Creutzberg E C, Wouters E F, Vanderhoven-Augustin I M, Dentener M A, Schols A M
Department of Pulmonology, Heart and Lung Function Laboratory, University Hospital Maastricht, Maastricht, The Netherlands.
Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 1):1239-45. doi: 10.1164/ajrccm.162.4.9912016.
Previously we reported an impaired energy balance in patients with chronic obstructive pulmonary disease (COPD) during an acute disease exacerbation, but limited data are available on the underlying mechanisms. Experimental and clinical research supports the hypothesis of involvement of the hormone leptin in body weight and energy balance homeostasis. The aim of this study was to investigate the course of the energy balance in relation to leptin and the soluble tumor necrosis factor (TNF) receptors (sTNF-R) 55 and 75, plasma glucose, and serum insulin in patients with severe COPD during the first 7 d of hospitalization for an acute exacerbation (n = 17, 11 men, age mean [SD] 66 [10] yr, FEV(1) 36 [12] %pred). For reference values of the laboratory parameters, blood was collected from 23 (16 men) healthy, elderly subjects. On admission, the dietary intake/resting energy expenditure (REE) ratio was severely depressed (1.28 [0.57]), but gradually restored until Day 7 (1.65 [0. 45], p = 0.005 versus Day 1). Glucose and insulin concentrations were elevated on admission, but on Day 7 only plasma glucose was decreased. The sTNF-Rs were not different from healthy subjects and did not change. Plasma leptin, adjusted for fat mass expressed as percentage of body weight (%FM), was elevated on Day 1 compared with healthy subjects (1.82 [3.85] versus 0.32 [0.72] ng%/ml, p = 0.008), but decreased significantly until Day 7 (1.46 [3.77] ng%/ml, p = 0. 015 versus Day 1). On Day 7, sTNF-R55 was, independently of %FM, correlated with the natural logarithm (LN) of leptin (r = 0.65, p = 0.041) and with plasma glucose (r = 0.81, p = 0.015). In addition, the dietary intake/REE ratio was not only inversely related with LN leptin (-0.74, p = 0.037), but also with sTNF-R55 (r = -0.93, p = 0. 001) on day seven. In conclusion, temporary disturbances in the energy balance were seen during an acute exacerbation of COPD, related to increased leptin concentrations as well as to the systemic inflammatory response. Evidence was found that the elevated leptin concentrations were in turn under control of the systemic inflammatory response, and, presumably, the high-dose systemic glucocorticosteroid treatment.
此前我们报道过，慢性阻塞性肺疾病（COPD）患者在急性疾病加重期能量平衡受损，但关于其潜在机制的数据有限。实验和临床研究支持激素瘦素参与体重和能量平衡稳态的假说。本研究的目的是调查重度COPD患者在急性加重期住院的前7天内，与瘦素、可溶性肿瘤坏死因子（TNF）受体55和75、血浆葡萄糖及血清胰岛素相关的能量平衡变化过程（n = 17，男性11例，年龄平均[标准差]66[10]岁，第1秒用力呼气容积（FEV₁）为预计值的36[12]%）。为获取实验室参数的参考值，采集了23例（16例男性）健康老年受试者的血液。入院时，饮食摄入量/静息能量消耗（REE）比值严重降低（1.28[0.57]），但逐渐恢复，至第7天达到1.65[0.45]，与第1天相比，p = 0.005。入院时葡萄糖和胰岛素浓度升高，但至第7天仅血浆葡萄糖降低。可溶性TNF受体与健康受试者无差异且未发生变化。以体重百分比表示的体脂校正后的血浆瘦素水平在第1天高于健康受试者（1.82[3.85]对0.32[0.72]ng%/ml，p = 0.008），但至第7天显著降低（1.46[3.77]ng%/ml，与第1天相比，p = 0.015）。在第7天，可溶性TNF受体55独立于体脂百分比，与瘦素的自然对数（LN）相关（r = 0.65，p = 0.041），也与血浆葡萄糖相关（r = 0.81，p = 0.015）。此外，在第7天，饮食摄入量/REE比值不仅与瘦素的自然对数呈负相关（-0.74，p = 0.037），还与可溶性TNF受体55呈负相关（r = -0.93，p = 0.001）。总之，在COPD急性加重期观察到能量平衡出现暂时紊乱，这与瘦素浓度升高以及全身炎症反应有关。有证据表明，升高的瘦素浓度反过来受全身炎症反应以及可能的高剂量全身糖皮质激素治疗的控制。
