Diminished insulin clearance during late pregnancy in patients with type I diabetes mellitus.

1. Intensive insulin treatment of patients with Type I diabetes mellitus during pregnancy is associated with a high frequency of serious hypoglycaemic events. A potential change in insulin metabolism during pregnancy may affect both the frequency and the severity of insulin-induced hypoglycaemia.2. In 10 patients with Type I diabetes, during the third trimester of pregnancy and 5 to 13 months after delivery, hypoglycaemia was induced by the hyperinsulinaemic hypoglycaemic clamp technique. A constant high-dose intravenous insulin infusion was administered for 150 min and arterial blood glucose was clamped at 2.2 mmol/l by counterregulation with intravenous glucose. During the experiment venous samples were collected for later analysis of free plasma insulin, whereby the metabolic clearance rate of insulin could be calculated.3. The desired blood glucose level was approached after approximately 60 min of insulin infusion. After just 30 min the insulin levels were significantly higher during pregnancy compared with after delivery. In addition, the steady-state insulin level from 90 to 150 min was significantly higher during pregnancy.4. From the steady-state insulin levels at 90 to 150 min, the metabolic clearance rate of insulin was calculated, being 24% higher after delivery.5. We conclude that there is a decreased metabolic clearance rate of insulin during pregnancy. This might be due to altered blood-flow distribution, decreased hepatic insulin extraction and relative increase in body fat during pregnancy. A decreased clearance of insulin will contribute to the risk for serious hypoglycaemic events in patients with Type I diabetes during pregnancy.

Placental hormones during induced hypoglycaemia in pregnant women with insulin-dependent diabetes mellitus: evidence of an active role for placenta in hormonal counter-regulation.

OBJECTIVE: To study the effect of induced hypoglycaemia on serum levels of the placental hormones oestriol, human placental lactogen, placental growth hormone and progesterone in the third trimester of pregnancy. DESIGN: A prospective experimental investigation. SETTING: High risk pregnancy unit and diabetes research unit at Karolinska Institutet Danderyd Hospital, a university hospital. PARTICIPANTS: Ten women with insulin-dependent diabetes mellitus in the third trimester of pregnancy. METHODS: Venous blood samples were collected every 15 minutes for analyses of oestriol, progesterone, human placental lactogen and placental growth hormone, during the 150 min of a hyperinsulinaemic hypoglycaemic clamp, which maintained arterial blood-glucose level of about 2.2 mmol/l. MAIN OUTCOME MEASURES: Levels of analysed placental hormones during hypoglycaemia. RESULTS: A statistically significant increase was observed in placental growth hormone during hypoglycaemia (P < 0.0001), whereas the placental hormones progesterone, human placental lactogen and oestriol did not show changes of clinical significance. CONCLUSIONS: The increase in placental growth hormone indicates that the placenta is an endocrine organ which may take an active part in acute metabolic processes, such as here in the hormonal counterregulation of hypoglycaemia.

Effects of hypoglycaemia on fetal heart activity and umbilical artery Doppler velocity waveforms in pregnant women with insulin-dependent diabetes mellitus.

OBJECTIVE: To study the effect of induced hypoglycaemia on fetal wellbeing as indicated by fetal heart rate and umbilical artery flow velocity waveforms. DESIGN: A prospective experimental investigation. SETTING: High risk pregnancy unit and diabetes research unit at Karolinska Institutet, Danderyd Hospital, a university affiliated hospital. PARTICIPANTS: Ten women with insulin-dependent diabetes mellitus in the third trimester of pregnancy. INTERVENTIONS: The fetal heart rate, the blood flow velocity waveforms in the umbilical artery and the maternal catecholamine levels were investigated during a 150-minute hyperinsulinaemic hypoglycaemic clamp with induction and maintenance of an arterial blood glucose level of about 2.2 mmol/l. MAIN OUTCOME MEASURES: 1. Fetal: changes of fetal heart rate pattern and pulsatility index of the umbilical artery flow velocity waveforms. 2. Maternal: levels of plasma adrenaline and plasma noradrenaline. RESULTS: Maternal hypoglycaemia was associated with an increase in frequency and amplitude of fetal heart rate accelerations, a slight decrease in the pulsatility index of the umbilical artery and a rise in the maternal catecholamine levels. CONCLUSIONS: We speculate that the increased number of fetal heart rate accelerations reflects an increased sympathico-adrenal activity during the hypoglycaemia clamp. No potentially harmful effects on the fetus were observed in the fetal heart rate or in the umbilical artery Doppler waveform analysis during hypoglycaemia.

Hormonal counterregulation of hypoglycaemia in IDDM patients during and after pregnancy

An increased frequency of hypoglycaemic events is commonly observed during pregnancy in intensively treated IDDM patients. It has been speculated upon whether this is due in part to impairment of the hormonal counterregulation. The main aim of this study was to clarify if the hormonal response to hypoglycaemia is modified during pregnancy. Therefore we assessed plasma levels of catecholamines, GH and cortisol as well as subjective symptoms and cognitive functions during a hyperinsulinaemic, hypoglycaemic clamp in the third trimester of pregnancy and 6-12 months after delivery. Venous samples for the analysis of hormones and free insulin were taken every 15 minutes and symptoms of hypoglycaemia were recorded on a visual analogue scale at 30-min intervals. Cognitive functions were studied by a psychological test system at normoglycaemia and at hypoglycaemia. The Wilcoxon signed rank test was used for statistical calcuations. The levels of noradrenaline (mean at hypoglycaemia pregnant 2.30, and non-pregnant 2.44 nmol/l, n.s.) increased the same way on the two occasions, while the adrenaline response was some what higher in the pregnant state (2.09 vs 1.66 nmol/l non-pregnant, p<0.05). The cortisol increase was faster and more pronounced during pregnancy (mean increase 327 vs 130 nmol/non-pregnant, p<0.0001) while the increase in GH was higher in the non-pregnant state (mean increase 23.6 vs 8.7 æg/l pregnant, P<0.0001). We conclude that the present study does not, with the exception of GH, give evidence that pregnancy per se diminishes the counterregulatory hormones response (AU)