Gerald F Watts

Orygen The National Centre of Excellence in Youth Mental health, Melbourne, Victoria, Australia

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Publications (637)2884.08 Total impact

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    ABSTRACT: Objective: To evaluate the performance of a new electronic screening tool (TARB-Ex) in detecting general practice patients at potential risk of familial hypercholesterolaemia (FH). Methods: Medical records for all active patients seen between 2012 and 2014 (n=3708) at a large general practice in Perth, Western Australia were retrospectively screened for potential FH risk using TARB-Ex. Electronic extracts of medical records for patients identified with potential FH risk (defined as Dutch Lipid Clinic Network Criteria (DLCNC) score ≥5) through TARB-Ex were reviewed by a general practitioner (GP) and lipid specialist. High-risk patients were recalled for clinical assessment to determine phenotypic FH diagnosis. Performance was evaluated against a manual record review by a GP in the subset of 360 patients with high blood cholesterol (cholesterol ≥7 mmol/L or low-density lipoprotein cholesterol ≥4.0 mmol/L). Results: Thirty-two patients with DLCNC score ≥5 were identified through electronic screening compared with 22 through GP manual review. Sensitivity was 95.5% (95% CI 77.2% to 99.9%), specificity was 96.7% (95% CI 94.3% to 98.3%), negative predictive accuracy was 99.7% (95% CI 98.3% to 100%) and positive predictive accuracy was 65.6% (95% CI 46.9% to 8%). Electronic screening was completed in 10 min compared with 60 h for GP manual review. 10 of 32 patients (31%) were considered high risk and recalled for clinical assessment. Six of seven patients (86%) who attended clinical assessment were diagnosed with phenotypic FH on examination. Conclusions: TARB-Ex screening is a time-effective and cost-effective method of systematically identifying potential FH risk patients from general practice records for clinical follow-up.
    No preview · Article · Feb 2016 · Heart (British Cardiac Society)
  • Alpo Vuorio · Gerald F. Watts · Petri T. Kovanen
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    ABSTRACT: According to current estimates, as many as 4.5 million people in Europe suffer from the heterozygous form of familial hypercholesterolemia (HeFH).1 Their plasma concentration of low-density lipoprotein cholesterol (LDL-C) is two to three times above normal from birth, and accordingly, if untreated, the risk of coronary heart disease (CHD) and acute myocardial infarction (AMI) is markedly increased compared with non-HeFH populations.1 Indeed, in the pre-statin era, a clinical study on the incidence of CHD in patients with molecularly defined HeFH showed that the mean age of onset of symptomatic CHD was 42 ± 7 (SD) years for men and 48 ± 11 years for women, and that the corresponding ages at the time of first AMI were 47 ± 12 and 59 ± 13 years, respectively (Figure 1).2 The early onset of clinically significant CHD in the pre-statin era is understandable, since the plasma concentration of LDL-C strongly elevated from birth. It also explains the early onset of subclinical coronary atherosclerosis in these patients. Thus, extrapolation of coronary angiographic data from HeFH males and HeFH females predicted that, on average, coronary stenosis starts at 17 and 25 years of age, respectively (Figure 2).3 Corresponding non-invasive data have been obtained recently by assessing accumulation of coronary plaque burden with computed tomography angiography in a HeFH patient population on suboptimal statin therapy, which had been initiated in adulthood.4 When the plaque burden was extrapolated to age, the data suggested that atherosclerotic plaques may start to develop in HeFH males and females at a mean age of ∼20 and 30 years, respectively. Moreover, the total plaque burden significantly predicted future coronary …
