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Hussain S.M.,Monash University | Wang Y.,Monash University | Wluka A.E.,Monash University | Shaw J.E.,Diabetes Institute | And 3 more authors.
Arthritis Care and Research | Year: 2015

Objective Low birth weight (LBW) and preterm birth have been associated with adverse adult outcomes, including hypertension, insulin resistance, cardiovascular disease, and reduced bone mass. It is unknown whether LBW and preterm birth affect the risk of osteoarthritis (OA). This study aims to examine whether LBW and preterm birth were associated with the incidence of knee and hip arthroplasty for OA. Methods A total of 3,604 participants of the Australian Diabetes, Obesity and Lifestyle Study who reported their birth weight and history of preterm birth and were age >40 years at the commencement of arthroplasty data collection comprised the study sample. The incidence of knee and hip replacement for OA during 2002-2011 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. Results One hundred and sixteen participants underwent knee arthroplasty and 75 underwent hip arthroplasty for OA. LBW (yes versus no; hazard ratio [HR] 2.04, 95% confidence interval [95% CI] 1.11-3.75, P = 0.02) and preterm birth (yes versus no; HR 2.50, 95% CI 1.29-4.87, P = 0.007) were associated with increased incidence of hip arthroplasty independent of age, sex, body mass index, education level, hypertension, diabetes mellitus, smoking, and physical activity. No significant association was observed for knee arthroplasty. Conclusion Although these findings will need to be confirmed, they suggest that individuals born with LBW or at preterm are at increased risk of hip arthroplasty for OA in adult life. The underlying mechanisms warrant further investigation. © 2015 by the American College of Rheumatology.


Ukena C.,Klinik fur Innere Medizin III | Mahfoud F.,Klinik fur Innere Medizin III | Kindermann I.,Klinik fur Innere Medizin III | Barth C.,Klinik fur Innere Medizin III | And 9 more authors.
Journal of the American College of Cardiology | Year: 2011

Objectives: This study sought to investigate the effects of interventional renal sympathetic denervation (RD) on cardiorespiratory response to exercise. Background: RD reduces blood pressure at rest in patients with resistant hypertension. Methods: We enrolled 46 patients with therapy-resistant hypertension as extended investigation of the Symplicity HTN-2 (Renal Denervation With Uncontrolled Hypertension) trial. Thirty-seven patients underwent bilateral RD and 9 patients were assigned to the control group. Cardiopulmonary exercise tests were performed at baseline and 3-month follow-up. Results: In the RD group, compared with baseline examination, blood pressure at rest and at maximum exercise after 3 months was significantly reduced by 31 ± 13/9 ± 13 mm Hg (p < 0.0001) and by 21 ± 20/5 ± 14 mm Hg (p < 0.0001), respectively. Achieved work rate increased by 5 ± 13 W (p = 0.029) whereas peak oxygen uptake remained unchanged. Blood pressure 2 min after exercise was significantly reduced by 29 ± 17/8 ± 15 mm Hg (p < 0.001 for systolic blood pressure; p = 0.002 for diastolic blood pressure). Heart rate at rest decreased after RD (4 ± 11 beats/min; p = 0.028), whereas maximum heart rate and heart rate increase during exercise were not different. Heart rate recovery improved significantly by 4 ± 7 beats/min after renal denervation (p = 0.009). In the control group, there were no significant changes in blood pressure, heart rate, maximum work rate, or ventilatory parameters after 3 months. Conclusions: RD reduces blood pressure during exercise without compromising chronotropic competence in patients with resistant hypertension. Heart rate at rest decreased and heart rate recovery improved after the procedure. (Renal Denervation With Uncontrolled Hypertension; [Symplicity HTN-2]; NCT00888433) © 2011 American College of Cardiology Foundation.


Cameron J.,Australian Catholic University | Worrall-Carter L.,Center for Nursing Research | Page K.,Center for Nursing Research | Riegel B.,University of Pennsylvania | And 2 more authors.
European Journal of Heart Failure | Year: 2010

Aims: Cognitive impairment occurs often in patients with chronic heart failure (CHF) and may contribute to sub-optimal self-care. This study aimed to test the impact of cognitive impairment on self-care. Methods and results: In 93 consecutive patients hospitalized with CHF, self-care (Self-Care of Heart Failure Index) was assessed. Multiple regression analysis was used to test a model of variables hypothesized to predict self-care maintenance, management, and confidence. Variables in the model were mild cognitive impairment (MCI; Mini-Mental State Exam and Montreal Cognitive Assessment), depressive symptoms (Cardiac Depression Scale), age, gender, social isolation, education level, new diagnosis, and co-morbid illnesses. Sixty-eight patients (75%) were coded as having MCI and had significantly lower self-care management (η2= 0.07, P, 0.01) and self-confidence scores (η2= 0.05, P < 0.05). In multivariate analysis, MCI, co-morbidity index, and NYHA class III or IV explained 20% of the variance in self-care management (P < 0.01); MCI made the largest contribution explaining 9% of the variance. Increasing age and symptoms of depression explained 13% of the variance in self-care confidence scores (P < 0.01). Conclusion: Cognitive impairment, a hidden co-morbidity, may impede patients' ability to make appropriate self-care decisions. Screening for MCI may alert health professionals to those at greater risk of failed self-care. © The Author 2010.


