.74 and r=-0.76; respectively; P<0.0001). The ratio of circulating leptin to SLR was strongly related to the percentage of body fat (r=0.91; P<0.0001). Interestingly a gender difference was observed in SLR levels, which were higher in obese and overweight men than in obese and overweight women. In obese subjects after a 3 month low-calorie diet, SLR levels increased in proportion to the decrease in fat mass. In the gel filtration profile, SLR coeluted exactly with the bound leptin fractions. CONCLUSION: Obesity, in humans is associated with decreasing levels of the circulating soluble leptin receptor (SLR). The relationship of SLR with the degree of adiposity suggests that high SLR levels may enhance leptin action in lean subjects more than in obese subjects.     

Plasma levels of agouti-related protein are increased in obese men

To investigate the relationship between peripheral blood levels of agouti-related protein (AGRP) and various parameters of obesity, we measured the plasma level of AGRP in 15 obese and 15 nonobese men and evaluated its relationship with body mass index (BMI), body fat weight, and visceral, sc, and total fat areas measured by computed tomography, fasting insulin levels, glucose infusion rate during an euglycemic hyperinsulinemic clamp study, serum leptin, and plasma alpha-MSH. Obese men had significantly higher plasma concentrations of AGRP than nonobese men (P < 0.01). Univariate analysis showed that the plasma levels of AGRP are proportionally correlated with BMI, body fat weight, and sc fat area in obese men (BMI: r = 0.732, P < 0.01; body fat weight: r = 0.603, P < 0.02; sc fat area: r = 0.668, P < 0.01) and in all men (BMI: r = 0.839, P < 0.0001; body fat weight: r = 0.818, P < 0.0001; sc fat area: r = 0.728, P < 0.0001). In all men, the plasma levels of AGRP were significantly correlated with the visceral fat area (r = 0.478, P < 0.01), total fat area (r = 0.655, P < 0.0001), fasting insulin level (r = 0.488, P < 0.01), glucose infusion rate (r = -0.564, P < 0.01), serum level of leptin (r = 0.661, P < 0.0001), and the plasma level of alpha-MSH (r = 0.556, P < 0.01). In all subjects, multiple regression analysis showed that the plasma levels of AGRP are significantly (F = 15.522, r = 0.801, P < 0.03) correlated with the plasma levels of alpha-MSH, independently from the total fat area. However, the correlation between plasma levels of AGRP and serum levels of leptin was found to be dependent on the total fat area. In brief, these findings showed that the circulating levels of AGRP are increased in obese men and that they are correlated with various parameters of obesity. Although correlation does not prove causation, the results of this study suggest that peripheral AGRP may play a role in the pathogenesis of obesity.     

Circulating IGF binding protein-1 is inversely associated with leptin in non-obese men and obese postmenopausal women

OBJECTIVE: Hyperleptinaemia and hyperinsulinaemia interrelate to insulin-like growth factor binding protein 1 (IGFBP-1), and disturbances in the growth hormone-IGF-I axis are linked to obesity and cardiovascular diseases. However, whether the association between leptin and the GH-IGF-I axis is altered with increasing obesity is not known. We therefore examined the relationship between leptin, IGF-I, IGFBP-1, insulin and proinsulin in men and women with or without obesity in a population study. DESIGN AND SUBJECTS: Healthy subjects (n=158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cross-sectional design. METHODS: Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Radioimmunoassays were used for the analyses of leptin, IGF-I and IGFBP-1, and ELISAs for specific insulin and proinsulin. RESULTS: Leptin inversely correlated to IGFBP-1 in non-obese men (P<0.05) and obese postmenopausal women (P<0.05). In contrast, leptin did not correlate to IGF-I. IGFBP-1 was also significantly associated with proinsulin in non-obese men (P<0.01) and non-obese premenopausal women (P<0.05). The association between leptin and IGFBP-1 was lost after adjustment for insulin. In multivariate analyses taking measures of adiposity into account, low proinsulin, and IGF-I in combination with old age, but not leptin, predicted high IGFBP-1 levels. CONCLUSIONS: Leptin was inversely associated with IGFBP-1 in non-obese men and obese postmenopausal women, and proinsulin was inversely associated with IGFBP-1 in non-obese men and premenopausal women. However, these associations were lost with increasing central obesity in men and premenopausal women and after control for insulin. Therefore, this study suggests (i) that leptin is of minor importance for regulation of IGFBP-1 levels and (ii) that the insulin resistance syndrome is characterised by an altered relationship between leptin, IGFBP-1 and insulin.     