    No preview · Article · Feb 2016 · European Heart Journal
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    ABSTRACT: Context: The metabolism of HDL is severely impaired in individuals with abdominal obesity. However the specific metabolism of apoA-II, the second major apolipoprotein of HDL remains poorly known. The relationships between HDL apoA-II catabolism and other metabolic variables that may be modified in abdominal obesity, such as VLDL subspecies (VLDL1, VLDL2) kinetics, remain to be investigated. Objectives: Our aim was to study the associations between apoA-II fractional catabolic rate (FCR) and the kinetics of VLDL subspecies and apoA-I. Design: We carried out a multicentre in vivo kinetic study using stable isotopes (deuterated leucine and glycerol) in 62 individuals with abdominal obesity. Results: In univariate analysis, apoA-II FCR was positively correlated with BMI, subcutaneous fat, liver fat, apoA-I FCR, apoA-I PR, apoA-II pool, apoA-II PR, VLDL1-triglycerides PR, VLDL2-triglycerides PR, VLDL2-triglycerides FCR, VLDL2-apoB FCR and negatively with HDL-C/apoA-I ratio. After adjustment for apoA-I FCR, a strong positive correlation between apoA-II FCR and VLDL1-TG indirect FCR was observed (r=0.520, p<0.0001). In multivariate analysis, apoA-II FCR was independently and positively associated with apoA-I FCR (p<0.0001) and VLDL1-TG indirect FCR (p<0.0001). Both variables explained 59.7% of the variability in apoA-II FCR. Conclusions: We show that, in abdominally obese individuals, apoA-II FCR is positively and independently associated with both apoA-I FCR and VLDL1-TG indirect FCR. These data suggest that, in a condition of delayed VLDL1 catabolism, such as abdominal obesity, retention of apoA-II in the VLDL1 pool may occur, with an effect on apoA-II catabolism. The consequences of this link between VLDL1 catabolism and apoA-II catabolism remain to be determined.
    Full-text · Article · Feb 2016 · Journal of Clinical Endocrinology & Metabolism
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    ABSTRACT: Purpose: Patients with familial hypercholesterolemia (FH) are at markedly increased risk of coronary artery disease. Regular participation in three self-management behaviors, physical activity, healthy eating, and adherence to medication, can significantly reduce this risk in FH patients. We aimed to predict intentions to engage in these self-management behaviors in FH patients using a multi-theory, integrated model that makes the distinction between beliefs about illness and beliefs about self-management behaviors. Methods: Using a cross-sectional, correlational design, patients (N = 110) diagnosed with FH from a clinic in Perth, Western Australia, self-completed a questionnaire that measured constructs from three health behavior theories: the common sense model of illness representations (serious consequences, timeline, personal control, treatment control, illness coherence, emotional representations); theory of planned behavior (attitudes, subjective norms, perceived behavioral control); and social cognitive theory (self-efficacy). Results: Structural equation models for each self-management behavior revealed consistent and statistically significant effects of attitudes on intentions across the three behaviors. Subjective norms predicted intentions for health eating only and self-efficacy predicted intentions for physical activity only. There were no effects for the perceived behavioral control and common sense model constructs in any model. Conclusions: Attitudes feature prominently in determining intentions to engage in self-management behaviors in FH patients. The prominence of these attitudinal beliefs about self-management behaviors, as opposed to illness beliefs, suggest that addressing these beliefs may be a priority in the management of FH.
