Camastra S, Manco M, Frascerra S, Iaconelli A, Mingrone G, Ferrannini E
Department of Internal Medicine and Metabolism Unit of the C.N.R. Institute of Clinical Physiology at the University of Pisa, Via Savi 8, Pisa, Italy.
Int J Obes (Lond). 2009 Jan;33(1):166-72. doi: 10.1038/ijo.2008.226. Epub 2008 Dec 9.
Moderate obesity is known to be associated with multiple endocrine abnormalities. Less information is available on the hormonal status of patients with morbid obesity and on the effects of major weight loss. We studied 16 severely obese (BMI 40.6-69.9 kg/m(2)) nondiabetic patients and 7 nonobese (BMI range 24.6-27.7 kg/m(2)), sex- and age-matched healthy volunteers. During 24 h in a metabolic ward, four meals were administered and hourly blood samples were drawn from a central venous catheter for the measurement of glucose, insulin, leptin, thyrotropic hormone (TSH), growth hormone (GH) and prolactin. Insulin sensitivity was measured by a euglycaemic hyperinsulinaemic clamp. Studies were repeated 6 months after biliopancreatic diversion, a mainly malabsorptive surgical approach, which caused an average weight loss of 35+/-4 kg (or 26+/-2% of initial weight). Compared with controls, patients were hyperinsulinaemic (290+/-31 vs 88+/-4 pmol l(-1), P=0.0002), insulin resistant (23.5+/-2.8 vs 52.9+/-4.9 micromol min(-1) kg(FFM)(-1), P=0.0006) and hyperleptinaemic (52.5+/-5.8 vs 10.9+/-3 ng ml(-1), P=0.0002). Plasma TSH levels were increased throughout the day-night cycle (averaging 2.02+/-0.18 vs 1.09+/-0.19 muU ml(-1) of controls, P=0.01), whereas serum GH levels were suppressed (0.46+/-0.10 vs 3.01+/-1.15, P=0.002). Following surgery, the hyperinsulinaemia and insulin resistance were fully normalized; in concomitance with a major drop in leptin levels (to 14.4+/-2.7 ng ml(-1), P=0.02), TSH decreased and GH increased to near-normal levels. In the whole dataset, mean 24-h leptin levels were directly related to mean 24-h TSH levels after controlling for confounders this relationship was lost only after adjusting for fat mass. We conclude that in morbid obesity leptin is a determinant of changes in pituitary function.
已知中度肥胖与多种内分泌异常有关。关于病态肥胖患者的激素状态以及大幅体重减轻的影响,目前可用信息较少。我们研究了16名严重肥胖(BMI 40.6 - 69.9 kg/m²)的非糖尿病患者以及7名非肥胖(BMI范围24.6 - 27.7 kg/m²)、性别和年龄匹配的健康志愿者。在代谢病房的24小时内,给予四餐,并通过中心静脉导管每小时采集血样,用于测量葡萄糖、胰岛素、瘦素、促甲状腺激素(TSH)、生长激素(GH)和催乳素。通过正常血糖高胰岛素钳夹技术测量胰岛素敏感性。在采用主要通过吸收不良起作用的胆胰转流手术6个月后重复进行研究,该手术导致平均体重减轻35±4 kg(或初始体重的26±2%)。与对照组相比,患者存在高胰岛素血症(290±31对88±4 pmol l⁻¹,P = 0.0002)、胰岛素抵抗(23.5±2.8对52.9±4.9 μmol min⁻¹ kg(FFM)⁻¹,P = 0.0006)和高瘦素血症(52.5±5.8对10.9±3 ng ml⁻¹,P = 0.0002)。血浆TSH水平在昼夜周期中均升高(平均2.02±0.18对对照组的1.09±0.19 μU ml⁻¹,P = 0.01),而血清GH水平受到抑制(0.46±0.10对3.01±1.15,P = 0.002)。手术后,高胰岛素血症和胰岛素抵抗完全恢复正常;随着瘦素水平大幅下降(至14.4±2.7 ng ml⁻¹,P = 0.02),TSH降低,GH升高至接近正常水平。在整个数据集中,在控制混杂因素后,24小时平均瘦素水平与24小时平均TSH水平直接相关——仅在调整脂肪量后这种关系消失。我们得出结论,在病态肥胖中,瘦素是垂体功能变化的一个决定因素。