血清瘦素水平与胰岛素原、真胰岛素及胰岛素敏感性的关系

目的　研究中国人群空腹瘦素水平与真胰岛素 (TI)、胰岛素原 (PI)、PI/TI比值及胰岛素敏感性之间的关系。方法　 90 2例非糖尿病者均系 2 0 0 0年接受糖尿病流行病学调查者。测定空腹瘦素、TI和PI浓度以及空腹及餐后 2h血糖。瘦素、TI及PI检测采用本室建立的特异的酶联免疫分析法 (ELISA)。胰岛素敏感性以HOMA胰岛素抵抗指数 (HOMA IR)评价。结果　血清瘦素水平女性高于男性。相关分析显示血清瘦素水平与空腹TI、PI及HOMA IR显著正相关 (男性 792例 ,r分别为0 345、0 2 36和 0 364 ;女性 1 1 0例 ,r分别为 0 574、0 375和 0 576 ,P <0 0 0 1 ) ,但与空腹血糖仅在男性呈弱相关 (r=0 1 5 ,P =0 0 1 5) ,与空腹PI/TI比值不相关。在调整年龄、体重指数 (BMI)和腰臀围比(WHR)后 ,尽管相关性减弱 ,瘦素水平仍然与TI、PI以及HOMA IR显著相关。结论　本组的血清瘦素浓度与TI、PI以及胰岛素抵抗显著正相关 ,且在一定程度上独立于肥胖和脂肪分布。瘦素水平高或瘦素抵抗的个体可能存在高胰岛素血症和胰岛素抵抗 ,提示其瘦素 胰岛素轴的调节异常。本研究未发现瘦素水平与空腹PI/TI比值的相关 ,提示瘦素可能与这一反映胰岛 β细胞的功能异常的标志无关。本研究揭示的高瘦素 高胰岛素血症或胰岛素抵抗之间的     

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.     

原发性高血压血清瘦素水平变化

将76例原发性高血压患者按有无糖代谢异常及肥胖分为单纯高血压组、高血压 糖代谢异常组及高血压 肥胖组;健康体检者68例按体质量指数(BMI)分为正常对照组、单纯肥胖组.检测各组血清瘦素、空腹胰岛素(FINS)、空腹血糖(FBG)及餐后血糖(PBG)、总胆固醇、甘油三酯水平.发现高血压各亚组血清瘦素水平均高于正常对照组;直线相关分析显示,瘦素分别与BMI、SBP、DBP、FINS呈正相关;多元逐步回归分析示,瘦素与性别、FBG、FINS、SBP、BMI、WHR相关.认为原发性高血压患者血清瘦素水平明显高于正常人群,血清瘦素水平增高与高血压、胰岛素抵抗关系密切.     

体脂含量与分布对胰岛素抵抗影响的相关研究

目的 研究不同体脂含量与分布对胰岛素抵抗(IR)的影响。方法 874例受试者根据体重指数(BMl)和腰臀比值(WHR)分成4组：1组(腹旗型肥胖)：BMI≥25且WHR≥0．9；2组(外周型肥胖)：BMI≥25且WHR＜0．9；3组(正常体重代谢性肥胖)：BMI＜25且WHR≥0．9；4组(正常对照)：BMI＜25且WHR＜0．9。观察指标包括血压、空腹血糖、餐后2小时血糖、血浆甘油三酯、总胆固醇、空腹胰岛素、餐后2小时胰岛素和尿微量白蛋白排泄率，并计算胰岛素抵抗指数(HOMA-IR)。结果(1）HOMA-IR与以上多变量显著正相关，其中WHR和BMI是互相独立的两个IR危险因素，且WHR对IR的影响程度超过BMI；(2)HOMA-IR在4个组之间差异显著，从高到低依次为排列1组、3组、2组、4组。(3)决定HOMA-IR的主要变量是甘油三酯、BMI。(4)正常体重代谢性肥胖与肥胖组间比较，以上各指标比较差异均无显著性。结论 无论是脂肪组织增加或脂肪组织的中心型分布，都可引起胰岛素抵抗，其中以脂肪中心型分布的作用更加显著。     