Nagareddy P.R.,Columbia University | Nagareddy P.R.,University of Kentucky | Kraakman M.,Diabetes Institute | Masters S.L.,Walter and Eliza Hall Institute of Medical Research | And 19 more authors.
Cell Metabolism | Year: 2014

Obesity is associated with infiltration of macrophages into adipose tissue (AT), contributing to insulin resistance and diabetes. However, relatively little is known regarding the origin of AT macrophages (ATMs). We discovered that murine models of obesity have prominent monocytosis and neutrophilia, associated with proliferation and expansion of bone marrow (BM) myeloid progenitors. AT transplantation conferred myeloid progenitor proliferation in lean recipients, while weight loss in both mice and humans (via gastric bypass) was associated with a reversal of monocytosis and neutrophilia. Adipose S100A8/A9 induced ATM TLR4/MyD88 and NLRP3 inflammasome-dependent IL-1β production. IL-1β interacted with the IL-1 receptor on BM myeloid progenitors to stimulate the production of monocytes and neutrophils. These studies uncover a positive feedback loop between ATMs and BM myeloid progenitors and suggest that inhibition of TLR4 ligands or the NLRP3-IL-1β signaling axis could reduce AT inflammation and insulin resistance in obesity. © 2014 Elsevier Inc.


Siebel A.L.,Diabetes Institute | Natoli A.K.,Diabetes Institute | Yap F.Y.T.,Diabetes Institute | Carey A.L.,Diabetes Institute | And 7 more authors.
Circulation Research | Year: 2013

RATIONALE:: High-density lipoprotein cholesterol elevation via cholesteryl ester transfer protein (CETP) inhibition represents a novel therapy for atherosclerosis, which also may have relevance for type 2 diabetes mellitus. OBJECTIVE:: The current study assessed the effects of a CETP inhibitor on postprandial insulin, ex vivo insulin secretion, and cholesterol efflux from pancreatic β-cells. METHODS AND RESULTS:: Healthy participants received a daily dose of CETP inhibitor (n=10) or placebo (n=15) for 14 days in a randomized double-blind study. Insulin secretion and cholesterol efflux from MIN6N8 β-cells were determined after incubation with treated plasma. CETP inhibition increased plasma high-density lipoprotein cholesterol, apolipoprotein AI, and postprandial insulin. MIN6N8 β-cells incubated with plasma from CETP inhibitor-treated individuals (compared with placebo) exhibited an increase in both glucose-stimulated insulin secretion and cholesterol efflux over the 14-day treatment period. CONCLUSIONS:: CETP inhibition increased postprandial insulin and promoted ex vivo β-cell glucose-stimulated insulin secretion, potentially via enhanced β-cell cholesterol efflux. © 2013 American Heart Association, Inc.


Carey A.L.,Diabetes Institute | Formosa M.F.,Diabetes Institute | Van Every B.,Alfred Hospital | Bertovic D.,Diabetes Institute | And 9 more authors.
Diabetologia | Year: 2013

Aims/hypothesis: Brown adipose tissue (BAT) activation increases energy consumption and may help in the treatment of obesity. Cold exposure is the main physiological stimulus for BAT thermogenesis and the sympathetic nervous system, which innervates BAT, is essential in this process. However, cold-induced BAT activation is impaired in obese humans. To explore the therapeutic potential of BAT, it is essential to determine whether pharmacological agents can activate BAT. Methods: We aimed to determine whether BAT can be activated in lean and obese humans after acute administration of an orally bioavailable sympathomimetic. In a randomised, double-blinded, crossover trial, we administered 2.5 mg/kg of oral ephedrine to nine lean (BMI 22 ± 1 kg/m2) and nine obese (BMI 36 ± 1 kg/m2) young men. On a separate day, a placebo was administered to the same participants. BAT activity was assessed by measuring glucose uptake with [18F] fluorodeoxyglucose and positron emission tomography-computed tomography imaging. Results: BAT activity was increased by ephedrine compared with placebo in the lean, but unchanged in the obese, participants. The change in BAT activity after ephedrine compared with placebo was negatively correlated with various indices of body fatness. Conclusions/interpretation: BAT can be activated via acute, oral administration of the sympathomimetic ephedrine in lean, but not in obese humans. © 2012 Springer-Verlag Berlin Heidelberg.