    No preview · Article · Jan 2016 · International Journal of Behavioral Medicine

  • No preview · Article · Jan 2016 · Journal of atherosclerosis and thrombosis
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    ABSTRACT: Aim: The aim of this meta-analysis was to evaluate the effect of statin therapy on plasma FFA concentrations in a systematic review and meta-analysis of controlled clinical trials. Methods: PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched (from inception to February 16, 2015) to identify controlled trials evaluating the impact of statins on plasma FFA concentrations. A systematic assessment of bias in the included studies was performed using the Cochrane criteria. A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. Random-effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of potential moderators. Results: Meta-analysis of data from 14 treatment arms indicated a significant reduction in plasma FFA concentrations following treatment with statins (WMD: -19.42%, 95% CI: -23.19, -15.64, p < 0.001). Subgroup analysis confirmed the significance of the effect with both atorvastatin (WMD: -20.56%, 95% CI: -24.51, -16.61, p < 0.01) and simvastatin (WMD: -18.05%, 95% CI: -28.12, -7.99, p < 0.001). Changes in plasma FFA concentrations were independent of treatment duration (slope: -0.10; 95% CI: -0.30, 0.11; p = 0.354) and magnitude of reduction in plasma low-density lipoprotein cholesterol concentrations (slope: 0.55; 95% CI: -0.17, 1.27; p = 0.133) by statins. Conclusions: The results of the present study suggest that statin therapy may lower plasma FFA concentrations. The cardiovascular and metabolic significance of this finding requires further investigation. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · British Journal of Clinical Pharmacology
  • Anthony S. Wierzbicki · Gerald F. Watts
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    ABSTRACT: Purpose of review: Familial hypercholesterolaemia is the commonest autosomal dominant disorder in man, but many questions about familial hypercholesterolaemia remain to be answered. Guidelines are increasing in importance as healthcare becomes standardized. The review suggests areas that require more investigation or where pertinent guidelines may need to be reviewed. Recent findings: Familial hypercholesterolaemia is commoner than previously thought, but its epidemiology needs further investigation against a background of changing environmental and lifestyle factors that may bear on its phenotypic expression. Screening for familial hypercholesterolaemia may be more difficult than might be thought as cascade testing may not capture all cases effectively and universal screening appears compelling, but requires testing and evaluation. Cardiovascular disease guidelines are moving to being risk based, but familial hypercholesterolaemia stands alone as defined by large database of lipids-cholesterol criteria. A risk-based approach may need to be considered for familial hypercholesterolaemia, but a good evidence base is required. The effects of older therapies on prognosis in familial hypercholesterolaemia are based on surrogate as opposed to cardiovascular disease outcomes. Novel efficacious but expensive therapies are on the horizon, but no specific outcome trials in familial hypercholesterolaemia are planned and they may not be cost-effective outside very severe familial hypercholesterolaemia. Further research is also required to trial and test different models of care for familial hypercholesterolaemia. Summary: Despite familial hypercholesterolaemia being a common genetic condition, aspects of basic epidemiology, risk assessment, treatment, and models of care remain uncertain.
    No preview · Article · Dec 2015 · Current Opinion in Lipidology
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    ABSTRACT: Familial hypercholesterolemia (FH) significantly increases the risk of coronary heart disease. Most individuals are unaware they have the condition. In the Western Australian Pregnancy Cohort (Raine) Study, 1 in 267 adolescents were found to have FH. Universal cholesterol screening in childhood may offer the best strategy for diagnosing FH.
    No preview · Article · Dec 2015 · The Journal of pediatrics
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    ABSTRACT: Background: Evacetrapib, a new cholesteryl ester transfer protein inhibitor, is being investigated as a potential therapeutic option for reducing cardiovascular events through increasing high-density lipoprotein cholesterol (HDL-C) concentrations. How evacetrapib affects other lipid parameters is less certain. The present study aimed to estimate the effect of evacetrapib on plasma lipid concentrations and to assess its safety through a systematic review and meta-analysis of randomized controlled trials. Methods: SCOPUS, Medline, and Google Scholar were searched to identify randomized controlled trials investigating the impact of evacetrapib on blood lipid concentrations published before December 29, 2014. A random-effects model (using the DerSimonian-Laird method) and the generic inverse variance method were used to examine the effect of evacetrapib on plasma lipid concentrations. The safety of evacetrapib was assessed by comparing the pooled incidence of adverse events (total adverse events, adverse events leading to study discontinuation, elevations in hepatic and muscular enzymes and blood pressure) between treatment and placebo groups. Sensitivity analyses were conducted using the one study remove approach. Meta-regression was performed to evaluate the association between changes plasma lipid concentrations and administered doses of evacetrapib. Results: Meta-analysis of 14 randomized treatment arms over a mean of 2 months suggested that evacetrapib significantly reduces low-density lipoprotein cholesterol (LDL-C) (weighted mean difference [WMD]: -21.11%, 95% confidence interval (CI): -24.89, -17.33, p<0.001) and elevated HDL-C (WMD: +86.00%, 95% CI: +67.63, +104.37, p<0.001) concentrations following treatment with evacetrapib. Evacetrapib had no significant effect on plasma triglycerides (WMD: -2.97%, 95% CI: -8.63, +2.69, p = 0.303) concentrations. The effects of evacetrapib on all three lipid indices (LDL-C, HDL-C and triglycerides) did not differ between subsets of trials administering evacetrapib as monotherapy or as add-on to statin therapy. Meta-regression suggested a dose-dependent effect of evacetrapib on plasma LDL-C and HDL-C, but not triglycerides concentrations. Meta-analysis suggested equivalent rates of adverse events in subjects receiving evacetrapib and placebo. Conclusion: Results of this meta-analysis suggested that evacetrapib, either as monotherapy or in combination with a statin, reduces LDL-C and increases HDL-C levels but has no effect on triglyceride concentrations. Adverse events appeared to be similar in subjects receiving evacetrapib and placebo in short-term follow-ups.
