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Biomedical subjects

R Urquhart

Publications and source records attributed to R Urquhart.

13 recordsLinked to original sources
PubMed2006

The insulin sensitiser pioglitazone does not influence skin microcirculatory function in patients with type 2 diabetes treated with insulin.

AIMS/HYPOTHESIS: Insulin resistance is associated with abnormal microvascular function. Treatment with insulin sensitisers may provoke oedema, suggesting microvascular effects. The mechanisms underlying the peripheral oedema observed during glucose-lowering treatment with thiazolidinediones are unclear. Therefore we examined the effect of pioglitazone on microvascular variables involved in oedema formation. METHODS: Subjects (40-80 years) with type 2 diabetes and on insulin were randomised to 9 weeks of pioglitazone therapy (30 mg/day; n=14) or placebo (n=15). The following assessments were performed at baseline and 9 weeks: microvascular filtration capacity; isovolumetric venous pressure; capillary pressure; capillary recruitment following venous or arterial occlusion; postural vasoconstriction; and maximum blood flow. A number of haematological variables were also measured including vascular endothelium growth factor (VEGF), IL-6 and C-reactive protein (CRP). RESULTS: Pioglitazone did not significantly influence any microcirculatory variable as compared with placebo (analysis of covariance [ANCOVA] for microvascular filtration capacity for the two groups, p=0.26). Mean VEGF increased with pioglitazone (61.1 pg/ml), but not significantly more than placebo (9.76 pg/ml, p=0.94). HbA(1c) levels and the inflammatory markers IL-6 and CRP decreased with pioglitazone compared with placebo (ANCOVA: p=0.009, p=0.001 and p=0.004, respectively). CONCLUSIONS/INTERPRETATION: Pioglitazone improved glycaemic control and inflammatory markers over 9 weeks but had no effect on microcirculatory variables associated with oedema or insulin resistance in type 2 diabetic patients treated with insulin.

Adult↗
PubMed2005

Long-term efficacy and tolerability of add-on pioglitazone therapy to failing monotherapy compared with addition of gliclazide or metformin in patients with type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this analysis was to examine the long-term effects of pioglitazone or gliclazide addition to failing metformin monotherapy and pioglitazone or metformin addition to failing sulphonylurea monotherapy in patients with type 2 diabetes. METHODS: Two 2-year, randomised, multicentre trials were performed in patients with inadequately controlled type 2 diabetes (HbA1c 7.5-11% inclusive), who were receiving either metformin or a sulphonylurea at > or = 50% of the maximum recommended dose or at the maximum tolerated dose. In the first study, patients on metformin received add-on therapy with pioglitazone (15-45 mg/day, n = 317) or gliclazide (80-320 mg/day, n = 313). In the second study, patients on sulphonylurea therapy were randomised to receive add-on therapy with either pioglitazone (15-45 mg/day, n = 319) or metformin (850-2,550 mg/day, n = 320). HbA(1)c, fasting plasma glucose, insulin and lipids were investigated. RESULTS: At week 104, the mean reduction from baseline in HbA(1)c was 0.89% for pioglitazone and 0.77% for gliclazide addition to metformin (p = 0.200). There was a statistically significant between-group difference for the change in mean fasting plasma glucose at week 104 (-1.8 mmol/l for pioglitazone vs -1.1 mmol/l for gliclazide, p < 0.001). There were no significant differences in changes from baseline in glycaemic parameters for pioglitazone compared with metformin addition to sulphonylurea therapy. Whether added to metformin or sulphonylurea, pioglitazone caused significantly greater decreases in triglycerides and significantly greater increases in HDL cholesterol than the comparator regimens (p < or = 0.001). There were decreases in LDL cholesterol in the comparator groups and these were significantly different from the small changes observed with pioglitazone (p < 0.001). All treatment regimens were well tolerated. There were weight increases of 2.5 kg and 3.7 kg in the pioglitazone and 1.2 kg in the gliclazide add-on groups, and there was a mean decrease of 1.7 kg in the metformin add-on group. CONCLUSIONS/INTERPRETATION: As add-on therapy to existing sulphonylurea or metformin therapy, pioglitazone improved glycaemic control and this improvement was sustained over 2 years. Furthermore, there were potential benefits in terms of improvements in specific lipid abnormalities. This could offer an advantage over the addition of other oral agents in the long-term treatment of diabetes.

Adult↗
PubMed2005

Pioglitazone elicits long-term improvements in insulin sensitivity in patients with type 2 diabetes: comparisons with gliclazide-based regimens.

