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Biomedical subjects

Aidan McElduff

Publications and source records attributed to Aidan McElduff.

15 recordsLinked to original sources

Insulin levels in insulin resistance: phantom of the metabolic opera?

Insulin resistance is considered a core component in the pathophysiology of the metabolic syndrome. Some clinicians measure serum insulin concentrations in the mistaken belief that they can be used to diagnose insulin resistance. Serum insulin levels are poor measures of insulin resistance. Furthermore, there is no clinical benefit in measuring insulin resistance in clinical practice. Measurements of fasting serum insulin levels should be reserved for large population-based epidemiological studies, where they can provide valuable data on the relationship of insulin sensitivity to risk factors for diabetes and cardiovascular disease. Clinicians should shift from identifying "insulin resistance" to identifying risk factors, such as fasting glucose and lipid levels, hypertension and central obesity. These proven risk factors converge within the metabolic syndrome. Individuals "at risk" of diabetes and atherosclerotic cardiac disease can be identified simply and inexpensively, using classic clinical techniques, such as history-taking, physical examination, and very basic investigations.

Cardiovascular Diseases↗

The Australasian Diabetes in Pregnancy Society consensus guidelines for the management of type 1 and type 2 diabetes in relation to pregnancy.

Strict control of blood glucose levels should be pursued before conception and maintained throughout the pregnancy (glycohaemoglobin [HbA(1c)] level as close as possible to the reference range). Before conception: high-dose (5 mg daily) folate supplementation should be commenced; oral hypoglycaemic agents should be ceased; and diabetes complications screening should take place. Management should be by a multidisciplinary team experienced in the management of diabetes in pregnancy. Blood glucose monitoring is mandatory during pregnancy, and targets are: fasting 4.0-5.5 mmol/L; postprandial < 8.0 mmol/L at 1 hour; < 7 mmol/L at 2 hours. A first trimester nuchal translucency (possibly with first trimester biochemical screening with pregnancy-associated plasma protein A and beta-human chorionic gonadotropin) should be offered. Ultrasound should be performed for fetal morphology at 18-20 weeks, if required, for cardiac views at 24 weeks and for fetal growth at 28-30 and 34-36 weeks. Induction of labour or operative delivery should be based on obstetric and/or fetal indications. Level 3 neonatal nursing facilities may be required and should be anticipated when birth occurs before 36 weeks, or if there has been poor glycaemic control. Insulin requirements fall rapidly during labour and in the puerperium. At this time, close monitoring and adjustment of insulin therapy is necessary.

Antihypertensive Agents↗

Neonatal thyrotropin as measured in a congenital hypothyroidism screening program: influence of the mode of delivery.

CONTEXT: Many developed countries are reexperiencing iodine deficiency. One World Health Organization index of iodine deficiency in populations is the percentage of neonates with TSH levels greater than 5 mIU/liter 72 h after delivery. Measured TSH levels vary with methodology and are influenced by external factors including iodine exposure at time of delivery. OBJECTIVE: We wished to determine whether babies delivered by cesarean section have higher levels of TSH than babies delivered vaginally because this factor could influence determination of iodine deficiency. DESIGN AND SETTING: This was a cohort study of mothers delivering at a teaching hospital in 2002-2003 and their babies. PATIENTS AND METHODS: Women delivering a live infant were eligible for the study. Demographic data, mode of delivery, and subsequent routine newborn screening TSH levels were recorded. RESULTS: Of 2031 infants, 31.2% were delivered by cesarean section; 1864 babies were born after 37 wk, with blood samples collected by d 5 (>91% on d 3). Significant predictors of TSH concentration were the day TSH was measured and type of delivery. The distribution curve of TSH values was right shifted in infants born by cesarean section. The percentage of neonates born by cesarean with at TSH value greater than 5 was 7.1%. The figure for those born vaginally was 4.3%. CONCLUSIONS: Babies delivered by cesarean section are significantly more likely to have TSH levels greater than 5 mIU/liter on d 3 than those delivered vaginally. With the rise in the rate of births by cesarean, this could be an important factor in assessing population iodine deficiency using neonatal TSH levels.