Relationship of adiponectin to body fat distribution,insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex

AIMS/HYPOTHESIS: Increased intra-abdominal fat is associated with insulin resistance and an atherogenic lipoprotein profile. Circulating concentrations of adiponectin, an adipocyte-derived protein, are decreased with insulin resistance. We investigated the relationships between adiponectin and leptin, body fat distribution, insulin sensitivity and lipoproteins. METHODS: We measured plasma adiponectin, leptin and lipid concentrations, intra-abdominal and subcutaneous fat areas by CT scan, and insulin sensitivity index (S(I)) in 182 subjects (76 M/106F). RESULTS: Adiponectin concentrations were higher in women than in men (7.4+/-2.9 vs 5.4+/-2.3 micro g/ml, p<0.0001) as were leptin concentrations (19.1+/-13.7 vs 6.9+/-5.1 ng/ml, p<0.0001). Women were more insulin sensitive (S(I): 6.8+/-3.9 vs 5.9+/-4.4 x 10(-5) min(-1)/(pmol/l), p<0.01) and had more subcutaneous (240+/-133 vs 187+/-90 cm(2), p<0.01), but less intra-abdominal fat (82+/-57 vs 124+/-68 cm(2), p<0.0001). By simple regression, adiponectin was positively correlated with age ( r=0.227, p<0.01) and S(I) ( r=0.375, p<0.0001), and negatively correlated with BMI ( r=-0.333, p<0.0001), subcutaneous ( r=-0.168, p<0.05) and intra-abdominal fat ( r=-0.35, p<0.0001). Adiponectin was negatively correlated with triglycerides ( r=-0.281, p<0.001) and positively correlated with HDL cholesterol ( r=0.605, p<0.0001) and Rf, a measure of LDL particle buoyancy ( r=0.474, p<0.0001). By multiple regression analysis, adiponectin was related to age ( p<0.0001), sex ( p<0.005) and intra-abdominal fat ( p<0.01). S(I) was related to intra-abdominal fat ( p<0.0001) and adiponectin ( p<0.0005). Both intra-abdominal fat and adiponectin contributed independently to triglycerides, HDL cholesterol and Rf. CONCLUSION/INTERPRETATION: These data suggest that adiponectin concentrations are determined by intra-abdominal fat mass, with additional independent effects of age and sex. Adiponectin could link intra-abdominal fat with insulin resistance and an atherogenic lipoprotein profile.     

Interactions between sex steroid hormones and leptin in women. Studies in vivo and in vitro

OBJECTIVE: To investigate the associations between sex hormones and leptin. In addition, to investigate the direct effect of sex hormones by incubations of human subcutaneous adipose tissue explants, in vitro. DESIGN: Cross-sectional study and an experimental in vitro study. SUBJECTS: 36 women (age, 23-65 y; body mass index, BMI, 19-65 kg/m2) participated in the cross-sectional study. Subcutaneous abdominal biopsies were taken from nine women (age, 28 - 46 y; BMI, 25.5-36.0 kg/m2) for the in vitro study. MEASUREMENTS: Fat distribution parameters (by dual-energy X-ray absorptiometry and anthropometry), sex hormones, leptin and insulin. RESULTS: Leptin correlated significantly with most estimates of adipose tissue mass (r= 0.5 - 0.9, P< 0.05). However, when the study group was divided in three equal groups (non-obese, obese, and very-obese) it revealed that the correlation predominantly was found in non-obese. In simple correlation analysis leptin was significantly associated with estimates of adipose tissue, insulin and several sex hormones. However, in multiple regression analysis only insulin (partial correlation coefficient = 0.55, P < 0.004) and percentage fat mass (partial correlation coefficient = 0.72, P<0.001) were significantly and independently correlated with leptin without any independent effect of sex hormones. These findings were in agreement with the in vitro studies where neither estrogen nor androgens (testosterone or DHT) affected subcutaneous adipose tissue leptin production. Dexamethasone (10nM) stimulated adipose tissue leptin production 3-fold (P < 0.001). CONCLUSION: In regression analysis, where both insulin and measurements of fat mass were taken into account, androgens or estrogens did not independently contribute to the variation in leptin levels. Estrogens and androgens had no direct effects on adipose tissue leptin production in vitro. Thus, the sexual dimorphism evident in serum leptin is not likely to be due to a direct influence of sex hormones on leptin production in females.