    No preview · Article · Nov 2015 · Current pharmaceutical design
  • Damon A Bell · Gerald F Watts
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    ABSTRACT: Purpose: The purpose of this review was to outline the current and emerging therapeutic options for the treatment of hypertriglyceridemia, with an emphasis on emerging therapies. Methods: A systematic literature search was conducted with the use of PubMed and Embase for articles on hypertriglyceridemia, with a focus on therapeutics, pharmacology, and management. Abstracts from recent international meetings were also reviewed for presentations of Phase I and II data on agents with triglyceride-lowering effects. A further review of the references identified from these articles was also performed. Findings: Consistent with the multifactorial cause of hypertriglyceridemia, the therapeutic options are broad and numerous. This review explores the current and potential therapeutic options for treating hypertriglyceridemia and outlines the potential mechanisms of action. However, the mechanism of triglyceride reduction is complex, multifactorial, or not fully elucidated for some of these agents. The magnitude of triglyceride reduction and findings of outcome studies are described. Implications: Management of hypertriglyceridemia is about to enter an exciting phase, with multiple emerging therapies in the final stages of development. However, caution is warranted, because studies of therapeutic agents over the previous decade have often not found cardiovascular outcome benefits despite encouraging effects on triglyceride concentrations.
    No preview · Article · Nov 2015 · Clinical Therapeutics
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    ABSTRACT: Background: Atherosclerosis is a lipid-driven inflammatory disease of the arterial wall involving complex and multifactorial processes. Proprotein convertase subtilisin kexin type 9 (PCSK9) may play a role in the development of atherosclerosis. Methods: We investigated the associations between serum PCSK9 and carotid intima-medial wall thickness (IMT), a measure of subclinical atherosclerosis that predicts cardiovascular events, in 295 asymptomatic subjects from community. Carotid IMT was determined by high-resolution B-mode carotid ultrasonography and serum PCSK9 was measured by immunoassay. Results: In univariate analysis, serum PCSK9 concentration was positively (P<0.05 in all) associated with age (r=0.204), BMI (r=0.149), waist circumference (r=0.139), systolic blood pressures (r=0.116), glucose (r=0.211), insulin (r=0.178), HOMA score (r=0.195), plasma triglyceride (r=0.285), total cholesterol (r=0.241) and LDL-cholesterol concentrations (r=0.172). In multivariate regression including male gender, hypertension, smoking status, HOMA score, obesity, LDL-cholesterol, lipoprotein (a) or markers of inflammation, serum PCSK9 remained an independent predictor of mean carotid IMT (P<0.001). Conclusions: These data suggest that serum levels of PCSK9 may contribute to increased risk of subclinical carotid atherosclerosis independent of conventional risk factors. Whether PCSK9 inhibition improves cardiovascular outcomes remains to be demonstrated in large, ongoing clinical trials.
