S F O'Brien

Royal Perth Hospital, Perth City, Western Australia, Australia

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Publications (7)25.9 Total impact

  • S F O'Brien · G F Watts · D.A. Playford · V Burke · D N O'Neal · J D Best
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    ABSTRACT: We examined endothelial function (nitric-oxide mediated) in 29 men with diet-treated non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and 18 male age-matched controls. Forearm blood flow was measured by venous occlusive plethysmography during intra-arterial administration of acetylcholine (ACh, 7.5 and 15 microg min(-1)) and sodium nitroprusside (SNP, 3 and 10 microg min(-1)). LDL particle size was estimated by non-denaturing gel electrophoresis. Serum lipids, blood pressure, and glycated haemoglobin were also measured. LDL particle size was smaller (p = 0.048) in the diabetic patients than controls. In the diabetic patients, LDL particle size was a significant positive predictor (p = 0.01) of the area under the dose-response curve for ACh, after adjusting for age, HbA1c, systolic BP, and cholesterol (R2 0.20). In stepwise regression including serum lipid and lipoprotein concentrations and LDL particle size, decreased HDL cholesterol was the best predictor of an impaired vasodilatory response to ACh. Vasodilatory responses to sodium nitroprusside were not significantly correlated with LDL particle size or serum lipid and lipoprotein concentrations. We conclude that in men with NIDDM, small, dense LDL particle size is associated with abnormal endogenous release of nitric oxide. The contribution of small, dense LDL particles to the development of endothelial dysfunction and early diabetic vasculopathy may not, however, be as great as decreased HDL cholesterol.
    No preview · Article · Nov 1997 · Diabetic Medicine
  • S F O'Brien · J K Powrie · G F Watts