不同糖耐量状态的原发性高血压患者血清抵抗素水平

目的　了解不同糖耐量状态原发性高血压患者血清抵抗素浓度 ,探讨肥胖与糖尿病(DM)的关系。方法　酶免疫测定法检测 71例原发性高血压患者〔2型DM 18例 ,糖耐量低减 (IGT)2 6例 ,正常糖耐量 (NGT) 2 7例 ;男 33例 ,女 38例〕的空腹血清抵抗素水平 ,口服葡萄糖耐量试验和胰岛素释放试验 ,测定血浆葡萄糖浓度和血清胰岛素浓度 ,计算葡萄糖曲线下面积 (AUCG) ,根据Cederholm公式计算胰岛素敏感指数 (ISI) ;测量收缩压 (SBP)、舒张压 (DBP)、身高、体重、腰围、臀围 ,计算体重指数 (BMI)、体内脂肪百分比 (BF % )及腰围 /臀围比 (WHR)。结果　空腹血清抵抗素浓度(μg/L) :DM组 (2 9.8± 12 .1)显著高于NGT组 (2 2 .0± 8.4 ) (P <0 .0 5 ) ,略高于IGT组 (2 5 .1± 10 .4 )(P >0 .0 5 )。空腹血清抵抗素浓度与AUCG(r =0 .38,P <0 .0 0 1)及BF % (r=0 .35 ,P <0 .0 1)呈显著正相关 ,与ISI呈显著负相关 (r =- 0 .2 4 ,P <0 .0 5 ) ,与SBP、DBP、BMI及WHR无相关。结论　 2型DM患者空腹血清抵抗素水平升高 ,血清抵抗素浓度与血糖浓度及BF %的相关性提示人体抵抗素可能是肥胖与糖尿病连系所在     

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。     

瘦素:胰岛素抵抗的独立危险因素?

目的　探讨江苏南京地区人群中体重指数、腰臀比、腹围这 3种人体测量值以及脂代谢指标、糖代谢指标与瘦素的相关性。方法　将 188名南京地区长期居住汉族成人按BMI及糖尿病诊断标准分为正常组、肥胖组和糖尿病组 ,均检测身高、体重、腰围、腹围、臀围 ,并测定空腹血清胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、载脂蛋白A、载脂蛋白B和空腹血糖 (FPG)、真胰岛素 (TI)、免疫反应性胰岛素 (IRI)和瘦素 ,以ISI1=1/ (FPG×TI)和ISI2 =1/ (FPG×IRI)作为胰岛素敏感指数 ,对瘦素与 3种人体测量值和脂代谢指标及胰岛素抵抗的相关性进行分析。结果　对空腹血浆瘦素水平起决定作用的是性别的差异 (女性为男性的 4倍 ) ;其次是体重指数 (r =0 .5 7,P<0 .0 0 1) ;真胰岛素与瘦素呈现显著正相关 (r =0 .32 ,P <0 .0 0 1) ,ISI1与瘦素呈现显著负相关 (r =- 0 .39,P <0 .0 0 1) ,未发现血脂指标与瘦素有任何相关性。结论　南京地区人群中 ,空腹瘦素水平是由性别、肥胖程度 (主要是体重指数 )决定的 ,同时与胰岛素抵抗密切相关     