    No preview · Article · Nov 2015 · Heart, Lung and Circulation
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    ABSTRACT: Objective: The effects of extended-release niacin (ERN; 1-2 g/d) on the metabolism of lipoprotein(a) (Lp(a)) and apolipoprotein (apo) B-100-containing lipoproteins were investigated in 11 statin-treated white men with type 2 diabetes mellitus in a randomized, crossover trial of 12-weeks duration. Approach and results: The kinetics of Lp(a) and very low-density lipoprotein (VLDL), intermediate-density lipoprotein, and low-density lipoprotein (LDL) apoB-100 were determined following a standardized oral fat load (87% fat) using intravenous administration of D3-leucine, gas chromatography-mass spectrometry, and compartmental modeling. ERN significantly decreased fasting plasma total cholesterol, LDL cholesterol, and triglyceride concentrations. These effects were achieved without significant changes in body weight or insulin resistance. ERN significantly decreased plasma Lp(a) concentration (-26.5%) and the production rates of apo(a) (-41.5%) and Lp(a)-apoB-100 (-32.1%); the effect was greater in individuals with elevated Lp(a) concentration. ERN significantly decreased VLDL (-58.7%), intermediate-density lipoprotein (-33.6%), and LDL (-18.3%) apoB-100 concentrations and the corresponding production rates (VLDL, -49.8%; intermediate-density lipoprotein, -44.7%; LDL, -46.1%). The number of VLDL apoB-100 particles secreted increased in response to the oral fat load. Despite this, total VLDL apoB-100 production over the 10-hour postprandial period was significantly decreased with ERN (-21.9%). Conclusions: In statin-treated men with type 2 diabetes mellitus, ERN decreased plasma Lp(a) concentrations by decreasing the production of apo(a) and Lp(a)-apoB-100. ERN also decreased the concentrations of apoB-100-containing lipoproteins by decreasing VLDL production and the transport of these particles down the VLDL to LDL cascade. Our study provides further mechanistic insights into the lipid-regulating effects of ERN.
    No preview · Article · Oct 2015 · Arteriosclerosis Thrombosis and Vascular Biology
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    Full-text · Article · Oct 2015 · Circulation
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    ABSTRACT: Background-Android fat distribution (abdominal obesity) is associated with insulin resistance, hepatic steatosis, and greater secretion of large very low-density lipoprotein (VLDL) particles in men. Since abdominal obesity is becoming increasingly prevalent in women, we aimed to investigate the relationship between android fat and hepatic lipid metabolism in pre-and postmenopausal women. Methods and Results-We used a combination of stable isotope tracer techniques to investigate intrahepatic fatty acid synthesis and partitioning in 29 lean and 29 abdominally obese women (android fat/total fat 0.065 [0.02 to 0.08] and 0.095 [0.08 to 0.11], respectively). Thirty women were premenopausal aged 35 to 45 and they were matched for abdominal obesity with 28 postmenopausal women aged 55 to 65. As anticipated, abdominal obese women were more insulin resistant with enhanced hepatic secretion of large (404 +/- 30 versus 268 +/- 26 mg/kg lean mass, P<0.001) but not small VLDL (160 +/- 11 versus 142 +/- 13). However, postmenopausal status had a pronounced effect on the characteristics of small VLDL particles, which were considerably triglyceride-enriched (production ratio of VLDL2-triglyceride: apolipoprotein B 30 +/- 5.3 versus 19 +/- 1.6, P<0.05). In contrast to postmenopausal women, there was a tight control of hepatic fatty acid metabolism and triglyceride production in premenopausal women, whereby oxidation (r(s)=-0.49, P=0.006), de novo lipogenesis (r(s)=0.55, P=0.003), and desaturation (r(s)=0.48, P=0.012) were closely correlated with abdominal obesity-driven large VLDL-triglyceride secretion rate. Conclusions-In women, abdominal obesity is a major driver of hepatic large VLDL particle secretion, whereas postmenopausal status was characterized by increased small VLDL particle size. These data provide a mechanistic basis for the hyperlipidemia observed in postmenopausal obesity.
