Reducing adverse events associated with the glucagon stimulation test for the assessment of growth hormone deficiency in adults with a high prevalence of pituitary hormone deficiencies.

DESIGN: A retrospective review of the adverse events (AEs) in 78 patients during the glucagon stimulation test (GST) for the assessment of growth hormone deficiency (GHD) before and after protocol amendments which aimed to reduce AEs in a group of patients with a high prevalence of pituitary hormone deficiencies. PATIENTS: Based on our observations of frequent AEs during the standard GST protocol in an initial 25 patients (cohort 1), a modified protocol was introduced to include the routine administration of 20 mg of hydrocortisone pre-GST in a subsequent 53 patients (cohort 2). Post hoc analysis of the effect of glucocorticoid dosing pre-GST on AEs was examined in those receiving <20 mg hydrocortisone (group A, n = 19) vs ≥20 mg hydrocortisone (group B, n = 59). MEASUREMENTS: AEs including hypotension, hypoglycaemia and nausea/vomiting. RESULTS: Of the 78 patients undergoing the GST, 79% had ≥2 hormone deficiencies. Rates of AEs were 41% vs 30% for hypotension, 60% vs 28% for hypoglycaemia (p < .05) and 20% vs 13% for nausea/vomiting in cohort 1 compared with cohort 2, respectively. Post hoc analysis revealed lower rates of AEs in those receiving ≥20 mg hydrocortisone (group B) compared to those receiving <20 mg due to a reduction in hypoglycaemic events (82% vs 26%, p < .001) and hypotension (50% vs 27%, p = .05). Similar numbers of patients in group A and group B met criteria for GHD. CONCLUSIONS: In patients with a high prevalence of pituitary deficiencies, a modified GST protocol of additional stress dose glucocorticoid attenuated the frequency of AEs without appearing to compromise the performance of the GST.

The role of continuous glucose monitoring in clinical decision-making in diabetes in pregnancy.

BACKGROUND: The continuous glucose monitoring system (CGMS) is a novel tool to assess 24-h glucose fluctuations. In pregnancies complicated by diabetes, where excellent glucose control is desired to improve maternal and fetal outcomes, CGMS may have a role in fine-tuning management. AIMS: To assess the usefulness of CGMS in pregnant women with diabetes for medical decision-making and to evaluate patient tolerability and perception of usefulness. METHODS: Pregnant women with diabetes at the Werribee Mercy Hospital were offered CGMS in the setting of their standard diabetes care. Treating clinicians were asked if the CGMS altered management decisions from those based on conventional glucose monitoring. The accuracy of the CGMS was assessed by comparison with the patients' finger-prick glucose readings. Patients completed a feedback questionnaire after having the CGMS and viewing their results. RESULTS: CGMS traces (n = 68) were obtained in 55 pregnant women - 37 with gestational diabetes, ten with type 2 and eight with type 1 diabetes. Forty-two of 68 (62%) traces were assessed as providing additional information which altered clinical management decisions. This included showing undetected postprandial hyperglycaemia and overnight hypoglycaemia. Subject feedback was generally positive, with 37 of 48 (77%) respondents reporting that the benefits of the CGMS outweighed the inconvenience. CONCLUSION: CGMS is a well-tolerated clinically useful tool in the management of gestational diabetes and pre-existing diabetes in pregnancy.

Do adiponectin, TNFalpha, leptin and CRP relate to insulin resistance in pregnancy? Studies in women with and without gestational diabetes, during and after pregnancy.