不同糖耐量个体血清瘦素水平与特异胰岛素、胰岛素原及胰岛素敏感性的关系探讨

目的　研究不同糖耐量人群空腹瘦素水平与特异胰岛素、胰岛素原及胰岛素敏感性之间的关系。方法　用放射免疫法测量 5 4例正常糖耐量 (NGT)、33例糖耐量低减 (IGT)、4 7例新发 2型糖尿病 (DM )的空腹瘦素水平、口服葡萄糖耐量试验 (OGTT) 0、1/2、1、2h的特异胰岛素 (SI)和胰岛素原 (PI)。结果　 (1)多元逐步回归分析显示 ,性别、体重指数 (BMI)、胰岛素敏感性指数是影响空腹瘦素水平最重要的因素 (校正的R2 分别为 0 .2 5 1、0 .4 19、0 .4 38,P值分别为 <0 .0 0 1、<0 .0 0 1、<0 .0 5 ) ;空腹血清瘦素水平与OGTT各时间点PI、SI、PI/SI值无相关性。 (2 )在校正性别、BMI等影响因素后 ,空腹血清瘦素水平在不同糖耐量组差异无显著性 ;DM组OGTT各时间点PI/SI值明显高于IGT组和NGT组 (P <0 .0 1) ;胰岛素敏感性 (ISI)为NGT组 >IGT组 >DM组 (P <0 .0 0 1)。结论　在测定特异胰岛素、胰岛素原时 ,血清瘦素水平除了与性别、BMI相关外 ,尚与胰岛素敏感性 (按SI水平计算 )相关 ;不同糖耐量状态对血清瘦素水平无明显影响 ;DM组存在胰岛素不敏感、PI/SI失调     

原发性高血压伴微量蛋白尿患者胰岛素抵抗性研究

目的 :研究原发性高血压 (EH)并发微量蛋白尿患者的胰岛素抵抗 (IR)状态。方法 :根据尿白蛋白排泄率将EH患者分为两组 :微量蛋白尿阳性组 (4 0例 )和微量蛋白尿阴性组 (35例 ) ,计算体重指数 (BMI)、腰臀比值 (WHR) ,空腹采血测血糖 (FBG)、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和空腹胰岛素(FINR)水平。按HOMA模型计算胰岛素抵抗指数 (HOMA IR) ,HOMA IR =(FBG×FINR) / 2 2 .5 ,再取其自然对数。两组进行比较。结果 :患者年龄、性别比例、高血压病程、血压水平和FBG、血脂水平在两组间差异均无显著性意义 (P >0 .0 5 ) ,但BMI、WHR、FINR和HOMA IR在微量蛋白尿阳性组显著高于阴性组 (P <0 .0 5 )。结论 :EH微量蛋白尿阳性患者存在明显的IR ,高血压肾病的发生与EH患者的胰岛素敏感状态密切相关。BMI、WHR可作为IR的初筛指标     

2型糖尿病Leptin与胰岛素抵抗的关系

目的　研究新诊断非肥胖 2型糖尿病患者血清leptin水平与胰岛素抵抗的相关关系。方法　以空腹血浆胰岛素与血糖乘积的倒数作为胰岛素抵抗程度的指标 ,采用酶联免疫法测定 31名正常人、2 9例新诊断非肥胖 2型糖尿病患者的血清leptin水平。 结果　新诊断非肥胖 2型糖尿病患者 ,血清leptin浓度与胰岛素敏感性指数有显著负相关 (r =-0 .37,P <0 .0 5 ) ,主要表现在男性 (r =-0 .6 6 ,P <0 .0 1)。leptin与空腹血胰岛素 (r =-0 .45 ,P <0 .0 5 )、空腹血糖(r =-0 .37,P <0 .0 5 )有正相关关系。男性患者leptin血清水平比正常男性有显著性升高 (P<0 .0 5 )。结论　新诊断非肥胖 2型糖尿病患者血清leptin水平与胰岛素抵抗程度有显著正相关关系 ,leptin与 2型糖尿病的发病有关     

Relationship between plasma leptin levels and the tumor necrosis factor-alpha system in obese subjects.

