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Biomedical subjects

A McElduff

Publications and source records attributed to A McElduff.

At least 19 recordsLinked to original sources

Is sex hormone-binding globulin associated with glucose tolerance?

BACKGROUND/AIM: Women with a reduced concentration of sex hormone-binding globulin (SHBG) in the first trimester of pregnancy are at increased risk of developing gestational diabetes. Furthermore, a lower concentration of SHBG in women with gestational diabetes identifies women at increased likelihood of requiring insulin treatment. The aim of this study was to explore the relationship of SHBG concentration in pregnancy to insulin resistance and glucose tolerance. METHODS: Prospective cohort study of 220 pregnant women who attended The Royal North Shore Hospital in Sydney, Australia between August 2002 and June 2003 for their 75-g glucose tolerance test. All tests were performed in the morning after the women had fasted for at least 10 h. To test for differences between patients with or without gestational diabetes, t-tests and chi-square tests were used. Stepwise linear regression was used to determine the independent predictors of SHBG. RESULTS: The mean concentration of SHBG increased linearly with gestational age. Statistically significant predictors of SHBG from the stepwise regression were gestational age (P < 0.001), insulin resistance (P < 0.001) and body mass index (P = 0.003). Glucose tolerance as assessed by either a fasting or 2-h glucose tolerance test did not predict SHBG concentration in this population. In addition, there was no significant difference in the concentration of SHBG between patients categorized as normal glucose tolerance or gestational diabetes (P = 0.77). This remained the case when SHBG was expressed as SHBG/insulin ratio as suggested by Bartha et al. (Sex hormone-binding globulin in gestational diabetes. Acta Obstet Gynecol Scanda 2000; 79: 839-845) (P = 0.10). CONCLUSION: In a cross-sectional study of pregnant women, we find no association between SHBG concentration and glucose tolerance.

Adult↗

Intravenous pamidronate in the treatment and prevention of osteoporosis.

BACKGROUND: Potent oral bisphosphonates are the mainstay of therapy for osteoporosis. However, there are patients who cannot have oral bisphosphonates (e.g. because of gastrointestinal side-effects). Therefore, we wanted to examine the effects of intermittent i.v. pamidronate (APD) on bone mineral density (BMD) in patients who needed bisphosphonate therapy but could not have oral bisphosphonates. AIM: To assess BMD before and after intermittent i.v. APD in patients requiring a bisphosphonate either for the prevention of osteoporosis on concurrent steroid therapy or for the treatment of osteoporosis. METHODS: This was a retrospective audit of 84 consecutive patients at risk of fractures commencing APD between October 1997 and May 2000. Patients were treated with intermittent i.v. APD. BMD as measured by dual-energy X-ray absorptiometry before and after APD was the main outcome. RESULTS: The mean length of treatment and mean total APD dose were 16.8 +/- 7.0 months and 186.1 +/- 79.5 mg respectively. The reasons for using APD were failure to qualify for oral bisphosphonates on the pharmaceutical benefits scheme due to lack of documented minimal trauma fractures (58%), symptomatic gastro--oesophageal disease (20%), intolerance of oral bisphosphonates (18%) and lack of efficacy of calcitriol (4%). Mean baseline T-score at lumbar (L) 2-4 spine and femoral neck were -1.54 +/- 1.22 and - 2.87 +/- 1.19, respectively. From baseline to after APD treatment, there was a significant increase in L2-4 BMD (0.883 +/- 0.175 vs 0.912 +/- 0.176 g/cm(2), P < 0.001, mean increase +3.5%), in femoral neck BMD (0.667 +/- 0.137 vs 0.680 +/- 0.134 g/cm(2), P= 0.001, mean increase +2.1%) and in trochanteric BMD (0.549 +/- 0.129 vs 0.566 +/- 0.132 g/cm(2), P < 0.001, mean increase +3.1%). One-third of the patients were on oral glucocorticoids at the time of the present study and they had a similar increase in BMD compared to patients not on gluco-corticoids. Mild side-effects occurred in seven patients, none of whom discontinued treatment. CONCLUSION: Intermittent APD increases BMD and may be a suitable alternative for patients who cannot have oral bisphosphonates.

Absorptiometry, Photon↗

Outcome of pregnancy complicated by pre-gestational diabetes--improvement in outcomes.

