Deficient counterregulation: A possible risk factor for excessive fetal growth in IDDM pregnancies

OBJECTIVE - The rate of macrosomia in infants born to women with IDDM remains high despite intensive insulin therapy and good glycemic control. We hypothesized that one of the factors contributing to this high rate of macrosomia is deficient counterregulatory hormonal responses to hypoglycemia. RESEARCH DESIGN AND METHODS - Hypoglycemia was induced in 17 women with IDDM and 10 normal control subjects at 24-28 at 32-34 weeks' gestation using the hypoglycemic clamp technique. Plasma glucose concentrations were decreased to 3.3 mmol/l and maintained at this level for 1 h. Blood samples were drawn every 15 min for measurement of counterregulatory hormone concentrations. RESULTS - All 17 women with IDDM had diminished epinephrine responses to hypoglycemia, compared with control subjects. Eight of the women with IDDM (nonresponders) had minimal or no responses (< 165 pmol/l above baseline) and nine women (responders) had a moderate response (244-764 pmol/l). Of the eight nonresponders, seven had large infants (birth weight in the upper quartile), while only three of the nine responders had large infants (P < 0.05). CONCLUSIONS - Severely impaired counterregulatory epinephrine responses to hypoglycemia in pregnant women with IDDM may be a factor contributing to excessive fetal growth. We speculate that in these women, recurrent episodes of hypoglycemia may result in frequent bouts of increased calorie intake, with repeated episodes of transient hyperglycemia leading to fetal hyperinsulinism and excessive fetal growth.