AIMS/HYPOTHESIS: Recent studies have demonstrated that pioglitazone (PIO) has beneficial effects on insulin sensitivity compared with placebo in patients with type 2 diabetes. The effects of PIO and gliclazide (GLIC)-based therapy on insulin sensitivity have not previously been directly compared. This analysis aimed to compare the effects of 52 weeks of treatment with PIO (30-45 mg/day) and GLIC (80-320 mg/day), both titrated to maximum tolerable doses, as monotherapy or in combination with metformin (MET), on insulin sensitivity and lipid parameters known to be related to insulin sensitivity in patients with type 2 diabetes. METHODS: We performed an analysis of 1,880 patients with inadequately controlled type 2 diabetes (HbA1c 7.5-11.0%) who were participants in two parallel-group, double-blind, double-dummy, randomised, multicentre, clinical trials. Measures of insulin sensitivity and lipids were assessed. RESULTS: The PIO- and GLIC-based regimens produced similar levels of glycaemic control (HbA1c). In both trials, insulin sensitivity as assessed using the homeostasis model assessment was improved in patients receiving PIO, but decreased in those receiving GLIC (mean change, baseline to endpoint: PIO 15.5, GLIC -15.6; p<0.001 and PIO+MET 18.9, GLIC+MET -5.3; p<0.001). Improvements in the atherogenic index of plasma (mean change: PIO -0.17, GLIC -0.08; p<0.001 and PIO+MET -0.17, GLIC+MET -0.02; p<0.001), triglycerides (mean change, mmol/l: PIO+MET -0.62, GLIC+MET -0.22; p<0.001) and NEFA (mean change, mmol/l: PIO+MET -0.12, GLIC+MET-0.05; p<0.001) were greater in PIO-treated patients than in patients receiving GLIC. CONCLUSIONS/INTERPRETATION: The PIO-based regimens resulted in improved insulin sensitivity and more favourable insulin sensitivity-related lipid profiles compared with the GLIC-based regimens. These benefits may be important in the management of cardiovascular risk in patients with type 2 diabetes.

Adult↗
PubMed2005

Long-term effects of pioglitazone and metformin on insulin sensitivity in patients with Type 2 diabetes mellitus.

AIM: Despite their comparable glycaemic effects in patients with Type 2 diabetes mellitus (T2DM), pioglitazone and metformin may have different effects on insulin sensitivity because they have different mechanisms of action. We studied the changes in insulin sensitivity, as assessed by the Quantitative Insulin Sensitivity Check Index (QUICKI), in patients with T2DM who used metformin or pioglitazone as monotherapy or in combination therapy with sulphonylurea. METHODS: Data in this report are from two multicentre, randomized, double-blind, double-dummy studies conducted in Europe (monotherapy) or in Europe and Canada (combination therapy study). Patients were randomized to 52 weeks of treatment consisting of a 12-week forced titration period and a 40-week maintenance period. HbA(1c), fasting plasma glucose (FPG) and fasting serum insulin (FSI) were quantified from a single blood sample at weeks 0, 8, 16, 24, 32, 42 and 52. Insulin sensitivity was assessed with QUICKI, which is calculated from FSI and fasting blood glucose (FBG) concentrations using the formula 1/(log(10) FSI + log(10) FBG). Time course effects of the treatments were compared by repeated measures analysis of covariance. RESULTS: As monotherapy, pioglitazone and metformin increased QUICKI compared with baseline (baseline vs. end point [mean +/- sem]; pioglitazone [0.303 +/- 0.001 vs. 0.321 +/- 0.001; P < 0.001] and metformin [0.304 +/- 0.001 vs. 0.315 +/- 0.001; P < 0.001]). Pioglitazone increased insulin sensitivity more than metformin from week 4 through week 52. There were significant increases in QUICKI from baseline in both combination therapy groups (baseline vs. end point; pioglitazone + sulphonylurea [0.305 +/- 0.001 vs. 0.319 +/- 0.001; P < 0.001] and metformin + sulphonylurea [0.306 +/- 0.001 vs. 0.317 +/- 0.001; P < 0.001]). Overall, pioglitazone + sulphonylurea significantly increased insulin sensitivity more than metformin + sulphonylurea. CONCLUSION: Pioglitazone differed from metformin in its effects on insulin sensitivity despite both drugs having comparable glycaemic effects.

Adult↗
PubMed2004

Effects of pioglitazone on the components of diabetic dyslipidaemia: results of double-blind, multicentre, randomised studies.

A total of 3,713 patients with poorly controlled type 2 diabetes were enroled into four multicentre, double-blind studies and randomised to receive pioglitazone, sulphonylurea, metformin or a combination of two of these agents for up to 52 weeks. Data from patients with a lipid evaluation, at week 52, were pooled, and treatment groups were compared using analysis of covariance. Pioglitazone, alone or combined with metformin or sulphonylurea, resulted in mean decreases in triglycerides (-9 to -11%), total/HDL cholesterol ratio (-9 to -10%) and free fatty acid (-0.051 to -0.123 mmol/l) and mean increases in HDL cholesterol (17 to 20%). The sustained, favourable effects of pioglitazone on important components of diabetic dyslipidaemia may contribute to reduced cardiovascular disease risk, among patients with type 2 diabetes.