    No preview · Article · Oct 2015 · Journal of the American Heart Association
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    ABSTRACT: Introduction: Increased plasma levels of von Willebrand factor Antigen (vWF:Ag) are associated with high risk of coronary artery disease. The effect of statin therapy on vWF:Ag levels remains uncertain. Therefore the aim of this meta-analysis was to evaluate the effect of statin therapy on vWF:Ag Levels. Methods: A systematic multiple-database search was carried out to identify RCTs that investigated the effect of statins on plasma vWF:Ag levels. Results: Random-effect meta-analysis of 21 treatment arms revealed a significant decrease in plasma vWF:Ag levels following statin therapy (SMD:-0.54, 95%CI: -0.87, -0.21, p=0.001). In subgroup analyses, the greatest effect was observed with simvastatin (SMD:-1.54, 95%CI: -2.92, -0.17, p=0.028) and pravastatin (SMD:-0.61, 95%CI: -1.18, -0.04, p=0.035), but not with fluvastatin (SMD:-0.34, 95%CI: -0.69, 0.02, p=0.065), atorvastatin (SMD:-0.23, 95%CI: -0.57, 0.11, p=0.179) and rosuvastatin (SMD:-0.20, 95% CI: -0.71, 0.30, p=0.431). The lowering effect of statins on plasma vWF:Ag levels was greater in the subset of studies lasting ≥12 weeks (SMD:-0.70, 95%CI: -1.19, -0.22, p=0.005) compared with that of studies lasting <12 weeks (SMD:-0.34, 95%CI: -0.67, 0.003, p=0.052). Finally, low-intensity statin therapy was not associated with a significant reduction in vWF:Ag levels (SMD:-0.28, 95%CI: -0.82, 0.27, p=0.320), but a significant effect was observed in high-intensity statin trials (SMD:-0.66, 95%CI: -1.07, -0.24, p=0.002). Conclusions: This meta-analysis of available RCTs demonstrates a significant reduction in plasma vWF:Ag levels following statin therapy.
    Full-text · Article · Oct 2015 · Thrombosis and Haemostasis
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    ABSTRACT: Background: Vascular disease is a common cause of death in patients with chronic hepatitis C (CHC) infection, however, the association between CHC and atherosclerosis is unclear. Aims: We wished to determine whether patients with CHC have increased subclinical vascular disease and whether genotype or anti-viral treatment modifies this risk. Methods: Fifty CHC patients and 22 age and sex matched healthy controls underwent clinical and biochemical assessment for vascular risk factors. In addition, vascular risk was assessed by measuring arterial stiffness [aortic augmentation index (AIx) and carotid-femoral pulse wave velocity (PWV)], endothelial dysfunction [(brachial artery flow-mediated dilatation (FMD) and dilatation post GTN administration (GTNMD)] and carotid intima-media thickness (CIMT). Assessment was repeated in subset of CHC patients (n = 12) undergoing anti-viral treatment 18 months after initiation of treatment. Results: Baseline vascular risk factors and measures of arterial stiffness, endothelial dysfunction and CIMT were not different between cases and controls (p > 0.2 for all). Genotype 1 CHC patients had greater endothelial dysfunction with lower FMD (8.2 ± 3.5% vs 10.9 ± 5.2%, p = 0.03) and higher right CIMT (0.6 ± 0.1 mm vs 0.5 ± 0.07 mm, p = 0.04) compared with non-genotype 1. Patients who achieved sustained virological response (7/12) showed significant improvement in insulin resistance (HOMA-IR 2.3 ± 1.2 vs 1.8 ± 0.8, p = 0.02) and arterial stiffness (PWV 7.4 ± 1.1 m/s vs 6.5 ± 0.6 m/s, p = 0.04). Conclusions: Subclinical vascular disease is not greater in CHC subjects compared with controls. However, among CHC subjects, genotype 1 infection is associated with greater endothelial dysfunction and increased carotid-intima medial thickness compared with non-genotype 1 infection. Successful viral eradication may improve insulin resistance and arterial stiffness. This article is protected by copyright. All rights reserved.