Cesarean Section↗

Influence of acute upper respiratory tract infection on the absorption of inhaled insulin using the AERx insulin Diabetes Management System.

AIMS: To assess the effects due to an uncomplicated acute upper respiratory tract infection (URTI) on the pharmacokinetics and glucose response of insulin when delivered by oral pulmonary absorption. METHODS: Normally healthy adult men (n = 11) and women (n = 9) received a single dose of inhaled human insulin, equivalent to approximately 6 IU subcutaneous, using the AERx insulin Diabetes Management System (iDMS), during and following recovery from an URTI. The first dose was administered with ongoing symptoms of < 3 days' duration, the second dose following recovery, and within 3 weeks of the first. Blood sampling for determination of insulin pharmacokinetics (serum AUC(0-6 h), AUC(0-8), C(max),t(max), t(1/2), MRT) and glucose response (plasma AOC(0-6 h)) was performed from 15 min predose to 6 h postdose. RESULTS: Insulin pharmacokinetics were not different for subjects during and following recovery from URTI [e.g. URTI: no URTI ratio in serum AUC(0-6 h) = 0.92 (95% confidence interval 0.81, 1.05)]; this was reflected by a similar glucose response. Inhaled insulin delivered by AERx iDMS was well tolerated by all subjects; no significant changes were observed in pulmonary function tests. No safety concerns arising from the mode of insulin administration were raised by either dose. CONCLUSIONS: The results suggest that insulin can be administered via AERx iDMS to nondiabetic subjects experiencing a URTI without any statistically significant changes in insulin pharmacokinetics or pharmacodynamics, and that the necessity for dose adjustments will not differ from subjects with an acute URTI who are receiving subcutaneous insulin.

Administration, Inhalation↗

Type 2 diabetes in pregnancy: a wolf in sheep's clothing.

Type 2 diabetes is now the most common form of pregestational diabetes. Recent data suggest that pregnancies complicated by type 2 diabetes are associated with unacceptably high fetal mortality and morbidity, at an incidence comparable to pregnancies complicated by type 1 diabetes. This review examines the literature on type 2 diabetes in pregnancy, including its incidence and potential complications. There is a need to highlight the dangers of type 2 diabetes in pregnancy to both patients and medical practitioners. Peri-conception care needs to improve to achieve better pregnancy outcomes.

Adult↗

Activating antibodies to the calcium-sensing receptor in two patients with autoimmune hypoparathyroidism.

Autoimmune hypoparathyroidism is thought to result from immune-mediated destruction of the parathyroid glands. We encountered two patients with hypoparathyroidism and other autoimmune conditions (Graves' disease and Addison's disease, respectively) in whom autoimmune destruction of the parathyroid glands had not taken place. In the first, a histologically normal parathyroid gland was observed at the time of subtotal thyroidectomy; and in the second, the hypoparathyroidism remitted spontaneously. Both patients had antibodies that reacted with the cell surface of bovine parathyroid cells and human embryonic kidney (HEK293) cells transfected with the extracellular calcium-sensing receptor (CaR) but not with nontransfected HEK293 cells. The antibodies also reacted with the same bands on Western analysis of extracts of bovine parathyroid tissue and CaR-transfected HEK293 cells that were identified by an authentic, polyclonal, anti-CaR antiserum and reacted with several peptides with sequences from the CaR's extracellular domain. These anti-CaR antibodies activated the receptor based on their ability to increase inositol phosphate accumulation, activate MAPK, and inhibit PTH secretion. These results, therefore, demonstrate that patients with the biochemical findings of primary hypoparathyroidism can harbor activating antibodies to the CaR, which, in the two cases studied here, did not produce irreversible destruction of the parathyroid glands.

Addison Disease↗

Postpartum maternal iodine status and the relationship to neonatal thyroid function.