Adult↗
PubMed1992

Clinical versus ultrasound estimation of fetal weight.

A prospective study was carried out on 50 patients who had their fetal weight estimated by 3 clinicians of different seniority and compared to the ultrasound estimated fetal weights using 3 different formulas. All the patients delivered within 24 hours of their clinical and ultrasound estimates. A wide range of birth-weights (1,800-4,500 g) was estimated among the 3 different races (Malay, Chinese and Indians). The results showed that there was no significant difference in birth-weight estimation amongst the 3 clinicians as well as between the 3 ultrasound formulas used. There was however significant difference between these 2 groups when compared with the actual birthweight with clinical estimation being superior to ultrasound estimation in our population. This level of significance did not extend beyond 4,000 g fetal weight (actual) thus making both clinical and ultrasound estimation of fetal weight equally accurate after 4,000 g. This has important implications for developing countries where there is a lack of technologically advanced ultrasound machines capable of doing sophisticated functions like fetal weight estimations but has experienced clinicians who could perform this function equally well if not better.

Birth Weight↗
PubMed1992

omega-6 and omega-3 fatty acids: monolayer packing and effects on bilayer permeability and cholesterol exchange.

It has been suggested that the polyunsaturated omega-3 fatty acid, docosahexaenoic acid (DHA), can adopt unique closely packed arrays in lipid bilayers (Glomset and Applegate. (1986) J. Lipid Res. 27, 658-680). These conformations are predicted on the basis of molecular dynamics calculations and are in contrast to the expanded conformations characteristic of omega-6 unsaturated fatty acids. It has also been suggested that close packing of omega-3 acyl chains could have a substantial affect on the physical properties of lipid bilayers (e.g. permeability). We report here some experimental tests of these predictions. Surface pressure-area experiments have been carried out on DHA and its mixtures with stearic and oleic acids. At low surface pressures DHA is more expanded than oleic acid. Extrapolation to the high surface pressures characteristic of lipid bilayers indicates that the area per molecule of DHA is only marginally less than that for oleic acid. Thus there is no compelling evidence to suggest that the average area per molecule of the omega-3 fatty acid is substantially different from the omega-6 fatty acid at high surface pressures. Experiments also show that the permeability of bilayers to glucose and the rates of dissociation of pyrenyl cholesterol from bilayers were similar for bilayers containing DHA compared to bilayers containing oleic acid or linoleic acid.

Cholesterol↗
PubMed1991

Grandmultiparity in Malaysian women.

Grandmultiparity is an ill defined term, but it is generally believed that increasing parity after the fifth delivery increases the risks of child bearing for both the mother and fetus. Four hundred seventy-seven women aged less than 35 years of parity 5 and above who delivered during one year period at the University Hospital, Kuala Lumpur were studied. There were 406 women of parity 5 and 6 and 71 women of parity 7 and above. The 2 groups as a whole comprised 7.5% of the obstetric population for that year. Obstetric performance in the 2 groups of grandmultipara was compared with 1,135 women, aged 25 to 34 years, having their second baby during the same period. Women of parity 7 and above were significantly more likely to be from lower socioeconomic groups, and suffer from anaemia, hypertension and pre-eclampsia. They were also significantly at risk of preterm delivery and delivering infants weighing less than 2.5 kg. In addition, the perinatal mortality rate was significantly greater in the highly parous group (Para greater than 7) than in women of parity 5 and 6 or the control group. Apart from a significant increase in the incidence of anaemia, women of parity 5 and 6 had a similar obstetric performance and perinatal outcome to that of the control group. We conclude that grandmultiparity per se is not an obstetric risk factor until after the seventh delivery. These findings have implications for those who plan the provision of obstetric services for the community.

Adult↗
PubMed1991

Efficacy of laparoscopic electrocoagulation in infertile patients with minimal or mild endometriosis.

The cumulative pregnancy rates in 17 infertile patients with minimal or mild endometriosis who underwent laparoscopic electrocoagulation were compared with those of 20 similar patients who underwent only diagnostic laparoscopy. A life-table method of analysis was used. No significant differences in pregnancy rates was evident at either 6 months (p greater than 0.5) or 12 months (p greater than 0.5) of follow-up. These results question the use of laparoscopic electrocoagulation for the treatment of infertile patients with minimal or mild endometriosis.

Adult↗
PubMed1991

Causes for infertility: a comparative study.

A representative group of 204 infertile couples from Kuala Lumpur, Malaysia were compared to a similar group of 633 couples from Aberdeen, UK in an attempt to study if there was any regional difference in the pattern of infertility seen. The protocol for investigation and diagnostic criteria for both centres were standardised. A significant difference (X2 = 63.43; p less than 0.001) was seen. The reasons for these differences are discussed.

Adolescent↗