    No preview · Article · Oct 2015 · Internal Medicine Journal
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    ABSTRACT: Background: Psychosis is associated with an increased risk of diabetes mellitus. A positive synergy between antipsychotic drug effects and a pre-existing liability to diabetes mellitus might explain the especially high relative risk of diabetes mellitus in young adults with psychosis. We aimed to assess the individual and joint effect of age, family history of diabetes mellitus, and currently prescribed antipsychotic drug treatment on risk for diabetes mellitus. Methods: In this study, we used data from the 2010 Australian National Survey of Psychosis-an observational study done at seven sites in five Australian states. We included data from 1155 people with psychosis aged 18-64 years who were in contact with psychiatric services and who gave a fasting blood sample to test for current diabetes mellitus. Using logistic regression, we modelled the association of diabetes mellitus with age, family history of diabetes mellitus, and current antipsychotic drug treatment. We compared model fit with and without two-way and three-way interaction terms and used likelihood ratio tests to establish which terms to include in the final model. Findings: After adjustment for older age, which was an independent risk factor, compared with not taking antipsychotic drugs, antipsychotic drug treatment was associated with diabetes mellitus only in those without a family history of diabetes mellitus (clozapine adjusted odds ratio [OR] 7·22, 95% CI 1·62-32·20, p=0·01; quetiapine 5·91, 1·33-26·30, p=0·02; aripiprazole 5·06, 0·86-29·64, p=0·07; risperidone 4·17, 0·90-19·24, p=0·07; and olanzapine 2·23, 0·45-11·06, p=0·32). Antipsychotic drug treatment was not associated with additional risk of diabetes mellitus in those with a family history (clozapine adjusted OR 1·51, 95% CI 0·64-3·54, p=0·34; quetiapine 1·09, 0·49-2·43, p=0·82; aripiprazole 0·43, 0·12-1·49, p=0·18; risperidone 1·12, 0·48-2·63, p=0·79; and olanzapine 0·67, 0·26-1·71, p=0·39). Interpretation: People with psychosis are at increased risk of diabetes mellitus if they have a family history of diabetes mellitus or if they have no family history of diabetes mellitus but are taking antipsychotic drugs. Increasing age increases risk but independently of family history or antipsychotic drug treatment. Clinicians should not think the absence of a family history of diabetes mellitus protects their patients from the diabetic side-effects of antipsychotics. Funding: Australian Federal Government and Orygen.
    Full-text · Article · Oct 2015 · The Lancet Psychiatry
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    Full-text · Dataset · Oct 2015
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Publication Stats

16k Citations
2,884.08 Total Impact Points


  • 2015
    • Orygen The National Centre of Excellence in Youth Mental health
      Melbourne, Victoria, Australia
  • 1995-2015
    • Royal Perth Hospital
      Perth City, Western Australia, Australia
    • University of Western Australia
      • • School of Medicine and Pharmacology
      • • Western Australian Institute for Medical Research (WAIMR)
      Perth City, Western Australia, Australia
  • 2014
    • University of Brighton
      • School of Sport and Service Management
      Brighton, England, United Kingdom
    • Baker IDI Heart and Diabetes Institute
      Melbourne, Victoria, Australia
    • University of Pennsylvania
      • Institute for Translational Medicine and Therapeutics
      Philadelphia, Pennsylvania, United States
  • 2001-2014
    • University of Adelaide
      • Discipline of Medicine
      Tarndarnya, South Australia, Australia
    • University of Cape Town
      • Faculty of Health Sciences
      Kaapstad, Western Cape, South Africa
  • 2013
    • Gold Coast University Hospital
      Southport, Queensland, Australia
  • 2006-2008
    • Sir Charles Gairdner Hospital
      Perth City, Western Australia, Australia
  • 2007
    • University of Sydney
      Sydney, New South Wales, Australia
  • 2005
    • Shahid Beheshti University of Medical Sciences
      Teheran, Tehrān, Iran
  • 2004
    • Hospital Universitario Ramón y Cajal
      Madrid, Madrid, Spain
    • Aristotle University of Thessaloniki
      Saloníki, Central Macedonia, Greece
  • 2003
    • Sandwell and West Birmingham Hospitals NHS Trust
      Birmingham, England, United Kingdom
    • Aarhus University Hospital
      Aarhus, Central Jutland, Denmark
  • 2001-2003
    • Curtin University
      Bentley, Western Australia, Australia
  • 1999
    • University of Washington Seattle
      Seattle, Washington, United States
  • 1994
    • University of London
      Londinium, England, United Kingdom
  • 1988
    • St. Mary Medical Center
      Long Beach, California, United States