    No preview · Article · Apr 1997 · Annals of Clinical Biochemistry
  • G F Watts · S F O'Brien · W Silvester · JA Millar
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    ABSTRACT: 1. We measured endothelium-dependent and independent dilatation of forearm resistance arteries in 29 men with diet-treated non-insulin-dependent diabetes mellitus and 18 age- and sex-matched control subjects. None of the diabetic patients had hypercholesterolaemia, overt hypertension or microproteinuria. 2. We examined endogenous and exogenous nitric oxide-mediated vasodilatation by measuring forearm blood flow with venous occlusive plethysmography after administration of acetylcholine (7.5 and 15 micrograms/min) and sodium nitroprusside (3 and 10 micrograms/min), respectively, into the brachial artery. NG-monomethyl-L-arginine was also infused to study the inhibition of basal and stimulated release of nitric oxide. 3. The vasodilatory response to acetylcholine, expressed as area under curve, was significantly decreased in the diabetic patients compared with the control subjects (P = 0.019). NG-monomethyl-L-arginine significantly reduced basal (P < 0.001) and acetylcholine-stimulated blood flow (P < 0.02) in both groups. The vasodilatory response (also expressed as area under curve) to sodium nitroprusside was significantly less (P = 0.044) in the diabetic patients than in the control subjects. 4. In the diabetic patients, impaired vasodilatory responses to acetylcholine were significantly correlated with higher serum triacylglycerols (P = 0.048) and lower high-density lipoprotein-cholesterol concentrations (P = 0.007); the association with high-density lipoprotein was independent of age, glycated haemoglobin and blood pressure. Sodium nitroprusside responses were not correlated with lipid and lipoprotein concentrations. 5. We conclude that there is impaired endothelial and smooth muscle cell function in men with diet-treated non-insulin-dependent diabetes mellitus uncomplicated by overt hypertension or microproteinuria. Endothelial dysfunction may be related to diabetic dyslipidaemia and associated metabolic disturbances.
    No preview · Article · Nov 1996 · Clinical Science
  • G.F. Watts · J.K. Powrie · S.F. O'Brien · K.M. Shaw
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    ABSTRACT: The purpose of the study was to examine the contribution of alterations in lipoprotein metabolism to the progression of very-low-level albuminuria in insulin-dependent diabetes mellitus (IDDM). We measured serum concentrations of lipids, lipoproteins, and apolipoproteins in 53 normoalbuminuric diabetic patients without overt hypertension, whom we restudied after 10 years. Albuminuria was measured as the urinary albumin to creatinine ratio (UA/UC) in repeated early-morning samples. Over 10 years, UA/UC increased significantly (P < .001), and five patients (9.4%) progressed to microalbuminuria. The increase in albuminuria was significantly and positively related to the baseline serum concentrations of total cholesterol (P < .05), low-density lipoprotein (LDL) cholesterol (P = .05), non-high-density lipoprotein (HDL) cholesterol (P < .05), and apolipoprotein (apo) B (P < .001), but no significant associations were found with triglycerides, HDL cholesterol, apo A-1, or lipoprotein(a) [Lp(a)]. The relative risk of developing microalbuminuria for a serum apo B concentration more than 1.1 g/L was 3.8 (95% confidence interval [CI], 1.9 to 7.7). In multiple linear regression analysis, serum apo B (P < .05) and glycated hemoglobin ([HbA] P < .05) at baseline were significant independent predictors of the increase in albuminuria, with no significant associations found for sex, smoking, duration of diabetes, mean arterial blood pressure (BP), or family history of cardiovascular disease and hypertension; the regression model predicted 42% of the variation in UA/UC at 10 years. The findings suggest that an abnormality in the metabolism of apo B may be independently associated with progression of very-low-level albuminuria and possibly with the development of early nephropathy in IDDM patients.
    No preview · Article · Sep 1996 · Metabolism
  • G.F. Watts · S.F. O'Brien · K.M. Shaw
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    ABSTRACT: The frequency of urinary infection was determined using quantitative microbiology in 172 insulin-dependent diabetic patients repeatedly being tested for microalbuminuria over 18 months on at least six occasions. The point prevalence of urinary infection at first screening for microalbuminuria was 3 %. Over the period of study, 20 of the patients (12 %) showed evidence of urinary infection, defined as a pure growth of a recognized pathogen >107 l−1. Infection was more common in women than men (20 % vs 5 %, p<0.01) and was significantly associated with the presence of peripheral neuropathy (p<0.05). Infection was not related to patient age, duration of diabetes, glycaemia, blood pressure, retinopathy or autonomic neuropathy. There were no significant within-patient differences in albumin excretion, glycaemic control or blood pressure in relation to the presence and absence of urinary infection. In only one patient (5 %) did urinary infection significantly increase the urinary albumin excretion and this was associated with pyuria. We conclude that the presence of urinary infection does not apparently affect the measurement of urinary albumin excretion unless pyuria is present. Unless diabetic patients are symptomatic, examination of the urine for infection is probably unwarranted when testing for microalbuminuria.
    No preview · Article · Jun 1996
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    ABSTRACT: We aimed to examine the relationship of serum lipids, lipoproteins, apolipoproteins and antioxidants with renal dysfunction as measured by urinary excretion of albumin and of retinol binding protein (RBP) in insulin-dependent diabetes mellitus (IDDM). We studied 121 patients with IDDM. Glomerular function was assessed as the urinary albumin/creatinine ratio (UA/UC), and tubular function as the urinary retinol-binding protein/creatinine ratio (UR/UC), both measured in three early morning spot urine samples. The mean (range) UA/UC was 1.95 mg/mmol (0.3-476.5) and UR/UC was 17.5 micrograms/mmol (1.0-1853.8). 17% of the patients had a UA/UC > 3 mg/mmol and 33% had a UR/UC > 20 micrograms/mmol. Significant positive correlations were observed between both UA/UC and UR/UC and the following: serum total cholesterol (P < 0.005); triglycerides (P < 0.001); apolipoproteins A-I (P < 0.05), A-II (P < 0.02) and B (P < 0.002); glycated haemoglobin (P < 0.002). No significant associations were found with serum vitamin E, beta-carotene or total antioxidant activity. In multiple regression, only UA/UC was independently associated with serum apo B and cholesterol concentrations. In conclusion, in IDDM glomerular dysfunction, as measured by UA/UC, is associated with elevated serum cholesterol, triglycerides, apo B, apo A-I and apo A-II, but not with HDL cholesterol or antioxidant status. Tubular dysfunction tends to occur with increasing albuminuria, but it is not independently associated with serum lipid, lipoprotein, apolipoprotein or antioxidant levels.
    No preview · Article · May 1996 · Diabetes Research and Clinical Practice
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    S F O'Brien · G F Watts · J K Powrie · K M Shaw
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    ABSTRACT: To determine the association between exercise-induced albuminuria and the development of microalbuminuria over 10 years in subjects with insulin-dependent diabetes mellitus (IDDM) who were initially normoalbuminuric. Thirty-two patients with IDDM and a resting urinary albumin/creatinine ratio (UA/UC) < 2.1 mg/mmol (< 15 micrograms/min) were exercised after water loading on a treadmill for 20 min at double their resting heart rate. UA/UC was determined before and after exercise. The exercise test was considered positive if the UA/UC was > 4.3 mg/mmol (> 30 micrograms/min). Results were compared with resting UA/UC after a 10-year follow-up. Persistent microalbuminuria was defined as a UA/UC > 2.1 mg/mmol (> 15 micrograms/min) in each of two early-morning urine collections. Five patients developed persistent microalbuminuria after 10 years, and four patients were predicted by a positive exercise test. Two patients with positive exercise tests did not develop persistent microalbuminuria. The sensitivity of the exercise test for the development of microalbuminuria was 80% (95% confidence interval [CI] 65.8-94.2%) and the specificity was 92.9% (95% CI 83.9-100%). The postexercise UA/UC was positively associated with the UA/UC after 10 years (P = 0.005, R2 = 0.31). This association was independent of HbA1, systolic blood pressure, body mass index, and duration of diabetes, but HbA1 remained an independent predictor (P = 0.02) of UA/UC at follow-up. Exercise testing may be useful for identifying normoalbuminuric IDDM patients who are susceptible to the later development of microalbuminuria.
    Preview · Article · Jan 1996 · Diabetes Care