Russell M.,University of South Australia | Williams M.,University of South Australia | May E.,University of South Australia | Stewart S.,Diabetes Institute
Nature Reviews Cardiology | Year: 2010

Individuals with undetected stable angina pectoris (SAP) as a consequence of undiagnosed coronary artery disease are at high risk of poor quality of life and a premature fatal event (for example, sudden cardiac death out of hospital). If the extent and distribution of SAP are accurately identified at the population level, clinical screening could potentially be targeted and evaluated to optimize the management and secondary prevention of underlying coronary artery disease. Common measures of SAP in populations have important limitations. Measures chosen to identify such cases should reflect their validity as measures of undiagnosed SAP, currently symptomatic angina or lifetime diagnosis of angina. © 2010 Macmillan Publishers Limited. All rights reserved.


Jordan J.,Hannover Medical School | Yumuk V.,Istanbul University | Schlaich M.,Diabetes Institute | Nilsson P.M.,Lund University | And 6 more authors.
Journal of Hypertension | Year: 2012

Obese patients are prone to arterial hypertension, require more antihypertensive medications, and have an increased risk of treatment-resistant arterial hypertension. Obesity-induced neurohumoral activation appears to be involved. The association between obesity and hypertension shows large inter-individual variability, likely through genetic mechanisms. Obesity affects overall cardiovascular and metabolic risk; yet, the relationship between obesity and cardiovascular risk is complex and not sufficiently addressed in clinical guidelines. The epidemiological observation that obesity may be protective in patients with established cardiovascular disease is difficult to translate into clinical experience and practice. Weight loss is often recommended as a means to lower blood pressure. However, current hypertension guidelines do not provide evidence-based guidance on how to institute weight loss. In fact, weight loss influences on blood pressure may be overestimated. Nevertheless, weight loss through bariatric surgery appears to decrease cardiovascular risk in severely obese patients. Eventually, most obese hypertensive patients will require antihypertensive medications. Data from large-scale studies with hard clinical endpoints on antihypertensive medications specifically addressing obese patients are lacking and the morbidity from the growing population of severely obese patients is poorly recognized or addressed. Because of their broad spectrum of beneficial effects, renin-angiotensin system inhibitors are considered to be the most appropriate drugs for antihypertensive treatment of obese patients. Most obese hypertensive patients require two or more antihypertensive drugs. Finally, how to combine weight loss strategies and antihypertensive treatment to achieve an optimal clinical outcome is unresolved. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Vigersky R.A.,Diabetes Institute
Journal of Diabetes Science and Technology | Year: 2011

Despite some progress in reducing the rate of diabetic complications, the epidemic rise in incidence of diabetes mellitus ensures that there will be an increasing number of patients in the coming decades with complex health care management issues who will need efficient and effective care. The management of patients with diabetes is an ever-challenging endeavor attributable to several factors. These include, among others, (1) limited provider expertise, (2) decreasing time of a patient visit, (3) increasing complexity of drug management, (4) limited use of self-monitoring of blood glucose by patients and/or providers, (5) clinical inertia, and (6) nonadherence. Technology-driven innovative solutions, including those using virtual reality, are desperately needed to assist both patients and their providers in overcoming the exigencies of this protean disease. © Diabetes Technology Society.


Coles L.T.,Diabetes Institute | Clifton P.M.,Diabetes Institute
Nutrition Journal | Year: 2012

Background: The consumption of beetroot juice on a low nitrate diet may lower blood pressure (BP) and therefore reduce the risk of cardiovascular events. However, it is unknown if its inclusion as part of a normal diet has a similar effect on BP. The aim of the study was to conduct a randomized controlled trial with free-living adults to investigate if consuming beetroot juice in addition to a normal diet produces a measureable reduction in BP. Method. Fifteen women and fifteen men participated in a double-blind, randomized, placebo-controlled, crossover study. Volunteers were randomized to receive 500 g of beetroot and apple juice (BJ) or a placebo juice (PL). Volunteers had BP measured at baseline and at least hourly for 24-h following juice consumption using an ambulatory blood pressure monitor (ABPM). Volunteers remained at the clinic for 1-h before resuming normal non-strenuous daily activities. The identical procedure was repeated 2-wk later with the drink (BJ or PL) not consumed on the first visit. Results: Overall, there was a trend (P=0.064) to lower systolic blood pressure (SBP) at 6-h after drinking BJ relative to PL. Analysis in men only (n=13) after adjustment for baseline differences demonstrated a significant (P<0.05) reduction in SBP of 4 - 5 mmHg at 6-h after drinking BJ. Conclusions: Beetroot juice will lower BP in men when consumed as part of a normal diet in free-living healthy adults. Trial registration. anzctr.org.au ACTRN12612000445875. © 2012 Coles and Clifton.

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