Smigaj D, Roman-Drago N M, Amini S B, Caritis S N, Kalhan S C, Catalano P M
Department of Reproductive Biology at MetroHealth Medical Center, Cleveland, Ohio 44109, USA.
Am J Obstet Gynecol. 1998 May;178(5):1041-7. doi: 10.1016/s0002-9378(98)70545-9.
Terbutaline, a selective beta2-agonist, is a frequently used tocolytic known to affect maternal metabolism. The purpose of this study was to evaluate the effect of oral terbutaline on maternal glucose metabolism and energy expenditure.
Six healthy pregnant women with normal glucose tolerance were evaluated between 30 and 34 weeks' gestation. Oral terbutaline was administered to determine the effects on hepatic glucose production with [6-6(2)H2] glucose tracer, insulin sensitivity (hyperinsulinemic-euglycemic clamp), and energy expenditure (indirect calorimetry). Terbutaline, insulin, and glucagon levels were also obtained. Subjects were randomly assigned to either oral terbutaline 5 mg every 6 hours for 24 hours or no medication. Repeat studies were conducted 1 week apart, each subject serving as her own control.
In the basal state terbutaline was associated with a trend toward increased basal glucose levels (81.6 +/- 6.6 vs 93.7 +/- 12.0 mg/dl, p = 0.06) but no significant increase in hepatic glucose production (3.2 +/- 0.3 vs 3.6 +/- 0.4 mg/kg fat-free mass/min, p = 0.23). However, there was a significant increase in basal insulin concentration (17.6 +/- 9.2 vs 25.6 +/- 10.4 microU/ml, p = 0.02). There was a 28% decrease in insulin sensitivity as measured by the glucose infusion rate during the euglycemic clamp plus residual hepatic glucose turnover (5.78 +/- 1.91 vs 4.16 +/- 1.49 mg/kg fat-free mass/min, p = 0.005). Glucagon concentration was significantly decreased both in the basal state (163 +/- 26 vs 144 +/- 27 pg/ml, p = 0.0007) and during the clamp (144 +/- 27 vs 133 +/- 27 pg/ml, p = 0.003). Basal oxygen consumption increased 9% (270 +/- 49 vs 294 +/- 50 ml oxygen/min, p = 0.007) and caloric expenditure 14% (1.32 +/- 0.23 vs 1.50 +/- 0.31 kcal/min, p = 0.025) or 260 kcal/day with terbutaline.
Decreased peripheral insulin sensitivity, and to a lesser degree increased endogenous glucose production, may represent the pathophysiology of abnormal glucose tolerance observed in many women treated with oral terbutaline. Common side effects such as tremors and tachycardia experienced by many women on a regimen of terbutaline are consistent with our finding of a significant increase in basal energy expenditure.
特布他林是一种选择性β2肾上腺素能激动剂，是常用的宫缩抑制剂，已知会影响母体代谢。本研究的目的是评估口服特布他林对母体葡萄糖代谢和能量消耗的影响。
对6名糖耐量正常的健康孕妇在妊娠30至34周期间进行评估。给予口服特布他林，以[6-6(2)H2]葡萄糖示踪剂测定对肝葡萄糖生成的影响、胰岛素敏感性（高胰岛素-正常血糖钳夹法）和能量消耗（间接测热法）。同时获取特布他林、胰岛素和胰高血糖素水平。受试者被随机分为每6小时口服5毫克特布他林共24小时组或不服药组。相隔1周进行重复研究，每位受试者作为自身对照。
在基础状态下，特布他林与基础血糖水平升高趋势相关（81.6±6.6 vs 93.7±12.0毫克/分升，p = 0.06），但肝葡萄糖生成无显著增加（3.2±0.3 vs 3.6±0.4毫克/千克去脂体重/分钟，p = 0.23）。然而，基础胰岛素浓度显著升高（17.6±9.2 vs 25.6±10.4微单位/毫升，p = 0.02）。通过正常血糖钳夹期间的葡萄糖输注率加残余肝葡萄糖周转率测定，胰岛素敏感性降低了28%（5.78±1.91 vs 4.16±1.49毫克/千克去脂体重/分钟，p = 0.005）。基础状态下和钳夹期间胰高血糖素浓度均显著降低（基础状态：163±26 vs 144±27皮克/毫升，p = 0.0007；钳夹期间：144±27 vs 133±27皮克/毫升，p = 0.003）。特布他林使基础耗氧量增加9%（270±49 vs 294±50毫升氧气/分钟，p = 0.007），热量消耗增加14%（1.32±0.23 vs 1.50±0.31千卡/分钟，p = 0.025），即每天增加260千卡。
外周胰岛素敏感性降低以及内源性葡萄糖生成在较小程度上增加，可能代表了许多口服特布他林治疗的女性出现糖耐量异常的病理生理机制。许多接受特布他林治疗方案的女性出现的诸如震颤和心动过速等常见副作用与我们发现的基础能量消耗显著增加一致。
