Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, 14558 Nuthetal, Germany.
Diabetes Technol Ther. 2010 Jan;12(1):57-64. doi: 10.1089/dia.2009.0129.
A progressive weight gain is associated with various pharmacological options improving glycemic control in type 2 diabetes mellitus (T2DM). Ghrelin has been implicated in the regulation of feeding behavior and energy balance in humans. Based on evidence that functional ATP-sensitive channels are present in ghrelin-producing cells, we hypothesized that meglitinides may affect circulating ghrelin levels in subjects with type 2 diabetes.
In a single-blinded randomized three-period crossover study (n = 20), repaglinide or nateglinide was given in combination with metformin for two treatment periods over a 1-week period, respectively, separated by a 1-week treatment with placebo. Liquid meal challenge tests (LMCTs) with single preprandial doses of repaglinide (2 mg), nateglinide (120 mg), or placebo were performed at the end of each treatment period. Ten control subjects without diabetes underwent a single LMCT without any medication.
Fasting ghrelin concentrations were not different between all treatments and between patients with diabetes and control subjects. Subjects with T2DM treated with placebo showed no suppression of ghrelin in the LMCT. After administration of meglitinides a nadir of serum ghrelin was observed at 60 min (8.6% of baseline [P = 0.038] for repaglinide and 7.5% of baseline [P = 0.081] for nateglinide), which was similar to the secretion pattern seen in control subjects. No correlations between postprandial insulin or glucose levels and circulating ghrelin concentrations were observed.
Treatment with meglitinides reconstructed postprandial ghrelin secretion patterns to those of controls without diabetes. This observation may help to improve the control of feeding behavior in patients with T2DM.
体重逐渐增加与各种改善 2 型糖尿病患者血糖控制的药物选择有关。Ghrelin 参与了人类摄食行为和能量平衡的调节。基于功能性 ATP 敏感性通道存在于产生 Ghrelin 的细胞中的证据，我们假设，在 2 型糖尿病患者中，美格列汀可能会影响循环 Ghrelin 水平。
在一项单盲、随机三交叉研究（n = 20）中，在 1 周的时间内，分别用两种治疗期（各 1 周）联合二甲双胍给予瑞格列奈或那格列奈，两种治疗期之间用 1 周的安慰剂治疗期隔开。在每个治疗期末，进行液体餐挑战试验（LMCT），单次餐前给予瑞格列奈（2mg）、那格列奈（120mg）或安慰剂。10 名无糖尿病的对照受试者在没有任何药物治疗的情况下进行了单次 LMCT。
在所有治疗组和糖尿病患者与对照受试者之间，空腹 Ghrelin 浓度没有差异。接受安慰剂治疗的 2 型糖尿病患者在 LMCT 中没有观察到 Ghrelin 的抑制。给予美格列汀后，血清 Ghrelin 在 60 分钟时出现最低点（瑞格列奈为基线的 8.6%[P = 0.038]，那格列奈为基线的 7.5%[P = 0.081]），与无糖尿病对照受试者的分泌模式相似。未观察到餐后胰岛素或血糖水平与循环 Ghrelin 浓度之间存在相关性。
用美格列汀治疗重建了餐后 Ghrelin 分泌模式，使其与无糖尿病的对照受试者相似。这一观察结果可能有助于改善 2 型糖尿病患者的进食行为控制。