UNLABELLED: Pre-gestational diabetes mellitus (DM) is associated with adverse fetal and maternal outcomes. We have previously reported outcomes for women with DM. To determine whether review, and discussion of the results, affected outcomes, pregnancies in women with DM from July 1998 to July 2001 were examined in a prospective cohort study. The results were then compared to the results from the previous review. METHODS: Thirty-five pregnancies were included (24 in 20 women with Type 1 DM, 11 in 11 with Type 2 DM). Type 1 women were more likely to be Caucasian (100% versus 22.2%, p < 0.0001), and had a longer duration of diabetes (13 +/- 6 versus 3 +/- 2 years, p < 0.0001). RESULTS: Pregnancy planning rates improved significantly for Type 1 DM (62.5% planned versus 18.9% in original study p = 0.01), and did not change for Type 2 DM. Caesarean section (LSCS) rate was high in the original study, particularly in Type 1 DM (77%), and was lower after review (47.6% in Type 1 DM p < 0.05 compared to original study, and 44.4% in Type2 DM, p = ns). Planning was associated with lower HbA1c before and during pregnancy (6.0 +/- 1.4% versus 8.1 +/- 1.8% (p = 0.0035), and 5.5 +/- 1 versus 6.5 +/- 1.5% (p < 0.001)), greater gestational age at delivery (38.2 versus 36.2 weeks p = 0.0318) and lower rate of LSCS (31.6% versus 72.7% (p = 0.0295)). CONCLUSIONS: It is important to continue improving pre-pregnancy planning. Extensive discussions involving a multi-disciplinary team improved planning rates and decreased the LSCS rate while maintaining outcomes.

Adult↗

Serum chromium does not predict glucose tolerance in late pregnancy.

BACKGROUND: Chromium is an essential element in human nutrition. Serum concentrations of chromium are not well characterized during pregnancy or in gestational diabetes mellitus. OBJECTIVE: The objective of this study was to determine whether low plasma chromium concentrations (< or =3 nmol/L) are associated with altered glucose, insulin, or lipid concentrations during pregnancy. DESIGN: The study was conducted prospectively and took place at the medical obstetric clinic of a tertiary referral hospital. Seventy-nine women with abnormal results of a 50-g glucose challenge test in the third trimester of pregnancy were studied. All women had a formal 75-g oral-glucose-tolerance test, and fasting insulin, lipid, and chromium concentrations were determined. Chromium was measured by graphite furnace atomic absorption spectrometry. RESULTS: The median chromium concentration was 2 nmol/L (95% CI: 0, 12). There were no significant differences in age, plasma glucose, insulin, lipids, calculated insulin resistance, or calculated ss cell function between women with normal and those with abnormal (< or =3 nmol/L) chromium concentrations. CONCLUSIONS: Plasma chromium during pregnancy does not correlate with glucose intolerance, insulin resistance, or serum lipids. Plasma chromium concentrations may not accurately reflect tissue stores of chromium. Several trials showed a beneficial effect of chromium supplementation on glucose tolerance, insulin, and lipids. A method for assessing body chromium stores is required to allow further study.

Adult↗

Effects of ethnicity on glucose tolerance, insulin resistance and beta cell function in 223 women with an abnormal glucose challenge test during pregnancy.

This study was conducted to investigate body-mass-index (BMI), insulin resistance and beta cell function in a group of pregnant women. Two hundred and twenty-three consecutive women with an abnormal 50 g glucose challenge test in the third trimester were studied. All underwent oral glucose tolerance testing; 97 had a 100 g test and 126 a 75 g test. Fasting insulin was measured. Insulin resistance and beta cell function were calculated using the homeostasis model. Among the 136 Caucasian, 60 Asian, 11 Indian and 16 Arabic women studied, there were no age differences. Arabic women had higher parity (p < 0.05). Asian women had lower BMI than Caucasian (p < 0.001), Indian (p < 0.01), and Arabic women (p < 0.01). Women with gestational diabetes had higher insulin resistance than women with normal glucose tolerance (2.9+/-4.0 vs. 2.3 +/- 2.5 p = 0.025). Women with gestational diabetes tended to have lower beta cell function 199 +/- 203 vs. 247 +/-380 p = 0.08). Asian women had higher glucose levels than Caucasian women after 50 g challenge (8.9 +/- 2.1 mmol/1 vs. 8.6 +/- 1.6; p = 0.034). Asian women were more likely to have gestational diabetes than Caucasian women (31.7% vs. 14%; p = 0.02). Fasting glucose and insulin were comparable in Asian and Caucasian women. Mean insulin resistance and beta cell function in Asian and Caucasian women were not significantly different. We concluded that Asian women had lower BMI than Caucasian women. Women with gestational diabetes were more insulin resistant. Insulin resistance and beta cell function in Asian and Caucasian women are similar. Gestational diabetes in Asian women is of similar aetiology to that seen in Caucasian women, but occurs at a lower BMI.