Iodine deficiency in the postpartum period has the potential to affect neonatal neuropsychointellectual development. We performed a cross-sectional study involving 50 postpartum women and their neonates, measuring maternal urine iodine, breast milk iodine, and neonatal thyroid stimulating hormone (TSH), and examining their interrelationships. Women were studied at a median (range) of 4 (3-9) days postpartum. Moderate to severe iodine deficiency (defined by urine iodine concentration < 50 microg/L) was found in 29 of the 50 subjects (58%). The median +/- standard deviation (SD) urine iodine was 46.8 +/- 28.5 microg/L and the mean urine iodine expressed in micrograms per gram of creatinine was 86.6 +/- 45.6. The median (range) breast milk iodine was 84.0 microg/L (25.0-234.0). Breast milk iodine was significantly correlated with urine iodine in micrograms per gram of creatinine (r = 0.52, p < 0.001) but not with urine iodine measured in micrograms per liter (r = 0.19, p = 0.2). Six percent of neonates had whole-blood TSH values of greater than 5 mIU/L. Neonatal TSH levels were positively correlated with higher breast milk iodine (r = 0.42, p = 0.003). There was no significant correlation between neonatal TSH levels and the mother's urine iodine content. There is a high prevalence of iodine deficiency in these lactating postpartum subjects. Urine iodine as micrograms per gram of creatinine is a good predictor of breast milk iodine content. In our study, higher breast milk iodine was correlated with a higher neonatal TSH. The impact of breast milk iodine content on neonatal TSH levels and neuropsychointellectual development needs further study.

Adult↗

Shared care: gestational diabetes.

BACKGROUND: Gestational diabetes (GD) is a common problem in pregnancy with potentially serious adverse outcomes for the baby. The diagnosis also identifies women at increased risk of subsequently developing type 2 diabetes. OBJECTIVE: The uncertainty surrounding the level of glucose intolerance that should be treated as GD is highlighted. Strategies for screening are discussed, and the public health importance of GD as identifying women at increased risk of developing type 2 diabetes is raised and discussed. A simple strategy for the delivery of these interventions to women with a past history of GD is outlined. DISCUSSION: Gestational diabetes offers an ideal opportunity to identify one high risk group at risk of developing type 2 diabetes. Type 2 diabetes can be prevented or delayed in high risk groups by attention to weight control, exercise and by modifying other risk factors. This can be effectively and efficiently done through primary care, however, monitoring follow up of women is the challenge.

Diabetes Mellitus, Type 2↗

Neonatal thyroid-stimulating hormone concentrations in northern Sydney: further indications of mild iodine deficiency?

OBJECTIVE: To determine whether thyroid-stimulating hormone (TSH) concentrations in a large sample of neonates meet World Health Organization criteria for an iodine-replete population (< 3% of neonates with whole-blood TSH concentrations > 5 mlU/L), and, in a small subset of neonates, to examine the correlation between maternal urinary iodine and neonatal TSH concentrations. DESIGN: Cross-sectional study of neonatal whole-blood TSH values obtained as part of a routine newborn screening program. SETTING: Royal North Shore Hospital (RNSH) in northern Sydney. PARTICIPANTS: Two anonymous samples of neonates born at RNSH (1316 infants born between August 1998 and April 1999 and 1457 infants born between 1 March and 31 December 2000); and 84 infants whose mothers had attended RNSH between September 1998 and August 1999 and supplied a urine sample for iodine measurement. MAIN OUTCOME MEASURES: Iodine status of neonates (proportion with whole-blood TSH values > 5 mlU/L), and urine iodine concentrations of pregnant women. RESULTS: In the two large population samples of neonates, 8.1% (95% CI, 6.6%-9.5%) and 5.4% (95% Cl, 4.3%-6.6%), respectively, had whole-blood TSH values > 5 mlU/L (prevalence range for mild thyroid deficiency, 3%-19%). Comparing the TSH values of the 1316 anonymous infants and the 84 identified infants showed no difference between the proportions with TSH values > 5 mlU/L (8.1% v 10.7%, respectively; P = 0.39). Urine iodine concentrations in the 84 pregnant women indicated borderline mild iodine deficiency. TSH values in their 84 infants were positively correlated with maternal urine iodine concentrations. CONCLUSIONS: Our results suggest that the population of northern Sydney may have mild iodine deficiency. However, the expected relationship between maternal urine iodine levels and neonatal TSH concentrations was not found.

Congenital Hypothyroidism↗