Lewitt Moira S, Hall Kerstin, Bang Peter, Brismar Kerstin
Unit of Endocrinology and Diabetes, Department of Molecular Medicine, Karolinska Institute, SE-171 76 Stockholm, Sweden.
Metabolism. 2005 Mar;54(3):275-80. doi: 10.1016/j.metabol.2004.09.005.
Circulating insulin-like growth factor-binding protein 1 (IGFBP-1) normally has a close inverse relationship to insulin secretion, which results in a characteristic diurnal variation. However, in type 2 diabetes the correlation with insulin may be lost and IGFBP-1 concentrations relatively increased. The aim of this study was to determine the effect of nutritional deprivation on the diurnal patterns of IGFBP-1 regulation in type 2 diabetes mellitus. After a baseline assessment period, food intake was reduced over 48 hours to 627.6 kJ/d (150 kcal/d) for 72 hours and increased again over 24 hours to baseline (refeeding). Blood samples were taken at 2-hour intervals, for 24 hours in the baseline period, 48 hours during nutritional deprivation, and 24 hours during refeeding. Six individuals with type 2 diabetes were compared with 2 groups that were selected for normal fasting glucose and insulin levels and comprised 6 obese and 6 lean subjects. During energy (caloric) restriction, fasting insulin levels decreased to a similar extent in each study group. At baseline, IGFBP-1 concentrations were similar in each of the study groups and at the end of the period of energy (caloric) restriction the 6:00 AM fasting levels had increased by 144% in the obese control group and by 245% in the lean individuals (each P < .001). In the patients with type 2 diabetes there was a blunted increase in IGFBP-1 concentrations with nutritional deprivation by 33% compared with baseline. During refeeding after nutritional deprivation the IGFBP-1 response to insulin was restored in the individuals with diabetes. In conclusion, patients with type 2 diabetes mellitus have altered IGFBP-1 regulation, relating to impaired hepatic insulin sensitivity, which improves after a period of energy (caloric) restriction.
循环胰岛素样生长因子结合蛋白1（IGFBP-1）通常与胰岛素分泌呈密切的负相关，这导致其呈现出特征性的昼夜变化。然而，在2型糖尿病中，与胰岛素的相关性可能丧失，IGFBP-1浓度相对升高。本研究的目的是确定营养剥夺对2型糖尿病患者IGFBP-1调节昼夜模式的影响。在基线评估期后，食物摄入量在48小时内减少至627.6千焦/天（150千卡/天），持续72小时，然后在24小时内再次增加至基线水平（再喂养）。在基线期的24小时内、营养剥夺期间的48小时以及再喂养期间的24小时，每隔2小时采集一次血样。将6名2型糖尿病患者与2组空腹血糖和胰岛素水平正常的受试者进行比较，这2组分别包括6名肥胖受试者和6名瘦受试者。在能量（热量）限制期间，每个研究组的空腹胰岛素水平均有相似程度的下降。在基线时，每个研究组的IGFBP-1浓度相似，在能量（热量）限制期结束时，肥胖对照组上午6点的空腹水平升高了144%，瘦受试者升高了245%（均P < 0.001）。在2型糖尿病患者中，营养剥夺导致IGFBP-1浓度升高幅度较基线时减弱了33%。营养剥夺后的再喂养期间，糖尿病患者的IGFBP-1对胰岛素的反应得以恢复。总之，2型糖尿病患者的IGFBP-1调节发生改变，这与肝脏胰岛素敏感性受损有关，但在一段时间的能量（热量）限制后有所改善。