Adult↗

The relationship among homocysteine, creatinine clearance, and albuminuria in patients with type 2 diabetes.

OBJECTIVE: Although it is accepted that elevated plasma homocysteine (tHcy) levels occur in end-stage renal disease and type 2 diabetes, the changes with milder renal dysfunction (e.g., microalbuminuria) are less clearly established. This study explores the relationship among tHcy, creatinine clearance (Ccr), and albumin excretion rate (AER) in a population with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 260 patients with type 2 diabetes were screened in our outpatient clinic during 10 months. Fasting blood samples were collected, and AER was calculated from an overnight timed urine sample. Ccr was calculated using the Cockroft-Gault formula. RESULTS: A total of 198 subjects (76%) had normoalbuminuria (<20 microg/min), 50 subjects (19%) had microalbuminuria (20-200 microg/min), and 12 subjects (5%) had macroalbuminuria (>or=200 microg/min). Those with microalbuminuria had higher levels of tHcy than those with normoalbuminuria (13.2 +/- 7.8 vs. 11.3 +/- 4.6 micromol/l, P < 0.05). Patients were then subdivided based on low Ccr (<80 ml x min(-1) x 1.73 m(-2)) and normal Ccr (>or=80 x min(-1) x 1.73 m(-2)). None of the patients with macroalbuminuria had normal Ccr. In those with normoalbuminuria, tHcy levels were higher than in those with low Ccr than in those with normal Ccr (12.0 +/- 4.6 vs. 10.0 +/- 4.4 micromol/l, P < 0.01). The same was found for those with microalbuminuria (low Ccr versus normal Ccr: 14.6 +/- 9.0 vs. 10.2 +/- 2.8 micromol/l, P < 0.02). For normal Ccr, tHcy was similar irrespective of AER (normoalbuminuria versus microalbuminuria: 10.0 +/- 4.4 vs. 10.2 +/- 2.8 micromol/l, NS). For low Ccr, tHcy was higher in those with microalbuminuria versus normoalbuminuria (14.6 +/- 9.0 vs. 12.0 +/- 4.6 micromol/l, P = 0.01). Using multivariate regression, Ccr, but neither AER nor the presence of albuminuria, was an independent predictor of tHcy. CONCLUSIONS: These data strongly suggest that in patients with type 2 diabetes, the relationship between plasma tHcy and AER is largely due to associated changes in renal function, as defined by Ccr.

Aged↗

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.

Administration, Inhalation↗

Outcome of pregnancies complicated by pre-gestational diabetes mellitus.

Pregestational diabetes mellitus (DM) is associated with adverse fetal and maternal outcomes. Studies suggest that optimal control of diabetes before and during pregnancy minimises these risks. There are few recent reviews of outcomes of pregnancies complicated by DM in Australia. Ninety-three pregnancies in women with DM at our hospital since 1989 were identified. We collected data for maternal age, type of diabetes, duration of therapy, complications of diabetes, maternal complications of pregnancy and fetal outcomes including malformations. The rate of pregnancy planning with optimal glycaemic control at conception was low in our population, particularly in patients with Type 1 diabetes. Women who smoked had worse glycaemic control, and a higher rate of miscarriage. There was a high rate of Caesarean section, particularly in those women with Type 1 diabetes (77.4%). The rate of Caesarean section was lower in planned pregnancies. There were no perinatal deaths. The number of neonates with major congenital anomalies was high (13%) in the Type 1 population. It is important to increase the rates of prepregnancy planning and to optimise glycaemic control before pregnancy. In many cases there has been a long interval between diagnosis and pregnancy, so all women with diabetes should receive counselling at frequent intervals about pregnancy and the importance of planning. Women who planned their pregnancies had improved outcomes, with decreased rate of Caesarean section, better glycaemic control and better neonatal Apgar scores. Women with diabetes should not smoke during pregnancy because of the increased risk of miscarriage and poorer glycaemic control.