OBJECTIVE: To evaluate the relationship between plasma leptin and the tumor necrosis factor-alpha (TNFalpha), TNF receptor p60 (TNF-R1) and TNF receptor p80 (TNF-R2) concentrations in obese subjects. DESIGN: Case-control study. SETTING: Outpatient's Service for Prevention and Treatment of Obesity at the University Hospital. MEASUREMENTS: Body mass index (BMI), waist circumference, hip circumference, waist-to-hip ratio (WHR), fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance (HOMA IR), plasma leptin, TNFalpha, TNF-R1 and TNF-R2 concentrations were evaluated in obese subjects (n = 42) and in age- and gender-matched, lean healthy controls (n = 16). RESULTS: In obese subjects, fasting plasma glucose and insulin, HOMA IR, plasma leptin, TNFalpha, TNF-R1 and TNF-R2 concentrations were significantly higher than in controls. Furthermore, females showed higher leptin, TNF-R1 and TNF-R2 plasma concentrations compared to males, in both control and obese subjects. In control subjects, plasma leptin concentrations showed a direct correlation with BMI (r=0.74, P<0.001), hip circumference (r=0.94, P<0.001), TNF-R1 (r=0.79, P<0.001) and TNF-R2 (r=0.64, P<0.01), and a negative correlation with WHR (r=-0.58, P<0.05). In obese subjects, we found a direct correlation between plasma leptin concentrations and BMI (r=0.67, P<0.001), hip circumference (r=0.66, P<0.001), fasting glucose (r=0.37, P<0.05), fasting insulin (r=0.31, P<0.05), HOMA IR (r=0.38, P<0.05), TNF-R1 (r=0.71, P<0.001) and TNR-R2 (r=0.66, P<0.001), while a negative correlation was found between circulating leptin and WHR (r=-0.44, P<0.01). In multivariate analysis, plasma leptin concentrations were significantly associated with BMI (P=0.015) and gender (P=0.047) in the control group, while in obese subjects, plasma leptin showed a significant association with BMI (P=0.019) and TNF-R1 (P=0.012). CONCLUSIONS: Our results are consistent with the hypothesis that the TNFalpha system could be involved in the regulation of plasma leptin concentrations in obese subjects.     

Microcirculatory damage of common carotid artery wall in obese and non obese subjects

The objective of the present study was to determine whether the intima-media thickness (IMT) is independently related with obesity, and central fat accumulation in healthy subjects. Common carotid artery IMT, parameters of body fat accumulation and distribution (body mass index, waist circumference, waist-to-hip ratio), blood pressure levels, and circulating fasting insulin, glucose, and lipid (cholesterol, HDL-cholesterol, triglycerides, LDL-cholesterol) levels were determined in a population of non-diabetic normal weight and obese subjects. Smoking habits (packs-years) were also taken into account. 239 healthy subjects (143 women and 96 men), with age ranging between 18 and 45 years, were enrolled into the study. They were divided indo two groups according to the body mass index (BMI), obese (132 subjects, 77 woman and 55 men, with BMI greater than 27.0) and controls (107 subjects: 66 women and 41 men, with BMI lower than 27.0). Common carotid artery intima-media thickness was measured by B-mode ultrasound imaging. Fasting plasma metabolic parameters (glucose and lipids) and insulin levels were determined by enzymatic and radioimmunological assays, respectively. Insulin sensitivity was estimated by insulin tolerance test (ITT) and the rate constant for plasma glucose disappearance (KITT) during the 3- to 15-min period following the regular insulin injection was taken as a measure of in vivo insulin action. Obese patients showed higher IMT than controls, and IMT was significantly associated with BMI in the whole population (r = 0.316, p < 0.001). Age (r = 0.327, p < 0.001), KITT (r = -0.201, p < 0.01), fasting blood glucose (r = 0.187, p < 0.01), LDL-chol (r = 0.201, p < 0.01), smoking (r = 0.147, p < 0.05), MBP levels (r = 0.154, p < 0.05), cholesterol (r = 0.152, p < 0.05) and HDL-chol (r = -0.159, p < 0.05) were also significantly associated with IMT. Age (r = 0.330, p < 0.05), BMI (r = 0.299, p < 0.01), waist (r = 0.312, p < 0.001), WHR (r = 0.266, p < 0.001) and KITT (r = -0.259, p < 0.01) were the parameters most strongly correlated with IMT in women, and age (r = 0.324, p < 0.001), BMI (r = 0.338, p < 0.001) waist (r = 0.325, p < 0.001) and LDL-chol (r = 0.283, p < 0.01) where the parameters most strongly correlated with IMT in men. When a stepwise multiple regression analysis was performed for the whole population, only age (p < 0.001) and BMI (p < 0.001) maintained a significant positive relationship with IMT. When a stepwise multiple regression analysis was performed separately for men and women, BMI or waist circumference or WHR were alternatively entered into the model; interestingly, only age, BMI and waist were still significantly correlated with IMT, whereas WHR did not maintain a significant correlation with IMT. In conclusion, BMI and waist circumference, but not WHR, are strongly and independently associated with the IMT of common carotid artery. These results suggests that central fat accumulation may accelerate the development of earlier clinically silent stages of atherosclerosis, thus possibly explaining the higher prevalence of cardiovascular diseases in patients with abdominal obesity.     

