Hormonal counterregulation and subjective symptoms during induced hypoglycemia in insulin‐dependent diabetes mellitus patients during and after pregnancy

BACKGROUND The objective was to elicit whether hormonal responses to and subjective symptoms of hypoglycemia are modified during pregnancy in patients with insulin-dependent diabetes mellitus. METHODS In ten type I diabetic women, hyperinsulinemic hypoglycemic clamps, with target arterial blood glucose content of 2.2 mmol/l, were performed during the third trimester of pregnancy and 5-13 months after delivery. The levels of arterial glucose and venous catecholamines, pituitary growth hormone, cortisol, glucagon, dehydroepiandrosterone and free insulin were assessed repeatedly. Subjective symptoms of hypoglycemia were recorded on a visual analog scale. The paired t-test and Wilcoxon signed rank test were used for statistical comparisons. RESULTS Adrenaline and dehydroepiandrosterone increased during hypoglycemia on both occasions, but dehydroepiandrosterone disclosed a significantly different pattern of response during pregnancy (p=0.016). The cortisol increase was augmented during pregnancy (420+/-50 vs. 310+/-30 nmol/l non-pregnant, p=0.039), while the increase in pituitary growth hormone (hGH) was diminished (5.4+/-1.2 vs. 27.9+/-5.4 microg/l non-pregnant, p=0.001), but nevertheless the increase during pregnancy was significant (p=0.002). Three of the eight subjective symptoms of hypoglycemia recorded were less prominent during pregnancy, namely 'inability to concentrate' (p=0.03), 'headache' (p=0.01) and 'pounding heart' (p=0.03). CONCLUSIONS Albeit some subjective symptoms were diminished during pregnancy, the study gives no evidence that, in diabetic patients, pregnancy per se impairs the counterregulatory response to hypoglycemia, with the exception of growth hormone. However, despite the suppressed basal growth hormone secretion in late pregnancy, the study disclosed a secretory response of this hormone at hypoglycemia.

[1]  P. Reichard,et al.  The Stockholm Diabetes Intervention Study (SDIS): 18 months' results. , 2009, Acta medica Scandinavica.

[2]  P. Lins,et al.  Effects of hypoglycaemia on fetal heart activity and umbilical artery Doppler velocity waveforms in pregnant women with insulin‐dependent diabetes mellitus , 1996, British journal of obstetrics and gynaecology.

[3]  J. Khoury,et al.  Counterrgulatory Hormonal Responses to Hypoglycemia During Pregnancy , 1996, Obstetrics and gynecology.

[4]  F. Pi-Sunyer,et al.  The Use of Areas Under Curves in Diabetes Research , 1995, Diabetes Care.

[5]  U. Hanson,et al.  Hormonal, Metabolic, and Circulatory Responses to Insulin-Induced Hypoglycemia in Pregnant and Nonpregnant Women with Insulin-Dependent Diabetes , 1994, American journal of perinatology.

[6]  U. Adamson,et al.  An Analysis of the Glucagon Response to Hypoglycaemia in Patients with Type 1 Diabetes and in Healthy Subjects , 1993, Diabetic medicine : a journal of the British Diabetic Association.

[7]  L. Heinemann,et al.  Severe Hypoglycemia Incidence and Predisposing Factors in 85 Pregnancies of Type I Diabetic Women , 1992, Diabetes Care.

[8]  E. Moberg,et al.  A high concentration of circulating insulin suppresses the glucagon response to hypoglycemia in normal man. , 1991, The Journal of clinical endocrinology and metabolism.

[9]  I. Macdonald,et al.  Patients with Type 1 Diabetes Adapt Acutely to Sustained Mild Hypoglycaemia , 1991, Diabetic medicine : a journal of the British Diabetic Association.

[10]  L. Parker Adrenal Androgens in Clinical Medicine , 1989 .

[11]  B. V. VON Schoultz,et al.  Dehydroepiandrosterone sulphate and dehydroepiandrosterone in serum: differences related to age and sex. , 1988, Maturitas.

[12]  W. Tamborlane,et al.  Effect of Intensive Insulin Therapy on Glycemic Thresholds for Counterregulatory Hormone Release , 1988, Diabetes.

[13]  R. DeFronzo,et al.  Rate of Glucose Fall Does Not Affect Counterregulatory Hormone Responses to Hypoglycemia in Normal and Diabetic Humans , 1987, Diabetes.

[14]  P. Cryer,et al.  Glycemic thresholds for activation of glucose counterregulatory systems are higher than the threshold for symptoms. , 1987, The Journal of clinical investigation.

[15]  S. Genuth,et al.  Diabetes Control and Complications Trial (DCCT): Results of Feasibility Study. The DCCT Research Group , 1987, Diabetes Care.

[16]  L. Ploughman,et al.  Severe hypoglycemia during pregnancy: Its frequency and predisposing factors in diabetic women , 1986, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[17]  N. Patel,et al.  In‐vivo accuracy of ultrasound measurements of intrauterine ume in pregnancy , 1984, British journal of obstetrics and gynaecology.

[18]  P. Brunetti,et al.  Abnormal Glucose Counterregulation in Insulin-dependent Diabetes Mellitus: Interaction of Anti-Insulin Antibodies and Impaired Glucagon and Epinephrine Secretion , 1983, Diabetes.

[19]  B. Fredholm,et al.  INSULIN‐INDUCED HYPOGLYCAEMIA IN DIABETIC WOMEN DURING LATE PREGNANCY AND ONE YEAR POST PARTUM , 1981, British journal of obstetrics and gynaecology.

[20]  P. Hjemdahl,et al.  Determination of plasma catecholamines by high performance liquid chromatography with electrochemical detection: comparison with a radioenzymatic method. , 1979, Life sciences.

[21]  P. Cryer,et al.  The role of adrenergic mechanisms in the substrate and hormonal response to insulin-induced hypoglycemia in man. , 1976, The Journal of clinical investigation.

[22]  S. Kalhan,et al.  Placental barrier to human insulin-I125 in insulin-dependent diabetic mothers. , 1975, The Journal of clinical endocrinology and metabolism.

[23]  I. Kjellmer,et al.  The outcome of diabetic pregnancies in relation to the mother's blood sugar level. , 1972, American journal of obstetrics and gynecology.

[24]  J. Hoekstra,et al.  Hypoglycaemia unawareness. , 1994, Presse medicale.

[25]  B. Frier,et al.  Hypoglycaemia and diabetes : clinical and physiological aspects , 1993 .

[26]  E. Reece,et al.  Impairment of counterregulatory hormone responses to hypoglycemia in pregnant women with insulin-dependent diabetes mellitus. , 1992, American journal of obstetrics and gynecology.

[27]  I Kiss,et al.  Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction. , 1991, The American journal of physiology.

[28]  Epidemiology of severe hypoglycemia in the diabetes control and complications trial. The DCCT Research Group. , 1991, The American journal of medicine.

[29]  R. Geirsson Intrauterine volume in pregnancy. , 1986, Acta obstetricia et gynecologica Scandinavica. Supplement.

[30]  F. Gomez,et al.  A human placental GH: increasing levels during second half of pregnancy with pituitary GH suppression as revealed by monoclonal antibody radioimmunoassays. , 1985, International journal of fertility.

[31]  A. Beckers,et al.  Monoclonal antibody to growth hormone the discovery of a new variant, human placental growth hormone , 1985 .

[32]  H. C. Miller Diabetes and pregnancy: Blood sugar of newborn infants , 1953 .