Adult↗

Prevalence of positive anti-neutrophil cytoplasmic antibody (ANCA) in patients receiving anti-thyroid medication.

OBJECTIVE: Vasculitis is a rare complication of anti-thyroid medications. There are 32 cases of anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis in association with anti-thyroid medication reported in the English literature. The objectives of this study were to assess the frequency of positive ANCA in patients on long-term anti-thyroid medication, and to follow patients prospectively from commencement of medication to determine whether they became ANCA-positive after therapy. DESIGN: Prospectively collected cross-sectional study of two groups of patients: (i) who had received long-term (>18 months) anti-thyroid medication, and (ii) newly diagnosed thyrotoxicosis before commencement of anti-thyroid medication attending clinic between 28 April 1998 and 30 September 1998. Data were collected for age, sex, ethnicity, underlying thyroid disease, medication and duration, and symptomatology. RESULTS: Eight of 30 patients on long-term anti-thyroid medication (26.7%) were ANCA-positive. All ANCA-positive patients were female, seven were taking propylthiouracil (PTU) at the time of testing. ANCA-positive patients had taken PTU for a mean +/- s.d. of 7.9+/-10.2 years, compared with 0.8+/-2.2 years in ANCA-negative patients (Mann-Whitney, P<0.0001). The ten patients with newly diagnosed thyrotoxicosis were ANCA-negative before commencement of carbimazole. One (10%) became ANCA-positive within 8 months of therapy. CONCLUSIONS: In our population, ANCA-positivity in association with long-term anti-thyroid medication is common (26.7%). One patient who was ANCA-negative prior to anti-thyroid therapy has become ANCA-positive. ANCA should be tested in patients receiving long-term anti-thyroid medications, and in patients with adverse reactions. As PTU is more commonly associated with vasculitis and positive ANCA, carbimazole may be the preferred medication for long-term use. Patients with positive ANCA should be followed, and considered for definitive anti-thyroid therapy, to allow cessation of medication. ANCA-positivity may resolve after cessation of anti-thyroid medication.

Adult↗

Iodine deficiency in ambulatory participants at a Sydney teaching hospital: is Australia truly iodine replete?

OBJECTIVE: To assess iodine status in four separate groups--pregnant women, postpartum women, patients with diabetes mellitus and volunteers. DESIGN AND SETTING: Prospective cross-sectional study at a tertiary referral hospital in Sydney. PARTICIPANTS: 81 pregnant women attending a "high risk" obstetric clinic; 26 of these same women who attended three months postpartum; 135 consecutive patients with diabetes mellitus attending the diabetes clinic for an annual complications screen; and 19 volunteers. There were no exclusion criteria. METHODS: Spot urine samples were obtained, and urinary iodine was measured by inductively coupled plasma mass spectrometer. OUTCOME MEASURES: Iodine status based on urinary iodine concentration categorised as normal (> 100 micrograms/L), mild deficiency (51-100 micrograms/L) and moderate to severe deficiency (< 50 micrograms/L). RESULTS: Moderate to severe iodine deficiency was found in 16 pregnant women (19.8%), five postpartum women (19.2%), 46 patients with diabetes (34.1%) and five volunteers (26.3%). Mild iodine deficiency was found in an additional 24 pregnant women (29.6%), nine postpartum women (34.6%), 51 patients with diabetes (37.8%) and 9 normal volunteers (47.4%). Median urinary iodine concentration was 104 micrograms/L in pregnant women, 79 micrograms/L in postpartum women, 65 micrograms/L in patients with diabetes mellitus and 64 micrograms/L in volunteers. CONCLUSIONS: The high frequency of iodine deficiency found in our participants suggests that dietary sources of iodine in this country may no longer be sufficient. Further population studies are required.

Adult↗

Measurement of free thyroxine (T4) levels in pregnancy.

Free T4 and TSH were measured in 119 pregnant women. Twenty of these women had the free T4 measured a second time during the pregnancy; 35 of the 119 had the free T4 measured by 2 different methods. The results showed that free T4 fell as pregnancy progressed but even at the early stages of pregnancy many measured free T4 concentrations were below the lower end of the nonpregnant normal range. This remained the case when the measurement was made by a dialysis kit method. These results challenge the current widely-accepted statement that free T4 concentrations remain within the normal nonpregnant range during pregnancy. This study highlights the need for each laboratory to develop its own normal range for free T4 levels in pregnancy.

Adult↗