A disparity between conventional lipid and insulin resistance markers at body mass index levels greater than 34 kg/m(2).

OBJECTIVE: The aim of this study was to examine changes in lipid profile and markers of insulin resistance with increasing body mass index (BMI) in the range 34-77 kg/m(2). In addition we compare the lipid profiles of severely obese patients with those of the Australian community. SUBJECTS AND METHODS: A total of 572 patients (85% F, 15% M) were assessed prior to gastric restrictive surgery. Conventional lipid profiles and markers of insulin resistance were measured. Lipids were compared with the Australian National Heart Foundation 1989 study (control group). RESULT: There was no difference in mean total cholesterol levels between the obese group (5.52 mmol/l) and the control group (5.47 mmol/l). The mean total cholesterol levels in the obese group fell with increasing BMI (r=-0.13, P<0.01). Obese subjects had elevated fasting triglyceride levels 1.96 mmol/l (control group, 1.12 mmol/l, P<0.001), but levels did not change with increasing BMI (r=0.0, NS). HDL-C levels were lower, 1.21 mmol/l (control group 1.44 mmol/l, P<0.001), and decreased with increasing BMI (r=-0.20, P<0.01). LDL-C levels were lower in obese men (3.65 mmol/l vs control group 4.17 mmol/l, P<0.01) but not women and levels fell with increasing BMI (r=-0.15, P<0.05). For the obese group, markers of insulin resistance (fasting plasma glucose, HbA1c, fasting plasma insulin and C-peptide) all rose significantly with increasing BMI. CONCLUSION: Raised total cholesterol is not a co-morbidity of severe obesity. There is a disparity between the conventional lipid measures and insulin resistance measures of the metabolic syndrome with increasing BMI. Conventional lipid measures may be poor indicators of dyslipidaemic risk in the severely obese.     

Oxidative stress is associated with adiposity and insulin resistance in men

To investigate the direct relationship of oxidative stress with obesity and insulin resistance in men, we measured the plasma levels of 8-epi-prostaglandin F2alpha (PGF2alpha) in 14 obese and 17 nonobese men and evaluated their relationship with body mass index; body fat weight; visceral, sc, and total fat areas, measured by computed tomography; and glucose infusion rate during a euglycemic hyperinsulinemic clamp study. Obese men had significantly higher plasma concentrations of 8-epi-PGF2alpha than nonobese men (P < 0.05). The plasma levels of 8-epi-PGF2alpha were significantly correlated with body mass index (r = 0.408; P < 0.05), body fat weight (r = 0.467; P < 0.05), visceral (r = 0.387; P < 0.05) and total fat area (r = 0.359; P < 0.05) in all (obese and nonobese) men. There was also a significant correlation between the plasma levels of 8-epi-PGF2alpha and glucose infusion rate in obese men (r = -0.552; P < 0.05) and all men (r = -0.668; P < 0.01). In all subjects, the plasma levels of 8-epi-PGF2alpha were significantly correlated with fasting serum levels of insulin (r = 0.487; P < 0.01). In brief, these findings showed that the circulating levels of 8-epi-PGF2alpha are related to adiposity and insulin resistance in men. Although correlation does not prove causation, the results of this study suggest that obesity is an important factor for enhanced oxidative stress and that this oxidative stress triggers the development of insulin resistance in men.     