BACKGROUND: The role of adiponectin, tumour necrosis factor alpha (TNFalpha), leptin and C-reactive protein in the insulin resistance of pregnancy is not clear. We measured their levels in women with gestational diabetes (GDM) and in controls, during and after pregnancy, and related them to insulin secretion and action. METHODS: Nineteen women with GDM and 19 BMI-matched healthy pregnant women underwent intravenous glucose tolerance tests in the third trimester of pregnancy and 4 months postpartum to determine insulin sensitivity (SI) and insulin secretion. Adiponectin, TNFalpha, leptin and high sensitivity CRP (hsCRP) were measured in fasted blood. RESULTS: Of the circulating factors, only leptin (r = -0.41, p = 0.01) correlated with SI in pregnancy. Leptin and hsCRP levels were elevated in pregnancy compared to postpartum (leptin (mean +/- SEM): 27.8 +/- 2.4 vs 19.3 +/- 2.1 ng/mL, p < 0.001; hsCRP: 5.2 +/- 0.7 vs 3.2 +/- 0.6 mg/L, p < 0.001). Adiponectin levels did not change from pregnancy to postpartum, despite a marked increase in SI. All four factors correlated with SI postpartum (adiponectin: r = 0.38, p = 0.01; TNFalpha: r = -0.48, p = 0.002; Leptin: r = -0.61, p = 0.001; hsCRP: r = -0.48, p = 0.002). TNFalpha correlated inversely with insulin secretion in pregnancy (r = -0.35, p = 0.03) and was significantly higher in the GDM group (2.62 +/- 0.3 vs 1.88 +/- 0.3 pg/mL, p = 0.01) in pregnancy. CONCLUSION: In our study, the influence of adiponectin, TNFalpha and hsCRP upon SI is overwhelmed by other factors in pregnancy. While leptin and SI correlated in pregnancy, it is unclear whether this represents cause or effect. Finally, TNFalpha may exert an inhibitory effect on insulin secretion in GDM, contributing to the associated hyperglycaemia.

Metformin in obstetric and gynecologic practice: a review.

Metformin is a common treatment for women who have insulin resistance manifesting as type 2 diabetes or polycystic ovarian syndrome (PCOS). With an increasing number of these patients conceiving, it is expected that the use of metformin in and around the time of pregnancy will increase. This article reassesses the mechanisms, safety, and clinical experience of metformin use in obstetrics and gynecology. Metformin is an attractive therapeutic option because administration is simple, hypoglycemia rare, and weight loss promoted. There is a large volume of research supporting the use of metformin treatment in diabetes mellitus, androgenization, anovulation, infertility, and recurrent miscarriage. Although metformin is known to cross the placenta, there is, as yet, no evidence of teratogenicity. Metformin has an array of complex actions, accounting for the varied clinical roles, many of which are still to be fully evaluated. Much research is still needed.

Gestational diabetes in Victoria in 1996: incidence, risk factors and outcomes.

OBJECTIVES: To describe the epidemiology of gestational diabetes mellitus (GDM) in Victoria. STUDY DESIGN: Population study of all women having singleton births in Victoria in 1996. METHODS: Probabilistic record linkage of routinely collected data and capture-recapture techniques to provide an estimate of the incidence of GDM. MAIN OUTCOME MEASURES: Risk factors for and the adverse outcomes associated with GDM compared with the non-diabetic population by univariate and multivariate analysis. RESULTS: The estimated incidence of GDM was 3.6% (95% confidence interval [CI], 3.60%-3.64%). GDM is associated with women who are older, Aboriginal, non-Australian born, or who give birth in a larger hospital. The adverse outcomes associated with GDM pregnancies were hypertension/pre-eclampsia (adjusted odds ratio [OR], 1.6; 95% CI, 1.4-1.9), hyaline membrane disease (1.6; 1.2-2.2), neonatal jaundice (1.4; 1.2-1.7) and macrosomia (2.0; 1.8-2.3). Interventions during childbirth were also associated with GDM - for example, induction of labour (3.0; 2.7-3.4) and caesarean section (1.7; 1.6-1.9). CONCLUSION: Women with GDM had increased rates of hypertension, pre-eclampsia, induced labour, and interventional delivery. Their offspring had a higher risk of macrosomia, neonatal jaundice and hyaline membrane disease.