The effect of oral terbutaline on maternal glucose metabolism and energy expenditure in pregnancy.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Smigaj
D
D
Department of Reproductive Biology at MetroHealth Medical Center, Cleveland, Ohio 44109, USA.
Roman-Drago
N M
NM
Amini
S B
SB
Caritis
S N
SN
Kalhan
S C
SC
Catalano
P M
PM
D000318:Adrenergic beta-Agonists / Q000009:adverse effects / Q000494:pharmacology; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002153:Calorimetry, Indirect; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000096:biosynthesis; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D013726:Terbutaline / Q000009:adverse effects* / Q000494:pharmacology; D015149:Tocolytic Agents / Q000009:adverse effects* / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D007328:Insulin; D015149:Tocolytic Agents; D019344:Lactic Acid; D005934:Glucagon; D005947:Glucose; D013726:Terbutaline