Relationships of obesity indices to serum insulin and lipoproteins in relatives of black patients with noninsulin-dependent diabetes mellitus (NIDDM)

We have examined the relationships between obesity indices and various metabolic parameters in seven obese (body mass index (BMI) mean +/- s.e.m. 42 +/- 2.5 kg/m2), ten nonobese (BMI 25.3 +/- 1.2 kg/m2) nondiabetic female relatives of black patients with NIDDM and eight healthy controls (BMI 24.5 +/- 1.1 kg/m2). Despite the greater BMI in the obese relatives, percent body fat was not different from that of the nonobese relatives (38 +/- 2 vs 34 +/- 3 percent). Both values were, however, significantly (P less than 0.05) greater than that of the healthy controls (25 +/- 3 percent). Mean waist-to-hip circumference ratio (WHR) was greatest in obese relatives (0.89 +/- 0.01), intermediate in nonobese relatives (0.83 +/- 0.01) and least in the healthy controls (0.77 +/- 0.04). Mean sum of skinfold thickness from biceps, triceps and subscapular (SS) region was also greatest in obese relatives, intermediate in nonobese relatives and least in controls. Centrality index was not, however, different among the groups. Mean fasting serum glucose levels were slightly higher but not significantly different in the relatives compared to controls (obese 82 +/- 3; nonobese 81 +/- 4; controls 75 +/- 3 mg/dl). Following oral glucose ingestion, serum glucose rose to significantly (P less than 0.05) greater levels at 30, 60 and 90 min in the relative subgroups vs controls. Mean fasting and post-prandial peak serum insulin concentrations were significantly (P less than 0.05-0.01) greater in both relative subgroups vs controls. While mean serum glucose profiles and glucose disappearance decay (KG) following intravenous glucose load were identical in the relatives and controls, serum insulin responses were significantly greater in the relatives. The mean basal and post-stimulation serum C-peptide concentrations were similar in all the three groups, irrespective of the stimulus; thus suggesting a reduced hepatic insulin extraction in the relatives. Fasting serum cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) as well as FFA levels were not different between the relatives and controls despite the hyperinsulinemia in the former group. WHR correlated with basal insulin in the relatives (r = 0.416, P less than 0.05) and controls (r = 0.68, P less than 0.01) but not with stimulated insulin, lipids and lipoproteins in any of the groups. In contrast, both percent BFM and SS thickness correlated significantly (P less than 0.001) with post-glucose insulin concentrations in the relatives only.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

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。     

Insulin dose response analysis of free fatty acid kinetics

Insulin regulation of free fatty acid (FFA) release is an important aspect of metabolic function; however, FFA release is exquisitely sensitive to insulin, which complicates the design and analysis of dose response experiments. We measured FFA ([(3)H]palmitate) and glucose ([(3)H]glucose) kinetics in 7 nonobese men, 7 nonobese women, 7 obese men, and 7 obese women by using a two-step insulin clamp (0.25 and 2.5 mU/kg fat-free mass per minute). Obese men and women were characterized as having a BMI of 28 or greater and body fat of 28% and 40% or greater for men and for women, respectively. Nonobese men and women had 22% and 35% or less body fat, respectively. All volunteers were Caucasian. Glucose disposal increased in a linear fashion with plasma insulin concentrations. The nonlinear suppression of plasma palmitate flux and concentrations could be linearized by logarithmically transforming both the insulin concentration and palmitate axes, except in nonobese men. We repeated the studies in 7 nonobese and 7 obese men, using 1.0 mU/kg fat-free mass per minute as the second insulin dose, which linearized the log-transformed lipolysis measures. The indices of insulin regulation of lipolysis predicted using 2 points (basal and second insulin dose) vs 3 points (basal, low, and high dose) were not different provided the proper second dose was selected. The EC(50) for insulin suppression of lipolysis correlated linearly with plasma triglycerides (r = 0.52, P < .001) and exponentially with insulin sensitivity(glucose) (r = 0.70, P < .001). We conclude that log transformation of insulin dose response data for FFA permits straightforward data analysis and simplifies the estimation of metabolically relevant parameters.     

