Objective To investigate whether pre-eclampsia is associated with an exaggeration of the insulin Design Minimal model analysis of a frequently sampled intravenous glucose tolerance test to assess Setting Royal Maternity Hospital, Belfast. Participants Eleven women with pre-eclampsia and 1 1 matched normotensive pregnant women. Results Insulin sensitivity (S,) was increased in the group with pre-eclampsia compared with the normotensive women (mean [HEM]: 2.6 [0-4] vs 1.6 [0.2] lo-" min-I per mU/L; P = 0.028). This was accompanied by a decrease in glucose effectiveness (S,) (1 * 1 f 0.1 vs 1.7 kO.1 1 0-2 m i d , P = 0.006) in the pre-eclamptic women. In the normotensive group there was a significant inverse correlation between S, and mean arterial blood pressure (Y = -0.65; P = 0.03), but no such relation existed in the group with pre-eclampsia.Conclusions As with other forms of secondary hypertension, and unlike essential hypertension, the pathophysiology of pre-eclampsia is not associated with insulin resistance.resistance seen in normotensive pregnancy.insulin sensitivity.Hypertensive disorders of pregnancy continue to be leading causes of maternal mortality'. It is known that pre-eclampsia, the most common of these disorders, is associated with failure of trophoblast invasion of the spiral arteries of the placenta. However, other aspects of its pathophysiology are still poorly understood. Elevated insulin levels in patients with hypertension were first reported in 1966*, but it was not until the large epidemiological study of Modan et aL3 in 1985 that interest in this area began to grow. Since then, other clinicalk7 and m e t a b o l i~~,~ studies have shown hyperinsulinaemia and insulin resistance to be linked with essential hypertension.Pregnancy is itself an insulin-resistant state. The diabetogenic influence of pregnancy has been recognised for over 100 years'O. As gestation advances, there is a progressive increase in the secretory response of the maternal pancreas to glucose, and the maintenance of euglycaemia is associated with progressively increasing levels of circulating insulin. Indirect evidence of insulin resistance in normal pregnancy is provided by the blunted response to an intravenous injection of exogenous insulin' l. Direct evidence of insulin resistance in pregnancy has been provided by studies using both euglycaemic clamp12 and minimal model method~logies'~.'~.Correspondence: Dr Ralph N. Roberts, Duchess of Gloucester Maternity Unit, The Ulster Hospital, Dundonald, Belfast BT16 ORH, UK.To our knowledge there are no reported studies in which insulin sensitivity has been measured in women with pre-eclampsia. In the 1950s, BurtI5 demonstrated that women with pregnancy-induced hypertension had higher glucose levels on intravenous glucose tolerance testing and an attenuated glucose response to intravenous insulin16. More recently, insulin concentrations were shown to be higher in response to an intravenous glucose load in women with hypertension in pregnancy than normotensive controls17. These ...
A 75 g oral glucose tolerance test was carried out on 953 pregnant women who were identified on the basis of clinical risk factors. The tests were analysed by the WHO criteria: 826 were normal, 120 showed impaired glucose tolerance, and 7 identified diabetes. A number of obstetric and perinatal outcome measures were compared between the groups with normal and impaired glucose tolerance, and also with 135 women who had pre-existing Type 1 diabetes and delivered during the study period. There was no significant difference in the incidence of antenatal complications between mothers with normal and impaired glucose tolerance. There was a higher rate of induced labour ( p < 0.05) and caesarean section ( p < 0.01) in the impaired glucose tolerance group compared to the normal group, but no difference in fetal outcome or neonatal morbidity. All of these outcome measures were increased in the Type 1 diabetic pregnancies. KEY WORDS Pregnancy Impaired glucose tolerance Fetal outcomeA further 16 patients had an antenatal glucose tolerance test but were excluded from the analysis (10 tests were incomplete due to vomiting after the glucose load, 3 patients delivered at other hospitals, and the case records of a further 3 patients could not be traced). A standard
We analysed a database of glycosylated haemoglobin (HbA1) in nondiabetic pregnant women to investigate the relation between glucose metabolism in the first and second trimesters and hypertensive complications of pregnancy. From a total of 1334 women, 13 had pre‐existing hypertension, 225 developed gestational hypertension and 51 developed pre‐eclampsia. At 28 weeks of gestation, the women who susequently developed gestational hypertension had a significantly higher mean HbAl than those who remained normotensive (6.33 vs 6.17%, P < 0.02). This difference remained significant after correcting for the effects of age and body mass index (regression coefficient 0.11, SE 0.06, P = 0.05). In contrast, there were no significant differences in HbAl between the women with pre‐eclampsia and their normotensive counterparts. This provides indirect evidence to support our hypothesis that gestational hypertension is associated with insulin resistance but pre‐eclampsia is not.
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