Counterregulatory hormonal responses to hypoglycemia during pregnancy

Abstract
Objective: To evaluate the counterregulatory responses to insulin-induced hypoglycemia in healthy women and in women with insulin-dependent diabetes during pregnancy and in the nonpregnant state. Methods: Hypoglycemia was induced using the hypoglycemic clamp technique in 17 women with insulin-dependent diabetes and in ten healthy controls, both in the nonpregnant state (study 1), at 24–28 weeks' gestation (study 2), and at 32–34 weeks' gestation (study 3). Plasma glucose concentrations were decreased to 60 mg/dL and maintained at this level for 1 hour. Blood samples were drawn every 15 minutes to measure epinephrine, glucagon, growth hormone, and cortisol concentrations. Statistical analyses compared counterregulatory responses between women with and without diabetes, and between the pregnant and nonpregnant state. Results: Women with diabetes had significantly diminished peak epinephrine responses to hypoglycemia compared with controls (mean ± standard error of the mean [SEM]): 52 ± 11 versus 191 ± 42 pg/mL in study 1, 30 ± 9 versus 102 ± 47 pg/mL in study 2, and 38 ± 10 versus 148 ±38 pg/mL in study 3 (P < .05). Their responses during pregnancy were also diminished compared with their own nonpregnant epinephrine responses. Women with diabetes also had no recognizable cortisol or glucagon responses to hypoglycemia, and in healthy controls the glucagon responses were significantly diminished during pregnancy compared with their own nonpregnant responses. In both groups, growth hormone responses (mean ± SEM) diminished progressively during pregnancy from study 1 (14.6 ±2.5 and 12.5 ± 5.2 ng/mL) to study 2 (4.4 ± 1.1 and 7.3 ± 2.7 ng/mL) to study 3 (2.5 ± 0.9 and 4.4 ± 2.3 ng/mL) in women with diabetes and in controls, respectively. Conclusion: Counterregulatory epinephrine and growth hormone responses to hypoglycemia are diminished in women with insulin-dependent diabetes during pregnancy. This may be due, in part, to an independent effect of pregnancy, contributing to the increased incidence of hypoglycemia in these patients during pregnancy.

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