多囊卵巢综合征患者血清Ghrelin水平测定及其意义

目的探讨血清生长素(Ghrelin)与多囊卵巢综合征(PCOS)的关系。方法选择PCOS患者35例(P-COS组)及正常体检者33例(对照组),两组服75 g葡萄糖粉后,分别检测空腹与服糖1、2 h血脂,基础血激素(雌激素、孕激素、卵泡刺激素、黄体生成素、泌乳素、睾酮、雄烯二酮)及Ghrelin水平,计算BMI、腰臀比(WHR)、胰岛素抵抗指数及敏感指数。结果 PCOS组BMI、TG、HDL、胰岛素抵抗指数、空腹胰岛素、Ghrelin、睾酮及雄烯二酮在空腹与服糖1、2 h均低于对照组(P<0.05或<0.01)。相关分析显示,血清Ghrelin与BMI、WHR、雄激素、雄烯二酮、空腹血糖呈负相关(r分别为-0.504、-0.336、-0.440、-0.432、-0.414,P均<0.05),与HDL呈正相关(r=0.357,P<0.05)。结论血清Ghrelin可能在PCOS的病理生理过程中发挥作用。     

Metabolic correlates of eating behavior in severe obesity.

BACKGROUND: The benefit of spreading energy intake over many small meals ('nibbling') rather than few large ones ('gorging') for control of blood glucose, serum lipids and body fat accretion has been known for 60 y, but the mechanisms are poorly understood. Men exhibit more of a gorging eating pattern than women and are also more prone to the metabolic complications of obesity, as are women with a 'male', central distribution of adipose tissue. We have shown correlations between central fat distribution, and other components of the metabolic 'Syndrome X' and fatty infiltration of the liver. Here we study relationships between eating rate and fat distribution and test the hypothesis that gorging might be associated with fatty liver. SUBJECTS AND METHODS: In 30 non-alcoholic, non-diabetic, severely obese women (body mass index, BMI=47+/-1 kg/m(2); mean+/-s.e.m.) with a mean age of 36+/-1 y and 16 men (BMI: 52+/-3) age 38+/-2 y, who were candidates for anti-obesity surgery, we measured eating rate using an eating monitor, and fat distribution by the waist-hip circumference ratio (WHR). In addition in the 17 women and 11 men who had surgery, serum lipids were analyzed and routine liver biopsies were evaluated for steatosis by a pathologist blinded to the conditions of the study. RESULTS: Men ate significantly faster than women (188+/-28 vs 123+/-9 g/min; P<0.01), and had more liver fat (score: 2.7+/-03 vs 1.5+/-0.3; P<0.01), with no statistically significant sex differences in s-cholesterol or s-triglycerides. Eating rate correlated with WHR (r=0.46; P<0.01, n=46), liver fat (r=0.55; P<0.01), and s-triglycerides (r=0.42; P<0.05) adjusting for sex. Liver fat correlated with WHR (r=0.50; P<0.05), s-triglycerides (r=0.70; P<0.01) and s-cholesterol (r=0.50; P<0.05), while there were no significant correlations with BMI or body weight. In multivariate analysis eating rate (32%), meal size (8%) and WHR (6%) contributed 46% of the variance in liver fat. CONCLUSION: We showed increased eating rates in severely obese men and women with central fat distribution. Furthermore, increased eating rates were associated with fatty liver and elevated serum lipids. Eating rate in severely obese women and men may be a determinant of the metabolic syndrome.