Aidan McElduff

People With Mental Retardation Have an Increased Prevalence of Osteoporosis: A Population Study

Prevalence of and risk factors for osteoporosis in a community population of 94 young adults with mental retardation was examined. Results show lower bone mineral density in this group than in an age-matched reference population. Factors associated with low bone mineral density included small body size, hypogonadism, and Down syndrome in both genders and a high phosphate level in females. Low vitamin D levels were common in both genders, despite high levels of exposure to sunshine. A history of fracture was also common. Low bone mineral density and fracture were associated in females but not males. Because morbidity following fracture is likely to be more serious in this population, further investigation of osteoporosis and prevention strategies for both osteoporosis and fractures are important.

Maternal vitamin D deficiency, ethnicity and gestational diabetes

Aims  Vitamin D deficiency has been linked to impaired glucose metabolism. We determined whether serum 25‐hydroxyvitamin D (25OHD) is associated with glucose metabolism in pregnant women and the effect of ethnicity on this relationship.

Outcomes of pregnancies in women with pre-gestational diabetes mellitus and gestational diabetes mellitus; a population-based study in New South Wales, Australia, 1998–2002

Aim  To determine population‐based rates and outcomes of pre‐gestational diabetes mellitus (pre‐GDM) and gestational diabetes mellitus (GDM) in pregnancy.

Pulmonary Insulin Administration Using the AERx® System: Physiological and Physicochemical Factors Influencing Insulin Effectiveness in Healthy Fasting Subjects

BACKGROUND Orally inhaled insulin may provide a convenient and effective therapy for prandial glucose control in patients with diabetes. This study evaluated the influence of formulation pH and concentration and different respiratory maneuvers on pharmacokinetic and pharmacodynamic properties of inhaled insulin. METHODS Three, open-label crossover studies in a total of 23 healthy subjects were conducted in which the safety, pharmacokinetics, and pharmacodynamics of insulin inhalation were compared to subcutaneous (SC) injection into the abdomen of commercially available regular insulin. A novel, aerosol generating system (AERx Diabetes Management System, Aradigm Corporation, Hayward, CA) was used to deliver aqueous insulin bolus aerosols to the lower respiratory tract from formulations at pH 3.5 or 7.4 and concentrations of U250 (250 U/mL) or U500 (500 U/mL). RESULTS Time to maximum insulin concentration in serum (Tmax) after SC dosing occurred approximately 50-60 minutes with the time to minimum plasma glucose concentration (i.e., maximum hypoglycemic effect), (TGmin), occurring later, at around 100-120 minutes. In contrast, pulmonary delivery led to a significantly earlier Tmax (7-20 minutes) and TGmin (60-70 minutes), parameters that were shown to be largely unaffected by changing the pH or concentration of the insulin. However, investigation of changes in inhaled volume (achieved by different programming of the AERx system) for administration of the same sized aerosol bolus revealed significant effects. Significantly slower absorption and time to peak hypoglycemic activity occurred when aerosol delivery of insulin occurred during a shallow (approximately 40% vital capacity) as opposed to a deep (approximately 80% vital capacity) inspiration. In addition, it was shown that serum concentration of insulin increased immediately after a series of forced expiraratory maneuvers 30 minutes after inhaled delivery. CONCLUSIONS Pulmonary delivery of aqueous bolus aerosols of insulin in healthy subjects resulted in rapid absorption with an associated hypoglycemic effect quicker than is achieved after subcutaneous dosing of regular insulin. Inhaled insulin pharmacokinetics and pharmacodynamics were independent of formulation variables (pH, concentration) but affected by certain respiratory maneuvers.

Vitamin D and pregnancy: An old problem revisited

Vitamin D has historically been considered to play a role solely in bone and calcium metabolism. Human disease associations and basic physiological studies suggest that vitamin D deficiency is plausibly implicated in adverse health outcomes including mortality, malignancy, cardiovascular disease, immune functioning and glucose metabolism. There is considerable evidence that low maternal levels of 25 hydroxyvitamin D are associated with adverse outcomes for both mother and fetus in pregnancy as well as the neonate and child. Vitamin D deficiency during pregnancy has been linked with a number of maternal problems including infertility, preeclampsia, gestational diabetes and an increased rate of caesarean section. Likewise, for the child, there is an association with small size, impaired growth and skeletal problems in infancy, neonatal hypocalcaemia and seizures, and an increased risk of HIV transmission. Other childhood disease associations include type 1 diabetes and effects on immune tolerance. The optimal concentration of 25 hydroxyvitamin D is unknown and compounded by difficulties in defining the normal range. Whilst there is suggestive physiological evidence to support a causal role for many of the associations, whether vitamin D deficiency is a marker of poor health or the underlying aetiological problem is unclear. Randomised controlled trials of vitamin D supplementation with an appropriate assessment of a variety of health outcomes are required.

Recommended changes to diagnostic criteria for gestational diabetes: Impact on workload

Background:  Gestational diabetes mellitus (GDM) is recognised as a significant problem in pregnancy. Changes to GDM diagnostic criteria have been proposed following analysis of data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. We sought to assess the impact on the workload for GDM management in Australia that would occur if these changes were adopted.

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 mothers 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.

Perinatal risk factors for early onset of Type 1 diabetes in a 2000–2005 birth cohort

Aims  To examine perinatal risk factors for the onset of Type 1 diabetes before 6 years of age, in a 2000–2005 Australian birth cohort.

Issues With the Diagnosis and Classification of Hyperglycemia in Early Pregnancy

In 2010, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) panel published consensus-based recommendations on the diagnosis and classification of hyperglycemia in pregnancy (1). Within that document, the recommendations regarding early pregnancy testing were designed to facilitate early detection and treatment of hyperglycemia (HbA1c ≥6.5% [48 mmol/mol], fasting venous plasma glucose ≥7.0 mmol/L, random plasma glucose ≥11.1 mmol/L with confirmation) that, outside pregnancy, would be classified as diabetes. The term “overt diabetes” was suggested to describe these women. Subsequently, the World Health Organization (WHO) adopted the IADPSG criteria with some modifications and promoted the use of the term “diabetes in pregnancy” (2) for this group. Cognizant that milder degrees of hyperglycemia would also be detected by early pregnancy testing, the IADPSG also recommended that fasting …

Gestational Diabetes Mellitus: NICE for the U.S.?: A comparison of the American Diabetes Association and the American College of Obstetricians and Gynecologists guidelines with the U.K. National Institute for Health and Clinical Excellence guidelines

OBJECTIVE To compare recent U.S. and U.K. guidelines on gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS The guidelines from the American Diabetes Association, the American College of Obstetricians and Gynecologists, and the National Institute for Health and Clinical Excellence (NICE) in the U.K. were collated and compared using a general inductive approach. RESULTS There are substantial differences in the recommendations between the U.K. and the U.S. guidelines. Of particular note are the reduced sensitivities of the early and later antenatal and postnatal screening and diagnostic criteria. NICE undertook a cost-effectiveness analysis using lower prevalence estimates and limited outcomes and still showed screening for GDM to be cost-effective. CONCLUSIONS The latest NICE recommendations appear to reduce access to proven, cost-effective management of GDM, an issue relevant in the current U.S. health care policy debate.