Impaired hormonal counterregulation to biochemical hypoglycaemia does not explain the high incidence of severe hypoglycaemia during pregnancy in women with type 1 diabetes

Abstract

Aims. To explore hormonal counterregulation to biochemical hypoglycaemia during pregnancy. Methods. Observational study of 107 consecutive pregnant women with type 1 diabetes (median duration 16 years (range 1–36), HbA1c 6.6% (4.9–10.5) in early pregnancy) and 22 healthy pregnant women. At 8, 14, 21, 27 and 33 weeks (women with diabetes) and 15, 28 and 34 weeks (healthy women) blood was sampled for measurements of glucose, adrenaline, noradrenaline, cortisol and glucagon. Each woman's measurement of serum glucose was matched with her corresponding hormone concentrations. Severe hypoglycaemia (requiring help from another person) was recorded prospectively. Results. During normoglycaemia (serum glucose > 3.9 mmol/L), adrenaline concentrations were higher in early pregnancy compared with late pregnancy in women with diabetes (21 (7–111) pg/ml vs. 17 (2–131), p = 0.02) and healthy women (21 (10–37) pg/ml vs. 13 (5–49), p = 0.046). Biochemical hypoglycaemia (serum glucose ≤ 3.9 mmol/L) occurred in 70 women with diabetes (65%) in at least one of the five samplings. At 8 and 33 weeks, adrenaline concentrations at biochemical hypoglycaemia were similar (30 (5–164) pg/ml and 29 (9–152), p = 0.79). Adrenaline concentrations at biochemical hypoglycaemia increased from normoglycaemia at diabetes duration < 16 years (p = 0.03). In first trimester, adrenaline concentrations were comparable in women with or without severe hypoglycaemia (24 (14–164) pg/ml vs. 33 (5–86), p = 0.35). Noradrenaline, glucagon and cortisol concentrations did not increase during biochemical hypoglycaemia. Conclusion. Adrenaline response to biochemical hypoglycaemia was present at similar levels in early and late pregnancy, particularly in shorter diabetes duration, and was not associated with severe hypoglycaemia in early pregnancy.

Key Words::

• Catecholamines
• cortisol
• diabetes
• glucagon
• pregnancy

Acknowledgements

We are indebted to registered nurses E. Stage, Center for Pregnant Women with Diabetes, Rigshospitalet, Denmark and C. Barfred, Center for Pregnant Women with Diabetes, Rigshospitalet, Denmark and laboratory technicians K.M. Larsen, Center for Pregnant Women with Diabetes, Rigshospitalet, Denmark, and M. Wahl, Center for Pregnant Women with Diabetes, Rigshospitalet, Denmark, for careful handling of the patients and the data. We thank laboratory technician G. Alberts, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands for performing the measurements of adrenaline and noradrenaline and laboratory technician R. Krøncke, Department of Clinical Biochemistry, Rigshospitalet, Denmark, for performing the measurements of glucose, glucagon and cortisol.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.